I-Base Guide to Avaoiding and Managing Side Effects
ISSN 1475-0740 i-base 0808 800 6013
May 2008 Always watch for out-of-date info
Avoiding and managing side effects
When, what, why Changing treatment Regular and alternative treatment You and your doctor Further reading
HIV i-Base publications: Introduction to Combination Therapy Guide to Changing Treatment HIV, Pregnancy and Women’s Health Guide to HIV and Hepatitis Coinfection HIV Treatment Bulletin All publications are free Please call 020 7407 8488 www.i-Base.info guide to side effects FEBRUARY 2008 MAY 2008
Contents
Section 1: General information Introduction 3 General questions 4 How to report side effects 8 Side effects diary 9 How side effects are graded 10 Side effects and drug levels 12 Changing treatment 13 Side effects and adherence 15 You and your doctor 16 Section 2: Individual side effects General side effects: Diarrhoea 18 Nausea and vomiting 22 Fatigue – feeling tired 24 Skin rash 26 Dry skin, nail problems, hair loss, frozen shoulder 28 Sexual problems 29 Insomnia – disturbed sleep 31 CNS side effects: 33 mood alteration, anxiety, dizzyness & sleep disturbance Progressive and acute side effects Peripheral neuropathy 36 Liver toxicity, rash and nevirapine 40 Lactic acidosis, pancreatitis and fatty liver 42 Abacavir hypersensitivity reaction (HSR) 44 Kidney toxicity including kidney stones 45 Increased bilirubin, jaundice (yellow skin or eyes) 46 T-20: injection site reactions (ISRs) and other side effects 48 Lipodystrophy: fat loss, fat accumulation and metabolic changes 53 Heart disease 64 Bone mineral changes 68
Section 3: Further information 70
Disclaimer: Information in this booklet is not intended to replace information from your doctor. Decisions relating to your treatment should always be taken in consultation with your doctor. HIV information dates quickly, please call to see if up-dated information is available. Not-for-profit copying is encouraged or call for additional free copies. Produced by HIV i-Base. www.i-Base.info i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Introduction
This is the fourth edition of a booklet This may be because of poor that was first produced in 2001. Over communication when you see your 65,000 copies have been distributed doctor. This may be because there in the UK and it has been translated is not enough time, or perhaps your into over 20 languages including doctor doesn’t understand exactly how Spanish, Italian, Chinese, Bulgarian, you are affected. Sometimes you may Portuguese, Hindi, Nepali, Romanian just forget to mention a problem. Ways and Russian. of improving this communication are We now focus on the most commonly included throughout this booklet. used and recommended treatments, Sometimes, if side effects continue including new and recently approved for several months, you may think it drugs. is easier not to mention them at all This booklet will help you get the or to just put up with them. This is most out of your relationship with your not a good approach as they may be doctor and other health professionals. symptoms of a more serious illness. Newer treatments may also have It should help you get better medical care and improved health. It should become available since you first help you feel more in control of your reported them, which you may not treatment, and, most importantly, to know about. get a better quality of life. The first section of this booklet includes general information, including It has been written by people who are HIV-positive. We have been on many recording side effects, communication of these treatments and had many of with your doctor and your rights as a the side effects.Wehave also learnt to patient. negotiate our own health care in the The second section includes specific NHS with hospitals and clinics. information on each side effect or set Managing side effects is something of symptoms. We have included the that you need to be active about. range of approaches for managing each side effect, including regular Every drug will cause some side medications and alternative treatments effects in some people. But not where appropriate. We have also www.i-Base.info everyone will get the same side effects included information related to HIV with the same drugs. Although you and long-term health – for example may have difficulty with one treatment, heart disease and bone health – even there is nearly always something you though these are less likely to be a can do about it: by altering the dose, side effect of HIV drugs, changing to another drug, or using another drug to treat the side effect. Finally, there is a short list of recommendations for further reading However, many people do not receive online. These links will help you find as much help in managing side effects additional information and will help you as they need. keep up-to-date with future research. i-Base publications guide to side effects FEBRUARY 2008 MAY 2008
General questions
What are side effects? Sometimes side effects are so mild that they are rarely noticed, and they Every drug is generally licensed to may only affect a small proportion of treat a specific illness. Any other effect the people who use the drug. is called a side effect. Side effects are also called adverse events (ae’s) or Sometimes side effects only become drug toxicities. apparent after the drugs have been licensed and approved, when many In this booklet we will focus on more people use them over a much unwanted side effects of HIV longer period than the original studies. antiretroviral drugs (ARVs). All drugs have side effects, but not Many of the symptoms of side effects everyone taking drugs will experience are similar to symptoms of illnesses. the same effects and to the same Different treatments are needed when extent. What is important is how they these symptoms relate to illnesses. affect you. Why do side effects occur? The leaflet included with your drugs Although drugs are designed to (called the Summary of Product work against specific illnesses, they Characteristics or SPC) lists all the sometimes interfere with other ways reported range of possible side effects that your body works. associated with each drug. The SPC also includes other useful information It is difficult to develop a drug that including how the drug needs to works against HIV. Any drug that be taken, possible interactions with is approved has undergone a lot of other medications, and other useful research trying to minimise toxicity. information. Often, very promising drugs are never approved because of toxicity. The aim How are side effects for is always to develop safer and more tolerable, as well as better drugs. drugs reported? When drugs are first studied, every Most people – people living with HIV, side effect is recorded, even if it doctors and researchers – recognise cannot be directly linked to the drug that the current drugs available to treat being studied. This means that if you HIV are far from perfect. New drugs in look at the leaflet that comes with your the future should be easier to tolerate. treatment you usually find a long list of Do all drugs have side potential side effects. effects? The risk of getting most of these listed side effects is usually very low - often Most drugs have side effects of some less than a 1 in 10 or 1 in 100 chance. sort. In the majority of cases these will be mild and easily manageable. www.i-Base.info i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
If side effects only become apparent Often people are not given a choice after the drug has been approved, when starting treatment. This is not as with lipodystrophy, the drug leaflet right. your doctor should at least talk may not have this latest information. about two options. If you ever need to change a drug Starting treatment for the because of tolerability, you can first time? usually use it again later if you need Everyone worries about the risk of to [except for abacavir - see page 44]. side effects before they start HIV Just because you used a drug once, treatment. It will help if you know what doesn’t mean you have ‘used up your to expect from different drugs before option’ of using it again in the future. choosing your combination. Usually side effects improve after Ask for information about each of the the first few days, weeks or months, drugs you might take, including the but sometimes they don’t. See the likelihood of side effects. Ask what sections on each side effect in this percentage of people had side effects guide for an idea of how long you related to each drug and how serious should put up with them before they were. changing. You may be asked to consider You do not have to continue with a entering a study looking at side effects drug to prove anything to yourself in different combinations. These or your doctor. If something is studies are important to define the wrong, ask your doctor to change extent of side effects when different to something else. Some drugs are drugs are used together. just not for everyone. Can I change drugs easily? Can I know if I will get side If this is your first combination, you effects? will usually have a lot of flexibility in Generally you cannot know how choosing and changing drugs until you difficult or easy you will find any find a combination that works and is particular drug until you take it. Some tolerable. symptoms may make the risk of side www.i-Base.info There are more than 20 HIV drugs effects greater. approved in the UK, including several For example, if you have raised formulations that include more than liver enzymes, they may increase one drug in each pill. While you can’t even higher if you use nevirapine. quite mix and match them all, you If you start with high cholesterol or have a lot of choice. If one or more triglycerides, they may be more likely of the drugs in your combination are to increase if you use some protease difficult to tolerate, you can change it inhibitors. for another. i-Base publications guide to side effects FEBRUARY 2008 MAY 2008
Are side effects different in Getting your doctor to men and women? help… Most trials have enrolled too few Unfortunately, some doctors generally women to be able to study differences think that their patients overestimate between men and women. Sometimes side effects. differences in side effects are only • They think that people exaggerate reported later. side effects, and that they are not For example, women have higher really as bad as their patients say. rates of side effects in some It is also true that most patients nevirapine studies (both liver toxicity actually underestimate side effects. and rash), which highlights the • People generally say that side importance of careful monitoring. effects are less difficult than In this example it took many years they really are, or often forget to before we found out that women were mention them at all. at a higher risk if their CD4 count was This means there can be a big 3 over 250 cells/mm when they started difference between what is actually treatment with nevirapine, and this is going on and what your doctor thinks now not recommended. is going on. There may also be differences relating This is one reason that side effects are to lipodystrophy and gender (see often under-treated. pages 53-63). What happens if side What about side effects and effects continue? adherence? If the first treatment you are given to Whether you are starting your first help with a side effect does not work, treatment or have been using HIV there are usually other drugs that you drugs for a long time, your doctor can use. should have talked to you about the importance of adherence. This is why we listed a range of options, including alternative This is the term that describes taking treatments, for each main symptom. If the meds in your combination exactly one doesn’t work – try others. as they are prescribed - ie on time and following any diet advice. There is Changing treatment is an important special section about adherence and option. side effects on page 15. If your quality of life is bad because of the side effects, you may chose to look at experimental strategies like an immune-boosting treatment such as IL-2. www.i-Base.info i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
i-Base can answer your questions by email or online: [email protected] www.i-base.info/questions Using the Yellow Card scheme In the UK, both patients and healthcare professionals can report side effects directly to the Medicines and Healthcare products Regulatory Agency (MHRA). Side effects from new drugs often emerge after approval, and it is worth reporting them even if you aren’t sure. This contributes to an important safety database, especially for new and unexpected side effects. http://yellowcard.mhra.gov.uk/
If you are feeling more anxious or nervous, are not sleeping properly, have a lower sex drive... or are too nauseous to eat proper meals, it is www.i-Base.info important that your doctor understands this.
i-Base publications guide to side effects FEBRUARY 2008 MAY 2008
How to report side effects
If you want your doctor to understand • Recording how severe side effects your side effects and how they affect are when they occur is better than you, you need to be able to describe recording them later. them clearly. • Have you noticed anything that Your doctor can then check for other helps to reduce them? possible causes (ie that diarrhoea is Quality of life not related to food poisoning; or that This can really help your doctor low sex drive is not related to low understand how difficult the side testosterone levels). effects are for you. The best way to do this is to keep a • Many people put up with chronic side effects diary from when you start diarrhoea without explaining to a new treatment until you next see their doctor that it stops them ever your doctor. going to the pub or the cinema. Information about how to describe symptoms generally includes • If you are feeling more anxious or information about the following areas: nervous, are not sleeping properly, have a lower sex drive, have Frequency experienced taste changes, or are • How often do you get symptoms? too nauseous to eat proper meals, • Once or twice a week? Once every it is important that your doctor day, or 5 – 10 times a day etc? understands this. • Do they occur at night as well as Symptoms of lipodystrophy - the term during the day? for body fat changes - are difficult to Duration measure. Although minor changes • How long do the symptoms last? may not be a problem, more severe • If you feel sick or get headaches, symptoms can change your whole does this last for 20 minutes or for outlook on life, and lead to depression. 3 – 4 hours, or for different times? If side effects affect your adherence • Is there a pattern to when they (ie you are not taking all your meds at occur – ie when you take your the correct time), you must tell your medications or at a regular time doctor about this. afterwards? A side effects diary is included on Severity page 9. Take this diary with you when • How bad are the symptoms? you see your doctor at your next • Often it helps to rate them on appointment. a scale (from 1 for mild to 5 for severe). • A scale is a useful tool for describing anything that involves pain. www.i-Base.info i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm Side effects diary
Use this page to record any changes in your health that could be related to side effects. You may not get any side effects but if you do, then this diary will be useful. The most common side effects are listed below but include others even if they are not listed here.
1. Tingling in hands/feet 9. Stomach pains 17. Vivid dreaming 2. Pain in hands/feet 10. Hair loss 18. Feeling anxious 3. Nausea/vomiting 11. Body shape changes 19. Eyesight changes 4. Headache 12. Weight gain 20. Mood swings 5. Feeling tired 13. Weight loss 21. Feeling depressed 6. Dry skin 14. Changes in taste or appetite 22. Injection site reactions 7. Rash 15. Sexual problems 23. Yellow eyes or skin 8. Diarrhoea 16. Sleep disturbance 24. Other(s) specify
Side effect Date Time(s) Scale: 1= mild to 5 = severe 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 www.i-Base.info Other comments and questions to ask your doctor:
i-Base publications guide to side effects FEBRUARY 2008 MAY 2008
How side effects are graded
Most information about the risk of side GRADE 1 (Mild) effects comes from the studies when Transient (goes away after a short the drugs were first developed. This time) or mild discomfort; no limitation is why it is important to report all side in your daily activity; no medical effects if you take part in a trial. intervention/therapy required. Trials collect information about how GRADE 2 (Moderate) often all side effects occur and how serious they are. But studies for new Your daily activity is affected mild to HIV drugs only use relatively small moderately – some assistance may groups of people for relatively short be needed; no or minimal medical periods. intervention/therapy required. Some side effects only become GRADE 3 (Severe) apparent after the drugs have been Your daily activity is markedly reduced approved and they have been used by – some assistance usually required; thousands more people. medical intervention/therapy required, Knowing what the risk of side effects hospitalisation or hospice care are for a particular drug -– ie what possible. percentage of people get these side GRADE 4 (Potentially life effects – can help you to make an threatening) informed decision about which drugs to choose. Where a side effect is very Extreme limitation to daily activity, common, knowing what percentage of significant assistance required; people who needed to change therapy significant medical intervention/ because of it, is useful too. therapy, hospitalisation or hospice care very likely. Information can be provided by your doctor, a community treatment A indication of grading (from the organisation, your friends or the United States Division of AIDS) is internet. It is usually also included in shown opposite together with specific the information that you should get details for some common side effects. with all drugs. Although there are slightly different details for reporting the severity of each side effect, medical research grades these from 1 to 4. Grade 1 is mild and grade 4 is serious, life threatening or requiring hospitalisation. www.i-Base.info 10 i-Base publications Table 1: Examples of how common side effects are graded by level of symptoms AST or ALT levels Liver toxicity: Side effect Diarrhoea
Fatigue
Mood disturbance
Nausea
Rash
Vomiting
information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm 1.25–2.5 Grade 1 3–4 loose stools a day OR mild diarrhoea lasting less than one week Normal activity reduced by less than 25% Mild anxiety, able to continue daily tasks
Mild OR transient, but reasonable food intake Redness or itchy skin on part or whole body
2–3 episodes a day OR mild vomiting for less than one week
Upper Limit Normal Grade 2 5–7 loose stool a day OR diarrhoea lasting more than one week Normal activity reduced by 25–50 % >2.5–5.0 ULN Moderate anxiety/dist- urbance, interfering with ability to work, etc Moderate discomfort OR intake decreased for Rash that breaks skin, less than 3 days hard or soft pimples OR light peeling/scaling 4–5 episodes a day OR mild vomiting for more than one week
Grade 3 Bloody diarrhoea OR over 7 loose stools a day OR needing IV treatment Normal activity reduced by feeling dizzy when standing over 50 %; cannot work 5.0–7.5 ULN Severe mood changes requiring medical treatment Unable to work Severe discomfort OR minimal food intake for Blistering, open ulcers, wet more than 3 days peeling, serious rash over large areas Severe vomiting of all food and fluids over 24 hours OR needing IV treatment OR feeling dizzy when standing www.i-Base.info Grade 4 Hospitalisation required (possible also for Grade 3) Unable to care for yourself > 7.5 ULN Acute psychosis, suicidal thoughts Hospitalisation required Severe rash, Stevens Johnson syndrome. Severe broken skin, etc Hospitalisation for IV treatment (possibly also for Grade 3)
i-Base publications 11 guide to side effects FEBRUARY 2008 MAY 2008
Side effects and drug levels
There can be large differences in When is Therapeutic Drug levels of drugs absorbed between Monitoring (TDM) appropriate? different people and by the same TDM usually involves taking a blood people at different times. Many sample after you have been on a different drug and food interactions treatment for at least two weeks. The can affect drug levels. hospital will need to know the exact Side effects are often related to the time that you took your previous dose level of a drug in your blood. in order for the test to be effective. For some HIV drugs, these levels Sometimes a sample is taken just can be tested, and the dose can be before you are due to take your next changed if this is appropriate. dose, and sometimes it is also taken • Protease inhibitors and NNRTIs 2–3 hours afterwards as well. are suitable drugs to measure TDM is important for children and • Nukes (d4T, AZT, 3TC, FTC, ddI, people with pre-existing liver or kidney abacavir and tenofovir) are not damage when routine recommended suitable for drug level monitoring dosing is not always appropriate. because the important levels of these drugs are inside cells and It is also appropriate whenever drug tests to measure this are not levels or drug interactions may be currently available linked to side effects. For example, the adult dose of Some clinics do this test routinely but atazanavir is 300mg plus 100mg in others you may need to ask for it. ritonavir, both once daily. The ritonanvir boosts the levels of atazanavir and leaves a safer higher TDM is important for dose at the end of each 24-hour children and people period. with pre-existing liver or If you get side effects with ritonavir kidney damage ... and... boosting though, it may be possible to use a higher dose of atazanavir whenever drug levels or (400mg daily) and not use the ritonavir drug interactions may at all. This should always be checked be linked to side effects. with TDM. TDM is available in the UK through programmes subsidised by the manufacturers of most PIs and NNRTIs. Drug interaction websites: For more information see: http://www.HIV-druginteractions.org http://www.delphicdiagnostics.com http://www.HIVpharmacology.com www.i-Base.info 12 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Changing treatment
As many side effects become easier If your current combination is not your over the first few weeks of treatment, if first treatment, your treatment history your initial symptoms are only mild or will determine your options, moderate, seeing whether they settle Changing only one or two drugs in down before changing treatment, can a combination is only recommended be good advice. when viral load is undetectable prior to But, if you can’t tolerate one treatment, the switch. Some people may switch then you can switch to an alternative to four or more drugs if they have without it affecting your future options. resistance from earlier combinations. If you are considering stopping or Switching between nukes interrupting any treatment it is vital that Most combinations involve at least you discuss this with your doctor. two ‘nukes’ (AZT, d4T, ddI, 3TC, FTC, The decision to change treatment abacavir, tenofovir). in order to manage side effects will So long as you haven’t developed depend on whether: resistance to the other nucleosides i) there are other HIV drugs you can (and you don’t use AZT and d4T use together; or 3TC and FTC together ii) the side effects are likely to get in the same combination), you can worse if you remain on the same use these drugs in many different drugs combinations. iii) you think that the side effects are related to drugs. Even though • If you get peripheral neuropathy there may not have been a proven (pain or numbness in your hands link, this may be a new report, or feet) this may be due to d4T, ddI and you may be the first person to or 3TC and you should switch or experience this. reduce the doses of those drugs, before the neuropathy becomes Close monitoring after a change of more serious. drugs will help you know whether the • d4T and AZT are associated with treatment that you switched from was fat loss from the face, arm and causing that side effect. legs. Switching to abacavir or www.i-Base.info Switching individual drugs is safe and tenofovir will reduce this risk and can improve your quality of life - and may reverse previous fat loss. still keep your viral load undetectable. • If you continue to get nausea or When switching drugs it may be safer fatigue using AZT (or Combivir or to add in the new drug to check that Trizivir, which both contain AZT) it is tolerable before discontinuing the then you could switch to another drug that is causing the side effect. If nuke. you have a detectable viral load before switching you should also have a resistance test first. i-Base publications 13 guide to side effects FEBRUARY 2008 MAY 2008
Switching between NNRTIs Using new drugs and new classes Nevirapine and efavirenz have similar of drugs potency but they have different side One of the advantages of new drugs effect profiles. Nevirapine has been is that they hopefully have fewer side more associated with skin rash and effects. liver toxicity – usually in the first 1-2 In 2008 there are several new drugs months of treatment. Efavirenz is available including drugs that work in linked to mood disturbance, disturbed different ways. sleep patterns and vivid dreams when starting and more rarely in the long These include the integrase inhibitor term. raltegravir, the CCR5 inhibitor maraviroc, a new NNRTI called If you have difficult side effects from etravirine and a new protease inhibitor one of these drugs, you should called darunavir. be able to switch from one to the other without stopping treatment or Each of these drugs may have a changing your other drugs. different role as switch options based on their side effects. Switching between PIs For example, raltegravir does not Switching from one PI to another is increase cholesterol or triglycerides. also straight-forward, especially if both As a drug from a new class, it could PIs are being boosted by ritonavir. also be used as a switch option for • Switching from one boosted PI to people who are currently having another (such as from Kaletra to trouble with T-20. atazanavir/r) is likely to be okay Darunavir uses a lower boosting dose • Switching between PIs used in of ritonavir than some other protease dual-PI combinations, although inhibitors, and may be more tolerable less well studied, is also likely to than drugs that need a higher ritonavir be okay dose. • Switching from a boosted PI to an As each new drug becomes more unboosted PI is not recommended widely used, they will probably be unless drug levels are checked used as switch options. with TDM (see page 12). Each choice will be individually based on your situation and treatment history. It may also depend on how the drug is licensed and on practical issues like cost. www.i-Base.info 14 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Side effects and adherence
...94% of people reported at least one symptom after 4 weeks... If you are getting side effects, they need to be taken seriously, as early as possible by both you and your clinic...
Whether you are starting your first People reported an average of four treatment or have been using HIV side effects after four weeks, which drugs for a long time, your doctor dropped to an average of three at 16 should have talked to you about the weeks. And importantly, the severity importance of adherence. of these side effects reduced over this This is the term that describes taking time. the medications exactly as they are This study was run a few years ago, prescribed. This includes taking them and todays treatments are much on time and following any dietary more tolerable. Nevertheless, the advice. It also means taking them on conclusion was clear. If you are getting weekdays, at weekends and when you side effects, they need to be taken are away on holiday. seriously, and as early as possible by Numerous studies show that NOT both you and your clinic. getting adherence right will lead to There are many treatments that help early treatment failure. There have with nausea and diarrhoea. You can also been studies that look at the be given a small supply of these to relationship between adherence and take to prevent side effects when side effects. you first start treatment. You should One of these studies looked at side also be able to collect these easily effects over the first month on a new from your clinic as soon as you get treatment. symptoms. People who reported higher numbers Adherence can be more difficult when of side effects after the first month medications make you feel less well. of treatment were less adherent and Some of the longer-term side effects had lower viral load reductions three like lipodystrophy, may also reduce months later. adherence. If you have lipodystrophy and it is
This study provided a more realistic www.i-Base.info picture than is generally recognised affecting your self confidence, your of the real effect of side effects on social life and how you feel about everyday life. Ninety-four percent of yourself it is important to discuss this people reported at least one symptom with your doctor. after 4 weeks, which dropped slightly to 88% after 3 months. Feeling more tired and having diarrhoea were the most frequently reported side effects, 40% of which were mild and 7% were severe. i-Base publications 15 guide to side effects FEBRUARY 2008 MAY 2008
You and your doctor
Developing a good relationship with you always see a different doctor. your doctor and other healthcare However, it is often useful to see workers is essential for your care. a different doctor for a second Nurses and pharmacists are excellent opinion sources of support and advice on all • Plan to have your routine bloods aspects of your treatment including on taken 2–3 weeks before your side effects and adherence. regular appointment. The results will then be available to discuss They are able to make referrals when you see your doctor to other professionals including dieticians, psychologists and social • Book routine appointments in workers. plenty of time Both you and those involved in • Turn up for your appointments your care have certain rights and on time. Tell the clinic if you can’t responsibilities. Below is a list of make it, so they can give the things you can do, followed by the appointment to another patient rights you have as a patient. • Treat all people involved with your care with the same respect you Although you always have the right would wish to receive yourself to change your doctor or treatment centre, this is best seen as a last • Listen carefully to health advice resort. that you are given and act upon it • If you don’t understand anything, Things you can do to help... ask your doctor to explain it again • Find a clinic that is convenient and or in a different way that you feel comfortable with • Be honest with those caring for • Find a doctor who you feel you. comfortable with: if you’re a • Tell your doctor about any other woman and want to see a female drugs that you are taking – legal, doctor, or a gay man and want to street, recreational, prescription see a gay doctor, then this should or complimentary. Alternative be possible treatments and recreational drugs • Make a list of things you want to can cause side effects and can discuss with your doctor and take interact with HIV drus this to your appointment • Be honest about your adherence • Keep a list of your drugs, dosages, (taking your meds). If people when you need to take them, and managing your care don’t know whether you get these from your you are having problems, they clinic or GP can’t help • See the same doctor at each • Be interested in potential research. visit -– this is important. It is very Studies generate data that can difficult to develop a relationship if help yours and others future care www.i-Base.info 16 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Some of your rights as a • To receive a second opinion from a patient... suitably qualified doctor • To receive a written response • To be seen within 30 minutes of within 14 days from any letter that your appointment or expect an you write to your hospital or clinic explanation • To change your doctor or treatment • To have options for treatment centre without it affecting your explained. This includes the risks future care. You do not have to and benefits of each option give a reason for changing doctors • To be fully involved in all decisions or clinics although sometimes this regarding your treatment and care can help resolve a problem if there • To be treated with respect and has been a misunderstanding confidentiality • To have all test results and a • For your records to be kept summary of your treatment history securely and to be available for forwarded to your new doctor or you to see if you ask treatment centre if you decide to • To be able to make photocopies of change your clinic your medical notes • To decide not to participate in research without this affecting your current and future care • To make a complaint about your treatment without it affecting your future care. To have any complaint fully investigated www.i-Base.info
i-Base publications 17 guide to side effects FEBRUARY 2008 MAY 2008
Diarrhoea Most HIV medications list diarrhoea as a side effect. Ritonavir (Norvir) and other protease inhibitors are particularly associated with dirrhoea.
Diarrhoea remains one of the most Non drug-related causes common yet least talked about side If diarrhoea continues for more than a effects. few days ask your doctor to arrange HIV itself can also cause diarrhoea as for a stool sample to be analysed to can many HIV-related infections. look for the cause. Some tests can Most of us get diarrhoea at some take a couple of weeks for the results. point and having a lower CD4 count Depending on the severity and increases this risk. Diarrhoea can last history of the symptoms and following for a few days, weeks, months or, in examination, your doctor may some cases, years. prescribe a course of antibiotics along Diarrhoea relates to increased with anti-diarrhoea drugs to reduce the frequency as well as looser and more amount of times you need to go to the watery consistency of stool. toilet. It can be embarrassing to talk about If lab tests fail to show any bugs and diarrhoea or bowel habits. This may if symptoms persist, then your doctor be one of the reasons that it is so may want to perform an endoscopy. badly managed. For this, a biopsy (a tiny piece of tissue) is sent for analysis in the However, it is important that diarrhoea laboratory. This can rule out other is treated. Otherwise it can lead bowel problems such as colitis. As to dehydration, poor absorption of diarrhoea can be a symptom of other nutrients and drugs, weight loss and illnesses, it is important to run these fatigue. tests. Finding out the cause Treatment Often diarrhoea is temporary and If nothing shows up in these tests, may be due to starting or changing then the treatment of the symptom treatment. Symptoms often reduce itself becomes important. within a few days or weeks as you get used to the HIV drugs. Many HIV medications can cause diarrhoea and some are more In this case, short courses of problematic than others. If you are anti-diarrhoea medications such tolerating your combination generally, as loperamide (Imodium) or you may be able to manage diarrhoea diphenoxylate and atropine (Lomotil) with anti-diarrhoeal drugs or dietary can be effective. changes, both of which are listed If diarrhoea persists for more than a below. few days, and is not directly linked Depending on your treatment options to starting a new combination, it is you can also look at changing the drug important to run tests to check that it is that is likely to be causing this. not being caused by bugs or parasite infections. www.i-Base.info 18 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Diet • Don’t drink with your meals but • Many people have difficulty in make sure you take plenty of fluids digesting lactose, which is found in between meals to replace the fluid milk and dairy products. Reducing being lost due to diarrhoea. milk and dairy products in your • Eat foods rich in potassium such diet can really help. Alternatives as bananas, peaches, potatoes, such as rice and soya milk do not fish and chicken. Potassium is lost contain lactose. when you have diarrhoea. • ‘Rice water’ can help. Boil a • Try eating live yoghurt to enhance small amount of rice in water for the helpful bacteria in your gut. 30–45 minutes (or microwave for If you have a problem with dairy a shorter time), flavour with ginger, products then acidophilus can honey, cinnamon or vanilla when be taken in pill form. If your CD4 it cools, and then drink throughout count is under 50 this may not be the day. advisable. • Eating less insoluble fibre can also • Whatever changes you make to help. Foods that contain insoluble your diet, make sure it remains fibre include vegetables, whole balanced. Don’t live on just a wheat breads and cereals, skins, few food products, as you will be fruit, seeds and nuts. missing out on essential vitamins • Eat more soluble fibre. This is and minerals. Excellent advice and particularly helpful when watery support about diet can be obtained stools are a problem as they from the dietician at your treatment help to absorb the excess water centre. and bulk the stool. Soluble fibre Medications and supplements is in white rice, pasta. Ispaghula (psyllium) husk (i.e Fybogel • Fluid and electrolyte replacement or Isogel) and oat bran tablets (such as dioralyte and sports increase soluble fibre in your diet. rehydration solutions like Gatorade etc) • Caffeine can cause the gut to speed up and result in more bowel • Imodium (loperamide), Lomotil www.i-Base.info movements. Caffeine is in coffee, and codeine phosphate are the tea and cola. Recreational drugs drugs most commonly prescribed can have the same effect. for diarrhoea. They work by slowing gut motions and the speed • Avoid high fat, greasy and high that you process food, hopefully sugar foods. reducing the number of stools each day.
i-Base publications 19 guide to side effects FEBRUARY 2008 MAY 2008
• Your doctor will normally prescribe • Bulk forming laxatives are useful these first and, for many people, when watery stools are a problem. these medications work well. It is They absorb fluid and bulk out the important that the medications are stool – and lengthen the time the taken regularly until the diarrhoea stool stays in the bowel. These is well controlled. Start with drugs are generally taken following low doses. If you are taking the a meal and you should not drink maximum daily dose (for example for 30 minutes after taking them. 8 pills a day for Imodium) and you Don’t take at the same time as are still not getting the problem meds. Brands include Fybogel, under control, go back to your Isogel, Regulan, Celevac and doctor to try something else. Normacol. • Calcium supplements can help • Studies on oatbran tablets reduce diarrhoea associated taken by people with diarrhoea with nelfinavir and possibly other using protease inhibitors were protease inhibitors. The normal successful and work on the same dose is 500mg twice a day and principle. The dose was 2–3 will help those who are avoiding oatbran tablets before meals or dairy products as they are a major after each protease inhibitor dose. source of calcium in the diet. • Glutamine has been used Treatments: experimentally to try and improve • diet changes bowel function. There is still some debate about the dosage – opinion • dioralyte (electrolyte replacement) ranges from 5g to 40g a day. It is • Imodium (loperamide) or Lomotil available either as a powder that must be dissolved in water or a • calcium supplements regular pill. • Ispaghula (psyllium husk or seeds) • Glutamine • MST (slow-release morphine sulphate) • octreotide injections www.i-Base.info 20 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
It is important that Fig 1: how opiod anti-diarrhoeals work diarrhoea is treated Stomach wall as it can lead to dehydration, lack of absorption of i) Before opiates rapid bowel essential nutrients contractions prevents water and drugs, weight being absorbed ii) Opiates slow bowel contractions loss and fatigue. allowing more water to be absorbed
Fig 2: How bulk-forming agents work
Bulk forming agent
Bulk forming agents contain particles that absorb water and swell up making faeces firmer and more solid
-as a last resort... The liquid formulation of morphine sulphate can be used for diarrhoea Slow release morphine sulphate that occurs at specific times – ie in (MST) or octreotide injections the hours after dosing. can be used if all the usual medications have failed to make MST works because one of a difference – although it is used the side effects of opiates is www.i-Base.info less to control side effects and constipation, and it works by more to treat other causes of slowing down the gut. diarrhoea. The slow-release formulation of MST means that Because it is an opiate, many low doses of the drug are provided doctors do not readily offer MST, throughout the day. It comes in so you may have to be persistent a wide range of strengths, each to get to use it. For some people it coloured differently, so you can be is the only thing that works – and very careful about only taking the even very low doses mean you dose that you need. can get back to a normal life. i-Base publications 21 guide to side effects FEBRUARY 2008 MAY 2008
Nausea and vomiting Most HIV medications include nausea as a potential side effect
Nausea (feeling sick), and vomiting Medications used for nausea (being sick), is quite common when Domperidone (Motilium): 10-20mg starting a new combination. However, every 4-8 hours. Suppositories 30- for most people, this improves after a 60mg every 4-8 hours are a good few days or weeks as your body gets alternative to swallowing pills when used to the drugs. you are feeling sick. Using an anti-emetic (anti-sickness) Metoclopramide (Maxolon): usually pill regularly in the first few weeks is 10mg, 3-times a day. There are slow- often all that is needed. If one anti- release versions, which can be used emetic does not work, it is worth trying twice a day, including Maxolon SR and others. Some anti-emetics work by Gastrobin Continuous; however, they emptying your stomach more quickly should not be used in anyone under and others by stopping the signals that 20 years old. Be aware of dystonic tell your brain that you feel sick. reactions (twitching movements) at If the nausea does not improve, you higher doses. may need to change to other anti- Prochlorperazine (Stemetil): usually HIV medication. There may also 5-10mg, 2-3 times daily. A special be an underlying cause not related preparation is available called to HIV medication which should be Buccastem, 1 or 2 tablets are placed investigated. between the upper lip and gum and If you are taking abacavir and you are left to dissolve; not having to swallow feeling nauseous or vomiting, then more pills is useful when you are contact your clinic straight away to rule feeling sick. out a hypersensitivity reaction. (See Haloperidol: 1.5mg daily or twice daily page 44) where nausea is severe. Particularly How to describe nausea to your useful as can be taken at night to doctor avoid early morning nausea. • How often each day do you feel Sometimes these medications have sick, or are you sick? side effects themselves that you • How many days a week does this should ask your doctor about. happen? Where other medications and lifestyle • How long does the nausea last? changes have failed and nausea continues, then medications that • Has this affected how much you are normally reserved for patients can eat or drink? receiving very strong chemotherapy • Do you feel more tired or weak as may be prescribed. a result? These include granisetron, ondansetron and tropisetron and they are highly effective. www.i-Base.info 22 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Other suggestions If changing your medication is not an option and the nausea is continuous, then any of the following suggestions can help. • Eat smaller meals and snack more frequently rather than eating just a few larger meals • Try to eat more bland foods and avoid foods that are spicy, greasy or strong smelling • Leave some dry crackers by your bed and eat one or two of them before getting up in the morning • Ginger is very helpful and can be used as capsules, ginger root • Try not to drink with your meal or powder or fresh root ginger peeled straight after. It is better to wait an and steeped in hot water hour and then sip the drink slowly • If cooking smells bother you, then • Try eating cold rather than hot open the windows while cooking food, or let hot food cool well and keep the room well ventilated before you eat it • Microwave meals prepare food • Peppermint is also useful and can quickly and with minimum smells, be taken in tea, sweets or chewing so you can eat a meal as soon as gum you feel hungry. Getting someone • Acupressure and acupuncture can else to prepare your meals can also be very helpful, anti-nausea help, if this is possible acupressure bands are available • Don’t eat in a room that is stuffy or from most chemists that has lingering cooking smells • Try to avoid things that irritate the
• Eat meals at a table rather than stomach such as alcohol, aspirin www.i-Base.info lying down and don’t lie down and smoking immediately after eating
i-Base publications 23 guide to side effects FEBRUARY 2008 MAY 2008
Fatigue - feeling tired Most HIV medications include fatigue as a potential side effect
Fatigue is a general feeling of How to describe fatigue to your tiredness that does not really go away, doctor even after you have been able to rest. Fatigue can build up slowly, and build With physical fatigue you are not able up without you realising it. To describe to be as active as you used to, even this to your doctor it helps to give with simple tasks like going up stairs examples of when you feel more tired. or carrying shopping. If you can compare how you feel now With psychological fatigue, you are not with how you felt six months or a year able to concentrate as well as normal ago, this will also help. or you lose the motivation to do things. Describe how often you are tired or Fatigue can be caused by many things out of breath for example. As fatigue including: can be related to poor sleep, include • HIV information about your sleep patterns. • HIV drugs Treatments • lack of sleep • poor diet Blood tests can check whether your • stress fatigue is caused by anaemia (low red • depression blood cells). This can be a side effect • antihistamines (used to treat hay of AZT and can be treated easily with fever) and flu and cold remedies medication or with a blood transfusion • alcohol and recreational drug use in more serious cases. • underlying HIV-related illnesses. You may be feeling more tired Fatigue can also be caused from because you are not sleeping properly, being more active than you are able to and one study found this explained manage. fatigue in over 60% of cases. There is more information about difficulties with It can also be caused by a hormone sleep on page 31. imbalance such as low testosterone or DHEA (dehydroepiandrosterone) If you are not eating a balanced diet levels in both men and women. – ie not getting sufficient calories and nutrients for your body to function If you are feeling very tired and have normally – this can leave you feeling any of the other symptoms associated more tired. with lactic acidosis (vomiting, nausea, sometimes pain in the stomach and/or liver, unexplained weight loss, difficulty breathing etc - see page 42) it is very important that you report this to your doctor. www.i-Base.info 24 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Multivitamins can be prescribed by your doctor, and supplements of vitamin B12 can sometimes help you feel more energetic. You can also ask to be referred to a dietician who can help you assess and plan changes to your diet. Psychostimulants like methylphenidate (Ritalin) and pernoline (Cylert) used in low doses, have sometimes been used to treat HIV-related fatigue but side effects include hyperactivity, addiction, loss of appetite and liver toxicity. www.i-Base.info
i-Base publications 25 guide to side effects FEBRUARY 2008 MAY 2008
Skin rash
Many drugs are associated with rash including: abacavir (Ziagen and Trizivir), FTC (Emtriva), nevirapine (Viramune) and efavirenz (Sustiva), fosamprenavir (Lexiva/Telzir), atazanavir (Reyataz), tipranavir (Aptivus) and T-20 (enfuvirtide, Fuzeon).
Although many drugs are linked to but a symptom of an underlying rash, the severity of rash and how long disease (such as scabies). it lasts varies considerably. Other things that can help If you develop a rash during the first few weeks of therapy with some drugs • Bath or shower in cool or warm you must report this immediately water rather than hot water as this to your doctor. This is because it can irritate your rash. can sometimes lead to very serious • Avoid heavily scented or coloured reactions. These drugs are abacavir soaps and shower gels. Try to (Ziagen, and in Trizivir and Kivexa), use products that are marked nevirapine (Viramune), efavirenz hypoallergenic or wash with (Sustiva), fosamprenavir (Lexiva) and aqueous cream. T-20 (enfuvirtide, Fuzeon). • Use liquids and not powder to Other rashes are more likely to be wash your clothes as tiny amounts mild and disappear without treatment, of powder can build up on your or can be easily treated with clothes. Try using non-biological antihistamine drugs such as cetirizine makes that are designed for (Zirtek) or loratadine (Clarityn). sensitive skin. Atazanavir can cause a mild rash • Wear cool fibres such as cotton during the first two months in 10% of rather than synthetic ones. When people but this disappears without possible at home wear as few additional treatment within a few clothes as possible. weeks. • Try not to use too many bedclothes. Keep as cool as FTC studies reported rash on the possible in bed as being too warm palms of the hands or feet in up to can irritate your rash. Again, use 10% of African Americans, but these natural, cool fibres such as cotton. have been reported less frequently since the drug has been licensed. • Calamine lotion can be soothing when a rash is very irritating. Although antihistamines are available over the counter, it is important Nevirapine and efavirenz rashes that you check with your doctor or Up to 20% of people using nevirapine, pharmacist before taking them, as and 5% of people using efavirenz, will there can be interactions with HIV experience a mild to moderate rash in drugs. the first weeks of treatment. For most Rashes can also occur as a reaction people this disappears over the next from exposure to the sun, and will few weeks and they experience no normally resolve. Any rash that makes further side effects. you feel sick may not be a side effect www.i-Base.info 26 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Women are at a higher risk of rash with nevirapine than men. Women should not start treatment with © Beth Higgins nevirapine if their CD4 count is over 250 cells/mm3 or men if their CD4 count is over 400 cells/mm3. Nevirapine needs to be dosed in two stages. For the first two weeks, you should only take one 200mg tablet, once a day. After the first two weeks the dose increases to two 200mg tablets daily, split into one tablet every 12 hours. The dose should NOT be increased though if there are any symptoms of rash. Abacavir and rash If you get a rash with nevirapine, A rash can sometimes be one of the you should make sure your doctor symptoms of the hypersensitivity checks this carefully. Everyone reaction associated with abacavir starting nevirapine should visit their (Ziagen, Kivexa and Trizivir) that clinic every two weeks for the first two occurs in 4-5% of people using months to check for liver toxicity (see abacavir. page 40), so getting a rash examined should be very easy. It is very important that you see your doctor if a rash appears when Approximately 5% of people using abacavir in a combination. If discontinue nevirapine due to a rash. abacavir is not stopped - or if it is Anything more than a mild rash used again in the future, this can may require stopping nevirapine lead to a life-threatening reaction. – but only on the advice of your Page 44 has more details on the doctor. abacavir reaction. More serious rash (reported in 0.5% of cases) can be life-threatening www.i-Base.info (Stevens-Johnson Syndrome) and can be dependent on how early nevirapine is discontinued. This is why getting an expert medical assessment when a rash appears is essential.
i-Base publications 27 guide to side effects FEBRUARY 2008 MAY 2008
Dry skin, hair loss, nail problems Associated drugs: indinavir (Crixivan), 3TC (Epivir) and hydroxyurea (Hydrea), AZT (nails discolouration)
Dry skin, chapped lips and nail Hair loss problems are a problem for HIV- People have reported that the positive people but this is often more thickness and quality of their hair related to HIV than HIV drugs. changed while using indinavir Indinavir was particularly linked to – usually becoming thinner – and that skin, nail and hair problems. As this this has been reported for both head drug is now used so rarely, switching and body hair. to an alternative is the first option. Usually this is reported as being All the measures listed about mild and reversing when indinavir is rashes are helpful where dry skin switched to another drug. is a problem, along with the use of Balding patches of head hair, called emollients (moisturisers) such as alopecia, has also been reported, aqueous cream, diprobase, oilatum, though rarely, with 3TC. and balneum. Try to drink plenty of fluids as well. Nail problems Vitamins and a healthy diet are also Paronychia (inflammation around the important for better skin health. finger nails) and ingrown toe nails have both been reported as rare side Where rashes and dry skin are effects with indinavir and 3TC. unmanageable with medications or simple interventions then ask your Many of the people using indinavir are doctor to change the medication that is likely to have also used 3TC - so the responsible. cause and contribution of each drug is uncertain. You can also ask to be referred to a specialist dermatologist. If you are using indinavir consider switching to another drug. Chapped lips have been linked to indinavir in a similar way to dry Hydroxyurea and AZT have been skin. Regularly using a lip balm and associated with nail changes and skin checking indinavir blood levels are pigment changes in African people. both recommended. www.i-Base.info 28 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Sexual problems
Sexual dysfunction, whether due to HIV, side effects of HIV treatments, or other factors, can have a big impact on the quality of your life. Sexual dysfunction includes reduced sex drive (a loss of interest in sex) and physical difficulties (such as loss of erection or difficulty reaching orgasm).
Although sexual dysfunction is not • Depression can affect sexual generally a side effect of HIV drugs, health. several reports linked this to protease • Many treatments for depression inhibitors. (including fluoxetine (Prozac), Under-reporting in studies and at citalopram (Cipramil), paroxetine clinics is likely because many people (Seroxat) and sertraline (Lustral) find it difficult to talk to their doctor can decrease libido and lead about this aspect of their lives. It is to erection difficulties in men. something that doctors rarely ask Mirtazapine (Zispin) may be patients about directly. considered as it has little or no effect on sex drive and fewer Although most research into sexual interactions with HIV drugs. dysfunction associated with HIV has been carried out in men, when women • Sedatives, tranquillisers and other have been included in these studies, medications can cause sexual a similar level of concern has been dysfunction, as can smoking, reported. alcohol and recreational/illegal drug use. For example, a study by anonymous • Long-term use of steroids or male questionnaire in over 900 HIV-positive hormones. people using combination therapy • Relationship or work-related stress (80% men, 20% women) found that can be a factor. 38% of men and 29% of women reported a decrease in sexual interest. • Lipodystrophy and neuropathy are A decrease in sexual potency was also associated with higher rates www.i-Base.info reported by 29% of men. of sexual dysfunction. • Sexual dysfunction is more Causes common in HIV-positive people Sexual dysfunction in HIV-positive who are not using anti-HIV drugs people can be caused by a wide range compared to HIV-negative people. of medical and psychological issues. • Age (>40 years), diabetes, • HIV-positive men and women pelvic surgery, fear of failure, have reduced testosterone levels hypertension can also cause compared to HIV-negative people. changes is sexual function. i-Base publications 29 guide to side effects FEBRUARY 2008 MAY 2008
Treatments Psychological issues Different approaches are used How you feel about yourself and your depending on the most likely body and how you feel about HIV can cause. Approaches to treat erectile affect your sexual health. HIV-negative dysfunction include counselling, people and society in general can vacuum devices, cockrings and react in irrational ways to HIV, which treatments like Muse (an implant) can contribute to how you feel as an and caverject (an injection). Oral HIV-positive person. medications include sildenafil (Viagra), Dealing with an HIV diagnosis, vardenafil (Levitra), tadalafil (Cialis), whether or not you are on treatment, apomorphine (Uprima) and yohimbine takes a lot of courage and (Yohimbine, Yocon). perseverance. If treatments work well, Testosterone levels you can be faced with new choices in life and if they are not working well If you have a reduced sex drive then and you are dealing with illness or ask to have your testosterone levels side effects, you would expect this to checked with a simple blood test. impact on other areas of your life. For men, the range for normal levels Talk to your doctor. Referral to sexual is 10-30nmol/l but this does not allow dysfunction clinics or counselling for changes in age. If your levels support is often appropriate. Many are lower than this, testosterone clinics have psychologists who are replacement treatment can be given trained and experienced in sexual by patch, gel, implant or injection. dysfunction. If you have other symptoms (low sex Sildenafil (Viagra) drive, fatigue, etc) then testosterone treatment is one option you can try, Oral medications can sometimes even if you are within ‘normal’ levels. help reduce psychologically difficult situations. For HIV-positive people If your testosterone levels are low, they should be available on the NHS you should have your bone density (after a consltation) or by asking your monitored as HIV-positive people are doctor for a private script. at higher risk of osteoporosis. Some HIV medications interact with If effective, increased testosterone Viagra. Lower doses – usually one levels should reduce depression and 25mg in any 48-hour period – are fatigue and increase sex drive. used for people using a PI or NNRTI Testosterone (at much lower doses) based combination. is being studied as a treatment for Viagra should never be used with sexual dysfunction in women. Hair poppers (amyl nitrate). growth, deeper voice and clitoral enlargement are side effects that Viagra and apomorphine (Uprima) require caution in women. are not currently licensed for women although studies are underway. www.i-Base.info 30 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Insomnia - disturbed sleep NOTE: - See pages 33-35 for sleep disturbance associated with efavirenz
Sleep is an essential part of a healthy • Include details about your sleep life as it is a time when your body is environment. How comfortable is able to rest and repair. your bed? Is the room warm and If you are not able to get regular, good quiet? quality sleep, either in the long or • Include when you normally eat. short term, your ability to think, speak Leaving a couple of hours between and concentrate will be reduced. You your last meal and going to sleep can become more irritable and have will improve the chance of a better slower reactions, and your memory sleep. and judgement will be affected. Stress and worry can easily disrupt Sleep problems are generally under- your sleep pattern, as can ongoing reported, under-diagnosed and under- health concerns, especially if they are treated. Keeping a sleep diary for the painful or uncomfortable. week before you see your doctor can Your doctor should also give you a help diagnose some of the problems. physical check up and blood tests to Factors affecting sleep include check for cardiovascular, respiratory or • Do you have problems falling hormonal reasons, especially thyroid asleep at night? function, that may be causing sleep disturbance. • Do you wake up too early in the morning? Suggestions to help • Do you wake throughout the night It is important that the causes of and only get intermittent sleep? insomnia are diagnosed before any Your sleep diary should include when treatment is given. The wide range of you fall asleep and when you wake up causes mean that non-pharmaceutical on week days and weekends. Include approaches, such as having a warm any naps you have during the day. bath or hot milky drink before bedtime, can often make a big difference and • Record how you feel about the are sometimes sufficient. general quality of your sleep, including vivid dreaming or Do...
nightmares. • Sleep only enough to be refreshed www.i-Base.info • Get into a routine where you can • Record drug and alcohol use -– or go to sleep and wake up at the changes in use such as withdrawal same time each day or cutting back on either. • Try to exercise every day • Caffeine in tea, coffee and cola • Avoid extremes of noise or can affect your ability to sleep, temperature even many hours before you go to • Drink chamomile and other herbal bed. Keep a record of how much teas caffeine you drink during the day • Make your bedroom as and see if changing to a non- comfortable and relaxing as caffeine alternative helps. possible. i-Base publications 31 guide to side effects FEBRUARY 2008 MAY 2008
• Eat an evening meal so that you Sleeping pills reduce the amount are not hungry when you go to bed of ‘dream sleep’ that you get which Don’t... is an important component of good • If you use sleeping pills, don’t use sleep. Sometimes this can leave you them every night feeling drowsy the next day. They can • Drink caffeine drinks or alcohol become less effective after even a before bedtime as this will reduce few days’ use, and you can develop a the chance of sleeping well physical or psychological dependency • Smoke close to bedtime – it makes if they are used for more than 1–2 sleeping difficult weeks. • Try not to nap during the day, so Although benzodiazepines (ie that you are more tired at night temazepam) have relatively few side when you need to sleep effects they can interact with protease inhibitors. Non-benzodiazepines such Medication as zopiclone and zolpidem work in a Sleeping pills are only usually similar way, are shorter acting, and prescribed when other self-help are preferred when anxiety is not a remedies have been tried. They are contributing factor. used to help re-establish a pattern Melatonin is a hormone produced at or habit of sleeping. They are not night linked to your ‘biological clock’. recommended or generally prescribed As a supplement it is used to help deal for long-term use. with jet lag and may help to help return Sleeping tablets should only be used sleep patterns to normal, although for the shortest period and at the side effects include vivid dreams. lowest dose. All sleeping pills work in a similar way by reducing brain activity, but the type of sleep they produce varies between different types of drug. They can help you sleep, but the depressed brain activity means that the quality of sleep is often not as good as natural sleep, and you may still not feel rested the next day. www.i-Base.info 32 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
CNS side effects: Mood changes, anxiety, dizzyness, sleep disturbance
Associated drugs: efavirenz (Sustiva), Atripla (contains efavirenz).
The side effects associated with You should therefore start efavirenz at efavirenz affecting the central nervous the weekend or when you have some system (CNS) are not broadly linked time off work, when you are more with other anti-HIV drugs. relaxed and less worried or stressed. Although case reports of similar Efavirenz may be a difficult drug if you side effects have been reported with work shifts that require sometimes atazanavir/r, nevirapine, abacavir and working days and sometimes working other ARVs, these are very rare. nights. There are several difficult things about Many of the symptoms described these side effects. here can also be symptoms of HIV- Firstly, nearly everyone will get some related diseases that are now seen of these side effects but for most less frequently such as dementia, people they will be mild and easy to TB or cryptococcal meningitis. These manage. can develop slowly over time, so describing symptoms to your doctor, This means that you may have some in order that they can rule out these strange dreams, or find yourself factors is very important. daydreaming or getting more worried, or you may get more upset than usual. Severe side effects Secondly, if you have been told about Some people will experience these this before you start treatment, they side effects much more intensely. If will be easier to manage and should this is the case, it is essential that you be less alarming. Information about get more support as soon as you need what to expect before you start taking it. Perhaps 2-3% people switch to a efavirenz is therefore essential. different treatment very quickly. Efavirenz CNS side effects can occur But, more people only chose to switch after a few hours or after several days after trying efavirenz for several and are more common over the first months. Up to 20% people may switch few weeks and months of treatment. over the first year or so. They also generally reduce and This is because although side effects
become easier to tolerate. usually get esier to tolerate, they may www.i-Base.info About a quarter of people in the first continue at a low level for longer than efavirenz studies recorded serious the first few months. CNS side effects. This definition CNS side effects can lead to or included ‘difficulty carrying out daily exaggerate clinical depression, work’. So although very few people including suicidal feelings and clinical stopped efavirenz in these studies paranoia. It is very important therefore because of the side effects, you have that you are aware that such moods about a 25% chance that it could swings can be related to efavirenz and make it difficult to work as normal until that you are not ‘going mad’. you get used to them. i-Base publications 33 guide to side effects FEBRUARY 2008 MAY 2008
If you are feeling paranoid and worried Haloperidol to reduce anxiety and about going outside, or have stopped sleeping pills to help with sleep seeing your friends as much, this may disturbance may also help, although be related to efavirenz side effects. these have not been formally studied. Why these symptoms are associated If you have difficult side effects with with efavirenz is not understood. It is efavirenz and you are not happy also not possible to predict who will with how you feel, then change it experience more severe symptoms. for another NNRTI (nevirapine) or to a protease inhibitor. Some studies have cautioned against using efavirenz if you are You do not have to continue with already depressed or have a history efavirenz to prove anything to yourself of psychiatric illness, but people or your doctor. If you know something without such a history have also found is wrong, don’t worry about asking to symptoms difficult. change to something else. Several reports have been published Even if you have only used efavirenz of severe reactions in people with for a few days, if you know it is not for no previous psychiatric symptoms or you, it is okay to change. Some drugs illness. are not for everyone. Some studies have linked higher How to report symptoms efavirenz levels to low body weight. Some of the symptoms associated Importantly, research in 2004 showed with efavirenz are easier to decribe that race may be an important factor. than others. The advantage of writing Several studies showed that a down the effects you experience will higher percentage of African women let you see whether they are getting metabolise efavirenz more slowly. This easier. results in higher doses than they need. Sleep disturbance Often side effects are related to high • Keep a diary of how often your blood levels of efavirenz. Measuring sleep is disrupted. drug levels with TDM can allow dose reductions without reducing the HIV • Try to describe this in a clear way. effect of the combination or risking Is this every night or several nights resistance. a week? • Can you estimate how much time Reducing CNS side effects you sleep each night, and how Although you can take efavirenz with much you slept in a normal night or without food, a high fat meal can before you started treatment? increase drug levels by 60% and this can increase side effects. Other HIV drugs have also been linked to insomnia, though more rarely. Taking efavirenz a couple of hours before you go to sleep, rather than at Concentration and memory bedtime, makes it more likely that you • Are you finding it more difficult to will be asleep when the drug levels concentrate? are at their highest – about four hours • Have you been aware of memory after taking efavirenz. loss recently? www.i-Base.info 34 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Dreams and nightmares • How often do you have dreams or nightmares? • Do these disturb you sufficiently to leave you unsettled the next day? Mood changes Information about what • If you get mood changes try to describe these clearly in a diary. to expect before you start • Have our family or friends noticed efavirenz is essential. a change in your behaviour, even if this is not clear to you? ... some African women • Examples of how your mood has clear efavirenz from their changed can give a clearer idea of how you are affected. bodies more slowly result- Depression and feelings of suicide ing in higher drug levels • A small percentage of people who experience severe side and risk of side effects. effects have reported feelings of unexplained depression that are Although many people use out of character, including suicidal thoughts. efavirenz without problems, • Symptoms at this level mean that this is a drug that is not for it is critical to discuss this with your doctor in order to change to everyone. another treatment. • If you are currently taking Symptoms include: efavirenz, you may find it easier to talk to a close friend about how • impaired concentration, confusion you feel and ask them to come and abnormal thinking.
with you for support when you • mood swings including anxiety, www.i-Base.info visit your doctor. There is never agitation, depression, paranoia a problem with taking a friend or (feeling very anxious or nervous) family member with you whenever and euphoria (feeling very happy). you see your doctor. • sleep disturbance including insomnia, drowsiness, vivid dreaming and nightmares.
i-Base publications 35 guide to side effects FEBRUARY 2008 MAY 2008
Peripheral neuropathy (peripheral = furthest away; neuro = nerve; pathy = damage) Associated drugs: ddC (Hivid), d4T (Zerit), ddI (Videx), 3TC (Epivir)
Peripheral neuropathy (PN) was a using a pin to test sensations from common side effect from some of the toes up the leg. A tuning fork will the first anti-HIV drugs but it is rarely show a reduced vibration in a foot with reported with more modern drugs. neuropathy. It is still is major problem in countries Recent studies have measured nerve that continue to use d4T. damage in skin in a biopsy sample. It can also be caused by HIV itself. Your doctor may just rely on what you It is sometimes difficult to know the report is happening. If your symptoms cause but if the numbness or pain is are causing you discomfort or pain, symmetrical in both hands or both feet you must make sure it is taken it is more likely to be a side effect than seriously. related to HIV. Sometimes doctors underestimate Symptoms include increased how much pain people experience sensitivity or numbness, or tingling because they think that their patients in your hands and/or feet. Often it is always exaggerate pain. In fact, most something you hardly notice, or that people underestimate pain when comes and goes. talking to their doctor. If neuropathy gets worse it can Sensitivity tests that measure your become very painful. It is a side effect reactions to different pressure, are that you should take very seriously. not used so frequently, and it can PN is mainly associated with sometimes take 4-6 weeks to get nucleosides, especially the ‘d’ the results. Getting these results drugs. These are ddC (no longer recorded regularly though can help manufactured), ddI, d4T and less you measure any worsening of the frequently with 3TC. symptoms. Using more than one of these drugs Is neuropathy reversible? together can increase the risk as The earlier you switch treatment, and can use of other drugs such as the less severe the side effects when hydroxyurea, dapsone, thalidomide, you switch, the more likely that the isoniazid and vincristine. symptoms will reverse, but this does Alcohol, smoking, amphetamines, not happen for everyone. deficiency of vitamins B12 and E Moderate and severe neuropathy and other illnesses like diabetes and very rarely resolves fully but switching syphilis can also cause and make drugs can stop the symptoms getting neuropathy worse; B12 and folate worse. If you have other drugs to use, levels can be tested. switching at the first sign of symptoms Can PN be measured? may be the best thing you can do. Neuropathy can be irreversible and Simple tests for neuropathy include debilitating. comparing ankle to knee reflexes, or www.i-Base.info 36 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
If d4T is the cause of your neuropathy Painkillers you can reduce the twice daily 40mg Treatments which are prescribed to dose to 30mg or even 20mg twice manage neuropathy are basically daily. used to mask the pain. Sometimes Your choices to switch drugs depend these painkillers can have side effects on your previous drug history and you themselves which make them difficult should talk through the possibilities to use. with your doctor. You still have to Amitriptyline, nortriptyline and consider your HIV treatment but gabapentin don’t reduce the pain, but avoidance of neuropathy altogether is change how your brain perceives it. the best way of treating it. Gabapentin (licensed at 600mg, three If you do stop using the drug you think times a day, though some reports of is responsible then you may have 1200mg have been used in the US) to wait up to two months to know may help. These drugs work for some how much this has helped. Often people but others find them too difficult symptoms can continue to get worse – even when they ease the pain from before you notice an improvement. neuropathy - because they make them Treatments for neuropathy feel too drowsy. There are currently no approved Opiate-based painkillers such as treatments to repair or regrow methadone, morphine and codeine, damaged nerves. One study has although not always appropriate for shown that acetyl-L-carnitine (Alcar) neurological damage, sometimes help at a dose of 1500mg, twice daily, can with severe symptoms. It sometimes lead to nerve improvement. Acetyl- takes several days to find the L-carnitine can be prescribed on a appropriate dose, and these drugs can named-patient basis. Some clinics interact with some HIV drugs. A side in the UK already use this treatment effect of opiates is constipation. routinely. You should also have appropriate care from a pain control nurse specialist, Research into a synthetic human rather than your HIV doctor. They will Nerve Growth Factor (hNGF) in the
be able to make a full assessment www.i-Base.info US which looked promising has since of your level of pain, and adequately been put on hold and the development prescribe medication to reduce it. has been stopped. More rarely, when pain is so great that it is not treatable, alcohol can be injected into a nerve junction. Nerve blocks can be very effective when they work, and are a specialist procedure, but can also cause loss of sensation and sometimes produce unpredictable results. i-Base publications 37 guide to side effects FEBRUARY 2008 MAY 2008
Alternative treatments? Cod liver oil – One or two Alternative treatments often produce a tablespoons a day has anecdotally more acceptable, and more effective, produced beneficial reports, especially way of managing neuropathy. if the symptoms have not become very severe. This is not as bad as it sounds Although not proven in studies, there as modern oils are palatable and also has been substantial anecdotal reports come in flavours. on all of the approaches listed below. Topical Aspirin – suggested in one With a condition that is so painful, it is recent study that aspirin, crushed worth trying all of these in case they and dissolved in water or gel and help. applied to the painful area can relieve Acetyl-L-carnitine (Alcar) is a symptoms. supplement that has been effective Vitamin B6 (pyridoxine) – requires in small studies and anecdotally. caution with dosing as B6 can also Acupuncture is a lifeline for many worsen neuropathy (100mg daily is people who report improved quality of sometimes recommended). life. A study comparing acupuncture to placebo showed no benefit, but Vitamin B12 – available as injections, the acupuncture was a standardised lozenges, or nose-gel. B12 levels rather than individualised treatment. It should be checked by your doctor. is definitely worth trying to decide for Dosage varies but if levels are too yourself. high this can worsen neuropathy. Magnets – Using magnetic insoles Magnesium – 250mg – 2 capsules have reported benefits in diabetic- each morning related neuropathy. Calcium – 300mg – 2 capsules each Local anaesthetic creams such evening as Lidocaine (5%), and Lidocaine patches reported benefit in a recent Other suggestions study. • Avoid tight fitting shoes and socks Capsaicin – Topical cream made from which restrict blood circulation. chilli peppers that causes increased • Keep your feet uncovered at night local blood flow when applied to the - keeping them cooler and out of skin. Mixed reports, many of them not contact with sheets or bedding. encouraging. • Try deep tissue massage. Voltarol (NSAID) – a nonsteroidal • Don’t walk or stand for long anti-inflammatory drug. periods. Alpha-Lipoic Acid – 600 to 900mg • Soak your feet in cool water. daily may help protect nerves from inflammation. www.i-Base.info 38 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Further reading: Useful recommended reference books written in non-technical language are Numb Toes and Aching Soles (July 1999) and Numb Toes and Other Woes (July 2001) both by John A. Senneff. ISBN: 0967110718 and 0967110734. Lark Lands has led community- based interest in the use of diet and supplements for PN: http://www.larklands.net/TR12_ Neuropathy-Nutrients.PDF http://www.larrylands.com/lark/ larktreatments.htm Neuropathy Trust (UK) offer
information and support: © Beth Higgins http://www.neurocentre.com Neuropathy Association (US): Treatments that may help: http://www.neuropathy.org • Change HIV drug(s) that are responsible • Acetyl-L-carnitine (Alcar) Neuropathy can be very • Cod liver oil painful and debilitating... • Painkillers such as gabapentin, amitriptyline or nortriptyline (or It is a side effect that you marujuana) may mask symptoms should take very seriously. • Acupuncture • Magnetic insoles www.i-Base.info
i-Base publications 39 guide to side effects FEBRUARY 2008 MAY 2008
Liver toxicity, rash and nevirapine Associated drugs: nevirapine (Viramune), ritonavir (Norvir), tipranavir (Aptivus). Most anti-HIV drugs have potential for liver toxicity.
Most HIV drugs can affect your liver Where liver toxicity is suspected, as this is the way that they are filtered the drugs will normally be stopped by your body. This is why your routine to allow the liver to rest and return blood tests will include tests to check to normal. When the liver tests have your liver function. returned to normal HIV drugs may be Ritonavir, nevirapine and tipranavir restarted. This is often with a different are particularly associated with liver combination of drugs or reduced toxicity. Several studies have shown doses. that liver toxicity may be similar Nevirapine between nevirapine and efavirenz. The risk of nevirapine-related liver The following factors can increase the toxicity is different between men and risk of liver complications from HIV women. This risk is related to CD4 treatment. count when starting treatment. • Gender: women are more prone to Women starting treatment for the first liver problems with HIV drugs. time should not use nevirapine if their • Viral hepatitis: hepatitis A, B or C CD4 count is over 250 cells/mm3 and (or other liver disease). men should not use nevirapine if their CD4 count is over 400 cells/mm3. • Increased alcohol consumption. • Use of other drugs, including These CD4 levels are not thought recreational drugs, that are toxic to important if you already have an the liver. undetectable are switching one of your current drugs to nevirapine. They do Your doctor will normally test your liver not relate to pregnant women who are function at the same time as testing using a single dose of nevirapine as CD4 count and viral load. If you have part of treatment to reduce the risk of hepatitis or previous liver damage, transmitting HIV to their baby. it is important to use therapeutic Close monitoring (every two weeks) drug monitoring (TDM) when using in the first two months of therapy is protease inhibitors or NNRTIs, as you recommended for anyone who starts a may need to use a lower dose. nevirapine-based combination. This is When taking anti-HIV drugs you when liver problems first start to occur. should report any side effects to Liver toxicity may also build up slowly your doctor. Especially if you have and so routine monitoring after the first abdominal pain, nausea and vomiting, two months is also important. yellowing of the skin or the whites of Nevirapine must be taken as one the eyes. tablet (200mg) once daily for the first two weeks. www.i-Base.info 40 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Only if you have none of the If at any point your liver function tests symptoms listed below and your get to five times the normal limit or liver function tests are within the mild symptoms get worse, then your acceptable levels can you increase nevirapine must be stopped. Your your nevirapine dose to one tablet doctor will recommend whether you (200mg) twice a day. need to stop all your treatments or just Blood samples should be taken every switch the nevirapine to another drug. two weeks in the first two months to If you stop nevirapine for these check liver function, then at the end reasons, you must not take it again of the third month, and then every in the future. three to four months if they are within normal limits. During this first eight weeks you should contact your doctor straight away if you have any of the following symptoms: • Rash • Blistering of the skin – seek immediate medical attention • Mouth sores • Facial or general swelling • Fever • Flu-like symptoms, aching muscles or joint pains Your doctor will do another liver function blood test if you have one of these symptoms. If the results are not higher than twice the normal limit, and depending on the severity of your symptoms, a decision will be made whether or not to www.i-Base.info continue with nevirapine. If a decision is made to continue, you will be very closely monitored to ensure that the symptoms do not progress or your liver function tests get worse.
i-Base publications 41 guide to side effects FEBRUARY 2008 MAY 2008
Lactic acidosis, pancreatitis and fatty liver All nukes - d4T, ddI, abacavir, tenofovir, FTC, 3TC, AZT and hydroxyurea - have been linked to reports of lactic acidosis and/or pancreatitis. PIs and efavirenz have also been associated with pancreatitis.
Lactic acidosis abdominal CT scan or liver biopsy. Lactic acid is a by-product formed Although this toxicity is believed to be when the body breaks down starches a result of damage to part of the cell and sugars. Levels of lactic acid called mitochondria, there is no simple are normally carefully regulated by test for determining people at highest the liver. Small increases in lactic risk. acid (called hyperlactataemia) are Although lactic acid in blood can be relatively frequent, and are temporary, measured, it is not clear whether especially after exercise. high levels increase the risk of lactic If they reach a higher level, there acidosis. Over 50% of people showing is a risk of lactic acidosis. This is a a high reading on one result, return potentially fatal side effect related to to normal with the confirmatory test. nucleoside/tide analogues. It is now There appears to be no pattern rarely reported. between high levels and risk of severe toxicity. Not only are nukes included in nearly all HIV combinations, but Because lactic acid increases with any the symptoms of lactic acidosis are physical activity, confirmatory tests common side effects or symptoms. should be taken after complete rest for at least 20 minutes. Even going to Symptoms include: the gym the day before may affect the • unexplained tiredness, often results. severe • sickness (vomiting) and nausea Treatment and monitoring • pain in the stomach, abdomen Early diagnosis is essential – and and/or liver contacting your doctor if you have any • unexplained weight loss of the symptoms is important. HIV • difficulty breathing treatments may need to be stopped • poor blood circulation – cold hands immediately depending on blood or feet or bluish skin colour levels. • sudden peripheral neuropathy High doses of vitamin B complex Before combination therapy was with L-carnitine (both IV) until lactate available, this was only very rarely levels normalise were reported in a seen in HIV, and may well have been Dutch study to improve the chances of under diagnosed. Drug packaging now survival. includes a clearer caution about this risk. Antioxidants may help to overcome mitochondrial toxicity and use of oral Pregnancy may be an additional risk antioxidant supplements such as factor for lactic acidosis when using vitamin C, vitamin B complex, L- nukes. carnitine or co-enzyme-Q may help Lactic acidosis is diagnosed through and are prescribed by some doctors. examination, lab tests and an www.i-Base.info 42 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
There are no clear guidelines for Pancreatitis restarting nucleoside therapy after a Pancreatitis is an inflammation of the serious case of mitochondrial toxicity. pancreas characterised by abdominal Although caution is warranted, lack of or back pain and vomiting. It can also other antiretroviral options has lead be alcohol induced and there is little to people restarting without further specific treatment. toxicity. Blood tests measuring amylase lipase Mitochondrial toxicity is thought to are usually checked to confirm a be responsible for other side effects diagnosis of pancreatitis. including nerve and muscle damage. Pancreatitis can be fatal if not treated early, and can be prevented by Diagnosis and treatment: stopping or changing HIV drugs. • Measure levels of lactic acid and blood pH. • If lactic levels are >5mmol and if Fatty liver you have symptoms or levels are Hepatic steatosis is a medical term over 10 mmol discontinue HIV for ‘fatty liver’ which can develop from medication immediately. alcohol use, hepatitis, obesity and • Use of intravenous anti-oxidants: drug toxicity with nucleosides. L-carnitine and vitamin B This build-up of fat in the liver can complex including thiamine, affect the way it processes fats. riboflavine, nicotinamide, Hepatic steatosis often also leads pyridoxine, dichloracetic acid and to lactic acidosis, described above. dexpanthenol is recommended. People who weigh over 70kgs, especially women, may be more at risk of developing hepatic steatosis and lactic acidosis. Ultrasonography is a sensitive, accurate, non-invasive screening
tool to detect steatosis as this is not www.i-Base.info always shown in liver function tests. Steatosis is also common in HIV- infected children. It has no impact on disease, testing or management.
i-Base publications 43 guide to side effects FEBRUARY 2008 MAY 2008
Abacavir hypersensitivity reaction (HSR) Associated drugs: abacavir (Ziagen), Trizivir, Kivexa
The main side effect associated with These symptoms are very general abacavir is a hypersensitivity reaction and can be mistaken for many other (HSR) which occurs in around 5% of illnesses including cold, flu and chest people. However, a recent screeing infections, especially during the winter test (called B*5701), reduces this risk. period. This test is recommended for all It is very important that if you get patients in the UK prior to using any of these symptoms after starting abacavir, so should make this side abacavir, you see your doctor straight effect now extrmemly rare. away so that hypersensitivity can HSR means that the body be ruled out. A few people who test is oversensitive to the drug. negative for B*5701 may still get HSR. Hypersensitivity reactions can Even if you tested negative, if you get also occur with nevirapine, T-20, these symptoms, then contact your fosamprenavir and cotrimoxazole doctor. (Septrin). Genetic screening test are If these symptoms get progressively not available for these drugs. worse each day it is an indication Hypersensitivity reaction to abacavir that this is HSR. A rash is not always occurs during the first six weeks of present. therapy in over 90% of cases, but Do not stop taking your medication can occur at any time during abacavir until you have seen a doctor and a use even after over a year without diagnosis of hypersensitivity has previous symptoms. been made. It is very important that people are If you stop using abacavir before aware of the symptoms of abacavir you have seen a doctor with these HSR before starting therapy, even if symptoms then you will not be able the B*5701 genetic test indicates they to restart, as hypersensitivity can’t are at low risk. These include: be ruled out. This means you will be • Temperature reducing your future treatment options. • Rash – normally raised and If HSR is diagnosed by a doctor then differing in colour from surrounding abacavir will be stopped straight skin away. These symptoms should then • Diarrhoea and abdominal pain disappear very quickly after abacavir • Tiredness and feeling generally is stopped. unwell • Nausea and vomiting Abacavir must never be restarted • Headache at any time if you have had the • Flu-like aches and pains including hypersensitivity reaction, as this muscle pain can prove fatal. • Cough and shortness of breath Abacavir is one of the drugs in Trizivir • Sore throat (abacavir+AZT+3TC in one pill) and Kivexa (abacavir+3TC in one pill). www.i-Base.info 44 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Kidney toxicity and kidney stones (Crystalluria = crystals in urine; Nephrolithiasis: nephro = kidney; lithiasis = stone formation) Associated drugs: indinavir (Crixivan) for kidney stones, more rarely: atazanavir, efavirenz. Other drugs cleared by the kidney with potential for renal toxicity include AZT, 3TC, FTC, tenofovir, Truvada, Atripla and maraviroc.
Indinavir-related kidney stones Indinavir used to be a widely used protease inhibitor, especially when boosted with ritonavir. One side effect included kidney stones - largely avoided by drinking an additional 1-2 litres of water daily. It is now rarely used and so the detailed information relating to kidney is a caution against using other such stones and indinavir is only available drugs with tenofovir. in the online edition of this guide. Recently there has been concern In 2007 there were several case that tenofovir-related toxicity may reports of kidney stones that contained be greater when tenofovir is used high levels of atazanavir or efavirenz, with ddI. Until this interaction is cautioning that this may be a rare side understood, these two drugs are effect with other drugs. generally not recommended to be Tenofovir-related toxicity used in the same combination. Tenofovir is mainly cleared from body Tenofovir is included in the by your kidneys and side effects combination pills Truvada reported with tenofovir include (tenofovir+FTC) and Atripla (efavirenz kidney toxicity. This includes reduced +tenofovir+FTC). creatinine clearance, low phosphate In people who have HIV-related levels and renal tubular complications kidney disease, HIV treatment is including Fanconi’s Syndrome. recommended and is likely to improve These side effects are usually kidney function. quickly reversible when tenofovir is discontinued. Drugs that are metabolised by the
kidneys (including AZT, 3TC, FTC www.i-Base.info Routine blood tests (including tenofovir and maraviroc) include urinalysis and estimated GFR - recommendations for using reduced glomerular filtration rate) should be doses in people whose kidney function used before starting tenofovir and for is reduced (usually indicated by montioring when on treatment. reduced creatinine clearance less than The risk of kidney toxicity may be 60 ml/min). higher if you are using other drugs See the individaul prescibing cleared by the kidney, or if you have information provided with each of used these drugs in the past. There these drugs for details. i-Base publications 45 guide to side effects FEBRUARY 2008 MAY 2008
Increased bilirubin, jaundice (yellow skin/ eyes) (Bilirubin is a orange waste product; Hyper = increased; aemia = ‘in blood’) Associated drugs: atazanavir (Reyataz); indinavir (Crixivan)
An increase in bilirubin Two types of bilirubin (hyperbilirubinaemia) is a common There are two types of bilirubin in the side effect in 25-50% of people who blood. use the protease inhibitors atazanavir or indinavir. Only a small percentage • Unconjugated (indirect) bilirubin is of people with increases in bilirubin insoluble in water. This is the bilirubin develop jaundice. before it reaches the liver The main symptoms of jaundice are a • Conjugated (direct) bilirubin has yellowing skin, or the white of the eyes been converted to soluble bilirubin in being more yellow. This side effect in the liver. It then goes into the bile to itself does not damage your body. be stored in the gall bladder or sent to the intestines. What is bilirubin? Routine blood tests for total bilirubin Bilirubin is an orange-yellow part measure both unconjugated and of bile. Bile is the bright green fluid conjugated bilirubin. secreted by the liver to help digestion. Increases in bilirubin with atazanavir Bilirubin is mainly formed by the are of unconjugated bilirubin. This normal breakdown of haemoglobin. occurs in around 30% of people using Haemoglobin carries oxygen in red atazanavir. People who have lower blood cells. levels of the enzymes responsible for Bilirubin passes through the liver. It converting bilirubin in the liver will be is then excreted as bile through the at a higher risk of increases in bilirubin intestines. from atazanavir. When this process is interrupted, Normal lab values: when to change excess bilirubin stains other body Normal values may vary between tissues yellow. Fatty tissues like skin, different labs but are within the eye tissue and blood vessels are the following ranges. most easily affected. Total bilirubin 3 – 17 mmol/l. Increased levels of bilirubin are linked with a range of illnesses and Direct bilirubin 0 – 3 mmol/l. conditions. This includes jaundice Jaundice becomes clinically detectable associated with hepatitis and cirrhosis, at levels above 40 mmol/l. You need anaemia, Gilbert’s disease and sickle good natural light to see this. cell disease. Jaundice is common in babies. Very high levels in babies can cause permanent damage. www.i-Base.info 46 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Treatment doesn’t usually need to be High levels of bilirubin may be a changed or the dose of atazanavir marker of high levels of atazanavir. (or ritonavir) modified unless bilirubin You can’t guess this though - you need levels become five times the upper to use TDM (see page 12). limit of normal (5xULN). This is at In practice, people who get yellow around 60-70 mmol/l. skin or eyes when they use 300mg/ This yellowish skin can be unusual. day atazanavir boosted with 100mg When related to atazanavir though it is ritonavir are often able to change to harmless and it is not causing damage unboosted atazanavir (at 400mg/day). to your body. Note that the daily unboosted dose Only a few percent of people using of atazanavir (2 x 200mg) is a higher atazanavir discontinue because of dose than the boosted dose (2 x jaundice. Jaundice reverses within a 150mg capsules). couple of days of stopping atazanavir. It is very important that your doctor Using ritonavir changes the formulation when not using ritonavir. Just like many other protease inhibitors, atazanavir produces better Other drugs that affect bilirubin results when used with ritonavir. Other drugs can also increase bilirubin levels. These include anabolic • Atazanavir levels are higher after you have taken a dose, and lowest steroids, some antibiotics, anti-malaria when you are due to take the next drugs, codeine, diuretics, morphine, dose. Ritonavir produces higher oral contraceptives, rifampin and and more consistent levels of sulfonamides. atazanavir thoughout. Drugs that can decrease bilirubin • The higher levels of atazanavir measurements include barbiturates, at the end of the dose will reduce caffeine and penicillin. the risk of resistance in people with low levels. Higher drug levels Key points: may make atazanavir stronger at • When related to atazanavir, high reducing viral load. www.i-Base.info • Atazanavir uses the lowest daily billirubin is not causing your body dose of ritonavir compared to other any damage ritonavir-boosted regimens. • If this is too disturbing or unpleasant then it often Because some people absorb higher disappears when using higher levels of drugs anyway, some people dose atazanavir without ritonavir may not need the additional boost from ritonavir. • Check atazanavir levels with TDM.
i-Base publications 47 guide to side effects FEBRUARY 2008 MAY 2008
T-20: injection site reactions (ISRs) and other side effects Associated drugs: T-20 (enfuvirtide, Fuzeon)
T-20 is the first drug in a new class of ISRs - Injection site reactions HIV drugs called entry inhibitors. Nearly everyone who uses T-20 gets The main advantages of T-20 are: some level of skin reaction where • that it is active against HIV that the T-20 is injected but some people is resistant to any of the other report no problems at all. Less than classes of drugs 5% of people discontinue treatment for this reason. • that it is an ‘entry inhibitor’. This means that it works on HIV before These reactions can include soreness CD4 cells are infected. Nukes, and redness; nodules, bumps or cysts; PIs and NNRTIs work on cells and itching or other irritation. ISRs that are infected by HIV. Side commonly last for a week or less in effects associated with some 75% people. nukes, PIs and NNRTIs, such Often these symptoms are mild as mitochondrial toxicity and and manageable, and they may be lipodystrophy, are unlikely to be minimised by good injection practice caused by entry inhibitors. described below The main disadvantages are that: The severity of the reactions is difficult • T-20 has to be used in combination to predict, and can vary in the same with other active drugs. Otherwise person. Some people follow all the the benefit is only temporary and best advice and are still unlucky and resistance develops get erratic reactions. Sometimes this may be due to factors that you can’t • It is not an oral drug. T-20 is given control. by sub-cutaneous injection (under the skin, not into a vein or muscle). The information in this guide only provides a limited overview on how to Because the benefits are significant reduce the risk of these reactions. and life saving for people with both resistance to existing drugs, and who The manufacturer (Roche) has have a low CD4 count, and because developed extensive support material of the more complicated way that the that everyone receiving T-20 is drug is given, we have taken several given. You will be given this detailed pages to cover T-20 in detail. information, together with training before you use T-20. Comments and suggestions for this section were provided by people who This pack includes: already use T-20 successfully in their • detailed printed information combination. • 1-2-1 training from nurses (or from your hospital) • a training video (if appropriate) • phone numbers of patients already on treatment www.i-Base.info 48 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Preparation and reconstitution Inject the water slowly into the T-20 T-20 needs to be given twice a day. vial at an angle. It should drip down the side of the vial into the powder. Although one study looked at giving • Gently tap the vial to start the T-20 both doses at the same time once a day, this was not as effective as twice dissolving. Then set it to one side daily. In some people, drug levels at to let it slowly finish dissolving the end of the 24 hour period were completely. This may take up to 45 too low, and this increased the risk minutes. of the treatment failing, and getting • Don’t shake the vial as this will resistance to T-20. cause the mixture to foam and it will However, each day both doses T-20 take longer to settle down before can be mixed up at the same time. It you can inject it. is very safe to mix both doses in the When the T-20 is fully dissolved, the morning,for example, and leave the liquid should be clear. There should evening dose in the fridge until you not be any powder left on the sides of come to use it later. the vial. If there is, you should not use this vial. • Set aside an hour for preparation, especially when starting out, so that There should also not be any air you are not rushed or hurried. bubbles or foam. If there is, then the • Wash you hands before starting vial needs more time to settle. the preparation and don’t touch Once mixed, the reconstituted T-20 anything other than the preparation should be used straight away, or put materials during this process. into the fridge for use in the evening. • Don’t touch the needles or the tops Reconstituted T-20 that is kept in the of the vials after they have been fridge needs to be used within 24 cleaned with alcohol swabs. hours. • Prepare a clear space that is not Detailed information on how to use cluttered with anything else. Use the syringes is provided in the training the preparation mat to lay out all the pack given to every patient. Different equipment. syringes have been used, including www.i-Base.info fine diabetic needles, and these may • Lay out all the materials before you change again in the future. This is why start and make sure that nothing is we have not included information on already opened or used. specific syringes in this guide. • Only use the sterile water to Choice of injection sites reconstitute T-20. Never use tap water or other water. T-20 is injected under the skin so you need to pick an area that has most • Always use the exact quantities tissue or fat. Do not inject into muscle, recommended. Take your time when and never inject into a vein. drawing up water into the syringe. i-Base publications 49 guide to side effects FEBRUARY 2008 MAY 2008
Recommended injection sites are: Clean the area to inject with an alcohol • Thighs - the top of legs swab and allow to air-dry. • Abdomen - your stomach, but not Pinch the area of skin that will be near your belly button injected. Make sure the skin is dry and the cleaning alcohol has evaporated. • Upper arms and back • Buttocks are not generally • Make sure that no T-20 touches recommended unless you have no the surface of the skin and that it other options and your doctor or is only injected once the needle is nurse agrees to try this. under the skin. Both these things will limit any burning sensation. Changing where you inject T-20 each day is important. Then insert the needle at a 45-degree angle with the flat angled edge facing • Do not inject into an area that up, and inject the T-20 very slowly. is still swollen or inflamed from an earlier injection. Feel for any Several posts to the FuzeonSupport earlier bumps under the skin so email discussion group have included that you can avoid these. varying the angle up to 90 degrees. It may be that you have to experiment to • Do not inject into moles, scars, see if one method is better for you. bruises, not the area around your belly button or any area of skin A half-inch needle should go all the that will be rubbed - ie by a belt. way in to the hub. • If you are prone to ISRs, wearing The injection needs to be under the lose clothing can help skin and not so deep that it reaches muscle. If you have very little body fat • You may want to ask a friend to then choosing the area with the most help you with injections, especially fat is recommended. in some of the more difficult to After injecting, put all the used inject sites like the upper arms. syringes and needles into the sharps This person should also receive container. training, including precautions if they This should be kept away from accidentally prick themselves with a children and collected by your clinic needle after giving you an injection. when it is full. Because T-20 is injected under Never throw needles into general the skin, and not into a vein, it is rubbish bins. very unlikely to be a risk for HIV transmission. Massage and ice packs • Some people report that having Gently massaging the injection a warm bath first helps to soften site after giving the injection may the skin and make the injection help reduce the risk of injection site process easier. reactions. This can be using your www.i-Base.info 50 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
hands, with or without non-irritating strange when you first have to think oils, or using an electrical massager. about it. Talking to someone already It will also help distribute the drug using T-20 may help and your hospital more quickly and more evenly. The can arrange this. nodules that sometimes occur have Needle free injections T-20 in those tissues, although the Over the last few years some patients inflammatory reaction is unlikely to be in the US were able to use a new related to the local concentration of system to inject T-20. T-20. Instead of needles, the ‘Bioject’ Some people find that an ice pack system uses pressurised gas to inject afterwards can help reduce the T-20 though the surface of the skin. swelling. Some people use a warm hot-water bottle. You will have to Unfortunately this research has not experiment to see whether or not been continued, and this in not going these options help you. to be an option for European patients, Creams such as a mild hydrocortisone Quality of life or benedryl cream may help with more T-20 studies have reported overall severe reactions. increases in quality of life. This was Getting used to needles despite having to inject T-20 twice a day, on top of taking other pills, Most people report that they get used to using needles very quickly. But it This may be related to knowing may seem strange at first. Try to focus that HIV treatment is working. on the benefit you are getting against Often, people who have used many HIV. For example, contact lenses are treatments in the past, are eventually strange when you use them for the able to get an undetectable viral load first time and this may be a bit similar. using T-20. This is especially true when T-20 is used with other new Carrying needles, travelling and active drugs. leading a normal life Switching from T-20 - not a drug to Many people are able to fit using T-20 use forever.... into a normal and active life. If you www.i-Base.info travel you can always find a quite T-20 may be a drug that you only need space to inject if you need too. One to use for a short time. If a new drug person took their first dose of T-20 in is developed that you are not resistant an aeroplane on their way to Moscow. to, you may be able to switch from T-20 to the new drug. Take a letter with you from your doctor, that says you need the syringes for In 2008 this includes the integrase medical treatment, and that you are fit inhibitor raltegravir, a new PI called and healthy to travel. darunavir, a new NNRTI called etravirine and a CCR5 inhibitor called The injection process may sound maraviroc. i-Base publications 51 guide to side effects FEBRUARY 2008 MAY 2008
Other T-20 side effects This ‘euphoria’ can last for up to a couple of hours after injecting. It can include a general sense of well-being, Hypersensitivity reaction contentment, excitement, or feeling A very small percentage of people get ‘buzzy’. a ‘hypersensitivity reaction’ to T-20, This was not seen in the large T- but this is rare. 20 studies but has been reported Symptoms include difficulty breathing, anecdotally since T-20 was approved. fever, nausea and vomiting, rash, If you already receive T-20, then keep chills, stiffening of muscles, low an eye out for this. blood pressure and increased liver enzymes. This can be serious and Other information life-threatening. If you have any such reaction, you should stop taking T-20 Please refer to the patient information and call your doctor immediately. leaflet and support material in your pack for full details. Bacterial pneumonia You can join a community-run email People in the main T-20 studies were support group by sending a blank at higher risk of bacterial pneumonia email to: if they used T-20 in their combination. The reason for this is not clear. FuzeonSupport-subscribe@ yahoogroups.com People with HIV are more susceptible to getting bacterial pneumonia than Patent support material provided by HIV-negative people. the drugs manufacturer is available at: This risk is higher if your viral load http://www.fuzeon.com/ remains high, and your CD4 count is The i-Base phoneline is a source low. If you have trouble breathing, or of information about all aspects of develop a cough with a fever, then you treatment, including whether T-20 is should once again contact your doctor an appropriate choice. immediately. The phoneline can also put you in Mood changes - including euphoria touch with HIV-positive people who Some people have reported a feeling are using T-20. of euphoria when using T-20. This has 0808 800 6013 often been after using T-20 for many months. www.i-Base.info 52 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Lipodystrophy (lipid = fat; dystrophy = disorder)
Lipodystrophy is a difficult side effect loss and fat accumulation have been to write because there is still no reported by people using NNRTI- agreement on the underlying cause of based combinations. At least one these symptoms. study showed that lipodystrophy This is important to understand, occured more often when using a because you may want your doctor to three-class combination with PIs, make changes in your treatment, even NNRTIs and nucleosides compared to though studies haven’t shown that one two-class regimens. particular approach will work. However, not all drugs in the same Although awareness of lipodystrophy class have the same risk of symptoms. has improved, you may still have to Lipodystrophy is likely to be the take an active role in getting the best result of several different factors monitoring and treatment. rather than any single cause. These This booklet was revised in May 2008. include HIV infection, individual Our understanding will hopefully drugs, when treatment was started advance over the next few years and it and family health. is important to follow results from new Lipodystrophy has been reported in research from scientific meetings. men, women and children from a wide What are the symptoms? range of racial backgrounds. There are three broad sets of How many people are affected? lipodystrophy symptoms: Depending on what is being defined • Fat loss (from legs and arms and measured, lipodystrophy has leaving veins more prominent, also been reported in 5-80% of people on from buttocks and the face) treatment. Only a smaller percentage • Fat gain (in the stomach, of people will show clinical symptoms. breasts in both women and men, In order to treat HIV, we need to shoulders, neck and sometimes recognise that many of the current lipoma - small lumps of fat under drugs affect the way our bodies the skin) process fats and sugar.
• Metabolic changes that increase Over the short-term, most people www.i-Base.info the levels of fats and sugar do not have serious problems. The in blood and intefere wth the benefits from treatment still clearly way your body produces and outweigh the risks. However, for a processes fat and sugar significant minority of people the Any discussion about lipodystrophy problems can occur more quickly, or therefore needs to refer to specific can become more serious. symptoms. Preventing lipodystophy is more Fat loss has been linked to nucleoside important and more successful than analogues and fat gain has been trying to treat lipodystophy after it has linked to protease inhibitors. Both fat developed. i-Base publications 53 guide to side effects FEBRUARY 2008 MAY 2008
As no one can predict who will be If you are worried that you have affected before starting treatment, lipodystrophy, make sure this is taken monitoring in order to change seriously. You should be offered treatment if you get early symptoms is monitoring and have any treatment very important. choices explained. Monitoring changes in fat Changing treatment distribution Switching from d4T or AZT can There are several ways that changes reverse fat lost from limbs. This is now in body fat distribution can be supported by several studies and is measured and monitored. discussed on pages 56-57. Most people are more sensitive With fat accumulation, most of the to physical changes related to studies looking at switching individual fat distribution in their body, than drugs have been less helpful. These their doctors are. This means are discussed in the section on fat that ‘self-reporting’, perhaps with accumulation on pages 58-59. careful measuring by a dietician, or But, just because studies haven’t photography is more likely to provide a shown a benefit, it doesn’t mean that record of any change. other treatments may not be better for Some HIV clinics may have access to you. Whether you decide to change scanning equipment, but in practice your treatment will depend on several lipodystrophy is rarely monitored in things, including: this way. MRI and DEXA scans look • How bad your lipodystrophy is at the breakdown within your body of • How effective your current fat and muscle. A test called BIA (Bio treatment is Impedance Analysis) is also reliable. • Your choice of other treatments (See side bar for more details). • Your HIV treatment history Getting a DEXA scan, or well-lit photo, • How serious your HIV was before even if you only have slight changes, you started treatment. will give you a reference to know how Many doctors are reluctant to change quickly symptoms are progressing or a combination which has worked well improving. Some specialist clinics, in terms of viral load and CD4 results, including the lipodystrophy clinic at St especially if you were previously Thomas’ Hospital in London (to which very ill. However, this may not be you can self-refer), provide baseline appropriate if lipodystrophy has DEXA scans to all patients. significantly reduced your quality of Like your CD4 and viral load results, life. single test results may not provide If you change your combination, much useful information, and you you have to change it to one that is may need several tests over time to effective against HIV. If you developed monitor changes. resistance to earlier combinations, this will affect your choices. www.i-Base.info 54 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Monitoring tests MRI scan (Magnetic Resonance These tests can monitor changes – Imaging): these scans are much less and baseline measures by a dietician readily available and the equipment for everyone before starting treatment required is more sophisticated and would make interpreting later changes expensive. An MRI scan provides a easier. computer image of the tissues, muscle and bone in a cross-section of any Measurement: careful measurement part of your body. An MRI scan can by a dietician using calipers can be show how fat is distributed – whether useful if nothing else is available. This it is subcutaneous (under the skin) or may be useful for fat increases but will visceral (around your central organs) be less sensitive for fat loss – and will – and is very accurate at measuring not help for facial fat loss. Unless the any changes. changes are very marked then this may not be sufficiently accurate and Bio-electrical Impedance Analysis may vary depending on the dietician. (BIA): BIA is a simple painless procedure DEXA scan (Dual X-ray that calculates the percentages of Absorptiometry): these scans are fat, muscle and water in the body available at most main hospitals as according to height, weight, sex and they are routinely used for checking age. bone changes as people get older. You lay on flatbed scanner for about It has mainly been used for HIV- 20 minutes for a full body scan (head related wasting but may also be useful is not included though). They are not in monitoring lipodystrophy. expensive (only about £70) and the Weight in people with lipodystrophy results provide a breakdown of your is generally stable. Fat redistribution body composition into fat, bone and rather than weight gain or loss that is muscle. Some doctors would like to usually the issue. However, weighing see DEXA scans provided before any yourself is important in case you have HIV treatment is started, and repeated lost or gained weight without realising annually to monitor for changes. it.
Using combinations without combination immediately, so there is www.i-Base.info nucleosides is one new strategy that is little to lose in at least seeing whether being studied. Another might be to use the lipodystrophy will improve. entry inhibitors like T-20 or maraviroc. It will be much easier to know if the If you make a treatment change, switch has worked if you have been test your viral load at least monthly monitored before you make any afterwards until you can confirm that change. the new combination is working. Even if this does not reverse the If your viral load rebounds, you symptoms, using different drugs can always return to your previous may stop them getting worse. i-Base publications 55 guide to side effects FEBRUARY 2008 MAY 2008
Fat loss (lipoatrophy) Associated drugs: d4T (Stavudine), AZT (zidovudine, Retrovir), possibly efavirenz (Sustiva).
Symptoms monitoring should pick this up if you Lipoatrophy is the medical term are using older drugs like AZT. for fat loss, and it is currently seen Role of other HIV drugs as the main symptom behind the Some studies report a higher risk lipodystrophy syndrome. when d4T or AZT are used with Symptoms include loss of fat from protease inhibitors. There is an even under the skin on your arms and legs, higher rate seen with combinations which can make your veins look more that include drugs from the three prominent. It also includes loss from main classes: i.e. nukes, a PI and an the face - generally resulting in sunken NNRTI. cheeks and temples. A US study called ACTG 5142 Fat can be lost from the soles of the reported higher rates of fat loss in feet making walking more tiring. people using efavirenz compared to Role of d4Tand AZT lopinavir/r. These findings are not fully Clinical ipoatrophy - where you understood. can see a change in body fat - is Switching treatment common after long-term treatment Switching d4T or AZT to either that includes either d4T or AZT. Both abacavir or tenofovir, or using other these drugs affect the way that fat combinations of drugs, can reverse cells are produced at a cellular level, the fat lost in limbs. Reversing fat loss sometimes after only a few weeks or from the fat or buttocks appears to be months of treatment. more difficult, but this may be possible Nucleosides have been shown to if you switch treatment at the first damage the energy producing part of symptoms. healthy cells called mitochondria. There may be a risk of viral load In most studies, d4T damages fat rebounding if you have resistance to cells at around twice the rate of AZT. other HIV drugs. Otherwise, switching d4T may also lead to lipoatrophy that is very safe. is more difficult to reverse than that Any reversal of the fat loss is caused by AZT. This is because it may likely to take at least six months to damage cells at an earlier stage. become noticeable. These symptoms Other nukes? developed slowly and if they are going Not all nukes cause lipoatrophy. 3TC, to reverse this will also take time. FTC, tenofovir and abacavir do not In studies where people switched to seem involved. The role of ddI is abacavir, the return of small amounts unclear. of leg fat (+ 0.3kg) was detected by The risk of lipoatrophy for people who scans at 6 months. It took about two are starting their first treatment should years (+1.3kg) before these patients now be low. Newer drugs do not noticed a difference themselves. cause this side effect, and increased www.i-Base.info 56 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Further info: a US community site with information on lipoatrophy treatment http://www.facialwasting.org
New-Fill (Sculptra) Bio-Alcamid New-Fill (polylactic acid, PLA) has Bio-Alcamid is a ‘gore-tex’ filler. This shown promising results in correcting can be injected in greater volumes the effect of facial fat loss and is than New-Fill, so that with severe approved in the US as a treatment facial lipoatrophy, only one or two for HIV-related lipoatrophy. Most treatments may be needed. people require 4-5 sets of injections The effect is likely to be permanent, but severe cases may require more whereas New-fill requires top-up sessions. treatment every few years. However, New-Fill does not replace fat but Bio-Alcamid is currently only rarely generates new collagen growth. available on the NHS, because it has The effect is that essentially your not been well-studied in trials. skin grows thicker, sometimes by Autologous fat transfer (Coleman up to 1cm. This process continues technique) for months after the injections have This process was an early intervention finished. before New-Fill became available. Fat New-Fill has also been used to correct is collected from one part of your body fat lost on the soles of the feet. - usually subcutaneous fat from the There is already good access to New- stomach - and is then transplanted to Fill on the NHS in some of the larger the face. HIV clinics in the UK. These include Fat that has accumulated as a result Brighton, Manchester, and any patient of lipodystophy, for example shoulder attending a London clinic. Since 2005, pad fat is not suitable for transplanting New-Fill has been available free on as it may continue to expand in a the NHS for any patient registered at a process that is not reversible with London clinic. liposuction. Access to treatment is clearly not This is a more traumatic surgical equally available throughout the UK. procedure and the process is now less Although access should continue frequently used. to improve, you may have to lobby Other injectable substances hard, or even change clinic in order to Most other approaches try to inject www.i-Base.info access this treatment. or implant material (fat or silicon) and Private treatment costs vary by clinic. hope it will stay in position. Very often, Private treatment should ONLY be it disperses, moves or appears lumpy. from a practitioner with experience of Silicon injections are both dangerous HIV-related lipoatrophy. and ineffective and were banned in UK HIV treatment guidelines the US many years ago, although a recommend that corrective treatment study of a new finer grade of silicon is such as New-Fill or surgery should be ongoing in the US. provided on the NHS. i-Base publications 57 guide to side effects FEBRUARY 2008 MAY 2008
Fat accumulation Associated drugs: nukes, NNRTIs and protease inhibitors
Symptoms investigational drugs. Abdominal fat accumulation Steroid treatment for lipodystrophy, associated with lipodystrophy particularly for fat accumulation, is is generally visceral rather than also being studied. Although steroids subcutaneous. Visceral fat is around have the potential to reduce fat the organs inside the abdomen rather accumulation, they should be used than fat just under your skin (‘love with caution as they may also worsen handles’). fat loss. With visceral fat your stomach walls Recombinant Human Growth are pushed out from the inside, so Hormone (rHGH) showed the potential your stomach muscles can sometimes to reduce visceral abdominal fat and be quite defined, but your stomach will fat pads from the back of the neck and still be very extended. shoulders in several small studies, but In severe cases, your internal organs the side effects profile limits use of can become compressed so that rHGH, even at lower doses. Dosing at normal functions like breathing and 2, 3 or 4 mg daily rather than the 6mg eating can be affected. in early studies reduces side effects. Fat accumulation appears to return if In these cases there is a greater rHGH is stopped. medical urgency to reverse the fat accumulation. This may help More recently, a Growth Hormone you access treatments like growth Releasing Factor called Tesamorelin hormone releasing factor (GHRF, (formerly TH-9507) produced similar Tesamorelin), growth hormone (rHGH) results (approximately 20% reduction or switch drugs like T-20 or raltegravir. in visceral fat) with a much safer side effect profile than rHGH. Fat can also accumulate across the back of your neck and shoulders. The benefits from GHRF are also only This is sometimes called buffalo short-term and fat is likely to return hump. Breast size can increase unless treatment is continued, The in both men and women. A fatty maintenance dose of Tesamorelin has deposit in the breasts of men is called not been established, gynaecomastia. Neither Tesamorelin nor rHGH are Small bumps or collections of fat, approved in Europe as treatments for called lipomas, can occur under lipodystrophy. the skin in other parts of the body Removing fat pads using liposuction including the pubis. or surgically has worked well for some Treatments for fat accumulation people. The fat returned, after several months, in 25-50% of people, but the Many of the approaches used to lower results were more sustained in about cholesterol and triglycerides are being half these reports. studied to treat fat accumulation. These include diet, exercise, and There may be a higher likelihood of a www.i-Base.info 58 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
No lipodystrophy Lipodystrophy Spine Back Back Sub- cutaneous fat (love handles)
Front Abdominal Front muscles Sub-cutaneous fat is ‘normal’ fat just under the surface of Visceral fat inside abdomen pushes against organs and
An MRI scan across your stomach shows that fat is inside the abdomen and around the organs rather than being directly under your skin. permanent result if HIV treatment is accumulation than with fat loss. modified at the same time. If you change your combination, you Unless the underlying metabolic have to change it to one that is just as mechanism is altered, as with effective against HIV. Tesamorelin or rHGH, fat accumulation Studies switching a PI to an NNRTI is likely to return after several months. have been too poorly designed to Liposuction cannot be used for show any change clearly. Often visceral fat accumulation in the background nucleosides were not abdomen. changed, when we now think that this would have helped too. There Anecdotally, testosterone cream are often reports of better adherence, massaged onto the fat pads has easier regimens, fewer pills, and most reduced fat pads on the shoulders. A importantly no viral load rebound, but much lower dose would be used for effect on fat is less clear. women than for men. There have been anecdotal Dihydrotestosterone gel (Andractim) reports and case studies of people has been used to treat breast whose shoulder and/or abdominal enlargement (gynaecomastia) in men. fat decreased after switching to Women with lipodystrophy may have atazanavir. higher levels of testosterone than Atazanavir does not cause the either HIV-positive women without elevated blood lipid levels associated lipodystrophy or HIV-negative women.
with other protease inhibitors, but long- www.i-Base.info It is not clear whether this is due to term impact on risk of other symptoms high insulin levels associated with of lipodystrophy is still being studied. lipodystrophy, although a link between Raltegravir, a new integrase inhibitor, the length of time on PI-therapy (but does not affect blood lipids, but the not other drugs) and a greater chance impact on lipodystrophy is unclear of higher testosterone was found in one study. In theory, if one particular drug is linked to these body changes then it is Switching studies very reasonable to at least try another Studies switching individual drugs one, in case this works for you. have been less helpful with fat i-Base publications 59 guide to side effects FEBRUARY 2008 MAY 2008
Cholesterol and triglycerides
Cholesterol and triglycerides are Cholesterol two types of fats (lipids) that can be Total cholesterol (TC) is measured measured in blood and plasma. first. If these results are high then a They should be measured before further test will break this down into starting or changing treatment, and two different types of cholesterol: repeated a month afterwards. Routine i) High Density Lipoprotein (HDL) monitoring for someone on stable is a ‘good’ cholesterol because it treatment should involve checking removes fats from your arteries; levels of cholesterol and triglycerides every 3-6 months. ii) Low Density Lipoprotein (LDL) is ‘bad’ cholesterol and is a small Most clinics will do this at the same molecule that carries fats from the time as your CD4 and viral load, but liver to other parts of your body you may need to check that this is and can lead to heart disease. being done. These tests are best done fasted so don’t eat or drink anything Target levels for total and LDL for breakfast on blood test days. cholesterol and desirable levels for HDL cholesterol and triglycerides are Management of lipid levels should be shown in Table 1. Target levels are part of an assessment of your risk for set lower for people who already have heart disease. high cardiovascular risk due to other This is generally related as much to factors. other risk factors, as to any single The TC:HDL ratio is used to determine elevated blood test. the importance of using lipid lowering Fasted triglyceride levels drugs, but is not used for monitoring High triglycerides are linked to afterwards. increasing the risk of heart disease. Changing HIV drugs in your For each increase of 1.1 mmols/L combination the 10-year risk of a heart attack Lipids generally improve after increases by about 25% in men and switching away from HIV drugs that 60% in women. have caused this change. Although there is a lot of individual This usually involves switching from variability target fasted levels of under a protease inhibitor combination 2.2 mmol/l are considered normal - particularly if it includes ritonavir - to and of 2.2-4.4 mmol/l are borderline. nevirapine, abacavir or atazanavir/r. Above this, the risk of heart disease increases. Levels above 11 mmol/L Abacavir may have a greater are considered very high. impact on reducing cholesterol, and Untreated HIV also causes nevirapine may help with increasing triglycerides to increase. HDL (good cholesterol). The debate on the impact of different strategies on reducing risk for heart disease is likely www.i-Base.info 60 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Table 1: Target/desirable levels for fasted lipids For further Total cholesterol under 5.0 mmol/L (under 4.0 if high risk) information LDL cholesterol under 3.0 mmol/L (under 2.0 if high risk) see the HDL cholesterol over 0.9 mmol/L European (EACS) metabolic Triglycerides less than 1.7 mmol/L guidelines: http://www.eacs.eu to develop and change over the next If diet, supplements, and exercise are few years. not enough, then lipid-lowering drugs (fibrates to reduce triglycerides and/or This became more complicated in statins to reduce LDL cholesterol) are 2008 when the D:A:D study reported recommended. that abacavir was independently associated with a 90% increased risk Lipid-lowering drugs need to be of heart disease. This is discussed on prescribed by an HIV-specialist as pages 64-66 in the section on heart they can interact with HIV drugs. For disease. example some statins should never be used and some require increased or Atazanavir is a once-daily protease decreased dosing when used with PIs inhibitor that is being widely used or NNRTIs. because it does not cause lipid increases, although the boosting Studies are also looking at metformin dose of 100mg ritonavir reduces this (an insulin sensitising drug), benefit. rosiglitazone and growth hormone. The choice of individual drugs will A study of HIV-positive men in a study depend on your previous treatment looking at the effects of exercise and history and previous history of testosterone found that testosterone resistance. significantly reduced levels of ‘good’ cholesterol (HDL). This is a concern Diet, exercise and lipid lowering for people with lipodystrophy who drugs already have elevated triglycerides Cholesterol and triglyceride levels and ‘bad’ cholesterol (LDL). can often be improved or controlled Although muscle gain and fat loss by reducing fat and cholesterol in were greater in the testosterone your diet and by starting or increasing group, levels of good cholesterol exercise. increased in people who used
Omega-3 supplements can also have exercise without testosterone, and this www.i-Base.info a significant reduce triglyceride levels. may be more appropriate for people This may be much more efficient than with lipodystrophy. trying to obtain sufficient quantities of Although anabolic steroids can omega-3 from diet alone. increase muscle mass they can also For example, a 4 g daily dose Omacor, reduce fat, and have the potential to (90% omega-3 acid ethyl esters) is worsen lipoatrophy and lipid levels. equivalent to 150g mackerel, 700g Improved blood lipids have not so far tuna, 210g herring, 1.1 kg cod, 280g shown an improvement in either fat salmon, 1.7kg eel or 850g shrimps. loss or fat accumulation. i-Base publications 61 guide to side effects FEBRUARY 2008 MAY 2008
Increased blood-sugar levels and risk of Type-2 diabetes Associated drugs: some protease inhibitors and some nukes
Glucose and insulin Diabetes increases the risk of having a Glucose is type of sugar and your heart attack as much as smoking. body relies on glucose to provide Fat and sugar metabolism are also energy. A hormone called insulin closely linked and insulin resistance processes the sugar and allows it to is a complication of HIV therapy that enter cells. is gets little recognition. It is directly Insulin also regulates production of related to some protease inhibitors new glucose by the liver, levels of and possibly indirectly related to nukes glucose in the blood, and metabolic through their effect on fat distribution. aspects of fat cells. Changes in blood glucose levels and Insulin resistance is the term for when insulin sensitivity are closely related to this system fails to work properly. other symptoms of lipodystrophy. Although your body produces more What can help insulin to compensate, if insulin As with HIV-negative people mild resistance continues, and sugar insulin resistance can be managed by levels remain high, you can develop diet, exercise and stopping smoking. diabetes. Switching HIV drugs associated Insulin levels are difficult to measure, with increases in blood-glucose is but glucose levels, usually checked by recommended when appropriate. fasting or non-fasting blood tests, are Dietary advice involves reducing routinely used for monitoring risk. processed sugars, refined and fast Types of diabetes foods, white flour and potatoes as Type-2 diabetes is a adult illness that they cause quick sugar ‘highs’. More develops slowly. It can take years or complex carbohydrates like wholemeal decades for mild insulin resistance to bread and wholemeal and al-dente progress to diabetes, but the impact pasta, porridge and most vegetables on the risk of heart disease is serious. provide energy more slowly with less Some protease inhibitors can increase impact on sugar levels. glucose levels and the risk of Type-2 Metformin may help people with insulin diabetes. resistance and fat accumulation. Type-2 diabetes is different from Type- Rosiglitazone or pioglitazone may help 1, which is a childhood illness caused people with insulin resistance and fat by low insulin production, and which is loss. The possibility of interactions managed by insulin injections. with other HIV drugs (PIs and NNRTIs) means that they should also be used Risk of long-term health problems with caution, and perhaps with drug- High untreated blood-sugar is related level monitoring (TDM). to many long-term health problems including the kidneys, nerves, eyes and vision, risk of heart disease and stroke, erectile dysfunction in men and pregnancy complications in women. www.i-Base.info 62 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Tests to diagnose and monitor Symptoms of high blood-sugar, and glucose and insulin levels diabetes Fasting glucose test - measures • Feeling thirsty or excessively blood sugar after an 8-hour fast. This hungry should be measured before starting • Feeling tired and after switching treatment, and at • Low concentration least anually after this. • Blurred vision Fasting levels over 5.6 mmol/L in plasma indicate insulin resistance, • Unexplained weight loss and need follow-up an oral glucose • Frequent need to urinate tolerance test (OGTT). • Slow healing of cuts Random glucose test - Unfasted glucose levels are less accurate but • Tingling in hands or feet (neuropathy) are taken shortly after someone has had something to eat or drink. If it is • Nausea and vomiting greater than 5.17 mmol/L other tests Risk factors for abnormal glucose are run. Diabetes is over 11.1 mmol/L. • Liver damage or coinfection with Oral glucose tolerance test (OGTT) - HepC Monitors levels of glucose every 30-60 minutes for two hours after fasting for • Family history of diabetes 8-hours and then drinking a measured • Overweight (BMI>30) glucose drink. Healthy glucose on this • Lipodystrophy or lipoatrophy test should be less than 3.62 mmol/L. • Low exercise If it is greater than 5.17 mmol/L other tests are run. Diabetes is over 11.1 • Age over 40 mmol/L. • High blood pressure (over 130/85 Haemoglobin A1c - tests how much but this depends on age and other glucose adheres to red blood cells. It risk for heart disease) is used to determine average glucose • High cholesterol and triglycerides levels over several months. Normal (over 1.7 mmol/L) and low HDL range for someone without diabetes (good) cholesterol (less than 0.9 is 4-6% and managed treatment for mmol/L) someone with diabetes should aim to • History of insulin resistance or high glucose keep this under 7%. www.i-Base.info Fasting insulin test - and results • Other meds, including niacin, used to calculate HOMA-IR score. glucocorticoids, megestrol and Measuring glucose is generally Growth Hormone and some PIs preferred to measuring insulin directly. Insulin tolerance test (also called For further information see the glycemic clamp) - where insulin European (EACS) metabolic in infused by intravenous line, and guidelines: glucose given until normal blood sugar levels are reached. This is expensive http://www.eacs.eu and again is rarely used. i-Base publications 63 guide to side effects FEBRUARY 2008 MAY 2008 Heart disease CVD=Cardiovascular disease
When lipodystrophy and metabolic In 2008 D:A:D also reported an changes associated with combination increased risk from current or therapy became more widely recent use of the nukes abacavir recognised, there was an initial (90%) or ddI (45%). concern that these symptoms could • People at high risk for heart increase the risk for heart attack or disease may need to take any stoke. additional risk more seriously This is because increased levels of blood lipids can lead to blocking blood • Risk factors for heart disease vessels (atherosclerosis) and are a in HIV-positive people are the well-established risk factor for heart same as for people who are HIV- disease. negative5 This concern was prompted by a • Making lifestyle changes that series of case reports of heart attacks minimise risk factors are now in HIV-positive men who were too strongly recommended as part of young to be considered as traditionally a long term plan for managing HIV- at high risk. positive patients. However, the risk of heart disease There is a lot of information and may be increased more by HIV than research about risk factors for heart by HIV treatment. disease in HIV-negative people. This has often come from very large Several large studies have reported studies (Framingham, Caerphilly etc) results that calm some of these initial that followed a large group of people fears. for many decades. These studies led • Benefits of combination therapy to the development of risk calculators still far outweigh the possible that are easy to access online (see slightly increased risk of heart page 71 for links). disease for most HIV-positive If you put in your age, gender, people cholesterol and triglyceride levels and • The SMART study found that other risk factors such as smoking, using HIV treatment with an you get your 5-year or 10-year risk of undetectable viral load was heart disease. protective of heart disease People with high risk factors for heart compared to not being on disease who need HIV treatment, treatment or having a detectable should use HIV drugs that have the viral load. least risk of increasing the risk of • The D:A:D study showed a small cardiovascular disease any further, additional increase in risk of and receive support for lifestyle heart disease from each year changes. on protease inhibitor treatment (10%), but not from using NNRTIs. www.i-Base.info 64 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Risk factors for heart disease • loss of balance or coordination • severe headache The following factors increase the • brief loss of consciousness. risk of heart disease; some of which are fixed and some are modifiable by If you experience these symptoms, lifestyle. you should seek urgent medical Fixed risk factors attention. • older age (men over 45, women Rapid treatment after a stroke (within over 55) 2-3 hours) can limit permanent brain • gender (men are at higher risk at damage. the same age) D:A:D Study • family history of heart disease The D:A:D study is the largest study Modifiable risk factors to look at the risk of heart disease in relation to HIV treatment. • smoking • high lipids - ie high cholesterol The study collected information from and/or triglyceride levels over 33,000 patients from Europe, the • lack of exercise US and Israel. • high blood pressure, especially This diversity of patients is one of the diastolic blood pressure study’s strengths. D:A:D found that • high levels of sugar in blood, duration of protease inhibitor-based insulin resistance and diabetes treatment was related to a small but Symptoms of heart attack or stroke significant increased risk of heart Symptoms of cardiovascular disease disease. This was found in different include: countries and in both men and • shortness of breath women. • fatigue The link to use of abacavir or ddI has • feeling dizzy or light-headed been more controversial as this was • fainting the first large study to report this. This • chest pains (that can extend to the risk was seen in people who were shoulders, back, arms, head and currently using, or who had recently jaw) used, either of these two drugs. The www.i-Base.info • Chest pains after exercise or risk did not continue once these drugs exertion. were switched to other treatments. Additional symptoms for a stroke include: Relative rate and actual risk • sudden numbness The D:A:D study showed that • paralysis of the face or limbs, the relative rate for heart disease especially affecting just one side of increased by around 10% for each the body year of protease inhibitor treatment, • difficulty speaking after allowing for other factors such as blood lipids. The impact on the use of i-Base publications 65 guide to side effects FEBRUARY 2008 MAY 2008
The website for the North Central London Cardiac Network includes detailed guidelines for managing heart disease: http://www.nclcn.org.uk/
abacavir almost doubled the absolute The most recent research risk. How these new results affect use suggests trying a range of of abacavir is likely to become clearer products over the first week or two later this year. to cope with nicotine withdrawal such as patches, gum, inhalers How much this affects your individual and sprays so that you find the risk depends on whether you are ones that work best for you. at a high or low risk to start with. Individualising HIV care will be linked Your HIV doctor can refer you to to your other risk factors. specialist services to help you quit. If you have high blood cholesterol • Diet changes are other significant for example but no other risk factors, changes that can reduce your risk then your absolute risk will still remain for heart disease. low. However, for a 50-year old male • Reducing fatty foods can reduce smoker who has high cholesterol lipids to some extent. Cutting down and is on HIV medication, it is more on salt reduces blood pressure. important to change one or more of Eating less processed sugars these factors. reduces your risk of developing For someone who has a high risk insulin resistance and diabetes. because of factors that can’t be • Eat more fruit and vegtables, fish changed (ie a familiy history of heart and lean meat and reduce use of disease) then it is more important not processed foods. to add to these risks by using any HIV drug with this potential side effect. • Exercise is the other main modifiable factor. Regular exercise How to make lifestyle changes and being more active in your Changing the risk factors for heart day-to-day life, by walking more disease can have a direct impact on and using the lift less, is more future risk. By implication, this will also important than very vigorous make HIV drugs safer to use. exercise. The advice given to the general Any change in level of activity will population is even more important if probably have to start gradually. you are using HIV treatment. People who start an exercise programme report benefits in • Stopping smoking is the most quality of life. This can include important lifestyle change in increased well-being and energy terms of general health and risk levels. of heart disease. Support groups and other interventions including replacement therapy like nicotine patches are now available on the NHS. www.i-Base.info 66 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Glossary (heart disease) Arteries are the blood vessels that take blood from the heart to the lungs. Veins are blood vessels that delivery blood back to the heart again. Arrhythmia is the medical terms for a disturbance of the heart’s natural rhythm. Tachycardia refers to when the heart beats too fast. Bradycardia is when the heart beats too slowly. Atherosclerosis refers to a narrowing or hardening of large and medium sized arteries. The narrowing is ie 120/80. The first number is systolic caused by a build-up of plaque, and BP - the pressure when your heart usually takes many years. As the walls beats. The second number is diastolic of the artery thicken, the heart has to BP, which is the pressure when you work harder to pump the same amount heart rests between beats. of blood through a narrower gap. Target range for BP is usually Cardiovascular refers to the heart quoted as 120/80, with interventions and blood vessels. sometimes recommended if this is Cardiovascular disease (CVD) is the above 130/85 or 140/90, but these general term for disease to the heart are dependent on risk factors for heart and related blood vessels. disease including your age. Cerebrovascular refers to the blood Hypertension increases the risk of a vessels taking blood to the brain. A heart attack, particularly when diastolic blockage that restricts blood to the BP is high. brain is called a stroke. Strokes can Hypotension is the medical name for occur when blood vessels in the low blood pressure. brain block, or when a clot formed in another part of the body is carried to Pulmonary hypertension refers to
the brain. high blood pressure in the arteries www.i-Base.info taking blood from the heart to the Coronary Heart Disease (CHD) lungs. HIV-positive people are refers to the three main arteries more likely to develop pulmonary that supply blood from the heart. A hypertension than HIV-negative coronary by-pass is an operation to people. provide a new route for blood to reach the heart when coronary arteries Myocardial Infarction (MI) is the become blocked. medical term for ‘heart attack’ Hypertension is the medical name Peripheral arterial disease refers to for high blood pressure (BP). Blood atherosclerosis in the arteries in the pressure is measured as two numbers arms or legs. i-Base publications 67 guide to side effects FEBRUARY 2008 MAY 2008
Bone mineral changes (osteo = bone; necrosis = death; porosis= thin)
HIV is one of several conditions that The focus on bone density is important are linked to bone changes. because it reduces with age, yet the Even though this may not be a side HIV population is also getting older. effect, we have included information Osteopenia and osteoporosis are as this is a new area of research that related to low weight and low Body is important for your long-term health. Mass Index (BMI). The two main bone problems are: These changes in bone structure often overlap with issues of lipodystrophy i) changes in content and structure of bone where your bone becomes and may be related to these metabolic thinner. This is called osteopenia changes and the way your body at mild levels and osteoporosis at processes sugar and fat. more severe levels that require Corticosteroids (like prednisone) and treatment. heavy alcohol use are associated with higher risk of bone problems. ii) interruption of proper blood supply to the bone, which causes death Other risk factors for osteoporosis of bone tissue - osteonecrosis and include Caucasian/Asian race, low avascular necrosis (AVN). body weight, smoking, lack of physical activity, family history of osteoporosis, Osteopenia and osteoporosis low testosterone levels in men and Rates of both osteopenia and early menopause in women. osteoporosis are significantly higher Leading an active life, and including in HIV-positive people compared to exercise, maintains healthy bone. age and sex-matched people who are This includes weight-bearing exercise HIV-negative. (walking, jogging, running, steps and It is still unclear if this is just related to dancing) and muscle strengthening HIV or whether side effects from HIV exercise. Improvements include better drugs also contribute. posture, balance and strength and a direct improvement in bone density. In some studies, protease-based combinations have been linked to Your bones are a living structure, reduced bone mass but other studies 10% of which naturally die each year have shown contradictory results. to be replaced by new cells. If the bone isn’t replaced quickly enough Tenofovir can cause a small drop in or in sufficient quantities, your bones bone mineral density in the first six become thinner and more brittle. months, but this does not appear to progress with longer use of treatment. Osteopenia is very common in older people and several studies showed high levels in people with lipodystrophy. www.i-Base.info 68 i-Base publications information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Osteoporosis is a more serious corrected by increasing dietary intake progression of osteopenia and can be or use of supplements. diagnosed with a DEXA scan. Unlike The (US) National Osteoporosis osteopenia this can lead to fractures Foundation 2008 guidelines (http:// and pain (commonly to the spine in www.nof.org) recommend adult targets men and the hip in women. of 1200mg daily for calcium and 800
Osteonecrosis and avascular -1000 IU/day for vitamin D3 (for people necrosis at higher risk). With osteonecrosis and AVN, These nutrients can be prescribed by inadequate blood supply reaches the your doctor and sometimes require bone, and these tissues then die as special monitoring and dosing. a result. It is much less common, The target level of vitamin D monitoring and usually affects hip, shoulder or is to get blood levels of 25(OH)D over knee joints, and requires replacement 75 nmol/L. surgery. A link has also been suggested It is very common for corticosteroid between bone damage and use to be a contributing factor in cases mitochondria damage, and a link to of AVN. high levels of lactic acid has also been Early diagnosis of AVN makes a big reported. The HIV medications related difference to the success of treatment to these changes may therefore be as well as your quality of life. If you nucleosides. This may be a reason to experience pain in these joints, ask use mitochondria protecting nutrients your doctor to refer you to a specialist, such as vitamins C and E, L-carnitine and to provide an MRI scan that can and co-enzyme Q. make an appropriate diagnosis. Other potential treatments to improve Protecting bones bone mineral density for people with Treatment and prevention measures diagnosed bone problems include are similar, regardless of whether bisphosphonates such as alendronate you are HIV-positive or not - although (Fosamax) and statins.
closer monitoring of HIV-positive www.i-Base.info people is clearly important. Links Reducing smoking and alcohol, taking National Osteoporosis Foundation (US) exercise and eating a diet adequate http://www.nof.org in calcium, protein and vitamin D (and National Osteoporsis Society (UK) spending some time in the sunshine) protect you against bone mineral loss. http://www.nos.org.uk/ Bone Research Society Bone-building nutrients include calcium and vitamin D3 (colecalciferol) http://www.brsoc.org.uk and any deficiency should be i-Base publications 69 http://www.prn.org/index.php/the_ prn_notebook
guide to side effects FEBRUARY 2008 MAY 2008
Further information
A good general home reference book Internet references (not just HIV-related side effects) The Canadian community organisation including illustrated information CATIE has a comprehensive guide on how drugs work and on many to side effects that may cover other individual drugs is the: areas and options ‘BMA New Guide to Medicines and http://www.catie.ca/sideeffects_e.nsf Drugs’. Produced by the British One of the most useful HIV sites with Medical Association, 2007 7th edition. search facilities for many community, Published by Dorling Kindersley for activist and medical professsional £16.99. publications is at: Much of the most easily readable and http://www.aegis.org up-to-date information on side effects AEGiS.com also includes an excellent and HIV is available on the internet. and comprehensive database of The following links were correct when conference abstracts, that are we went to press. If you have trouble posted to the internet shortly after finding an article or link call the i-Base international meetings. phoneline on 0800 800 6013 and we’ll http://www.aegis.org/conferences try to help. Many conferences publish studies If you are not reading this in electronic on the internet and some also let you format the i-Base website contains all hear lectures and see slides from these references as active links - to some sessions. Important sites for save you retyping addresses: 2005 meetings include... http://www.i-base.info/pub/guides/ Conference on Retroviruses and side0508 Opportunistic Infections: http://www.retroconference.org
Treatment guidelines International AIDS Society Conferences: Treatment guidelines often have good http://www.ias.se supportive information on managing Reports from these and other side effects: meetings are usually available shortly http://www.bhiva.org (UK) after the meetings on the following http://www.eacs.eu (Europe) sites: http://www.i-Base.info http://www.AIDSinfo.nih.org (US) http://www.aidsmap.com http://www.natap.org http://www.thebody.com http://www.medscape.com www.i-Base.info 70 i-Base publications http://www.prn.org/index.php/the_ prn_notebook
information phoneline: 0808 800 6013 mon > tues > wed > 12 noon – 4 pm
Alternative treatments Physicians Research Notebook (PRN) A useful site for supplements, - detailed articles on many current nutrients and alternative treatments for aspects of treating and mangaging HIV, neuropathy: including side effects. http://www.pn.uku.co.uk/links/ http://www.prn.org Treatments.html A community site with a range of information on fat loss. As well as Positive Nation magazine facial fat loss this is one of the few An excellent bi-monthly magazine sites that includes an overview of fat that includes features, interviews, loss from the buttocks. treatment and lifestyle issues is http://www.facialwasting.org/ available in print with archive online. General information http://www.positivenation.co.uk Excellent regularly updated fact sheets, written in a clear non-technical Websites on drug interactions language on many side effects are http://www.HIV-druginteractions.org available in English and Spanish on the New Mexico AIDS Infonet: http://www.HIVpharmacology.com http://www.aidsinfonet.org/factsheets.php The UK aidsmap site has a large Online calculators number of reports on all aspects of For risk of heart disease and kidney HIV and treatment function: http://www.aidsmap.com This site also has very useful Different calculators use different overviews of individual drugs and their data sets. None is 100% accurate or side-effects in the ‘Drugs used by validated for HIV. See: people with HIV’ link. http://cvrisk.mvm.ed.ac.uk/calculator/ A list of UK clinical trials is also available bnf.htm on aidsmap, but not all studies are A calculator that includes race may included, so you may want to also check help Black/non-Caucasian people: with your own hospital and the larger http://www.epi.bris.ac.uk/CVDethrisk/ London hopsitals. CHD_CVD_form.html A site with useful links to longer A research site with heart risk and
articles from community publications is www.i-Base.info kidney function (estimated GFR) the Opportunistic Infection (OI) page calculators is at: of The Bodys treatment publication section: http://www.cphiv.dk/TOOLS.aspx http://www.thebody.com/treat/oipage.html For BMI, smoking etc: BETA, the quarterly newsletter from A range of NHS calculators include San Francisco AIDS Foundation BMI (for weight) and savings (from includes articles on individual side stopping smoking): effects and older articles tend to remain useful and relevant. http://www.nhsdirect.nhs.uk/magazine/ http://www.sfaf.org/beta interactive
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