Current Report—HIV

Treatment of AIDS and HIV-Related Conditions: 2001 J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

Ronald H. Goldschmidt, MD, and Betty J. Dong, PharmD

Managing human immunodeficiency virus (HIV) offer the best opportunity to provide comprehen- disease and the acquired immunodeficiency syn- sive care. drome (AIDS) has become more standardized yet This Current Report—HIV updates our annual more complex during the past year. Antiretroviral treatment guidelines.3 These recommendations treatment guidelines now represent a general con- (Table 1) are based on our experience at San Fran- sensus on basic treatment principles and options1 as cisco General Hospital, published guidelines, a re- benefits and risks of therapy have become more view of the medical literature, and experience evident. Clinical manifestations of HIV infection, gained from answering telephone calls to our Na- prognosis, and quality of life are clearly improved tional HIV Telephone Consultation Service for most patients receiving potent antiretroviral (Warmline). Because HIV management changes therapy, yet viral resistance and chronic and short- rapidly, clinicians are advised to refer to the excel- term drug toxicities remain major problems. The lent federal guidelines for the use of antiretroviral markedly decreased incidence of opportunistic in- agents in HIV-infected adults and adolescents1 and fections among treated patients has made unusual for prevention of opportunistic infections,4 which infections less common in daily HIV management. are updated frequently on the Internet (Table 2). The role of resistance assays in HIV care is still These and other federal guidelines are available at being assessed, but they offer great possibilities for http://www.hivatis.org. improving our ability to find satisfactory antiretro- http://www.jabfm.org/ viral regimens when others have failed. Finally, for the patient and the primary care clinician, the uni- Initiating Antiretroviral Therapy versal challenges of maintaining adherence to com- Concerns about development of antiretroviral drug plicated medication regimens and avoiding toxici- resistance and long-term antiretroviral drug toxic- ties and drug-drug interactions remain enormous ity have tempered the enthusiasm for early treat- obstacles. ment of asymptomatic persons. The strategy that Excellent HIV care requires applying the prin- promoted early aggressive therapy to maximally on 1 October 2021 by guest. Protected copyright. ciples of primary care, family care, and chronic care reduce viral load at all costs has given way to a more management with knowledge and experience in cautionary approach. Current recommendations1 managing HIV infection.2 Multidisciplinary team for initiating antiretroviral therapy include the fol- collaboration among primary care clinicians, phar- lowing concepts: initiating (and continuing) ther- macists, case workers, nurses, and AIDS experts can apy should always be based on the willingness, readiness, and capability of the HIV-infected per- son to adhere to a rigorous and presumably life- Submitted, revised, 8 May 2001. long treatment program; all patients with symptom- From the Family Practice Residency Program, San Fran- atic HIV disease should be offered antiretroviral cisco General Hospital (RHG, BJD), and the Departments ϩ of Family and Community Medicine (RHG, BJD) and Clin- therapy; asymptomatic persons with a CD4 lym- ical Pharmacy (BJD), University of California, San Fran- phocyte count less than 350/␮L or HIV RNA lev- cisco. Address reprint requests to Ronald H. Goldschmidt, MD, Family Practice Inpatient Service, San Francisco Gen- els greater than 30,000 copies/mL (bDNA assay) or eral Hospital, 1001 Potrero Ave, San Francisco, CA 94110. 55,000 copies/mL (RT-PCR assay) should be This article is also available at http://www.ucsf.edu/hivcntr. offered antiretroviral therapy; and patients Supported in part by the National HIV/AIDS Clinicians’ ϩ Consultation Center Grant No. 1 H4A HA 00038–01 with with CD4 cell counts fewer than 200/␮L should the AIDS Education and Training Centers, HIV/AIDS Bu- reau, Health Resources and Services Administration, De- receive antiretroviral therapy whenever possible. partment of Health and Human Services. Persons who wish to have antiretroviral therapy

AIDS and HIV-Related Conditions: 2001 283 Table 1. Treatment Regimens for HIV Disease. General/Systemic p. 284 Oral cavity p. 296 Pulmonary p. 299

Skin/Mucocutaneous p. 292 Esophageal p. 297 Central Nervous System p. 303 J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from Ophthalmologic p. 294 Gastrointestinal p. 298

System, Problem, and Drug Regimen Duration Adverse Effects/Drug Interactions Comments

GENERAL/SYSTEMIC Antiretroviral (therapy) Combination antiretroviral (ARV) therapy is always recommended. Preferred regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) along with either 1 or 2 protease inhibitors (PIs) or with the nonnucleoside reverse transcriptase inhibitor (nNRTI) efavirenz. Preferred NRTI combinations are zidovudine plus lamivudine or didanosine, and stavudine plus lamivudine or didanosine. Preferred PI therapy is with nelfinavir or indinavir, or with dual PI combination therapy with ritonavir plus indinavir, saquinavir, or lopinavir. Alternative NRTI combinations are didanosine plus lamivudine, and zidovudine plus zalcitabine. Alternative agents that can be used with 2 NRTIs include abacavir, amprenavir, delavirdine, nevirapine, ritonavir, saquinavir, and nelfinavir plus saquinavir. Cross-resistance among PIs is common, as is cross-resistance among nNRTIs. Zidovudine and stavudine should not be used in combination. Indinavir and saquinavir should not be used in combination. Other drug combinations might be necessary; resistance testing and expert consultation can be helpful. See text for further discussion

Nucleoside reverse NRTI drug class effects: Nausea, vomiting; aminotransferase elevations (alanine transcriptase inhibitors transaminase [ALT], aspartate transaminase [AST]); lactic acidosis with hepatic (NRTIs) steatosis; mitochondrial toxicity; lipoatrophy

Zidovudine (AZT, Until efficacy See NRTI drug class effects, above. Monitor for signs of zidovudine Retrovir) 200 mg po tid or wanes or Malaise, headache, insomnia, seizures, toxicity and reduce dosage if required. 300 mg po bid; lower toxicity occurs myalgias. Anemia, granulocytopenia, Transfusions or erythropoietin (if dosages (eg, 100 mg 3 thrombocytopenia; macrocytosis is an endogenous erythropoietin level Ͻ times daily) for patients expected effect of zidovudine therapy 500 IU/L) therapy can be used if unable to tolerate higher and requires no intervention. Toxic anemia (eg, hemoglobin Ͻ 8.0 g/dL) dosages and patients with myopathy (with elevated creatine occurs in patients who require renal failure or cirrhosis. phosphokinase [CPK]) with long-term zidovudine therapy. Decrease dosage Available as liquid use. Blue to black discoloration of nails or interrupt for absolute neutrophil formulation. Available also and skin in pigmented races count (ANC) Ͻ 500/␮L; consider as fixed-dose granulocyte colony-stimulating factor Drug interactions combinations: zidovudine (G-CSF). Transfusions and http://www.jabfm.org/ 300 mg plus lamivudine Careful monitoring required when used erythropoietin and G-CSF therapies 150 mg (Combivir) given with other myelosuppressive drugs (ie, are expensive; changing to alternate as one tablet po bid; and trimethoprim-sulfamethoxazole, NRTI preferred zidovudine 300 mg plus ganciclovir). Probenecid can increase lamivudine 150 mg plus levels of zidovudine. Acetaminophen High-dosage (1200 mg po qd) abacavir 300 mg (Trizivir), (Tylenol) administration does not zidovudine therapy can be considered given as one tablet po bid. increase zidovudine toxicity. Avoid for HIV dementia and Take with or without food concomitant use with ribavirin thrombocytopenia. Toxicity of high- dosage zidovudine can be substantial Didanosine (ddI, Videx) Until efficacy See NRTI drug class effects, above. Monitor for signs of neuropathy. Two on 1 October 2021 by guest. Protected copyright. 400 mg po qhs as 2 200- wanes or Pancreatitis; painful peripheral buffered tablets must be given per mg buffered tablets, or 200 toxicity occurs neuropathy (dosage related, reversible); dose to provide adequate buffer for mg po bid as 2 100-mg abdominal cramps, diarrhea related to absorption. Can be difficult to chew; chewable tablets or 250- antacid in formulation; rash; tablets do not dissolve readily in mg po bid powder for hyperglycemia; hyperuricemia; water, can be crushed manually or patients Ͼ 60 kg; 125 mg headache, insomnia, seizures; elevated given with apple juice (tablets) or 167 mg triglyceride and amylase levels; (powder) po bid for thrombocytopenia; retinal atrophy Administer didanosine on empty patients Ͻ 60 kg. Available stomach 2 hours apart from antacids, as enteric-coated capsules Drug interactions H2 antagonists, and drugs (eg, (Videx EC) given as 400- Avoid alcohol and other pancreatic ketoconazole, itraconazole, indinavir, mg EC capsule po qd (Ͼ toxins (eg, systemic pentamidine). Avoid lopinavir, ritonavir, tetracyclines, 60 kg) or 250-mg EC concomitant neurotoxic drugs (eg, delavirdine, quinolone antibiotics) capsule po qd (Ͻ 60 kg). zalcitabine, vinca alkaloids, oral whose absorption is impaired by Dosage reduction (ie, 200 ganciclovir). Decreases absorption of buffered products mg/d) in renal failure. drugs whose absorption is impaired by buffered products (eg, ketoconazole, Enteric-coated capsules might cause Take on an empty less diarrhea and fewer drug stomach itraconazole, indinavir, lopinavir, delavirdine, ritonavir, tetracyclines, interactions quinolone antibiotics). Oral and Didanosine plus stavudine intravenous ganciclovir might increase combination should not be given to didanosine toxicity. Consider increasing pregnant women because of increased didanosine dosage with methadone use risk of fatal lactic acidosis

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System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

GENERAL/SYSTEMIC (cont.) Antiretroviral (therapy) (cont.) Nucleoside reverse transcriptase inhibitors (NRTIs) (cont.) Zalcitabine (ddC, Hivid) Until efficacy See NRTI drug class effects, above. Zalcitabine might be less potent than 0.75 mg po tid; 0.375 mg wanes or Painful peripheral neuropathy (dosage other NRTIs po tid for patients Ͻ 30 toxicity occurs related, reversible); rash; stomatitis, kg. Dosage reduction in aphthous ulcers; pancreatitis; renal failure. Take with or esophageal ulceration; seizures; without food cardiomyopathy Drug interactions Avoid alcohol and other pancreatic toxins (eg, systemic pentamidine). Avoid concomitant neurotoxic drugs (eg, didanosine, isoniazid, vinca alkaloids, oral ganciclovir)

Stavudine (d4T, Zerit) 40 Until efficacy See NRTI drug class effects, above. Lower dosages (20 mg po bid) might mg po bid for patients Ͼ 60 wanes or Painful peripheral neuropathy; anemia, have a lower incidence of peripheral kg; 15–30 mg po bid for toxicity occurs macrocytosis; psychological neuropathy and equivalent efficacy patients 40–60 kg; reduce disturbances, insomnia, anxiety, panic Do not use in combination with dosage for patients Ͻ 40 kg attacks zidovudine because of antagonistic and for patients with renal antiviral activity failure. Take with or Drug interactions without food. Available as Avoid concomitant use with zidovudine Didanosine plus stavudine liquid formulation or drugs that can cause neurotoxicity or combination should not be given to pancreatic toxicity pregnant women because of increased risk of fatal lactic acidosis http://www.jabfm.org/

Lamivudine (3TC, Epivir) Until efficacy See NRTI drug class effects, above. Provides some efficacy against 150 mg po bid; 2 mg/kg po wanes or Headache, fatigue, insomnia; peripheral hepatitis B. Once-daily dosing (300 bid for patients Ͻ 50 kg. toxicity occurs neuropathy, muscle aches; rash; rare mg po qd) under investigation Dosage reduction in renal neutropenia, thrombocytopenia; failure. Available as liquid paronychia formulation. Available also as fixed-dose combinations: zidovudine 300 mg plus lamivudine 150 mg on 1 October 2021 by guest. Protected copyright. (Combivir) given as one tablet po bid; and zidovudine 300 mg plus lamivudine 150 mg plus abacavir 300 mg (Trizivir), given as one tablet po bid. Take with or without food

Abacavir (Ziagen) 300 mg Until efficacy See NRTI drug class effects, above. Symptoms and signs of po bid. Available as liquid wanes or Headache, malaise; abdominal pain, hypersensitivity reaction can be solution. Available also as toxicity occurs diarrhea, rash. Hypersensitivity reaction progressive; will resolve if drug fixed-dose combinations: (2%–5%, usually in first 8 weeks): rash, stopped. Do not rechallenge, as zidovudine 300 mg plus flu-like symptoms, fever, malaise, anaphylactic reactions and deaths lamivudine 150 mg fatigue, dyspnea, cough, pharyngitis, reported (Combivir) given as one abdominal cramping, anorexia, nausea, tablet po bid; and vomiting, diarrhea, elevations in zidovudine 300 mg plus transaminases and CPK levels lamivudine 150 mg plus abacavir 300 mg (Trizivir), given as one tablet po bid. Take with or without food

AIDS and HIV-Related Conditions: 2001 285 Table 1. Continued

System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

GENERAL/SYSTEMIC (cont.)

Antiretroviral (therapy) (cont.)

Protease inhibitors (PIs) PI drug class effects: Nausea, vomiting; aminotransferase elevations, hepatitis; hypertriglyceridemia, hypercholesterolemia, abnormal fat accumulation, hyperglycemia, insulin resistance; osteopenia, osteoporosis PI drug class interactions: Avoid concomitant use with rifampin (except ritonavir), St. John’s wort, garlic supplements, ergotamine, midazolam (Versed), and triazolam (Halcion); can use lorazepam (Ativan) and temazepam (Restoril). Decreased PI levels and increased phenobarbital, phenytoin, and carbamazepine levels when used in combination; dosage adjustments probably required. Avoid simvastatin (Zocor) or lovastatin (Mevacor) because of rhabdomyolysis; can use pravastatin (Pravachol), fluvastatin (Lescol), low-dose atorvastatin (Lipitor), or cerivastatin (Baycol). Limit sildenafil (Viagra) dosage to 25 mg q 48 h

Nelfinavir (Viracept) 750 Until efficacy See PI drug class effects, above. Resistant strains might be sensitive to mg po tid or 1250 mg po wanes or Diarrhea other PIs bid. Available as powder toxicity occurs for liquid formulation. Drug interactions Diarrhea is self-limiting; can be Take with food. See dual See PI drug class interactions, above. controlled with loperamide, calcium PI combinations below; Moderate P-450 enzyme inhibitor. carbonate, oat bran, psyllium, or note dosage differences Decrease rifabutin dosage to 150 mg pancreatic enzymes po qd or 300 mg po 2–3 times weekly and increase nelfinavir dosage to 1 g po tid

Indinavir (Crixivan) 800 Until efficacy See PI drug class effects, above. Take with at least 6 glasses of mgpoq8hdosage wanes or Nephrolithiasis, crystalluria, interstitial noncaffeinated liquid daily to avoid adjustment to 600 mg po q toxicity occurs nephritis; diarrhea, abdominal pain; nephrolithiasis http://www.jabfm.org/ 8 h in hepatic disease. asymptomatic hyperbilirubinemia; rash; Take on empty stomach or insomnia, headache, dizziness, metallic Must be taken every 8 hours, not 3 with skim milk, juice, taste; alopecia, dry skin; times daily when used as sole PI coffee, tea, toast. See dual thrombocytopenia PI combinations below; note dosage differences Drug interactions See PI drug class interactions above. Moderate P-450 enzyme inhibitor. Decrease indinavir dosage to 600 mg poq8hwhen given with on 1 October 2021 by guest. Protected copyright. ketoconazole. Increase indinavir to 1 gpoq8hwhen given with efavirenz or nevirapine. Indinavir administration must be at least 1 hour apart from didanosine or antacid administration

Ritonavir (Norvir) 600 mg Until efficacy See PI drug class effects, above. Not generally used as sole PI po bid; can increase from wanes or Diarrhea, anorexia in more than 50% 300 mg po bid to 600 mg toxicity occurs of patients; fatigue, weakness; headache, Capsules must be refrigerated; po bid over 4–7 days to dizziness, circumoral paresthesias; solution should not be refrigerated minimize gastrointestinal hyperuricemia, increased creatine Hepatotoxicity might be greater with symptoms. Take with phosphokinase; taste disturbances ritonavir than with other protease food. Available as liquid inhibitors formulation. See dual PI Drug interactions combinations below; note See PI drug class interactions above. High alcohol content of liquid dosage differences Potent hepatic P-450 enzyme formulation inhibitor. Dosages of desipramine and other antidepressants, narcotics, and oral contraceptives might need adjustment

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System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

GENERAL/SYSTEMIC (cont.) Antiretroviral (therapy) (cont.)

Protease inhibitors (PIs) (cont.)

Saquinavir soft-gel Until efficacy See PI drug class effects above. Hard-gel formulation (Invirase, 600 capsules (Fortovase) 1200 wanes or Headache, confusion; fever mg po tid within 2 hours of a high-fat mg po tid. Take with food. toxicity occurs meal to increase absorption) not See dual PI combinations Drug interactions recommended because of poor below; note dosage See PI drug class interactions, above. bioavailability (4%), even when taken differences Weak hepatic P-450 enzyme inhibitor. with high-fat meal Ketoconazole, ritonavir, delavirdine, and grapefruit juice increase saquinavir serum concentration. Avoid concomitant use of saquinavir with indinavir, rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, efavirenz (when saquinavir is used as the sole PI), dexamethasone, nevirapine, and other enzyme inducers

Amprenavir (Agenerase) Until efficacy See PI drug class effects above. Use with caution in patients with sulfa 1200 mg po bid. Take wanes or Diarrhea; oral paresthesias, headache; allergy. Contains vitamin E; avoid with or without food; toxicity occurs rash, Stevens-Johnson syndrome concomitant vitamin E avoid high fat meal. coadministration Available as liquid Drug interactions formulation. See dual PI See PI drug class interactions, above. Increase amprenavir dosage to 1200 combinations below; note Moderate P-450 enzyme inhibitor mg po tid when used as sole PI with dosage differences efavirenz Amprenavir solution contains

propylene glycol, which is http://www.jabfm.org/ contraindicated in pregnancy and should be used with caution in hepatic or renal failure or in combination with metronidazole or disulfiram Dual protease inhibitor combinations (Dual PIs) Ritonavir 200 mg po bid Until efficacy See PI class effects, drug interactions, Other bid dosing regimens that might plus wanes or and individual agents be equivalent: ritonavir 100 mg plus on 1 October 2021 by guest. Protected copyright. Indinavir 800 mg po bid toxicity occurs indinavir 800 mg; ritonavir 200 mg plus indinavir 600 mg Ritonavir 400 mg po bid Until efficacy See PI drug class effects, drug Might cause less nephrolithiasis plus wanes or interactions, and individual agents Indinavir 400 mg po bid toxicity occurs Ritonavir 400 mg po bid Until efficacy See PI drug class effects, drug Generally well tolerated. Combination plus wanes or interactions, and individual agents therapy provides higher saquinavir Saquinavir soft-gel toxicity occurs levels capsules 400 mg po bid Drug interactions Combination can be given with efavirenz without dosage adjustment. Reduce rifabutin dosage to 150 mg po 2–3 times weekly Nelfinavir 1250 mg po bid Until efficacy See PI drug class effects, drug Data limited plus wanes or interactions, and individual agents Indinavir 1200 mg po bid toxicity occurs Ritonavir 400 mg po bid Until efficacy See PI drug class effects, drug Data limited plus wanes or interactions, and individual agents Nelfinavir 500–750 mg po toxicity occurs bid

AIDS and HIV-Related Conditions: 2001 287 Table 1. Continued

System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

GENERAL/SYSTEMIC (cont.) Antiretroviral (therapy) (cont.) Dual protease inhibitor combinations (Dual PIs) (cont.)

Saquinavir soft-gel Until efficacy See PI drug class effects, drug Data limited capsules 800 mg po tid wanes or interactions, and individual agents plus toxicity occurs Nelfinavir 750 mg po tid or 1250 po bid

Ritonavir 200 mg po bid Until efficacy See PI drug class effects, drug Ritonavir 100 mg po bid might be plus wanes or interactions, and individual agents equally effective Amprenavir 600 mg po bid toxicity occurs Once-daily dosing under investigation Drug interactions Combination can be given with efavirenz without dosage adjustment

Lopinavir 400 mg plus Until efficacy See PI drug class effects, drug Refrigerate capsules; stable at room ritonavir 100 mg wanes or interactions, and individual agents. temperature for 2 months only combination (Kaletra); toxicity occurs Diarrhea; skin rash; headache, given as 3 fixed-dose weakness; edema Better tolerated than ritonavir alone. capsules po bid with Ritonavir-resistant strains can be food. Available as Drug interactions sensitive to lopinavir-ritonavir liquid formulation. See ritonavir, above combination Increase dosage to 4 capsules po bid if administered with efavirenz or nevirapine http://www.jabfm.org/

Nonnucleoside reverse transcriptase inhibitors (nNRTIs) Efavirenz (Sustiva) 600 mg Until efficacy Dizziness, anxiety, inability to Good central nervous system po qhs with or without wanes or concentrate, lightheadedness, penetration; resistance might food; 200 mg po tid if toxicity occurs headache, dysphoria, nightmares; develop more slowly than other insomnia or nightmares nausea; rash (less than other nNRTIs occurs nNRTIs); aminotransferase elevations, on 1 October 2021 by guest. Protected copyright. hepatitis. Avoid in pregnancy Rash from one nNRTI does not predict rash from other Drug interactions nNRTIs Mixed P-450 enzyme inducer and Avoid coadministration with St. inhibitor. Avoid use with either John’s wort and garlic tablets, as saquinavir or amprenavir when used they can reduce efavirenz levels as sole PIs. Increase indinavir dosage to1gpoq8hwhen used as sole PI in combination with efavirenz. Increase rifabutin dosage to 450–600 mg qd or 600 mg 2–3 times weekly. Increase lopinavir-ritonavir to 4 capsules po bid. Reduces methadone levels; dosage adjustment necessary

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System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

GENERAL/SYSTEMIC (cont.) Antiretroviral (therapy) (cont.)

Nonnucleoside reverse transcriptase inhibitors (nNRTIs) (cont.) Nevirapine (Viramune) Until efficacy Maculopapular rash, Stevens-Johnson Discontinue drug at any time if rash 200 mg po qd for 14 days; wanes or syndrome. Black box warning about is severe. Do not increase dosage if if no rash develops, toxicity occurs rare fulminant hepatotoxicity; risk any rash is present during first 14-day increase to 200 mg po bid. increased with concurrent chronic lead-in period. Dose escalation can Once-daily dosing (400 mg hepatitis and concomitant hepatotoxic minimize occurrence of rash; po qd) might be effective drugs. Nausea, vomiting, diarrhea; prophylactic antihistamines and fatigue, fever, headaches; rare corticosteroids remain controversial hematologic toxicity Rash from one nNRTI does not Drug interactions predict rash from other nNRTIs P-450 enzyme inducer; avoid concomitant use with saquinavir as sole PI, rifampin, and rifabutin. Decreases methadone and estrogen levels; dosage adjustment necessary. Increase lopinavir-ritonavir to 4 capsules po bid. Increase indinavir to1gpoq8h

Delavirdine (Rescriptor) Until efficacy Maculopapular rash; nausea; headache; Not a preferred nNRTI because of 400 mg po tid. Can wanes or aminotransferase elevations especially poor bioavailability and concerns dissolve in 3 oz water as toxicity occurs when taken with saquinavir; about delavirdine drug interaction slurry neutropenia when taken with nelfinavir profile. Delavirdine increases saquinavir and indinavir levels by Drug interactions 50%. Reduce indinavir dosage to 600 Moderate P-450 enzyme inhibitor. mgpoq8handsaquinavir dosage to

Avoid concomitant use of rifampin, 600 mg po tid when used in http://www.jabfm.org/ rifabutin, phenytoin, carbamazepine, combination with delavirdine. simvastatin, lovastatin, alprazolam, Separate didanosine or antacid midazolam, triazolam, ergotamine, St. administration from delavirdine John’s wort, and garlic supplements; administration by at least 1 hour can use lorazepam and temazepam. Ketoconazole, itraconazole, fluconazole, Rash from one nNRTI does not clarithromycin, and fluoxetine can predict rash from other nNRTIs increase delavirdine serum concentrations; dosage reduction might be necessary. Increased warfarin effects. on 1 October 2021 by guest. Protected copyright. Limit sildenafil to 25 mg q 48 h Other agents Tenofovir disoproxil Until efficacy Creatine phosphokinase elevation; Nucleotide analog. Role unclear; fumerate 300 mg po qd wanes or aminotransferase elevation. Other might offer benefit in salvage therapy. toxicity occurs toxicities not yet reported by Active against HBV. Approval manufacturer expected in 2001. Available through expanded access at 1-800-276-0231 Postexposure prophylaxis for health care workers Zidovudine 200 mg po tid 4 weeks Nevirapine should not be used; Administer within 2 hours or as or 300 mg po bid plus fulminant hepatic failure has occurred soon as possible after exposure. lamivudine 150 mg po bid from nevirapine use in occupational Can substitute other antiretroviral or Combivir one tablet po postexposure prophylaxis agents when source patient has bid with or without received extensive treatment with nelfinavir 750 mg po tid See above adverse effects and drug ARV drugs. Add nelfinavir, (preferred) or 1,250 mg po interactions. Zidovudine and lamivudine indinavir, or other PI for high-risk bid or indinavir 800 mg po appear safe in pregnancy exposures and when source patient q8h suspected to have ARV resistance. Can call 1-888-HIV-4911 for additional assistance

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Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

GENERAL/SYSTEMIC (cont.) Antiretroviral (therapy) (cont.) Pregnancy Combination ARV therapy Until end of See above adverse effects and drug Prenatal and intrapartum therapy with recommended according to pregnancy interactions zidovudine or zidovudine plus ARV guidelines. When lamivudine, along with postnatal possible, use zidovudine- Adverse effects on fetus not clear. treatment of infant, decreases HIV containing antiretroviral Anemia, neutropenia; possible transmission regimen during pregnancy, mitochondrial toxicity with neurologic plus intrapartum abnormalities (infant). Viral resistance Discussion of risks and benefits is zidovudine until delivery to lamivudine is commonly induced in essential. Consider cesarean section infants; clinical implications unknown

Wasting syndrome

Anabolic steroids (eg, Unknown Edema; cholestatic jaundice, peliosis Might improve well-being and testosterone 200 mg IM hepatis, aminotransferase elevations; increase lean body mass. Treatment every 2 weeks or 300 mg increased libido, testicular atrophy, should be accompanied by exercise IM every 3 weeks, priapism; insomnia oxandrolone [Oxandrin] 2.5 mg po bid–tid or testosterone patches [Testoderm, Androderm]) Dronabinol Indefinitely Restlessness, irritability, insomnia, Increases appetite and can cause (Tetrahydrocannabinol dizziness, loss of coordination, weight gain. Uncertain whether this [THC], Marinol) 2.5 mg psychotomimetic effects; fatigue; weight gain improves health. po bid 30 minutes to 1 tachycardia Antinauseant. Not recommended hour before meals. for persons sensitive to marijuana Maximum 20 mg qd effects Megestrol (Megace) Indefinitely Nausea, vomiting; edema; adrenal Megestrol can increase appetite and cause suspension (40 mg/mL) suppression; depression. Deep venous fat accumulation with weight gain. http://www.jabfm.org/ 800 mg po qd thrombosis; progestin side effects Uncertain whether this weight gain (hyperglycemia, decreased testosterone improves health. Available also as tablets, levels) but large number of tablets required for administration and more expensive

Human growth hormone Unknown Arthralgias, joint stiffness, carpal tunnel Can improve exercise endurance and (r-hGH, Serostim) 0.1 mg/ syndrome; hyperglycemia; increase weight, characterized by kg/d SQ (average dosage 6 hypertriglyceridemia increased lean body mass and mg/d) decreased fat on 1 October 2021 by guest. Protected copyright. Mycobacterium avium complex (MAC)

Primary prophylaxis Prophylaxis recommended Can discontinue MAC prophylaxis in for patients with CD4ϩ persons whose CD4ϩ cell count cell counts Ͻ 50/␮L increases to Ͼ 100/␮L for more than 3–6 months in response to antiretroviral therapy Clarithromycin (Biaxin) Indefinitely Clarithromycin and azithromycin side Clarithromycin might provide 500 mg po bid effects include nausea, vomiting, prophylaxis against Cryptosporidium dyspepsia, diarrhea, hearing loss, OR aminotransferase elevations

Drug interactions Azithromycin (Zithromax) Indefinitely Clarithromycin increases serum levels of 1200 mg po once weekly rifabutin and can lead to rifabutin or 500 mg po qd toxicity, including severe anterior uveitis. Clarithromycin and azithromycin increase levels of carbamazepine, theophylline, and digoxin

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Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

GENERAL/SYSTEMIC (cont.) Mycobacterium avium complex (MAC) (cont.)

Primary prophylaxis (cont.) OR Rifabutin (Mycobutin) 300 Indefinitely Nausea (can be reduced by administering Exclude Mycobacterium tuberculosis mg po qd 150 mg po bid). Rash. Uveitis with infection before initiating rifabutin dosages greater than 300 mg po qd and therapy in patients receiving concomitant clarithromycin, fluconazole, delavirdine, or PI therapy. Red-orange discoloration of body fluids. Rare neutropenia, thrombocytopenia, anemia; flu-like syndrome; elevated bilirubin and alkaline phosphatase levels, hepatitis Drug interactions Multiple interactions with antiretroviral drugs. See individual agents, above. Rifabutin increases metabolism of methadone, zidovudine, and clarithromycin; higher dosage of these drugs might be required. Clarithromycin increases rifabutin blood levels and can lead to rifabutin toxicity

Acute MAC disease Ethambutol (Myambutol) Indefinitely, if Optic neuritis (if Ͼ 25 mg/kg/d); Treatment indicated for documented 15 mg/kg po qd (1 g po tolerated hyperuricemia; nausea, vomiting MAC disease and patients with qd maximum); dosage (minimum of progressive signs, symptoms, and reduction in renal failure 12 weeks) laboratory abnormalities consistent with http://www.jabfm.org/ MAC disease. Clinical improvement plus either might take 2–4 weeks. Isolation of MAC in stool or sputum might not Clarithromycin 500 mg po indicate systemic disease but is usually bid. Higher dosages treated with ethambutol plus a associated with higher macrolide antibiotic mortality When both M tuberculosis and MAC or infections are suspected, add isoniazid, rifampin, and pyrazinamide to on 1 October 2021 by guest. Protected copyright. Azithromycin 500 mg po ethambutol and clarithromycin pending qd culture results. See M tuberculosis For serious illness or failure to respond within 1 month, can add one or two of the following: Rifabutin 300 mg po q Indefinitely Rifampin (Rimactane, Rifadin) 450– 600 mg po qd can substitute for rifabutin if concern about M tuberculosis infection

Ciprofloxacin (Cipro) 500– Indefinitely Nausea, vomiting, diarrhea. Reversible 750 mg po qd–bid pink to brown-black discoloration of skin, eyes, body secretions; rash. Hyperglycemia. Retinal degeneration Drug interactions Binds to cations, resulting in decreased ciprofloxacin absorption. Administer 2–4 hours after antacids, sucralfate, dairy products, and didanosine

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GENERAL/SYSTEMIC (cont.) Mycobacterium avium complex (MAC) (cont.)

For serious illness or failure to respond within 1 month, can add one or two of the following:

Amikacin (Amikin) 7.5– 2–8 weeks Nephrotoxicity, ototoxicity Monitor drug levels in patients with 10.0 mg/kg IM/IV qd renal failure

Mycobacterium tuberculosis Prophylaxis Isoniazid (INH) 300 mg 9 months Nausea, vomiting, abdominal pain; Prophylaxis for all HIV-infected po qd plus pyridoxine 50 aminotransferase elevations and persons with Ն 5-mm intermediate- mg po qd hepatitis; seizures; administer with strength tuberculin skin test or pyridoxine to prevent peripheral induration and those with strong Isoniazid 900 mg po plus neuropathy history of tuberculosis exposure pyridoxine 100 mg po, regardless of skin test reactivity both taken twice weekly Drug interactions Increases metabolism of ketoconazole; Active tuberculosis must be ruled larger dosages of ketoconazole might out be required. Increased phenytoin and carbamazepine toxicity; monitor levels Isoniazid can be administered concurrently with NRTIs, PIs, nNRTIs OR Rifabutin (variable dosage) 2 months See individual drug toxicities When short-course prophylaxis is

or administered with or without directly http://www.jabfm.org/ Rifampin 600 mg po qd Drug interactions observed therapy (DOT), consultation plus Rifabutin dosage adjustment with PIs with tuberculosis experts is Pyrazinamide 20 mg/kg po and nNRTIs; See individual agents, recommended. Effective antiretroviral qd above. PIs, except ritonavir, should not therapy should not be discontinued to be administered concurrently with permit use of specific antituberculosis rifampin drugs Active tuberculosis Combinations of isoniazid, Begin with 4 See individual drug adverse effects and Consultation with tuberculosis experts rifampin or rifabutin, drugs. After 2 drug required. Treatment guidelines on 1 October 2021 by guest. Protected copyright. pyrazinamide, ethambutol, months can available on Centers for Disease and streptomycin usually Multiple drug interactions with Control and Prevention Web site continue 2- antiretroviral agents. See references or drug therapy, consult with expert depending upon susceptibility testing results Cryptococcosis See CENTRAL NERVOUS SYSTEM, Cryptococcus neoformans

SKIN/MUCOCUTANEOUS Kaposi sarcoma Observation, local Treatment not required unless lesions treatment (radiation are symptomatic or cosmetically therapy, cryotherapy, bothersome. Effective antiretroviral excision, or intralesional therapy can improve systemic and vinblastine), systemic localized Kaposi sarcoma chemotherapy, or interferon-␣

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SKIN/MUCOCUTANEOUS (cont.) Seborrheic dermatitis Hydrocortisone (HC) Until resolved Commonly involves face, eyebrows, cream 2.5% plus retroauricular areas, nasolabial folds, itraconazole or and scalp. Addition of antifungal ketoconazole cream bid cream enhances therapeutic response and reduces the frequency of steroid application Mucocutaneous herpes simplex Acute Acyclovir (Zovirax) 200 7–10 days Oral: nausea, vomiting, diarrhea, Topical acyclovir ineffective for most mg po 5 times a day or dizziness episodes 400 mg po tid OR Valacyclovir (Valtrex) 500 10 days Nausea, vomiting, diarrhea; headache, mg–1 g po bid dizziness, fatigue, insomnia. Hemolytic uremic syndrome (if Ͼ 3 g/d) OR Famciclovir (Famvir) 250 10 days Nausea, vomiting, diarrhea; headache, mg po tid dizziness, fatigue, insomnia Maintenance Acyclovir 200 mg po bid Indefinitely Chronic maintenance therapy might or 400 mg po tid or be necessary for repeated episodes valacyclovir 500 mg po bidor1gpoqdor

famciclovir 500 mg po http://www.jabfm.org/ bid Disseminated, extensive, or persistent herpes simplex Acyclovir 5 mg/kg per 7–14 days or Intravenous: lethargy, tremors, Severe herpes infections (eg, dose IVq8h;dosage until lesions confusion, hallucinations; phlebitis; esophagitis, colitis, encephalitis) reduction in renal failure; resolve increased serum creatinine, reversible require intravenous acyclovir. maintenance as above crystalline nephropathy Maintain good urine output and

OR hydration to prevent acyclovir on 1 October 2021 by guest. Protected copyright. crystallization Valacyclovir1gpotid 7–14 days or See above until lesions resolve Herpes zoster (shingles, disseminated, or persistent zoster) Acyclovir 10 mg/kg per 7–10 days or Alternate drugs are foscarnet, dose IVq8h;oracyclovir until lesions vidarabine, cidofovir, and trifluridine 800 mg po 5 times a day; resolve (Viroptic) applied to skin covered reduce dosage of with polymyxin B-bacitracin intravenous acyclovir in (Polysporin) ointmentq8h. renal failure Keratoconjunctivitis requires more frequent (q 2 h) trifluridine application OR Valacyclovir1qpotid 7–10 days

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SKIN/MUCOCUTANEOUS (cont.) Acyclovir-resistant herpes infections Foscarnet 40 mg/kg per 10–14 days or See OPHTHALMOLOGIC, CMV, See OPHTHALMOLOGIC, CMV, dose IVq8h;dosage until lesions below below reduction in renal failure clear OR Trifluridine (Viroptic) 1% Same Rare hypersensitivity reactions Apply to affected areas and cover with solutionq8h antibiotic ointment such as bacitracin or polymyxin B Keratoconjunctivitis requires more frequent (as often as 2 hours, maximum 9 drops a day) trifluridine application Cidofovir (See Same See OPHTHALMOLOGIC, CMV, Cidofovir might be effective OPHTHALMOLOGIC, below CMV, below) Bacillary angiomatosis Erythromycin 500 mg po 2 months See GENERAL/SYSTEMIC, MAC, Skin lesions can resolve in 1–3 qid, clarithromycin 500– clarithromycin, azithromycin. Jarisch- weeks, but 2 months’ treatment 1000 mg po qd, or Herxheimer reaction with systemic needed. Systemic disease (eg, azithromycin1gpoqd disease hepatic, splenic, central nervous OR system, bone) or cutaneous recurrences require treatment for 4 Doxycycline 100 mg po 2 months months or indefinitely bid

OPHTHALMOLOGIC

Cytomegalovirus (CMV) http://www.jabfm.org/ Acute retinitis Induction Ganciclovir 5 mg/kg per 14 days for Neutropenia, leukopenia, anemia, Start G-CSF (filgrastim, Neupogen) dose IV q 12 h; dosage acute retinal thrombocytopenia (avoid if platelet 300 ␮g SQ qd to 3 times a week for reduction in renal failure infection: 14– count Ͻ 20,000/␮L); aminotransferase ganciclovir-induced neutropenia 21 days elevations; renal failure; phlebitis, (absolute neutrophil count [ANC] Ͻ usually rash; nausea, vomiting; confusion, 500/␮L) on two consecutive required for dizziness, headache. Discontinue measurements. High risk of catheter- extraocular zidovudine during induction to related sepsis on 1 October 2021 by guest. Protected copyright. infection minimize additive hematologic toxicity (neutropenia). To avoid hematologic toxicity, substitute didanosine, abacavir, or stavudine for zidovudine, or change to foscarnet OR Foscarnet (Foscavir) 90 14-day Nephrotoxicity common; tremors, Administered by infusion pump via mg/kg per dose IV q 12 h induction headaches, occasional seizures, muscle central line. Infusion of 500–1000 as 2-hour infusion, spasms; hypocalcemia, hypokalemia, mL normal saline or 2000 mL oral discontinuation or dosage hypophosphatemia, hypomagnesemia, fluids before each foscarnet reduction in renal failure hyperphosphatemia; anemia, administration can minimize granulocytopenia; aminotransferase nephrotoxicity. Creatinine clearance elevations; phlebitis, penile ulcerations (CrCl) should be measured in cachectic patients and in patients Drug interactions with renal insufficiency to ensure Avoid concurrent use of nephrotoxic proper use of administration agents when possible nomogram. Give calcium carbonate 500 mg po tid and magnesium supplementation to prevent deficiencies. High risk of catheter- related sepsis OR

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OPHTHALMOLOGIC (cont.) Cytomegalovirus (CMV) (cont.) Acute retinitis (cont.) Induction (cont.) Valganciclovir (Valcyte) 21-day Granulocytopenia, anemia, Oral prodrug of ganciclovir. 900 mg po bid with food. induction thrombocytopenia; diarrhea, nausea, Comparable efficacy to intravenous Dosage reduction in renal vomiting, abdominal pain; fever; ganciclovir in one study failure headache, insomnia, peripheral neuropathy, paresthesias; retinal detachment OR Ganciclovir plus foscarnet See individual agents above. Continue maintenance drug, induce Combination therapy not routinely with the alternative drug, then recommended as initial therapy continue maintenance therapy with both drugs Alternatives to ganciclovir or foscarnet Cidofovir (Vistide) 5 mg/ 14-day Life-threatening nephrotoxicity; fever; Not known whether cidofovir is as kg IV with probenecid (2 induction nausea, diarrhea; rash; uveitis, iritis, effective as ganciclovir or foscarnet. g po 3 hours before and 1 period sight-threatening ocular hypotonia; Indwelling catheter not required g po 2 and 8 hours after proteinuria, metabolic acidosis; infusion) each week for 2 neutropenia. Persons allergic to sulfa Prehydrate with 1 L normal saline. weeks, then every 2 weeks compounds can be allergic to Do not administer within 7 days of thereafter; contraindicated probenecid other potentially nephrotoxic agents. in renal insufficiency Patients previously treated with (serum creatinine Ն 1.5/ Drug interactions foscarnet are at increased risk for Յ Avoid concomitant administration with renal failure. Administer G-CSF if mg/dL, CrCl 55 mL/ Ͻ ␮ min, 2ϩ proteinuria) any potentially nephrotoxic agent, ANC consistently 500/ L including nonsteroidal anti- inflammatory drugs http://www.jabfm.org/ OR Ganciclovir implant Indefinitely Surgical complications, including retinal Intravitreal ganciclovir by injection or (Vitasert) q 6–9 months or detachment, intravitreal hemorrhage, implant appears effective if IV causes intravitreal fomivirsen and endophthalmitis; cataracts. unacceptable toxicity or patient is injection (Vitravene) on Ganciclovir implantation can cause unable to take intravenous therapy. day 1, 15, and 30, then temporary reduction in visual acuity Does not provide systemic therapeutic monthly thereafter after surgery effect or protection of contralateral eye. Intravitreal foscarnet can also be on 1 October 2021 by guest. Protected copyright. effective for resistant CMV plus Ganciclovir (Cytovene) 1 g Oral ganciclovir: Anemia, neutropenia; Oral ganciclovir absorption is erratic po tid nephrotoxicity; neuropathy when diarrhea is present. Administer on empty stomach to improve Drug interactions absorption Oral ganciclovir therapy causes 50% increase in didanosine blood levels; reduce didanosine dosage by 50% Maintenance (secondary prophylaxis) Indicated for persons with Can discontinue secondary CMV prior episode of CMV prophylaxis in persons with adequate retinitis vision and non-sight-threatening lesion whose CD4ϩ count increases to Ͼ 100–150/␮L for 3–6 months in response to antiretroviral therapy Valganciclovir 900 mg po Indefinitely See above qd with food OR

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OPHTHALMOLOGIC (cont.) Cytomegalovirus (CMV) (cont.) Maintenance (secondary prophylaxis) (cont.) Ganciclovir 5 mg/kg IV qd Indefinitely Administer G-CSF or change to 5–7 days per week as 1- foscarnet if ANC consistently Ͻ 500/ hour infusion; dosage ␮L reduction in renal failure OR Foscarnet 90–120 mg/kg Indefinitely Maintenance with 120 mg/kg/d might IV qd as 2-hour infusion; be more effective but also more toxic discontinuation or dosage reduction in renal failure OR Ganciclovir plus foscarnet Indefinitely See individual agents above Continue maintenance dosage of current drug; reinduce alternate drug, followed by maintenance with both drugs OR Fomivirsen injection or Indefinitely See above ganciclovir implant plus oral ganciclovir OR Ganciclovir1gpotid Indefinitely See above Oral ganciclovir is not as effective for maintenance therapy as other regimens OR Cidofovir 5 mg/kg as 1- Indefinitely Life-threatening nephrotoxicity; cannot Does not require indwelling catheter; hour infusion with oral be given with potentially nephrotoxic quality of life might be improved http://www.jabfm.org/ probenecid every 2 weeks drugs; ocular hypotonia can lead to at infusion center visual loss

ORAL CAVITY Candida Albicans Clotrimazole (Mycelex) 1–2 weeks or Minimal toxicity. Unpleasant taste, Troches have high sugar content and troches 10 mg 5 times a until resolved; nausea, vomiting; aminotransferase often require frequent administration. day or vaginal maintenance elevations Suppositories can be more convenient on 1 October 2021 by guest. Protected copyright. suppositories 100 mg qd. (with lowest Dissolve slowly in mouth effective dosage) might be required for severe or frequent recurrences OR Nystatin (Mycostatin) Same Large oral doses can produce diarrhea, Generally less effective than 100,000 U/mL, swish and nausea, vomiting ketoconazole, fluconazole, and swallow 5 mL poq6hor clotrimazole. Can be effective in one 500,000-U tablet fluconazole-resistant candidal dissolved slowly in mouth infection q6h

OR

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ORAL CAVITY (cont.) Candida Albicans (cont.) Fluconazole (Diflucan) Same See CENTRAL NERVOUS SYSTEM, Effective in oral candidiasis 100–200 mg po qd Cryptococcus neoformans unresponsive to above oral agents. followed by maintenance Fluconazole solution or itraconazole therapy 50–100 mg po qd; 200 mg po qd (or itraconazole 100–200 mg po once solution) might be effective against weekly is less effective. fluconazole-resistant Candida albicans Can add 5-flucytosine (Ancobon) 25 mg/kg per dose poq6hif unresponsive to fluconazole OR Amphotericin B oral Same Unpalatable; nausea, vomiting, diarrhea; Not absorbed. No systemic effects. suspension 100 mg/mL, rare urticaria Intravenous amphotericin B might be swish and swallow 1–5 mL necessary for severe disease qid Periodontal disease Hydrogen peroxide gargles Indefinitely Oral hygiene measures with manual for 30 sec bid removal of plaque are essential. Severe periodontal disease can require antibiotic therapy with metronidazole 250 mg po tid for 7–10 days (alternatives: clindamycin or amoxicillin-clavulanate [Augmentin]). Antiseptic mouthwash (Listerine) gargles can be effective OR Chlorhexidine gluconate Indefinitely Staining of teeth http://www.jabfm.org/ (Peridex) oral rinse 15 mL swished in mouth for 30 sec bid

ESOPHAGEAL Candida albicans Fluconazole 200–400 mg 14–21 days; See CENTRAL NERVOUS SYSTEM, Empiric treatment for patients with po qd; higher dosages maintenance Cryptococcus neoformans dysphagia or odynophagia who have on 1 October 2021 by guest. Protected copyright. might be required with lowest oral thrush. Endoscopy with biopsy effective and cultures appropriate for patients dosage who fail to respond within 1 week OR Itraconazole (Sporanox) Same as above Nausea, vomiting; hypokalemia; Teratogenic 200 mg po bid hypertension; aminotransferase elevations; adrenal insufficiency; rhabdomyolysis. Drug interactions Potent hepatic enzyme inducers, such as rifampin and phenytoin, increase metabolism of itraconazole; higher itraconazole dosages might be required. Avoid concurrent use with triazolam, alprazolam (Xanax), antacids, H2 blockers, and omeprazole OR Amphotericin B 0.3–0.4 10 days or Candidal esophagitis unresponsive to mg/kg IV qd until oral agents requires low-dose IV resolution amphotericin B

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ESOPHAGEAL (cont.) Cytomegalovirus Ganciclovir; foscarnet; see 14–21 days See OPHTHALMOLOGIC, CMV Diagnose by endoscopic appearance OPHTHALMOLOGIC, plus biopsy showing CMV inclusion CMV bodies and positive culture. Long- term suppressive therapy indicated only after multiple recurrences. Beware of drug resistance Herpes simplex Acyclovir IV or 10–14 days; See SKIN/MUCOCUTANEOUS, Diagnose by endoscopic appearance valacyclovir po; see maintenance disseminated, extensive, or persistent plus positive culture SKIN/MUCOCUTANEOUS, required herpes simplex disseminated, extensive, or persistent herpes simplex

GASTROINTESTINAL Hepatitis C Interferon Individualized Acute flu-like syndrome 2–4 hours Treatment with ribavirin plus plus after treatment (fever, chills, interferon or pegylated interferon can Ribavirin headache, lethargy, arthralgias, improve hepatitis C. Treatment myalgias); irritability, fatigue, decisions need to be individualized depression, headache, anorexia, because of substantial drug toxicities nausea, rash, alopecia; and the lack of predictable clinical thrombocytopenia, leukopenia, benefit hemolytic anemia, bacterial infections Nausea and vomiting Prochlorperazine As needed Fatigue, drowsiness, dizziness, Combinations of these agents often (Compazine) 2.5–10.0 mg depression; extrapyramidal reactions; necessary IV or 5–10 mg po, or IM dystonic reactions; aminotransferase http://www.jabfm.org/ q6h,or25mgprq12h elevations; constipation Haloperidol (Haldol) can also be effective Lorazepam (Ativan) 0.5– As needed Similar to benzodiazepines; antegrade Effective for anticipatory nausea 2.0 mg po or SL tid–qid amnesia Granisetron (Kytril) 1 mg As needed Constipation, diarrhea, abdominal pain; Reserved for intractable nausea and po q 12 h, or 10 mcg/kg/ fever, chills; headache; sedation vomiting unresponsive to other bid IV, or ondansetron agents. Ondansetron or granisetron in (Zofran) 0.15 mg/kg IV combination with droperidol helpful infusion for 15 minq6h for intractable nausea and vomiting. on 1 October 2021 by guest. Protected copyright. or 4–10 mg poq6h Other 5-hydroxytryptamine (5HT) antagonists available Dronabinol (Marinol) 2.5– As needed See GENERAL/SYSTEMIC, wasting Effective in drug-induced nausea. 10.0 mg po q 8–12 h syndrome Marijuana can be helpful Droperidol (Inapsine) 2.5 As needed Similar to prochlorperazine mg IM/IV q 4–6 h Metoclopramide (Reglan) As needed Same as above Increased risk of extrapyramidal 10 mg po qid or 10 mg reactions IM q 4–6 h. Dosage reduction in renal failure

Diarrhea Loperamide (Imodium) 4 As needed Abdominal cramps, nausea, abdominal Around-the-clock regimen more mg po initially then 2 mg distention, vomiting; dizziness, effective than prn. Treat to 2–3 bowel q 6 h around the clock and drowsiness movements per day prn (maximum 16 mg qd)

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GASTROINTESTINAL (cont.) Diarrhea (cont.) Diphenoxylate-atropine As needed Ileus; nausea, vomiting, abdominal Same as above. 2.5 mg diphenoxylate- (Lomotil) 2.5–5.0 mg po discomfort; anticholinergic side effects atropine is equivalent to 2 mg 3–6 times daily for 24–48 secondary to atropine morphine sulfate hours; then 2.5–5.0 mg tid and prn to control diarrhea (maximum 20 mg qd) Paregoric 0.4 mg As needed Ileus. Altered mental status, Same as above. 5 mL paregoric and morphine/mL, 5–10 mL hallucinations. Adverse effects common 0.2 mL tincture of opium are qd–qid, or tincture of to narcotic analgesics equivalent to 2 mg morphine sulfate opium 10 mg morphine/ mL, 0.3–1.0 mL po qid and prn (maximum 1 mL per dose or 6 mL/d), or equivalent Octreotide (Sandostatin) Indefinitely Nausea, steatorrhea; hyperglycemia; Not approved by FDA. Efficacy not 100 ␮g SQ tid, increase by pain at injection site shown. Long-term safety unknown. 100–200 mcg q 1–2 wk Octreotide does not improve until maximum of 500 mcg malabsorption SQ tid Cryptosporidium Paromomycin (Humatin) 10–14 days or Nausea, vomiting, diarrhea; rare No evidence of efficacy. Addition of 750mgpotidor1gpo indefinitely ototoxicity and nephrotoxicity (similar azithromycin 600 mg po qd might bid to other aminoglycosidesB) only if increase effectiveness absorbed through ulcerative bowel lesions Isospora belli and

Cyclospora cayetanensis http://www.jabfm.org/ Trimethoprim- 7 days See PULMONARY, PCP Usually effective. For persons who sulfamethoxazole (TMP- respond to initial therapy continue SMX, Septra, Bactrim) 1 TMP-SMX DS 1 tablet or DS (double-strength) ciprofloxacin 500 mg po 3 times tablet po bid or qid if no weekly for 10 weeks. Ciprofloxacin response 500 mg po bid for 7 days is an alternative OR

Ciprofloxacin (Cipro) 500 on 1 October 2021 by guest. Protected copyright. mg po bid Cytomegalovirus Ganciclovir; foscarnet; see 14–21 days See OPHTHALMOLOGIC, CMV Long-term suppressive therapy OPHTHALMOLOGIC, indicated only after multiple CMV recurrences. Beware of drug resistance PULMONARY Pneumocystis carinii pneumonia (PCP) Prophylaxis Prophylaxis indicated for Can discontinue PCP primary patients with AIDS prophylaxis in persons whose CD4ϩ (including CD4ϩ cell cell count increases to Ͼ200/␮L for count Ͻ 200/␮L) more than 3–6 months in response to symptomatic HIV disease, antiretroviral therapy or oral candidiasis Trimethoprim- Indefinitely See TMP-SMX below TMP-SMX considered most effective sulfamethoxazole (TMP- for prophylaxis. TMP-SMX provides SMX) 1 DS tablet po qd additional prophylaxis against or qod or 3 times a week toxoplasmosis and common bacterial (eg, M-W-F) infections

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PULMONARY (cont.) Pneumocystis carinii pneumonia (PCP) (cont.) Alternatives to TMP-SMX for prophylaxis Dapsone 50 mg po bid or Indefinitely Patients allergic to sulfa might tolerate Probably less effective than TMP- 100 mg po qd; or dapsone dapsone; some cross-sensitivity. See SMX; might be less toxic. Check 50 mg po qd plus dapsone, below glucose-6 phosphate dehydrogenase pyrimethamine (Daraprim) (G6PD) before starting dapsone. 50 mg po q wk plus Lower dosages (eg, 100 mg po 2 leucovorin 25 mg po q wk times a week) might be effective OR Atovaquone (Mepron) Indefinitely Headaches; nausea, diarrhea, Take with food to increase drug suspension (750 mg/5 mL) aminotransferase elevations; rash, drug absorption. Patients with enteropathy 1,500 mg po qd or 750 mg fever; neutropenia, anemia; transient might not absorb a sufficient amount po bid, with or without conjunctivitis; erythema multiforme. of atovaquone for adequate treatment. pyrimethamine 25–75 mg See atovaquone, below Better tolerated than dapsone; efficacy poqwk similar OR Inhaled pentamidine Indefinitely Bronchospasm and coughing are Effective for prophylaxis against (Aeropent) 300 mgq4wk common; pretreatment with inhaled primary PCP when CD4ϩ cell count using Respirgard II bronchodilator (eg, albuterol) can help. Ͼ 150/␮L. Does not prevent nebulizer Increased risk of spontaneous extrapulmonary disease. Do not use in pneumothorax. Minimal systemic patients with possible M tuberculosis effects. Rare pancreatitis, hypoglycemia; infection because of risk of M rare nephrotoxicity tuberculosis spread by aerosolization OR Clindamycin (Cleocin) 450– Indefinitely See Acute PCP below Efficacy and proper dosages for PCP

600 mg po bid–tid plus prophylaxis unknown http://www.jabfm.org/ primaquine 15 mg po qd OR Pyrimethamine 25 mg– Indefinitely Stevens-Johnson syndrome, toxic No studies clearly show efficacy sulfadoxine 500 mg epidermal necrolysis; bone marrow (Fansidar) 1 poq2wk suppression; gastrointestinal, central nervous system toxicity Acute PCP TMP-SMX; TMP 15 mg/ 21 days Adverse effects commonly appear TMP-SMX is the drug of choice and on 1 October 2021 by guest. Protected copyright. kg/d given in 3 divided between 7 and 14 days in more than should be used unless severe reactions doses either po or as 1- to 50% of patients (eg, anaphylaxis, Stevens-Johnson 2-hour IV infusions; lower syndrome) are of concern. Oral and dosages (TMP 12 mg/kg/ Rashes: maculopapular, exfoliative, intravenous routes equally effective d) can be effective and less Stevens-Johnson syndrome toxic Mild rash does not necessitate Hematologic: neutropenia, leukopenia, stopping or changing treatment; Note: Patients with thrombocytopenia, anemia substantial hypoxemia antihistamine might be helpful require concomitant Drug interactions If ANC Ͻ 500/␮L or if platelet count corticosteroids (see below) Concurrent leucovorin calcium therapy Ͻ 30,000/␮L and bleeding occurs, associated with increased rate of consider alternative treatment therapeutic failure Gastrointestinal: nausea, vomiting, Pretreatment with lorazepam, aminotransferase elevations prochlorperazine, metoclopramide, or dronabinol to reduce nausea. Nausea can be less with oral TMP-SMX. Aminotransferase elevations 4–5 times normal require treatment change Renal: increased blood urea nitrogen TMP decreases creatinine tubular (BUN) and creatinine; hyperkalemia secretion and can elevate serum secondary to effects of TMP creatinine levels. Discontinue TMP- SMX if serum creatinine Ͼ 3.0 mg/ dL

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PULMONARY (cont.) Pneumocystis carinii pneumonia (PCP) (cont.) Acute PCP (cont.) Hyponatremia Can be caused by large volume of 5% dextrose in water (D5W) needed for IV administration; dilute each 80 mg TMP in 75 mL D5W or change to oral TMP-SMX. For severe hyponatremia (Naϩ Ͻ 115 mEq/dL), can dilute in normal saline; administer within 1 hour of preparation to avoid TMP-SMX precipitation Neurologic: tremor, psychosis, aseptic Tremors can be confused with meningitis seizures Drug fever. Sepsis-like syndrome, Drug fever can herald onset of especially upon rechallenge neutropenia, rash, hepatitis, and bone marrow toxicity Alternatives to TMP-SMX for acute PCP Pentamidine isethionate 21 days Adverse effects commonly appear (Pentam) 4 mg/kg/d as 1- between 7 and 14 days to 2-hour IV infusion once Orthostatic hypotension can be severe Slow IV infusion for 2 hours can a day; 3 mg/kg/d might and occur with initial infusion prevent hypotension. Check blood also be effective pressure at end of infusion Pancreatitis; early or delayed Hypoglycemia can be profound and hypoglycemia (can occur after prolonged, requiring immediate IV discontinuation of therapy); D50W followed by D10W glucose

hyperglycemia infusions. Permanent diabetes can http://www.jabfm.org/ occur Drug interactions Avoid concomitant pancreatic toxins such as didanosine, zalcitabine, and alcohol Renal failure; hyperkalemia. Obtain accurate patient weight every Concomitant nephrotoxic agents (eg, 2–3 days to adjust pentamidine nonsteroidal anti-inflammatory agents) dosage. Discontinue pentamidine if and dehydration increase risk of creatinine Ͼ 3.0 mg/dL. Can resume nephrotoxicity administration if creatinine Ͻ 2 mg/ on 1 October 2021 by guest. Protected copyright. dL Rare: neutropenia, thrombocytopenia; hypocalcemia, hypomagnesemia; aminotransferase elevations; cardiac arrhythmias (rare) with prolongation of QT interval and T wave flattening OR Clindamycin 600 mg IV or 21 days Maculopapular rash (day 10–12 most Consider in patients with mild-to- potidor450mgpoq6h common, usually self-limiting), fever; moderate PCP, intolerant of or diarrhea, nausea, vomiting, abdominal unresponsive to TMP-SMX cramps, Clostridium difficile colitis, aminotransferase elevations plus Primaquine 30-mg base po Methemoglobinemia from primaquine, Check G6PD before initiating qd hemolysis in G6PD-deficient patients; primaquine therapy. Check leukopenia methemoglobin levels when clinically indicated (see dapsone). Vitamin C 1 g po tid might prevent methemoglobinemia. Lower dosage of primaquine (15 mg po qd) can be effective

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PULMONARY (cont.) Alternatives to TMP-SMX for acute PCP (cont.)

OR Dapsone 50 mg po bid 21 days See toxicities for TMP-SMX. Patients Effective in mild-to-moderate PCP plus either TMP 15 mg/ allergic to sulfa often tolerate dapsone. only. Check G6PD before starting kg/d po in 3–4 divided Methemoglobinemia, dose-related dapsone. Check methemoglobin doses or pyrimethamine hemolysis, bone marrow suppression; levels if symptomatic or discrepancy 50–75 mg po qd rash; fever; nausea, abdominal pain; between oxygen saturation and hyperkalemia; proteinuria, papillary simultaneous arterial PaO2. Treat necrosis methemoglobinemia Ͼ 20% (13%– 20% if anemic or respiratory Drug interactions compromise) with methylene blue Drug interactions with rifampin and 1% solution 2 mg/kg IV once; rifabutin can render dapsone ineffective methylene blue contraindicated in G6PD deficiency. VitaminC1gpo tid might prevent methemoglobinemia OR Trimetrexate (Neutrexin) 21 days Granulocytopenia, fever, rash; Can be effective in some patients as 45 mg/m2 IV qd aminotransferase elevations salvage therapy plus Dapsone 50 mg po bid 21 days See above plus Leucovorin calcium 24 days Must be administered for 72 hours (folinic acid) 20 mg/m2 IV after the last dose of trimetrexate. orpoq6h Large IV fluid load with leucovorin administration can result in volume overload http://www.jabfm.org/ OR Atovaquone suspension 21 days Rash, drug fever; headaches; nausea, Higher therapeutic failure rate than (750 mg/5 mL) 750 mg po diarrhea, aminotransferase elevations; TMP-SMX. For patients who fail or bid with food neutropenia, anemia; transient are intolerant to TMP-SMX, conjunctivitis; erythema multiforme pentamidine, dapsone-TMP, or plus clindamycin-primaquine. Take with food to increase drug absorption. Patients with on 1 October 2021 by guest. Protected copyright. Pyrimethamine 50–75 mg enteropathy might not absorb a po qd sufficient amount of atovaquone for adequate treatment Adjunctive corticosteroid therapy for acute PCP with Ն PaO2 70 mm Hg Prednisone po or 21 days Hyperglycemia, sodium retention, Corticosteroids indicated in methylprednisolone (Solu- potassium wasting. Psychiatric conjunction with antipneumocystis Յ Medrol) IV: 40 mg bid for syndromes. Exacerbation of Kaposi therapy in all patients with PaO2 5 days followed by 40 mg sarcoma, thrush, herpes infections, and 70 mm Hg. Begin corticosteroids qd for 5 days, followed by other opportunistic infections concurrent with PCP treatment or if Յ 20 mg qd for 11 days (can PaO2 decreases to 70 mm Hg be tapered to 0 mg for last within 72 hours of initiating PCP 11 days also) treatment Maintenance (secondary Indefinitely Same Discontinuing secondary prophylaxis prophylaxis) with agents appears safe in persons whose CD4ϩ used for primary cell count increases to Ͼ 200 ␮L for prophylaxis (above) 3–6 months in response to antiretroviral therapy. This strategy especially helpful for patients experiencing toxicity to drugs for PCP prophylaxis

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System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

CENTRAL NERVOUS SYSTEM Toxoplasma gondii

Prophylaxis PCP prophylaxis regimens Indefinitely See PULMONARY, PCP TMP-SMX, dapsone plus except aerosolized pyrimethamine, clindamycin plus pentamidine provide primaquine, atovaquone with or protection against without pyrimethamine, and toxoplasmosis. Prophylaxis pyrimethamine-sulfadoxine provide recommended for persons some prophylaxis against with immunoglobulin G toxoplasmosis. Clarithromycin and (IgG) antibody to azithromycin provide some benefit Toxoplasma and CD4ϩ count Ͻ 100/␮L

Acute Pyrimethamine 50–100 mg 6–8 weeks for Leukopenia, anemia, thrombocytopenia Clinical response or regression of po qd (every other day if acute therapy lesions on imaging studies is usually bone marrow suppression) noted within 2 weeks. Maintenance plus leucovorin calcium required indefinitely to prevent (folinic acid) 10–25 mg po relapse qd plus either Sulfadiazine 1.0–1.5 g po q Same Rash, drug fever; leukopenia, Sulfadiazine probably provides 6h thrombocytopenia; crystalluria with effective prophylaxis against PCP. renal failure Ensure adequate fluid intake. Patients or requiring concurrent treatment for acute PCP can receive pyrimethamine Clindamycin 600–900 mg Same See PULMONARY, PCP plus TMP/SMX instead of po or IV qid pyrimethamine plus sulfadiazine http://www.jabfm.org/ Alternative when intolerant of sulfadiazine and clindamycin Pyrimethamine plus Same See above leucovorin as above plus one of the following

Clarithromycin1gpobid Same See GENERAL/SYSTEMIC, MAC on 1 October 2021 by guest. Protected copyright. or azithromycin 500 mg–1 gpoqd or Atovaquone suspension Same See PULMONARY, PCP Not proved effective (750 mg/5 mL) 750 mg po qid with meals

Maintenance Pyrimethamine 25–75 mg Indefinitely Other agents used for acute po qd plus leucovorin 10– toxoplasmosis might be effective at 25 mg po qd lower dosage for maintenance plus either Sulfadiazine 500 mg–1 g Indefinitely po qid or Clindamycin 300–450 mg Indefinitely po q 6–8 h

AIDS and HIV-Related Conditions: 2001 303 Table 1. Continued

System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

CENTRAL NERVOUS SYSTEM (cont.) Cryptococcus neoformans Prophylaxis Fluconazole 100–200 mg Primary prophylaxis not routinely po qd provides limited recommended. Can be considered for prophylaxis patients with CD4ϩ cell counts Ͻ 50/␮L. No long-term survival benefit. Fluconazole resistance reported Acute meningitis or acute disseminated cryptococcosis Amphotericin B 0.7–1.0 6–8 weeks; Renal failure, hypokalemia, Pretreatment with diphenhydramine, mg/kg/d IV with or amphotericin hypomagnesemia. Liposomal acetaminophen or IV morphine can without 5-flucytosine 100 total dosage amphotericin B might decrease toxicity decrease amphotericin-induced fevers, mg/kg po qd in 4 divided not to exceed chills, and rigors. Pretreatment not doses for first 2–4 weeks. 2g Fever, chills; anemia, thrombophlebitis recommended routinely. Administer If clinically improved after Granulocytopenia; nausea, vomiting, for 4–6 hours in D5W. Addition of 7.5 mg/kg total diarrhea, aminotransferase elevations; heparin 500 U and hydrocortisone 25 amphotericin B rash from flucytosine mg to amphotericin IV solution can administration, can change decrease phlebitis. Infusion of 500– to fluconazole 400 mg po Flucytosine toxicities (rash, metallic 1000 mL normal saline before qd or itraconazole 200 mg taste, leukopenia, thrombocytopenia) administration of amphotericin B can po bid limit its usefulness minimize renal toxicity. 5-Flucytosine not indicated if granulocytopenia or thrombocytopenia is present Markedly increased intracranial pressure (Ͼ 240 mm) might require cerebrospinal fluid drainage (20–30 mL or more per day by lumbar

puncture or continuous lumbar drain), http://www.jabfm.org/ or possibly corticosteroid, mannitol, or acetazolamide (Diamox) therapy OR Fluconazole 400–800 mg 8–12 weeks Nausea, vomiting, diarrhea; dizziness; As effective as amphotericin B against po qd. Dosage reduction aminotransferase elevations; rare mild or moderate disease; unknown in renal failure. Higher cutaneous reactions, skin pigmentation, whether equally effective against dosages (eg, 800–1,200 mg alopecia severe disease. Fluconazole penetrates po qd) might increase central nervous system (CNS) and efficacy Drug interactions most body tissues, including prostate. on 1 October 2021 by guest. Protected copyright. Increased phenytoin (Dilantin) and Addition of 5-flucytosine might be of warfarin (Coumadin) levels; higher benefit fluconazole dosages might be necessary for patients taking rifampin Maintenance Fluconazole 200–400 mg Indefinitely Same Higher dosages might be necessary po qd for recurrent disease OR Itraconazole 200 mg po qd Indefinitely Same OR Amphotericin B 0.5–0.8 Indefinitely Same mg/kg/d 3–5 times a week

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System, Problem, and

Drug Regimen Duration Adverse Effects/Drug Interactions Comments J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from

CENTRAL NERVOUS SYSTEM (cont.) Syphilis Aqueous crystalline 10–14 days Usual penicillin adverse effects; Jarisch- Serologic and clinical follow-up penicillin G 3–4 mU IV q Herxheimer reaction; seizures from required to assess adequacy of 4 h (total 18–24 mU/d) high-dosage penicillin in renal failure neurosyphilis treatment. Persons with ophthalmic, auditory, or cranial nerve abnormalities or other OR syndromes consistent with neurosyphilis should receive daily penicillin therapy for 10–14 days. Procaine penicillin G 2.4 10–14 days Same. Probenecid rash Intravenous penicillin preferred for mU IM qd adequate CNS penetration. For penicillin-allergic patients, consultation with an expert advised. plus Administer additional benzathine penicillin 2.4 mU IM weekly after completion of neurosyphilis Probenecid 500 mg po qid 10–14 days treatment to ensure 3 weeks total penicillin therapy Peripheral neuropathy Gabapentin (Neurontin) Indefinitely Thrombocytopenia; somnolence, Can be helpful when other agents fail. 300–400 mg po tid via dizziness, ataxia, nystagmus, fatigue, Maximum dosage is 3,600 mg/d in dose escalation; dosage headache; nausea, vomiting, diarrhea divided doses reduction in renal failure Desipramine (Norpramin) Indefinitely Usual tricyclic side-effects; drowsiness; Pain relief occurs in 3–5 days. or amitriptyline (Elavil) orthostatic hypotension; anticholinergic Desipramine causes less sedation and 25–150 mg po hs symptoms fewer anticholinergic effects. Other tricyclic drugs might be equally effective

Carbamazepine (Tegretol) Indefinitely Leukopenia, bone marrow suppression, Less desirable because of bone http://www.jabfm.org/ 100–300 mg po bid rare agranulocytosis; rash; drowsiness, marrow effects. Need to monitor dizziness; aminotransferase elevations carbamazepine levels to avoid toxicity Capsaicin (Axsain, Zostrix- Indefinitely Minor burning sensation, skin irritation, Pain relief delayed 2–4 weeks. No HP) 0.075% topical cream erythema systemic effects qid Mexiletine (Mexitil) 150 Indefinitely Nausea, vomiting, epigastric pain; Less desirable because of side effects mg po bid–tid dizziness, tremor; bradycardia; rare seizures, leukopenia, agranulocytosis on 1 October 2021 by guest. Protected copyright.

ϩ initiated when their CD4 cell count levels are Antiretroviral regimens can be difficult to follow greater than 350 /␮L or when they have detectable even for the most well-intentioned and motivated viral loads at any level should be offered antiretro- patient. The primary care clinician and the patient viral therapy if they understand the risks and ben- must acknowledge these inherent difficulties and efits of therapy and are committed and able to develop realistic expectations, as suboptimal anti- adhere to the difficult medication regimens. The retroviral therapy can lead to irreversible drug re- new guidelines are in agreement with those who sistance. It might be better to withhold antiretro- favor the more conservative approach to antiretro- viral therapy for patients who cannot maintain viral therapy.3,5,6 In addition, patients with the adherence to treatment regimens, thus avoiding the acute retroviral syndrome and possibly patients risk of developing resistance. within 6 months of seroconversion should receive Some reduction in viral load should be appar- antiretroviral therapy whenever possible. The acute ent within 4 to 6 weeks of initiating therapy. retroviral syndrome can include fever, myalgias, Ideally, the viral load will decrease to undetect- sore throat, headache, rash, oral or genital ulcers, able levels (less than 50 copies/mL) within 4 to 6 and adenopathy. months. Effective therapy usually shows a viral

AIDS and HIV-Related Conditions: 2001 305 Table 2. Sources of Information for Treatment of AIDS and HIV-Related Conditions.

Guidelines

www.hivatis.org J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from Extremely easy to use, AIDS-specific Web site with access to key federal and other guidelines. Has up-to-date revisions of guidelines as they are announced, as well as some documents in draft form www.cdc.gov Contains all guidelines from the Centers for Disease Control and Prevention, including AIDS and Sexually Transmitted Disease General information, links to guidelines, and other Web sites www.hivinsite.ucsf.edu Comprehensive Web site with access to a wide range of resources, including the full text of the AIDS Knowledge Base, clinical articles, tables, and protocols, as well as links to other sites. Based in the AIDS Program at San Francisco General Hospital/ UCSF www.hopkins-aids.edu Comprehensive Web site with access to a wide range of resources, including Medical Management of HIV Disease, ask-the-expert question and answer series, and links to other sites. Based in the Johns Hopkins University AIDS Service www.ama-assn.org/special/hiv Provides news, articles, abstracts, and policy information on AIDS from JAMA and other AMA sources www.ucsf.edu/hivcntr National HIV Telephone Consultation Service (Warmline) and National Clinicians’ Post-Exposure Prophylaxis Hotline (PEPline) information. Based in the National HIV/AIDS Clinicians’ Consultation Center at San Francisco General Hospital Clinical trials www.actis.org Official AIDS Clinical Trials Information Service (ACTIS) Web site for information on clinical trials. Additional information available by calling ACTIS at 1-800-TRIALSA; or can be found on the National Institutes of Health Web site, www.niaid.nih.gov

Note: Standard library search engines, such as Galen and Grateful Med, and searches on www.medscape.com and others can also be helpful. http://www.jabfm.org/ load (HIV RNA) decrease of at least 1 log. A indinavir, saquinavir, or lopinavir. Ritonavir is ex- minimally significant viral load change is a 0.5- tremely effective in raising the blood levels of other log (3-fold) increase or decrease. Patients who PIs. Because of concerns about toxicities and the obtain substantial decreases in viral loads, but not potential for developing resistance to the PI class of to undetectable levels, can still obtain clinical drugs, some experts prefer efavirenz (in combina-

benefit from antiretroviral therapy. A sustained tion with two NRTIs) to preserve the PI class of on 1 October 2021 by guest. Protected copyright. ϩ rise in CD4 cell count of 100 /␮Lormore drugs for subsequent regimens. Alternative drug usually accompanies effective therapy. Divergent combinations are available but can lack the potency ϩ results in viral load and CD4 counts can also or have more toxicities than the preferred combi- occur. nations listed above. If the NRTI drugs must be changed, alternative NRTIs are didanosine plus Recommended Antiretroviral Drug lamivudine and zidovudine plus zalcitabine. If the Combinations PI or efavirenz component of therapy needs to be Potent antiretroviral drug combinations, also changed, the most suitable alternative is probably termed highly active antiretroviral therapy to change to the other class (eg, change from PI to (HAART), include two nucleoside reverse tran- efavirenz or to dual PI, or change from efavirenz to scriptase inhibitors (NRTIs) with the addition of PI therapy. either one or two protease inhibitors (PIs) or the Another suitable alternative is to change to (two nonnucleoside reverse transcriptase inhibitor NRTIs plus) abacavir if the viral load is less than (nNRTI) efavirenz. The preferred NRTI combi- 100,000 copies/mL.7 Other less suitable alterna- nations are zidovudine plus lamivudine, zidovudine tives to the PIs-efavirenz options listed above in- plus didanosine, stavudine plus lamivudine, and clude amprenavir; ritonavir, saquinavir, nevirapine; stavudine plus didanosine. The recommended PIs delavirdine; and nelfinavir plus saquinavir. Table 1 are nelfinavir, indinavir, and ritonavir plus either lists other alternative combinations.

306 JABFP July–August 2001 Vol. 14 No. 4 Antiretroviral Therapy Failure and Resistance Hyperglycemia and diabetes mellitus are Testing strongly associated with PI use. The lipodystrophy syndrome, including central obesity, peripheral fat Antiretroviral therapy can fail because of poor ad- J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from herence, acquired drug resistance, poor drug ab- wasting, visceral and dorsocervical (buffalo hump) sorption, drug-drug interactions, or lack of drug fat deposition, and sometimes lipid abnormalities, potency. New opportunistic infections and other is associated with PI and NRTI use but can occur in clinical illnesses, rising viral load (usually a 3-fold the absence of antiretroviral therapy. The clinical ϩ increase or more), or a falling CD4 cell count importance of the various lipid abnormalities has usually indicate failed therapy. Virologic failure as not been fully assessed. indicated by rising viral loads is not always accom- With improvement in the immune system, par- ϩ panied by either decreasing CD4 counts or clin- adoxical responses can occur. These include flare- ical progression. Many patients retain clinical ben- ups of latent opportunistic infections, such as cyto- efit even after the reemergence of high viral load.8 megalovirus (CMV) uveitis, or viral hepatitis (B or Resistance testing can be helpful in making de- C), herpes zoster, fungal and mycobacterial dis- cisions when changing therapies. The test should eases, and even Kaposi sarcoma and lymphomas.11 be obtained while the patient is taking the failing These clinical flares should not prompt discontin- regimen. Three kinds of resistance tests are avail- uation of antiretroviral therapy. able: genotypic, phenotypic, and virtual pheno- typic, which compares the patient’s genotypic re- Opportunistic Infections sults with phenotypic results from patients with Effective combination antiretroviral therapy has re- similar genotypic patterns. Some words of caution duced opportunistic infections and malignancies are in order about all these tests: none is well markedly during the past few years.12 Table 1 has standardized; laboratory variability is substantial; been revised, omitting some opportunistic infec- the results can be difficult to interpret, sometimes tions and malignancies, such as treatment of his- because of complexity and at other times because of toplasmosis, coccidioidomycosis, and eosinophilic oversimplification; only the predominant viral pop- folliculitis. Treatment recommendations for these ulation (not minor strains) is tested; and the corre- conditions can be found in our previous review.3 http://www.jabfm.org/ lation between resistance testing results and clinical Primary prophylaxis against Pneumocystis carinii drug effectiveness has not been established. Resis- pneumonia (PCP) and Mycobacterium avium com- tance testing cannot establish which drugs will be plex (MAC) disease can be discontinued if substan- effective, but it can help assess whether certain tial immune reconstitution has occurred in re- drugs or classes of drugs might be ineffective. sponse to antiretroviral therapy. Prophylaxis ϩ

Multiple drug resistance is often discovered on against PCP can be discontinued when CD4 cell on 1 October 2021 by guest. Protected copyright. resistance testing when regimens are failing. New counts have been 200/␮L or higher for a period of regimen selection often requires combinations of 3 to 6 months. Similarly, MAC prophylaxis can be ϩ agents from different antiretroviral classes and use discontinued if the CD4 cell count has been of dual PI therapy. Consultation with an expert 100/␮L or higher for 3 to 6 months.13,14 Discon- AIDS clinician is often required. tinuing secondary PCP prophylaxis (ie, mainte- nance therapy after PCP has occurred) after 3 to 6 ϩ Complications of Antiretroviral Therapy months of immune recovery of CD4 cell count to Table 1 lists the major complications of drugs used 200 /␮L appears safe as well.15,16 Discontinuing in HIV disease.9,10 The NRTI drug class is associ- CMV maintenance therapy (secondary prophy- ated with lipoatrophy, as well as with lactic acidosis, laxis) appears safe in patients who have maintained ϩ hepatomegaly, and steatosis. The lactic acidosis CD4 counts greater than 100 to 150/␮L for more syndrome, which usually begins with lactic aci- than 3 to 6 months in response to antiretroviral demia and nonspecific gastrointestinal symptoms, therapy. Primary prophylaxis against toxoplasmosis can progress to severe or fatal lactic acidosis. All is rarely necessary, as most PCP prophylaxis regi- NRTI drugs should be discontinued. Combina- mens, except aerosolized pentamidine, provide tox- tions of didanosine and stavudine appear to be oplasmosis prophylaxis. more problematic; cautious rechallenge using other Tuberculosis coinfection with HIV presents NRTIs has been successful. special management concerns.17,18 Therapy with

AIDS and HIV-Related Conditions: 2001 307 rifabutin, rather than rifampin, is required with We gratefully acknowledge the staff of the National HIV/AIDS coadministration of PIs and nNRTIs. Tuberculosis Clinicians’ Consultation Center and the faculty, staff, and house prophylaxis is essential for persons with a positive staff at San Francisco General Hospital for making this work J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from tuberculin skin test (Ͼ5 mm in HIV-infected per- possible, and Mary A. Hanville for assistance in preparation of this manuscript. sons), for persons with a previously positive tuber- culin skin test without prior chemoprophylaxis, and References for those who have had recent contact with active 1. Guidelines for the use of antiretroviral agents in tuberculosis. Treatment of active tuberculosis in HIV-infected adults and adolescents. Panel on Clin- HIV-infected persons and prophylaxis against pos- ical Practices for Treatment of HIV Infection. The sible multidrug-resistant tuberculosis usually re- Living Document, 28 Jan 2000. Available at http:// quire consultation with tuberculosis experts. www.hivatis.org. Accessed 11 April 2001. Hepatitis C and HIV coinfection is common and 2. Hecht FM, Wilson IB, Wu AW, Cook RL, Turner problematic.19 Progressive hepatitis C can add sub- BJ. Optimizing care for persons with HIV infection. stantially to morbidity and mortality. Therapy with Society of General Internal Medicine AIDS Task Force. Ann Intern Med 1999;131:136–43. interferon and ribavirin can be effective in some 3. Goldschmidt RH, Dong BJ. Treatment of AIDS and patients, but it can also be associated with unfavor- HIV-related conditions: 2000. J Am Board Fam able side effects. Selecting which patients might Pract 2000;13:274–98. benefit from combination interferon-ribavirin 4. 1999 USPHS/IDSA guidelines for the prevention of therapy should be individualized in concert with opportunistic infections in persons infected with hu- expert consultation. man immunodeficiency virus. US Public Health Ser- Table 1 gives our recommendations for treating vice (USPHS) and Infectious Diseases Society of America (IDSA). MMWR Morb Mortal Wkly Rep specific diseases and the major symptoms of HIV 1999; 48(RR-10):1–59, 61–6. Also available at http:// infection and AIDS. The recommendations are www.hivatis.org. principally in order of efficacy. Where more than 5. Henry K. The case for more cautious, patient-fo- one drug is effective for a specific condition, rec- cused antiretroviral therapy. Ann Intern Med 2000; ommendations are usually in an order that favors 132:306–11. the least expensive choice among equally effective 6. Harrington M, Carpenter CC. Hit HIV-1 hard, but http://www.jabfm.org/ options. The most common and clinically impor- only when necessary. Lancet 2000;355:2147–52. tant adverse effects and drug interactions are listed. 7. Staszewski S, Keiser P, Montaner J, et al. Abacavir- lamivudine-zidovudine vs indinavir-lamivudine- Sources of Information zidovudine in antiretroviral-naive HIV-infected adults. A randomized equivalence trial. JAMA 2001; The most helpful and up-to-date sources of infor- 285:1155–63. mation can now be found on the Internet. Espe- 8. Deeks SG, Wrin T, Liegler T, et al. Virologic and on 1 October 2021 by guest. Protected copyright. cially useful Web sites are listed in Table 2. A immunologic consequences of discontinuing combi- selected bibliography highlights some additional nation antiretroviral-drug therapy in HIV-infected articles of clinical interest.20–26 Our National HIV patients with detectable viremia. N Engl J Med 2001; Telephone Consultation Service (Warmline) in the 344:472–80. University of California, San Francisco, Depart- 9. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000;356:1423–30. ment of Family and Community Medicine at San 10. Piscitelli SC, Gallicano KD. Interactions among Francisco General Hospital (SFGH) provides clin- drugs for HIV and opportunistic infections. N Engl ical consultation and education for health care pro- J Med 2001;344:984–96. viders; the Warmline is in operation on weekdays at 11. DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflam- 1–800-933–3413. Our National Clinicians’ Post- matory reactions in HIV-1-infected persons after Exposure Prophylaxis Hotline (PEPline) at 1–888- initiation of highly active antiretroviral therapy. Ann HIV-4911 provides 24-hour advice and support Intern Med 2000;133:447–54. regarding occupational exposures to blood-borne 12. Kovacs JA, Masur H. Prophylaxis against opportu- pathogens. The AIDS Education and Training nistic infections in patients with human immunode- ficiency virus infection. N Engl J Med 2000;342: Centers (AIDS ETCs) of the Health Resources and 1416–29. Services Administration (HRSA) at 1–301-443– 13. El-Sadr WM, Burman WJ, Grant LB, et al. Discon- 6364 offers education, training, and consultation tinuation of prophylaxis against Mycobacterium avium services to health care providers. complex disease in HIV-infected patients who have a

308 JABFP July–August 2001 Vol. 14 No. 4 response to antiretroviral therapy. N Engl J Med immunodeficiency virus coinfection: clinical man- 2000;342:1085–92. agement issues. Clin Infect Dis 2000;31:154–61. 14. Currier JS, Williams PL, Koletar SL, et al. Discon- 20. Wilkin A, Feinberg J. Pneumocystis carinii pneumo- tinuation of Mycobacterium avium complex prophy- nia: a clinical review. Am Fam Physician 1999;60: J Am Board Fam Pract: first published as on 1 July 2001. Downloaded from laxis in patients with antiretroviral therapy—induced 1699–708. ϩ increases in CD4 cell count. A randomized, dou- 21. Williams B, Waters D, Parker K. Evaluation and ble-blind, placebo-controlled trial. AIDS Clinical treatment of weight loss in adults with HIV disease. Trials Group 362 Study Team. Ann Intern Med Am Fam Physician 1999;60:843–54, 857–60. 2000;133:493–503. 22. Sherman DS, Fish DN. Management of protease 15. Lopez Bernaldo de Quiros JC, Miro JM, Pena JM, et inhibitor-associated diarrhea. Clin Infect Dis 2000; al. A randomized trial of the discontinuation of pri- 30:908–14. mary and secondary prophylaxis against Pneumocystis 23. Public health service guidelines for the management carinii pneumonia after highly active antiretroviral of health-care worker exposures to HIV and recom- therapy in patients with HIV infection. N Engl mendations for postexposure prophylaxis. Centers J Med 2001;344:159–67. for Disease Control and Prevention. MMWR Morb 16. Ledergerber B, Mocroft A, Reiss P, et al. Discontin- Mortal Wkly Rep 1998;47(RR-7):1–33. uation of secondary prophylaxis against Pneumocystis 24. 1998 Guidelines for treatment of sexually transmit- carinii pneumonia in patients with HIV infection ted diseases. Centers for Disease Control and Pre- who have a response to antiretroviral therapy. Eight vention. MMWR Morb Mortal Wkly Rep 1998; European Study Groups. N Engl J Med 2001;344: 47(RR-1):1–111. 168–74. 25. Perinatal HIV Guidelines Working Group. Public 17. Prevention and treatment of tuberculosis among pa- Health Service Task Force recommendations for the tients infected with human immunodeficiency virus: use of antiretroviral drugs in pregnant HIV-infected principles of therapy and revised recommendations. women for maternal health and interventions to re- Centers for Disease Control and Prevention. duce perinatal HIV-1 transmission in the United MMWR Morb Mortal Wkly Rep 1998;47(RR-20): States. 24 January 2001. Available at http://www. 1–58. hivatis.org. Accessed 6 May 2001. 18. Havlir DV, Barnes PF. Tuberculosis in patients with 26. Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, human immunodeficiency virus infection. N Engl et al. Lamivudine-zidovudine combination for pre- J Med 2000;340:367–73. vention of maternal-infant transmission of HIV-1. 19. Poles MA, Dieterich DT. Hepatitis C virus/human JAMA 2001;285:2083–93. http://www.jabfm.org/ on 1 October 2021 by guest. Protected copyright.

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