General Practitioners and HIV In the primary care setting, General Practitioners (GPs) play a vital role in the prevention of transmission of the Human Immunodeficiency Virus (HIV), and the provision of care to people living with HIV (PLHIV), specifically in early diagnosis and management. mean age of the HIV‑positive population has increased quite This resource will address the following: dramatically since 1986. The health needs of the aging HIV positive population are similar to PREVENTION those of the general aging population. However, special attention • Pre‑exposure prophylaxis (PrEP) is required for their relatively higher susceptibility to co‑morbidities, • Post‑exposure prophylaxis (PEP) such as malignancies and cardiovascular disease. PLHIV will continue • Treatment as Prevention (TaSP) to need comprehensive general practice care to age successfully. DIAGNOSIS Breaking HIV down • Testing The Virus MANAGEMENT HIV is a single‑stranded ribonucleic acid (RNA) virus. It has an outer • GP shared care arrangements for PLHIV envelope that surrounds two copies of single‑stranded RNA as well • Becoming accredited to prescribe as a number of viral proteins. The HIV replication commences when antireretroviral therapy (ART) the envelope 120 glycoprotein (gp 120) attaches to CD4 receptors expressed on the surface of lymphocytes. Is HIV still a concern… the numbers Attachment allows fusion of the membranes of virus and cell at viral • At the end of 2017, 27,545 people were estimated to be living entry. The RNA is converted to deoxyribonucleic acid (DNA) which with HIV in Australia. migrates to the cell nucleus and integrates as proviral DNA into the • Prevalence highest in men who have sex with men (MSM). host cell DNA. • HIV prevalence has increased by 14% between 2016 and 2017 for those who only risky behaviour was heterosexual contact HIV throughout the life-span HIV infection is now considered a manageable chronic disease. Newly diagnosed PLHIV who adhere to ART have a similar life expectancy as the general population. ART vastly improves the lifespan of PLHIV because of its effectiveness and as a result, the Natural History the CD4 cell count has usually fallen below 200 cells/μL and the Following infection with HIV, there is a period of high level person becomes severely immunocompromised (Figure 1). viraemia associated with immunosuppression as measured by a reduction in the CD4 lymphocyte count. A host immune Transmission response then develops, partially controlling viral replication, In Australia, transmission most commonly occurs in MSM (63% but is unable to clear HIV from the body. of the 2017 notifications), whereas in developing countries, especially in Africa, HIV is predominantly acquired through The majority of PLHIV develop a mononucleosis‑like HIV heterosexual contact (Table 1). seroconversion illness characterised by fever, pharyngitis, lymphadenopathy, rash, splenomegaly and aseptic meningitis. Modes of transmission and increased risks of transmission Others may either be asymptomatic or have subclinical illness. i. Concurrent sexually transmissible infection (STI) ‑ also Symptoms of acute infection resolve as the immune system likely to increase risk of HIV infection. An STI can be a marker mounts an antiviral response that causes the viral load to of recent or past risk, and genital inflammation itself may decrease markedly. Simultaneously, there is a rebound increase place the individual at higher risk of HIV infection. in CD4 cell count to near baseline levels and the virus enters a ii. Injecting drug use (IDU) ‑ uncommon in Australia, ac‑ period of clinical latency, although very high levels of replication counting for 3% of newly acquired HIV infections in 2017 but continues, especially in lymphoid tissue. is particularly prevalent in parts of Europe, Asia and the USA. iii. Blood products ‑ largely occurred before the introduction The plasma HIV RNA plateaus to a level of viraemia known as the of antibody screening in 1985 in Australia and was virological ‘set point’. If left untreated, there is a gradual decline responsible for the high incidence of HIV among multiply in CD4 cell count, with a median loss of 80 cells/uL per year. transfused people, such as those with haemophilia. It is now However, starting antiretroviral therapy causes a decrease in viral exceedingly rare in countries where blood is screened. load which will reverse this decline in CD4 cells. Therefore, earlier iv. Needlestick injury - occurs in 0.3% of exposures from treatment can potentially protect the individual’s CD4 cell count. individuals with HIV infection where prophylaxis is not used. It also diminishes the size of the latent pool of HIV infected CD4 v. Perinatal transmission - occurs in 20–45% of infants born cells by reducing the number of infected CD4 cells. to mothers with HIV, but this rate can be reduced to less than 5% with the administration of antiretroviral therapy during If untreated, progression to AIDS, marked by the development pregnancy, labour and after delivery, and other interventions of opportunistic infections or specific malignancies, occurs a such as avoidance of breast feeding. Indeed, from 2013 to median of 10 years after initial infection with HIV. At this time 2017, the rate has reduced to 1% of newborns in Australia. Figure 1: HIV Natural History The various stages of untreated HIV infection depicting the development of different opportunistic infections with advanced immunodeficiency. 1200 107 Acute HIV syndrome ) 1100 3 1000 Minor infections 106 900 Skin conditions Primary Fever 800 Infection Weight loss 105 700 TB 600 Pneumonia Asymptomatic 500 Fever Thrombocytopenia 104 Myalgia Toxoplasmosis 400 Cryptosporidiosis 300 Rash Lymphoma (NHL) Pharyngitis 103 HIV RNA copies per mL plasma 200 CD4 lymphocyte count (cells/mm Adenopathy 100 Mouth ulcers PJP, KS MAC, CMV 2 0 10 0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11 weeks years mac: mycobacterium avium complex, cmv: cytomegalovirus, ks: kaposi sarcoma, pjp: pneumocystis jirovecii pneumonia, tb: tuberculosis 2 General Practitioners and HIV UNDECTABLE = UNTRANSMITTABLE COULD IT BE HIV? Importantly, recently published studies have shown that no Be alert in the context of flu-like illness, with transmission has occurred from a partner with undetectable symptoms such as: viral load within both homosexual and heterosexual couples, • Glandular fever‑like illness that is Epstein‑Barr virus where undetectable viral load is defined as less than 200 (EBV) seronegative copies /ml for 6 months and is achieved by taking ART • Flu‑like symptoms outside usual influenza season daily as prescribed. Treatment is therefore very effective at (e.g. myalgia, arthralgia, headache, malaise) reducing HIV transmission, which is known as ‘treatment as prevention (TaSP)’. • Fever for more than three days • Maculopapular rash Please refer to • Meningeal involvement ASHM Undetectable = Untransmittable: A guide • Transient neurological syndromes for clinicians to discuss for further details. https:// (e.g. Guillain‑Barré syndrome, neuropathies) www.ashm.org.au/products/product/UequalsU • Recent evidence of STIs or genital ulcers Signs and Symptoms • Signs and symptoms of acute HIV infection can present as early While no single symptom distinguishes acute HIV infection from as three days or as late as 10 weeks following transmission. other acute viral illnesses, there are some factors that should • Onset of symptoms often coincides with the appearance of alert the clinician to the possibility of acute HIV infection in the HIV antibodies although the enzyme linked immunosorbent context of. assay (ELISA) may be HIV antibody negative for up to three weeks after onset of symptoms. Please refer to ASHM Decision Making in HIV Tool • Duration of the seroconversion illness is most commonly 4 to for further referral and assessment suggestions. 14 days but may be longer. https://www.ashm.org.au/resources/hiv‑resources‑list/ Approximately 50 to 90% of PLHIV report signs or symptoms suggestive of primary HIV infection at the time of Co-infection with Hepatitis B (HBV) or Hepatitis C (HCV) seroconversion. PLHIV who experience a severe symptomatic Multiple blood‑borne viral infections in the same individual can primary HIV infection appear to have more rapidly progressive alter the natural history (course/progression) of disease. HIV disease than those who do not. HBV has no adverse effect on HIV or the development of Table 1: Exposure and transmission risk/exposure with knownHIV positive source Type of exposure with known HIV positive source Estimated risk of HIV transmission/exposure a Receptive anal intercourse ‑ ejaculation 1/70 ‑ withdrawal 1/155 Contaminated injecting equipment 1/125 Insertive anal intercourse (IAI) uncircumcised 1/160 Insertive anal intercourse (IAI) circumcised 1/900 Receptive vaginal intercourse (RVI) 1/1250 Insertive vaginal intercourse (IVI) 1/2500 Receptive or insertive oral intercourse Unable to estimate risk ‑ extremely low Needlestick injury (NSI) or other sharps exposure 1/440 Mucous membrane and non‑intact skin exposure <1/1000 a These estimates are based on prospective studies, not cross‑sectional data or figures derived from modelling. General Practitioners and HIV 3 AIDS, but HIV does influence HBV and can be associated with PEP involves: accelerated development of cirrhosis and liver failure. Drugs • Taking a combination of antiretroviral medication (either a that are effective against both HBV and HIV are available now 2‑drug regimen of Tenofovir and Emtricitabine,