Evaluating individuals with extreme phenotypes of HIV-1 contributes towards better healthcare management of all HIV-1 positive individuals

Human Immunodeficiency Virus (HIV)-1 disease progression is variable within patients where some remain asymptomatic for long periods (elite controllers (EC)) while others rapidly progress to disease (rapid progressors (RP)), representing the ‘extreme phenotypes’. There is substantial heterogeneity in how these phenotypes are defined, and we examined the relative merit of published definitions using data on HIV-1 seroconverters.

We propose standard definitions for future research of these rare groups: ECs – maintain consecutive HIV-RNA < 50 copies/ml for at least 6 months, RPs – at least one CD4 cell count < 100 cells/mm3 within one year of HIV-1 seroconversion. Evidence shows that less than 1% of individuals are EC and the majority should start treatment to maximise quality and length of life. We supported the ‘when to start’ evidence by demonstrating a 62% reduced risk of serious Aquired Immunodeficiency Syndrome (AIDS), non-AIDS events or death for those immediately initiating combination antiretroviral therapy (cART) (vs not immediately initiating) among those with high CD4 cell counts (>500cells/mm3) and high HIV-RNA (>100,000 copies/ml). We contributed towards the ‘what cART to start’ question; among individuals initiating boosted protease inhibitor, atazanavir might be preferable compared to lopinavir, with 30% lower mortality risk, and 9% lower virological failure risk, which could lead to lower transmitted drug resistance (TDR). We found TDR was significantly decreasing throughout Europe, but remains prevalent (8.5% in 2012); therefore, genetic testing among newly diagnosed remains justifiable.

For most, starting treatment is a lifelong commitment; however, some report on post treatment control (PTC) upon cART cessation. We found individuals having viral blips on cART had shorter time to viral rebound upon stopping treatment, but most do not become PTC and initiate lifelong cART. We investigated three cART associated toxicities, namely hypersensitivity reactions (HSR) due to abacavir (ABC) utilization, AIDS-defining neurological conditions related to cART, and immune reconstitution inflammatory syndrome (IRIS) shortly after cART initiation. We found that HSR from abacavir utilization is low (Incidence Rate (IR)=1.67/100 person-years follow-up), cART with high central nervous system penetration scores increase HIV-1 dementia risk, and apart from mycobacterial infections, unmasking IRIS may not be a cART complication in high-income countries.