There have been substantial advances in the use of antiretroviral drugs (ARVs) for the treatment and prevention of HIV infection since the last version of these recommendations in 2014,¹ warranting an update to the recommendations.

Antiretroviral therapy (ART) consists of a combination of drugs targeting the human immunodeficiency virus (HIV) life cycle with the aim of stopping HIV replication and preserving or restoring immune function. Since publication of the last recommendations in 2012,¹ there is more evidence supporting the initiation of ART regardless of CD4 cell count. New cohort data provide compelling evidence for the effectiveness of treatment to prevent transmission in heterosexual and same-sex couples.^2-4 In addition, morbidity and mortality from non–AIDS-defining illness did not differ from that of the general population if CD4 cell counts of greater than 500/µL were achieved.⁵ Several reports suggest that if ART is started early during acute infection, prolonged virologic suppression after discontinuation of ART may be achievable in rare cases.^6,7 New drugs with high potency, low toxicity, and good tolerability increase the feasibility of early, lifelong treatment. Even patients with prior treatment failure and multidrug resistance can usually be treated with suppressive ART. Recommendations provided herein for the optimal management of adults with HIV infection are based on the latest developments and available evidence.

To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In addition, we evaluated functional variants, copy-number polymorphisms, epistatic interactions, and biological pathways. This study thus represents a comprehensive assessment of common human genetic variation in HIV-1 control in Caucasians. The ability to spontaneously control HIV-1 upon infection is highly variable between individuals. To evaluate the contribution of variation in human genes to differences in plasma viral load and in disease progression rates, we performed a genome-wide association study in >2,500 HIV–infected individuals. This study achieved two goals: it completed the analysis of common variation influencing viral control, and it re-assessed the majority of previously reported genetic associations. We show that genetic variants located near the HLA-B and HLA-C genes are the strongest determinants of viral control, and that other independent associations exist in the same region of chromosome 6, the Major Histocompatibility Complex, known to contain a large number of genes involved in immune defense. We could not replicate most of the previously published associations with HIV candidate genes in this large, well-characterized cohort. Overall, common human genetic variation, together with demographic variables, explains up to 22% of the variability in viral load in the Caucasian population.

Resistance to antiretroviral drugs remains an important limitation to successful human immunodeficiency virus type 1 (HIV-1) therapy. Resistance test