Why Everyone (Almost) with HIV Needs to Be on Treatment: A Review of the Critical Data

Abstract

Since 2014, a consensus of landmark studies has justified starting antiretroviral therapy (ART) regardless of CD4 count. The evidence for immediate and universal ART is strong, clearly showing individual and population-level benefits, and is supported by all major guidelines groups. Altogether, improvements in ART and recognition of its clinical and epidemiologic benefits justify near-universal ART, preferably as soon after the diagnosis of human immunodeficiency virus (HIV) as possible. Case-based discussions provide a framework to explore the evidence behind the current recommendation for ART for all HIV-positive persons and specific scenarios are discussed in which ART initiation may be delayed.

Keywords: AIDS; Antiretroviral therapy; CD4; Guidelines; HIV; Rapid start; Treatment as prevention.

Fig. 1.

Summary of major advances and clinical trials supporting universal ART for HIV infection regardless of CD4 count. (A) Improvements in ART. The advent of HAART in 1995 led to significant improvements in ART efficacy but initially carried substantial side effects limiting tolerability of regimens. Single-tablet regimens and integrase strand inhibitors changed the landscape of ART after 2006. Modern ART regimens are more potent, durable, and efficacious, with substantially improved tolerability. (B) Clinical benefits. Summary of the 3 randomized clinical trials showing significant reductions in mortality or serious adverse events when ART is initiated at higher CD4 cell counts. (C) Decreased transmission. Three trials showed substantial reduction in HIV transmission among serodiscordant couples, including men who have sex with men. ^a In HPTN 052, no phylogenetically linked infections were observed when HIV-1 infection was stably suppressed in the HIV-positive partner. INSTI, integrase strand transfer inhibitor.