Virologic outcomes in early antiretroviral treatment: HPTN 052

Abstract

INTRODUCTION The HPTN 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. OBJECTIVE To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. METHODS 1,566 participants who had a viral load (VL) >400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 <250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs >1,000 copies/mL >24 weeks after ART initiation. RESULTS Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by 3 months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. CONCLUSIONS Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection–Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study

“…Moreover, it has been shown that starting ART in the initial phase of infection might allow for the preservation of the immune system, and specifically of: (1) the CD4+ T-cell count and CD4/CD8 ratio [13][14][15]; (2) HIV-specific immune responses, preserving the ability to control viral replication [16]; (3) higher levels of mucosal and systemic Th17 cells; (4) lower levels of B-lymphocyte activation, and (5) reconstitution of the NK phenotype [12, 17 ,18]. Despite the fact that evidence from multiple studies strongly supports the benefit of early ART in AEHI [19][20], the optimal ART strategy to achieve rapid viral suppression, optimal immune recovery, and longer durability of regimens needs to be clarified.…”

Rapid initiation of antiretroviral therapy for people living with HIV

“…Lower loss to follow‐up may increase the absolute number of PLWH achieving viral suppression (Pilcher 2017; Rosen 2016), reduce HIV transmission, and HIV‐related morbidity, and mortality (Eshleman 2017; Lesko 2016; Mfinanga 2015). The HIV continuum of care is however a complex process, in which every cascade step is influenced by multiple factors, as illustrated in our conceptual model (Figure 1).…”

Inferring transmission heterogeneity using virus genealogies: Estimation and targeted prevention

“…Infected individuals remain infectious until they are diagnosed-it is then assumed that individuals are immediately treated such that they no longer are infectious and instead immune [20]. The time to diagnosis, or more precisely to successful treatment, is assumed to be exponentially distributed with rate γ common for all individuals (hence random and with no systematic heterogeneity).…”