Additional file 1 of Delivering integrated strategies from a mobile unit to address the intertwining epidemics of HIV and addiction in people who inject drugs: the HPTN 094 randomized controlled trial protocol (the INTEGRA Study)

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Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052

<div><p>Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350–550 cells/mm³. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in <i>gag</i>, one in <i>pol</i>, and three in <i>env</i>) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV <i>env</i> regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.</p></div

Associations of baseline HIV diversity and treatment outcomes^*.

<p>Associations of baseline HIV diversity and treatment outcomes^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0177281#t002fn002" target="_blank">*</a>}.</p

Virologic outcomes in early antiretroviral treatment: HPTN 052

<p><b>Introduction:</b> The HIV Prevention Trials Network (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.</p> <p><b>Objective:</b> To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052.</p> <p><b>Methods:</b> 1566 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 > 1000 copies/mL > 24 weeks after ART initiation.</p> <p><b>Results:</b> 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 three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure.</p> <p><b>Conclusions:</b> 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.</p