CROI 2018 Abstract eBook

Abstract eBook

Oral Abstracts

months (37.9% to 60.6%, p=0.002 as compared to placebo (55.6% to 40.7%, p=0.294). The XR-NTX group was also more likely than placebo to improve to VS (30.3% vs.18.5%); maintain VS (30.3% vs. 27.3); and less likely to lose VS (7.6% vs. 33.3%) at 6 months (p=0.041). Independent predictor of VS was only receiving XR-NTX (aOR=2.90; 95% CI=1.04-8.14, p=0.043). There were no serious adverse events in either study. Conclusion: XR-NTX can improve or maintain HIV VS after release to the community for incarcerated PLH with OUD and AUD, thus benefiting both individual and public health.

ART (or those who recently initiated ART), mortality was also two-fold higher among those on ART for ≥ 1 year compared with individuals without HIV.

Oral Abstracts

97 HIGHER MORTALITY IN HIV - INFECTED VS - UNINFECTED ADULTS DESPITE ART, BOTSWANA

Tendani Gaolathe 1 , Kathleen Wirth 2 , Molly Pretorius Holme 2 , Etienne Kadima 1 , Unoda A. Chakalisa 1 , Kutlo Manyake 1 , Joseph Makhema 1 , Mompati O. Mmalane 1 , Jean Leidner 2 , Scott Dryden-Peterson 2 , Kathleen M. Powis 2 , Mosepele Mosepele 1 , Refeletswe Lebelonyane 3 , Lisa A. Mills 4 , Shahin Lockman 2 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Harvard University, Cambridge, MA, USA, 3 Ministry of Health, Gaborone, Botswana, 4 CDC Botswana, Gaborone, Botswana Background: Over the past 15 years, mortality in HIV-infected adults has declined markedly due to antiretroviral treatment (ART) coverage in southern African nations. The population-level impact of ART scale-up on the relative mortality among HIV-infected vs. –uninfected adults in these settings is unknown. Methods: We prospectively followed a random, population-based sample of HIV-infected and –uninfected adults (age 16-64 years) in 30 rural and peri-urban communities in Botswana, as part of an HIV prevention trial (the Botswana Combination Prevention Project). In this analysis, we present mortality rates approximately 1 year after enrollment, according to baseline HIV and ART status. Cox proportional hazard models accounting for clustering were used, and additional age- and sex-adjusted analyses were performed Results: We enrolled and followed 13,088 adults from 30 communities (median age 32.6 years, 64% female), 3,667 (28%) of whomwere HIV-infected. At enrollment, 2,653 (72%) of HIV-infected individuals were already on ART (median CD4 of those not on ART 404 cells/mm 3 ). Median follow-up time was 12.6 months (IQR 12.2, 29.1), and vital status was available for 11,981 (92%) of 13,088. Overall, 84 (0.70%, 95%CI 0.54–0.91%) died. The crude mortality rate per 100 person-years was significantly higher in HIV-infected vs. in HIV- uninfected individuals (0.93 vs. 0.26, adjusted hazard ratio [aHR] 3.0, 95%CI 1.9-4.8). In HIV-infected participants, ART was protective: not being on ART (aHR 2.3, 95%CI 1.2-4.4) or being on ART for less than 1 year (aHR 3.8, 95%CI 1.7-8.5) were each associated with significantly higher mortality compared with being on ART for >1 year. Mortality was significantly higher in HIV-infected persons on ART for >1 year compared with HIV-uninfected adults (aHR 1.8, 95%CI 1.0-3.2). Among HIV-infected individuals who died, infection was a more frequent cause of death than among HIV-uninfected individuals who died; deaths from cancer and other chronic medical conditions were common in both groups (Table 1). Conclusion: Despite high population ART coverage approaching 90 - 90 - 90 targets, mortality among HIV - infected adults remains 3 - fold higher than in uninfected individuals. Although mortality is highest among those not yet on

98 HIV ENV: STRUCTURE, FUNCTION, AND INHIBITION THEREOF Peter D. Kwong , National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA Like other type 1 fusion machines, the HIV-1 envelope (Env) trimer transitions between prefusion, pre-hairpin intermediate and postfusion conformations to merge viral and host cell membranes during virus entry. In addition to utilizing conformational change for entry, the HIV-1 Env trimer also uses conformational change to evade the humoral immune response. Single molecule FRET measurements indicate that the Env trimer spontaneously (and reversibly) transitions between three prefusion states: a pre-triggered state 1, a preferred intermediate state 2, and an activated state 3 that can be stably induced by receptor/co-receptor binding. This talk summarizes recent data connecting smFRET-defined states with high-resolution structures and details how small molecules and antibodies can freeze select Env conformations to inhibit entry. In specific, we have recently solved the structure of the HIV-1 Env trimer with small molecule inhibitors, including BMS-626529, the prodrug version of which is currently in late stage clinical trials. This structure indicates BMS-626529 to recognize an induced binding pocket and to prevent Env from transitioning to state 3. Meanwhile, most broadly neutralizing antibodies appear to bind preferentially to states 1 or 2, although many can also bind to state 3. By contrast, poorly or non-neutralizing antibodies either do not recognize the Env trimer or only recognize state 3, not states 1 or 2. These insights into antibody recognition and Env conformation are now being applied to the development of vaccines aimed at eliciting immune responses capable of neutralizing the diverse neutralization-resistant isolates that typify HIV-1 transmission. Recent results indicate the N terminus of the fusion peptide to be exposed in state 2 and that focusing the immune response to this functionally critical site can elicit humoral immune responses in mice and non-human primates with ~30% HIV-1 neutralization breadth. 99 ARCHITECTURE OF THE HIV-1 REVERSE TRANSCRIPTASE INITIATION COMPLEX Elisabetta Viani Puglisi , Stanford University, Stanford, CA, USA Reverse transcription of the HIV-1 RNA genome into double-stranded DNA is a central step in infection and a common target of antiretroviral therapy. The reaction is catalyzed by viral reverse transcriptase (RT) that is packaged in an

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CROI 2018