CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

annual prevalence of viremia was calculated for each patient’s last viral load test of a calendar year (≥200 RNA copies/mm 3 ) while mathematical modelling was used to estimate the proportion of HIV-positive GBM living with undiagnosed HIV infection (assuming 100% viremia); these outcomes were combined to estimate ‘community viremia’. A correlation coefficient was calculated to assess the temporal relationship between community viremia and HIV incidence, which was directly measured among HIV-negative sentinel surveillance patients using the repeat testing method. To account for the introduction of HIV pre-exposure prophylaxis (PrEP) in 2016, the analysis was repeated for the 2012-2015 period only. Results: HIV viremia among diagnosed GBM decreased from 27.9% in 2012 to 3.7% in 2017 (p<0.001) while the proportion living with undiagnosed HIV decreased from 10.0% to 8.4% (p=0.01). As shown in Figure 1, annual community prevalence of HIV viremia decreased from 28.6% in 2012 to 12.8% in 2017 (p<0.001) while HIV incidence decreased from 0.88/100 person years in 2012 to 0.22/100 person years in 2017 (p<0.001). The correlation coefficient between annual community prevalence of viremia and HIV incidence from 2012 to 2017 was 0.94 (p<0.001) and for 2012 to 2015 was 0.90 (p<0.001). Conclusion: Decreasing community viremia among GBM was strongly associated with decreasing HIV incidence, including before the implementation of PrEP. Our findings justify the significant investment in HIV treatment initiatives, highlighting that these should be sustained as key elements of HIV prevention.

increased viral suppression (63% vs. 74%, RR=1.18, 95% CI: 1.07-1.29) and the hybrid approach was non-inferior (63% vs. 68%, RR=1.08, 95% CI: 0.98-1.19, p=0.005 for non-inferiority). Both community strategies significantly increased viral suppression among men: community-based ART (73%, RR=1.34, 95% CI: 1.16-1.55) and hybrid approach (66%, RR=1.19, 95% CI: 1.02-1.40), compared to standard of care (54%). Viral suppression was similar for men (73%) and women (75%) in the community ART arm - compared to 54% for men and 73% for women in the clinic arm. Conclusion: Among PLWH who were not on ART, community-based HIV testing, same-day ART initiation, mobile van monitoring and ART resupply, significantly increased viral suppression compared to clinic-based ART. The UNAIDS 90-90-90 goal of 73% suppression was met for men and women in the community-based ART arm, eliminating disparities in viral suppression by gender. Combining decentralized ART initiation and refill is an effective strategy to increase viral suppression which should be implemented and evaluated in different contexts and populations who are not virally suppressed. Animal models have contributed extensively to biomedical investigation and specifically to virtually all areas of HIV research. Animal models provide a complex substrate for the evaluation of novel therapeutic interventions at very early stages that would not be suitable for testing in humans. They allow for exquisite control of variables that are normally impossible to control in human clinical studies such as the strain of virus, inoculum dose, and the timing and route of exposure. In addition to the evaluation of the success of any given intervention, they permit a very complete analysis of its mechanism of action, it’s possible risks such as toxicity and it’s benefits regarding efficacy all in a highly reproducible and reliable manner. Because animal models infected with HIV and treated with antiretroviral therapy can establish HIV persistence in vivo, they provide a unique tool for the evaluation of novel approaches to reverse latency. Furthermore, they allow for the evaluation of novel approaches for the killing of latently infected cells that have been reactivated. Currently, two animal models have been used for the majority of the published research in HIV CURE: non-human primates and humanized mice. There are significant differences between these two models that make them highly complementary to each other. This lecture will review the implementation of both models for HIV cure and provide recent examples of how both models synergize to provide helpful insight into the reproducibility and efficacy of novel interventions aimed at finding an HIV CURE. J. Victor Garcia-Martinez , University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Long-lasting, latently-infected resting CD4+ T cells are the greatest obstacle to curing HIV infection, as these cells can persist despite decades of treatment with antiretroviral therapy. One approach towards a cure is to reactivate HIV from its latent state, thus promoting virus mediated killing and/or facilitating immune recognition and clearance of infected cells. Interventions that successfully reverse latency, when combined with strategies to enhance the antiviral immune response, may result in a reduction in the size of the persistent HIV reservoir. This presentation will review promising latency reversal approaches that take into consideration the immunologic aspects of virus persistence. Emerging results from in vivo studies in humanized mice and nonhuman primates will be discussed. The immunologic and virologic effects of the selected latency reversal agents will be highlighted. 52 T-CELL AND HEMATOPOIETIC STEM CELL GENE THERAPIES FOR HIV CURE Christopher Peterson , Fred Hutchinson Cancer Research Center, Seattle, WA, USA Since the first reported cure of an HIV-1-infected individual over a decade ago, anti-HIV cell and gene therapies have remained a primary focus of numerous HIV cure efforts. To date, hematopoietic stem and progenitor cell (HSPC) transplantation remains the only known path to cure. Although this approach is not feasible for the vast majority of patients, lessons from Berlin, London, and elsewhere have contributed a wealth of knowledge regarding less toxic and more generalizable strategies. This presentation will discuss the current and most promising aspects of cell and gene therapy-based HIV cure approaches, offer a comparison of the pro’s and con’s of targeting HSPCs, 50 IN VIVO MODELS FOR THE EVALUATION OF NOVEL HIV CURE INTERVENTIONS 51 LRA 2.0: IMMUNE-BASED LATENCY REVERSAL Ann Chahroudi , Emory University, Atlanta, GA, USA

Oral Abstracts

49LB COMMUNITY ART INCREASES VIRAL SUPPRESSION AND ELIMINATES DISPARITIES FOR AFRICAN MEN Ruanne V. Barnabas 1 , Heidi van Rooyen 2 , Stephen Asiimwe 3 , Alastair van Heerden 2 , Deenan Pillay 4 , Adam Szpiro 1 , Torin Schaafsma 1 , Meighan Krows 1 , Kombi Sausi 2 , Nsika Sithole 5 , Bosco Turyamureeba 3 , Peter Ehrenkranz 6 , Jared Baeten 1 , Connie L.Celum 1 , for the The DO ART Study Team 1 University of Washington, Seattle, WA, USA, 2 Human Sciences Research Council, Pretoria, South Africa, 3 Kabwohe Clinical Research Center, Kabwohe, Uganda, 4 University College London, London, UK, 5 Africa Health Research Institute, Mtubatuba, South Africa, 6 Bill and Melinda Gates Foundation, Seattle, WA, USA Background: Community-based HIV testing, same-day ART start, and decentralized monitoring and ART refills could increase viral suppression, particularly among priority groups who engage less in clinic-based HIV care, community-based ART compared to clinic services in rural and peri-urban areas of Sheema District, Uganda, and KwaZulu Natal, South Africa - the Delivery Optimization for ART (DO ART) Study. Community-based HIV testing was conducted at home and in mobile vans. People living with HIV (PLWH) who were not on ART with CD4>100 cell/mL were eligible for randomization to: 1) same-day community-based ART start with quarterly monitoring and ART refills through mobile vans, 2) ART start at the clinic with monitoring and refills through mobile vans in the community (hybrid approach); or 3) clinic-based ART (standard of care). The primary outcome was HIV viral suppression at 12 months, assessed by modified intent to treat analysis using regression analysis; testing first for superiority and then non-inferiority (relative 5%) if not superior. Results: Between May 2016 and March 2019, 1,531 PLWH not on ART were randomized: 708 (46%) were men and 36%were <30 years. Retention at 12 months was 95%. Compared to standard clinic care, community-based ART such as men who are more likely to have detectable HIV viral load. Methods: We conducted a multi-site, household randomized trial of

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CROI 2020