CROI 2020 Abstract eBook

Abstract eBook

Oral Abstracts

93 INITIATING PREP DURING ACUTE HIV INFECTION: WHAT IS THE RISK FOR ARV DRUG RESISTANCE? Donn J. Colby 1 , Chanjiraporn Pondet 1 , Tippawan Pankam 1 , Prapaipan Plodkratok 1 , Rapee Trichaviroj 2 , Carlo Sacdalan 1 , Eugène Kroon 1 , Siriwat Akapirat 2 , Jintanat Ananworanich 1 , Mark De Souza 1 , Praphan Phanuphak 1 , Sandhya Vasan 3 , Nittaya Phanuphak 1 , for the RV254/SEARCH010 Research Group 1 Thai Red Cross AIDS Research Center, Bangkok, Thailand, 2 Armed Forces Research Institute of Medical Sciences in Bangkok, Bangkok, Thailand, 3 US Military HIV Research Program, Bethesda, MD, USA Background: Pre-exposure prophylaxis (PrEP) is very effective at preventing HIV infection. However, there is risk for antiretroviral drug (ARV) resistance if the 2-drug PrEP regimen is given to individuals with acute HIV infection. Methods: Individuals at risk for HIV infection were screened with 4th generation HIV antibody/antigen (4thG) testing at the Thai Red Cross Anonymous Clinic (TRCAC), the largest HIV testing center in Thailand, performing over 40,000 tests annually. PrEP (TDF/FTC) was offered as part of a combined HIV prevention package, and could be started the same day. Qualitative HIV RNA (Aptima HIV-1, Hologic, USA) was done on 4thG non- reactive specimens using pools of up to 17 specimens to identify acute HIV infection (AHI), with result available in 24-48 hours, and confirmation by quantitative HIV RNA (Roche AmpliPrep/Taqman v2.0). PrEP users had repeat HIV testing and counseling at 1 month, 3 months, and then every 3 months. Results: Through October 2018, 2,442 people started PrEP at the TRCAC; 93%were male and 83%were men who have sex with men (MSM). Median age was 32 (range 17-78) years. Seven individuals, or 1/350, had AHI at PrEP initiation. All 7 with AHI were MSM aged 22-39 years. AHI was identified by pooled qualitative HIV RNA in 5 cases; median quantitative HIV RNA was 317 (range 32-16,780) copies/mL. The remaining 2 cases were diagnosed by reactive HIV serology at the 1-month post-PrEP visit: in both the qualitative HIV RNA was negative, but quantitative HIV RNA on stored pre-PrEP specimens had detectable HIV RNA at 58-86 copies/mL. PrEP was used for a median 14 (range 2-121) days. ARV resistance data were available for 6 cases: 3 cases had single resistance mutations M184V/I, conferring high-level resistance to FTC. No cases had resistance mutations to TDF. The 3 cases that developed FTC-resistance took PrEP for 30, 34, and 121 days. The 3 cases without resistance mutations took PrEP for 2, 7, and 14 days. Conclusion: AHI at PrEP start occurs in 1/350 PrEP users at the TRCAC. Qualitative HIV RNA on pooled samples will identify most, but not all cases of AHI. If AHI is identified early, immediately initiating 3-drug antiretroviral therapy (ART) can prevent ARV drug resistance. FTC resistance begins to emerge after 2-4 weeks of PrEP use. There appears to be lower risk for resistance to TDF. If HIV infection occurs during PrEP use, ARV resistance testing should be performed and ART started immediately. 94 PEPFAR DREAMS INTERVENTION AMONG ADOLESCENT GIRLS AND YOUNG WOMEN IN RAKAI, UGANDA Hadijja Nakawooya 1 , Victor Ssempijja 2 , Dorean Nabukalu 1 , Anthony Ndyanabo 1 , Tom Lutalo 1 , Fred Nalugoda 1 , Ronald H. Gray 3 , Maria Wawer 3 , Steven J. Reynolds 4 , Joseph Kagaayi 1 , Gertrude Nakigozi 1 , Godfrey Kigozi 1 1 Rakai Health Sciences Program, Kalisizo, Uganda, 2 Leidos Biomedical Research, Inc, Frederick, MD, USA, 3 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 Johns Hopkins University School of Medicine, Baltimore, MD, USA Background: In 2016, the Presidents Emergency Plan for AIDS Relief (PEPFAR) initiated the DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe women) programs in10 sub-Saharan Africa countries including Uganda to reduce risk of HIV and domestic violence in adolescent girls and young women aged 15-24 (AGYW). We used population-based data to evaluate the impact of DREAMS in Rakai, south-central Uganda Methods: We identified girls aged 15-24 years who participated in Rakai community cohort study (RCCS) survey between June 2018 - August 2019 and provided information on HIV risk behaviors and were tested for HIV. Risk behaviors were sexual debut, being sexually active, having non marital sexual partners, transactional sex, alcohol use and condom use with non-marital partners. DREAMS packages assessed were; participation in any DREAMS programs, stepping stones (ST) a participatory intervention for HIV prevention and strengthening relationship skills, combined social economic approaches (CSEA), HIV testing and counseling (HTC). Generalized linear models was used to estimate prevalence rate ratios (PRR) and 95% CI associated with risk behavior outcomes.

Results: A total of 1945 AGYW participated in the RCCS; 979 (50.3%) aged 15-19 years of whom 40.5% (397) had participated in the DREAMS programs. Among women aged 20-24, 24.1% (233) had participated in DREAMS. Among girls aged 15-19, ≥10 sessions of ST were associated with significant reduction in non-marital sexual partners (aPRR 0.54 ,95% CI=0.36 -0.93), sexual debut (aPRR 0.61 ,95% CI=0.42 -0.86) and being sexually active (aPRR 0.55,95% CI=0.37 -0.81), while receiving ≥5 ST sessions was associated with a significant reduction in alcohol use (aPRR 0.23,95% CI=0.10 -0.52). Among girls aged 20-24, receiving ST had no significant impact on any risk behaviors. CSEA and HTC were not found to affect risk behaviors in either age groups. Conclusion: In this population-based study , a minimum of 10 ST sessions of the DREAMS ST program are required to reduce risk sexual behaviors among girls aged 15-19 years but no effects were observed with CSEA and HTC. No DREAMS interventions affected risk among women aged 20-24. DREAMS should be modified.

Oral Abstracts

95 STING IN THE TAIL: HOW DNA TRIGGERS IMMUNE RESPONSES TO VIRAL INFECTIONS Zhijian (James) Chen , University of Texas Southwestern, Dallas, TX, USA The presence of DNA in the cytoplasm is a danger signal that alerts the host immune system to eliminate microbial infections, but inappropriate activation of this pathway by self DNA can also lead to autoimmune and autoinflammatory diseases. My talk will focus on our discoveries of cyclic GMP-AMP synthase (cGAS) as an innate immune sensor for cytosolic DNA and microbial pathogens, including HIV. Upon binding DNA, cGAS converts GTP and ATP into cyclic GMP-AMP (cGAMP), which functions as a second messenger that binds and activates the ER membrane protein STING. STING then activates the protein kinases IKK and TBK1, which in turn activates the transcription factors NF-kB and IRF3 to induce type-I interferons and other cytokines that together combat microbial infections. I will discuss our recent work on the biochemical mechanism by which cGAMP activates STING and the downstream signaling cascade. 96 TRIM5 RECOGNITION AND RESTRICTION OF HIV-1 AND RETROVIRUSES Owen Pornillos , University of Virginia, Charlottesville, VA, USA Restriction factors and pattern recognition receptors make up innate or intrinsic cellular defenses against viral infection. TRIM5 proteins are restriction factors and receptors that recognize the incoming cores of retroviruses by binding to the capsid that surrounds and protects the core. Upon capsid binding, TRIM5 proteins accelerate dissociation of the viral core, inhibit reverse transcription of the viral genome, and activate ubiquitin-dependent interferon signaling. TRIM5 proteins contain the tripartite motif fold (RING, B-box, and coiled-coil domains) and a C-terminal domain (SPRY or CypA) that mediates direct binding to retroviral capsids. Retroviral capsids are fullerene structures composed of about 1,500 copies of the viral CA protein, which are organized on a hexagonal lattice composed of about 250 hexamers and exactly 12 pentamers. TRIM5-mediated capsid recognition is driven by avidity, requiring higher-order assembly of multiple TRIM5 protein molecules on the capsid surface. I will discuss a series of studies, which collectively show that TRIM5 binds a retroviral capsid through a mechanism of hierarchical assembly. A limited number of local interaction

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CROI 2020