CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

Methods: Subtype B (n=7) and non-B subtypes (n=5) strains were amplified from PBMCs of primary HIV infections through co-culture in cord blood mononuclear cells (CBMCs). CBMCs were serially passaged in escalating concentrations of DTG, EVG, BIC, and/or CAB for 36-46 weeks. Sanger and ultradeep sequencing ascertained the acquisition of resistance mutations under selective drug pressure at weeks 8-9, 16, 24-30, and 43-46. Results: Parallel in vitro selections found resistance mutations in more strains for EVG (12/12), followed by CAB (8/12), and BIC and DTG (6/12 each). For EVG, T66I (n=8), E92 G/V/Q (n=3) or R263K (n=1) were followed by the accumulation of mutations leading to viral escape and high-level resistance (bold). With CAB, at the final passages, 8/12 selections resulted in R263K (n=3), Q148K, S153Y, or S147G with acquisition of Q148R/K in two strains leading to viral escape. For DTG and BIC at the final passages, 6/12 strains had singleton mutations R263K, S153Y or H51Y which conferred low-level (<3-fold) resistance and reduced replicative fitness, precluding escalations in DTG and BIC beyond 5-25 nM. Conclusion: There is a high genetic barrier to resistance to BIC and DTG compared to CAB and EVG. Emergent resistance mutations by singleton mutations, R263K or S153Y confers <1.5-3 resistance retaining antiviral activity to DTG and BIC, whereas more complicated patterns of high-level resistance were selected by CAB and EVG. Ongoing studies will deduce resistance to INSTIs in larger panel of viral strains.

(compared to Blantyre, Malawi [p=0.003], Cape Town, South Africa [p=0.022], and Soweto, South Africa [p=0.016]), and men who reported that they were engaged in HIV care with current or prior ARV drug use (p<0.001). Conclusion: Most of the HIV-infected men screened for participation in HPTN 075 were not on ART at the screening visit, and many of those on ART were not virally suppressed. Among those who were taking ARV drugs and were not virally suppressed, more than half had drug-resistant HIV and many were at risk of acquiring additional resistance. These findings underscore the importance of improving HIV care for African MSM. 551 ARV DRUG USE AND HIV DRUG RESISTANCE AMONG YOUNG WOMEN IN SOUTH AFRICA (HPTN 068) Yinfeng Zhang 1 , Mariya V. Sivay 1 , Sarah E. Hudelson 1 , Jing Wang 2 , Yaw Agyei 1 , William Clarke 1 , Autumn Breaud 1 , Erica Hamilton 3 , Kathleen Kahn 4 , Xavier Gomez-Olive 4 , Catherine MacPhail 5 , James P. Hughes 6 , Audrey Pettifor 7 , Susan H. Eshleman 1 1 The Johns Hopkins University, Baltimore, MD, USA, 2 Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA, 3 FHI 360, Durham, NC, USA, 4 University of the Witwatersrand, Johannesburg, South Africa, 5 University of Wollongong, Wollongong, Australia, 6 University of Washington, Seattle, WA, USA, 7 University of North Carolina Chapel Hill, Chapel Hill, NC, USA Background: Antiretroviral (ARV) drugs are widely used for HIV treatment and prevention, and may be used for other reasons in some populations. We analyzed ARV drug use and HIV drug resistance among young women enrolled in the HIV Prevention Trials Network (HPTN) 068 study. HPTN 068 was conducted in rural northeast South Africa and evaluated the impact of cash transfer on HIV incidence conditional on high school attendance (study period: 2011-2015). Methods: In the main study, young women were enrolled in high school and were tested for HIV infection annually until their expected graduation date. Some women had a post-graduation follow-up visit 1-2 years later. ARV drug testing was performed using a qualitative assay based on high resolution mass spectroscopy that detects 20 ARV drugs in five drug classes. HIV genotyping was performed using the ViroSeq HIV-1 Genotyping System v2.8. Results: We analyzed two sample sets: (1) enrollment samples (2,526 women: 80 infected; 2,446 uninfected), and (2) samples from the first HIV-positive visit (162 seroconverters; 107 in the main study, 55 in the follow-up study). ARV drugs were detected in enrollment samples from 10 (12.5%) of 80 HIV-infected women (six had 1 NNRTI with 1 or 2 NRTIs; three had 1 NNRTI alone; one had 1 NRTI alone). ARV drugs were also detected in samples from 16 (9.9%) of 162 seroconverters (14 had 1 NNRTI with 1 or 2 NRTIs; two had 1 NNRTI alone). None of 2,446 HIV-uninfected women had ARV drugs detected. Among the 242 HIV- infected women (80 infected at enrollment; 162 seroconverters), 211 (87.2%) had viral loads >400 copies/mL. HIV genotyping results were obtained for 198 of the 211 women (67 infected at enrollment; 131 seroconverters); this included 7 (26.9%) of the 26 women who had ARV drugs detected. Eighteen (9.1%) of the 198 women had NNRTI resistance, including 9 (13.4%) of 67 women infected at enrollment and 9 (6.9%) of 131 seroconverters; five of the 18 women also had NRTI resistance. Conclusion: In this cohort, 12.5% of the women who were HIV infected at enrollment and 9.9% of the women with new HIV infection were taking ARV drugs. ARV drugs were not detected in >2,400 HIV-uninfected women. Among women who were not virally suppressed, 9.1% had NNRTI resistance and 2.5% had multi-class resistance. This study provides novel information about ARV drug use and HIV drug resistance among young women in rural South Africa. These findings may help inform future studies using ARV drugs for HIV prevention and treatment in this population. 552 PREVALENCE OF NRTI, NNRTI AND PI MUTATIONS ACROSS BOTSWANA IN 2013 − 2015 Sikhulile Moyo 1 , Simani Gaseitsiwe 1 , Melissa Zahralban-Steele 1 , Dorcas Maruapula 1 , Baitshepi Mokaleng 1 , Terence Mohammed 1 , Erik van Widenfelt 1 , Madisa Mine 2 , Elliot G. Raizes 3 , Etienne Kadima 1 , Tendani Gaolathe 1 , Joseph Makhema 1 , Shahin Lockman 1 , Max Essex 1 , Vlad Novitsky 4 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Ministry of Health, Gaborone, Botswana, 3 CDC, Atlanta, GA, USA, 4 Harvard University, Cambridge, MA, USA Background: In the context of antiretroviral therapy (ART) scale-up and treat-all strategy, population-level monitoring of HIV drug resistance is critical. This study aimed to survey the prevalence of HIV-1 mutations associated with

Poster Abstracts

550 ARV DRUG USE AND HIV DRUG RESISTANCE AMONG MSM IN SUB- SAHARAN AFRICA (HPTN 075) Yinfeng Zhang 1 , Jessica M. Fogel 1 , Xu Guo 2 , William Clarke 1 , Autumn Breaud 1 , Vanessa Cummings 1 , Erica Hamilton 3 , Arthur Ogendo 4 , Noel Kayange 5 , Ravindre Panchia 6 , Karen Dominguez 7 , Ying Q. Chen 2 , Theodorus Sandfort 8 , Susan H. Eshleman 1 1 The Johns Hopkins University, Baltimore, MD, USA, 2 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 3 FHI 360, Durham, NC, USA, 4 Kenya Medical Research Institute, Kisumu, Kenya, 5 Malawi Coll of Med–Johns Hopkins Univ Rsr Proj, Blantyre, Malawi, 6 University of the Witwatersrand, Soweto, South Africa, 7 University of Cape Town, Cape Town, South Africa, 8 Columbia University, New York, NY, USA Background: African men who have sex with men (MSM) are at increased risk of HIV infection and may have limited access to quality health care because of social discrimination, stigmatization or criminalization. The HIV Prevention Trials Network (HPTN) 075 evaluated the feasibility of recruiting and retaining MSM in sub-Saharan Africa, in preparation for HIV prevention trials. The study enrolled HIV-infected and HIV-uninfected men at four sites in Kenya, Malawi, and South Africa. We analyzed antiretroviral (ARV) drug use and HIV drug resistance among HIV-infected men screened for participation in HPTN 075. Methods: Laboratory testing was performed using plasma samples collected at the screening visit. ARV drug testing was performed using an assay that detects 20 ARV drugs in 5 drug classes. HIV viral load was measured for men who had ARV drugs detected. Viral suppression was defined as a viral load <400 copies/mL. HIV drug resistance testing was performed using the ViroSeq HIV-1 Genotyping Assay v3.0 for men who had ARV drugs detected with a viral load ≥400 copies/mL. Men who reported knowledge of their HIV status were asked if they were in care and if they had been prescribed ARV drugs for HIV treatment. Results: ARV drugs were detected in samples from 63 (34.4%) of 183 HIV- infected men at screening. In 57 (90.5%) of the 63 cases, the drugs detected were consistent with ARV treatment (ART; unusual combinations of drugs were detected in two of the 57 cases; efavirenz alone was detected in the remaining six cases). Eleven (17.5%) of the 63 men with ARV drugs detected were not virally suppressed; 6 of those men had drug-resistant HIV (4 NNRTI+NRTI resistance; 1 NNRTI resistance alone; 1 NRTI resistance alone). In multivariate logistic regression, detection of ARV drugs was more frequent among older men (26-44 years; compared to 18-25 years p=0.019), men from Kisumu, Kenya

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