CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

mutations. TDR conferring high-level resistance to any ART was found in 44 (9.2%) individuals (95% CI: 6.8, 12.2). Cis-MSM were not more likely than TW to have acquired TDR (16.9% vs 16.7%, p=1.00). Year of diagnosis, age, diagnosis as incident or prevalent infection, or residence district were likewise not associated with risk of TDR. Conclusion: TDR prevalence within these cohorts was nearly 4-fold higher than the highest previously reported prevalence in any population in Peru. Over half of observed TDR conferred high level resistance to drugs used in first-line ART, and resistance was largely to NNRTIs. Our findings support the WHO recommendation to consider integrase strand transfer inhibitors in first-line regimens, since empiric use of NNRTIs may often fail in this population. Our study also represents the first differentiated evaluation of TDR in cis-MSM vs TW in Peru and demonstrates that although TW are at higher risk of HIV acquisition than cis-MSM, they are at similar risk of acquiring virus with TDR.

K103N/S, 1.2%; V106M, 1.2%) and InSTI (E92Q, 1.2%; Q95K 1.2%; G163K/R, 1.2%, R263K, 1.2%). Conclusion: We found a low prevalence of pre-treatment NRTI-, NNRTI- and InSTI-associated SDRM and TDR among ART-naïve persons in this large population-based sample of HIV-positive adults from across Botswana. Seroconverters identified in large cohorts and trials provide valuable assessment of TDR mutations on a population level.

Poster Abstracts

531 HIV DRUG RESISTANCE IN ADOLESCENTS AND ADULTS ON SECOND-LINE ART IN KWAZULU-NATAL Benjamin Chimukangara 1 , Benn Sartorius 1 , Richard Lessells 1 , Jennifer Giandhari 1 , Kerusha Govender 1 , Nokukhanya Mdlalose 1 , Reshmi Samuel 1 , Kogieleum Naidoo 1 , Tulio de Oliveira 1 , Pravi Moodley 1 , Raveen Parboosing 1 1 University of KwaZulu-Natal, Durban, South Africa Background: Increasing numbers of HIV-positive adolescents and adults in South Africa are developing virological failure on second-line, protease inhibitor-based antiretroviral therapy (ART) regimens. HIV drug resistance testing is performed routinely in the public sector to determine the need for third-line ART and to inform regimen selection. We conducted an analysis of the routine data to assess the frequency and patterns of HIV drug resistance and to estimate the predicted need for third-line ART. Methods: Cross-sectional analysis of all HIV genotypic resistance tests conducted by the National Health Laboratory Service in KwaZulu-Natal, South Africa (Jan 2015 – Dec 2016), for adults and adolescents (age ≥10 years) on second-line, protease inhibitor-based ART, with two consecutive viral loads ≥1000 copies/mL. We genotyped HIV-1 reverse transcriptase (RT) and protease (PR) genes by Sanger sequencing, and assessed drug resistance using the Stanford HIVdb algorithm. PR mutations were defined as major, accessory, or other according to the HIVdb algorithm. Results: Three hundred and fifty-two people were included (59% female, median age 34 years). The median duration of second-line ART was 30 months (IQR 18-48), and 93%were on a lopinavir/ritonavir-based regimen. Median viral load at time of genotyping was 4.98 log10 copies/mL. Overall, 284/352 (81%) had at least one RT mutation and 117 (33%) had at least one major PR mutation. Among those with major PR mutations, the median number of major PR mutations was 3 (IQR 3-4) and the median number of total PR mutations was 5 (IQR 4-6). Presence of at least one major PR mutation was associated with longer duration on second-line ART (>24 months vs. ≤24 months, aOR 2.28, 95% CI 1.39-3.73) and older age (for each additional year, aOR 1.03, 95% CI 1.01-1.05). Of those requiring third-line ART, 21 (18%) had intermediate or high- level resistance to darunavir/ritonavir, 34 (29%) had intermediate or high-level resistance to etravirine, and 44 (38%) had intermediate or high-level resistance to both tenofovir and zidovudine (Figure). Conclusion: Most people did not have major PR mutations and thus would not need third-line ART. Of those requiring third-line ART, most would need an integrase inhibitor ± etravirine in addition to DRV/r and recycled nucleoside reverse transcriptase inhibitors to form a suitable third-line regimen.

530 PRE-TREATMENT HIV DRUG RESISTANCE IN BOTSWANA

Simani Gaseitsiwe 1 , Sikhulile Moyo 1 , Melissa Zahralban-Steele 2 , Dorcas Maruapula 1 , Tapiwa Nkhisang 2 , Jean Leidner 2 , Ontlametse Bareng 1 , Molly Pretorius Holme 2 , Kara Bennett 3 , Kathleen Wirth 2 , Tendani Gaolathe 1 , Joseph Makhema 1 , Shahin Lockman 2 , Max Essex 2 , Vlad Novitsky 2 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 Harvard University, Boston, MA, USA, 3 Bennett Statistical Consulting, Inc, New York, NY, USA Background: Population-level monitoring of pre-treatment drug resistance (PDR) to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and integrase strand transfer inhibitors (InSTI) in the era of antiretroviral therapy (ART) scale-up and the treat-all strategy, can inform public health strategies and interventions. Methods: We investigated the rate of PDR in a large community cluster- randomized study termed Botswana Combination Prevention Project (BCPP) conducted across 30 Botswana communities in 2013-2018. BCPP enrolled all consenting adult citizen residents age 16-64 who lived in a random sample of approximately 20% of households. Blood specimens from HIV-positive ART- naïve participants including seroconverters were collected from 2013 to 2018. HIV sequences were obtained by long-range HIV genotyping. PDR was identified by the presence of surveillance drug resistance mutations (SDRM) associated with NRTI, NNRTI and major InSTI according to the Stanford HIV DRM database. Viral sequences were screened for G-to-A hypermutations (HM). Results: Among 4473 participants with available viral sequences, 807 (18%) were ART-naïve at the time of sampling. Prevalence of pre-treatment SDRM associated with NRTI-, NNRTI- and InSTI among ART-naïve participants was 1.6%, 4.9% and 1.5%, respectively. The proportion of communities with pre- treatment SDRM and ranges of SDRM across communities are shown in Table 1. Overall, prevalence of SDRMs was low across participating communities. Among NRTI SDRM, M184V was the most common and was identified in 20% of the communities. NNRTI SDRMwere detected in all the communities, with the most common K103N found in 30% of communities. The most common InSTI SDRM was R263K which was identified in 17% of communities. In a subset of 83 ART-naïve seroconverters, the prevalence of TDR mutations associated with NRTI-, NNRTI- and InSTI-resistance was 1.2%, 3.6% and 5.2%, respectively. The most common TDR mutations were: NRTI (K219E/S, 1.2%), NNRTI (A98G, 1.2%;

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