CROI 2020 Abstract eBook

Abstract eBook

Poster Abstracts

516 HIV VIROLOGIC FAILURE AND DRUG RESISTANCE AMONG HOSPITAL INPATIENTS IN MALAWI Ankur Gupta-Wright 1 , Katherine Fielding 1 , Elizabeth L. Corbett 1 , Joep J. van Oosterhout 2 , Melanie Alufandika-Moyo 3 , Doug K. Wilson 4 , Daniel Grint 1 , Elizabeth Chimbayo 3 , Judith Heaney 5 , Matthew Byott 5 , Eleni Nastouli 6 , Ravindra K. Gupta 6 1 London School of Hygiene & Tropical Medicine, London, UK, 2 Dignitas International, Zomba, Malawi, 3 Malawi–Liverpool–Wellcome Trust Clinical Rsr Prog, Blantyre, Malawi, 4 Edendale Hospital, Pietermaritzburg, South Africa, 5 University College London Hospitals NHS Trust, London, UK, 6 University College London, London, UK Background: Since antiretroviral therapy (ART) scale-up in high prevalence settings, most HIV+ hospital inpatients are taking ART at admission. However, few data exist on the prevalence of ART failure or HIV drug resistance (DR) in this population. We conducted a large cohort study, nested in a TB screening trial, to describe the proportion of adult inpatients established on ART with virological failure (viral load [VL] >1000 copies/ml), and HIVDR. Methods: Patients were eligible if taking ART for ≥6 months at admission. Stored plasma samples from admission were tested for HIV-1 RNA by real time qPCR. HIVDR mutations were detected by ultra deep sequencing on Illumina MiSeq platform for patients with VL >1000 copies/ml. Interpretation of HIVDR mutations used the Stanford HIVDR Algorithm. Drug resistance was defined as having intermediate or high-level resistance to specific drugs. Results: Overall, 814/1316 (61.9%) patients recruited between Oct 2015 and Sept 2017 were on ART for ≥6 months. 28/814 patients had missing VL. 252/786 (32.1%) of patients had VL >1000 copies/ml. Of these, mean age was 38 years, 62%were female and median CD4 was 60 cells/µL, and 97.6% patients reported being treated with first-line ART (lamivudine[3TC], tenofovir[TDF] and efavirenz[EFV]). Successful sequencing and HIVDR results were available for 237/252 (94.0%). 195/237 (82.3%) of samples were resistant to 3TC, 128/237 (54.0%) to TDF and 219/237 (92.4%) to EFV. Protease and integrase inhibitor resistance was rare (1/233 and 2/225 had major mutations respectively). 84/237 (35.4%) patients had thymidine analog-associated mutations (TAMs). 127/237 (53.6%) of patients were resistant to all 3 drugs in their ART regimen, and 196/237 (82.7%) to at least 2. Assuming patients with VL<1000 copies/ml had no HIVDR, the prevalence of HIVDR to at least 2 drugs was 25.4% in all inpatients on ART ≥6 months. 2-month mortality was higher in patients with HIVDR to ≥2 or more drugs (28.1%) compared to ≤1 drugs (9.8%, p=0.014). Conclusion: These data demonstrate high prevalence of virological failure and HIVDR in hospitalised patients in Malawi. Critically, HIVDR was associated with increased mortality and therefore targeted interventions for virological failure are warranted. The high prevalence of resistance to first-line nucleotide-reverse transcriptase inhibitors is concerning, and has public health implications.

515 PRETREATMENT AND ACQUIRED ANTIRETROVIRAL DRUG RESISTANCE IN 4 AFRICAN COUNTRIES Trevor A. Crowell 1 , Brook Danboise 1 , Ajay Parikh 1 , Allahna L. Esber 1 , Alex Kasembeli 2 , Samoel Khamadi 3 , Michael Iroezindu 4 , Francis Kiweewa 5 , John Owuoth 2 , Joanna Freeman 1 , Jennifer Malia 1 , Linda Jagodzinski 1 , Julie Ake 1 , Christina Polyak 1 , for the AFRICOS Study Group 1 US Military HIV Research Program, Silver Spring, MD, USA, 2 Kenya Medical Research Institute, Nairobi, Kenya, 3 National Institute for Medical Research–Mbeya Medical Research Center, Mbeya, Tanzania, United Republic of, 4 US Army Medical Research Directorate-Africa, Nairobi, Kenya, 5 Makerere University Walter Reed Project, Kampala, Uganda Background: Standardized HIV management protocols that emphasize adherence counseling and forego genotypic testing for HIV drug resistance (HIVDR) have facilitated expanded access to antiretroviral therapy (ART) in resource-limited settings. However, emerging HIVDR could jeopardize the success of such approaches. We characterized HIVDR among ART-naïve and experienced participants in the ongoing African Cohort Study (AFRICOS). Methods: From January 2013 to July 2019, adults with HIV RNA ≥1000 copies/ mL underwent HIVDR testing upon enrollment at 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. ART history was obtained by medical record review. HIV pol subtype was assigned using five tools to achieve a consensus assignment. We calculated resistance scores for specific drugs and tallied major mutations to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) using Stanford HIVDB 8.8 and SmartGene IDNS software. For ART-naïve participants, World Health Organization surveillance drug resistance mutations (SDRMs) were noted. Results: Of 1024 eligible participants, 976 (95.3%) underwent HIVDR testing with median age 36 (interquartile range [IQR] 30-43) years and median CD4 295 (IQR 142-478) cells/mm 3 . Among 710 ART-naïve participants, SDRMs were seen in 75 (10.6%), with highest prevalence in Nigeria (15/90, 16.7%) and Uganda (38/275, 13.8%). Pre-treatment major NNRTI mutations were seen in 57 (8.0%) and NRTI mutations in 29 (4.1%), including 37 (5.2%) with K103N 10 (1.4%) M184V/I, respectively. Among 266 ART-experienced participants, 153 (57.5%) had major NNRTI and 124 (46.6%) major NRTI resistance mutations, again led by K103N (86/266, 32.3%) and M184V/I (116, 43.6%). Variations by country were seen in Pol subtypes (Figure Panel A) and acquired resistance to specific drugs (Figure Panel B), with 51 (19.2%) participants showing medium or high-level resistance to both tenofovir and lamivudine. Conclusion: There was a moderate prevalence of pre-treatment HIVDR. Participants on failing ART regimens had a high burden of HIVDR that potentially limits the efficacy of standard regimens containing tenofovir and lamivudine. Programmatic gaps need to be addressed to prevent HIVDR propagation, particularly with rollout of new first-line ART in Africa. Management strategies that emphasize adherence counseling while delaying ART switch may promote accumulation of drug resistance mutations and should be reconsidered.

Poster Abstracts

517 HIGH LEVELS OF DRUG RESISTANCE IN ART-NAIVE AND PLWH FAILING FIRST-LINE ART IN HAITI Samuel Pierre 1 , Santiago Avila-Rios 2 , John Wu 3 , Claudia García-Morales 2 , Vanessa A. Rouzier 1 , Gaetane R. Julmiste 1 , Patrice Severe 1 , Alexandra Apollon 1 , David Rice 3 , Gustavo Reyes-Terán 2 , Marie Marcelle Deschamps 1 , Bernard Liautaud 1 , Serena Koenig 4 , Jean William Pape 1 1 GHESKIO, Port-au-Prince, Haiti, 2 National Institute of Respiratory Diseases, Mexico City, Mexico, 3 Analysis Group, Inc, Boston, MA, USA, 4 Brigham and Women's Hospital, Boston, MA, USA

CROI 2020 184

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