CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

746

HIV Drug Resistance Among Individuals on Dolutegravir With Low-Level Viremia in Malawi Newton L. Kalata 1 , Barbara Bighignoli PhD 2 , Sherri Pals 3 , Alinune Kabaghe 1 , Jonathan Mkungudza 2 , Loise Panje 2 , Grace Kusakala 2 , Andreas Jahn 4 , Joep J. van Oosterhout 5 , Bianca Alvarez 3 , Elfriede Agyemang 3 , George Bello 2 , Nellie Wadonda 1 , Juliana D. Da Silva 3 , Duping Zheng 3 , for the Malawi HIV Drug Resistance Team 1 US Centers for Disease Control and Prevention Lilongwe, Lilongwe, Malawi, 2 I-TECH Malawi, Lilongwe, Malawi, 3 Centers for Disease Control and Prevention, Atlanta, GA, USA, 4 Malawi Department of HIV and AIDS, Lilongwe, Malawi, 5 Partners in Hope, Lilongwe, Malawi Background: The clinical consequences of a low-level viremia (LLV) result (HIV-1 RNA 50-999 copies/mL) after a high viral load (VL) result (≥1,000 copies/ mL) and intensive adherence counseling (IAC) are uncertain. The probability of future virological failure may be determined by the presence of drug resistance mutations (DRMs), but WHO does not recommend HIV drug resistance (HIVDR) testing for individuals with LLV. We determined the prevalence of major DRMs among Malawian adults and children on dolutegravir (DTG)-based antiretroviral therapy regimens (DBR) who had LLV following a high VL. Methods: Between November 2022 and March 2023, we enrolled participants at 19 randomly selected high-volume ART clinics in all geographical regions of Malawi. Eligibility criteria were being on a DBR for ≥9 months; return visit after a previous unsuppressed VL; and completing ≥1 IAC session per guidelines. From second plasma samples obtained for VL retesting, specimens with LLV (150-999cps/mL) and high VL (≥1000cps/mL) were genotyped for the protease reverse transcriptase (PRRT) and integrase (IN) regions, using the ThermoFisher® HIV-1 Genotyping kit with Integrase. Results were interpreted using Stanford University HIVDR Database Algorithm (9.5). We present prevalence of major DRMs by drug class and to DTG. Results: Of 74 samples with LLV, 54 were from adults, 20 from children aged 2-14 years. We successfully amplified PRRT and IN in 59.5% and 75.6% of the LLV samples following a high VL, respectively. Amplification success increased with higher VL, with rates for PRRT and IN reaching 79.2% and 87.5%, respectively from ≥300cp/mL. Prevalence of major DRMs to any nucleotide reverse transcriptase inhibitors (NRTI) was 28% (95%CI:14%-42%) and to any non-NRTIs (NNRTI) was 49% (95%CI:33%-64%). Prevalence of major DRMs to DTG was 9% (95%CI:1%-17%). No DRMs to protease inhibitors were observed. The prevalence of major DRMs to any NRTIs, NNRTIs and to DTG in LLV samples was like samples with two consecutive VL ≥1,000 copies/mL (figure). Conclusions: Amplification of PRRT and IN regions was successful in the majority of LLV samples when VL was ≥300cps/mL. Prevalence of major DRMs to DTG among Malawian adults and children with LLV, after a high VL and IAC adherence counselling, was 7% and 13% respectively, comparable to rates observed among adults and children with confirmed virological failure in the same survey. Prospective studies may help explain the clinical relevance of DTG resistance in LLV samples in this setting.

nanopore sequencing may be a suitable alternative to conventional HIVDR testing with excellent concordance between mutation detection by both technologies.

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HIV Drug Resistance by Next-Generation Sequencing After Transition to TLD in Uganda and South Africa Suzanne McCluskey 1 , Winnie Muyindike 2 , Gugulethu Shazi 3 , Victoria Nanfuka 2 , Taing Nandi Aung 1 , Jennifer Giandhari 4 , Daniel Omoding 2 , Bethany Hedt Gauthier 5 , Vincent C. Marconi 6 , Mahomed-Yunus S. Moosa 7 , Deenan Pillay 8 , Richard Lessells 9 , Ravindra K. Gupta 10 , Mark J. Siedner 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 Mbarara University of Science and Technology, Mbarara, Uganda, 3 Africa Health Research Institute, Mtubatuba, South Africa, 4 KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa, 5 Harvard Medical School, Boston, MA, USA, 6 Emory University, Atlanta, GA, USA, 7 University of KwaZulu-Natal, Durban, South Africa, 8 University College London, London, UK, 9 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 10 Cambridge University, Cambridge, UK Background: Studies have identified an increased risk of dolutegravir (DTG) resistance in people with nucleos(t)ide (NRTI) resistance after transitioning from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) to tenofovir/lamivudine/dolutegravir (TLD). However, the frequency of this occurrence in programmatic settings, as well as the impact of NRTI resistance on emergence of DTG resistance minority variants, is not known. Methods: We conducted a prospective cohort study in Uganda and South Africa of adults with HIV (age ≥18) who were in care at public-sector clinics and were transitioned from NNRTI-based ART to TLD. Participant HIV-1 RNA viral loads (VL) were measured on the date of TLD transition and again 24 and 48 weeks later. Illumina next-generation sequencing (NGS) of pol was performed on all specimens with a VL>500 copies/mL. We examined the frequency of HIV-1 resistance mutations at 2%, 5%, and 20% thresholds. Genotypic susceptibility scores (GSS) were calculated using the Stanford algorithm, ranging from 0 (resistant) to 1 (susceptible). We defined resistance as GSS≤0.5. Results: We enrolled 999 participants (median age 44 years (IQR 36-51 years), 61% female) who had been on ART for a median of 7 years (IQR 5-11 years) prior to TLD transition. At TLD transition, 3% of participants (n=27/999) had a VL>500 copies/mL of which 25 (93%) were successfully sequenced, and 15 had resistance to both tenofovir (TDF) and lamivudine (3TC) at the 2%, 5% and 20% thresholds. Of these 15 with confirmed resistance, ten (67%) achieved viral suppression (<50 copies/mL) by 48 weeks (compared to 90% among those with viral suppression at transition, (P=0.015)), two never suppressed, and three were lost to follow-up. At 24 weeks, 1% of participants (n=11/999) underwent NGS, of whom 10 were successfully sequenced. Of these 10, one participant had resistance to both TDF and 3TC at 2-20% thresholds and resuppressed by 48 weeks. At 48 weeks, 2% of participants (n=20/999) had a VL>500 copies/ mL and underwent NGS. However, no study participants, including those with resistance to TDF and 3TC at the time of TLD transition or 24 weeks later, had resistance to DTG at the 2-20% thresholds after one year on TLD. Conclusions: In a cohort of approximately 1,000 people who transitioned from NNRTI-containing ART to TLD in public sector clinics in Uganda and South Africa, resistance to TDF and FTC at transition was not associated with emergent DTG resistance, including minority variants.

Poster Abstracts

CROI 2025 217