CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

678

Emerging Dolutegravir Resistance in Lesotho Nadine Tschumi 1 , Blaise Lukau 2 , Lipontšo Motaboli 2 , Katleho Tlali 2 , Mpho Kao 2 , Mathebe Kopo 2 , Moleboheng Mokebe 2 , Klaudia Naegele 1 , Irene Ayakaka 3 , Karoline Leuzinger 1 , Jennifer A. Brown 1 , Niklaus D Labhardt 1 1 University Hospital Basel, Basel, Switzerland, 2 SolidarMed, Partnerships for Health, Maseru, Lesotho, 3 SolidarMed, Maseru, Lesotho Background: Since 2018, the World Health Organization has recommended dolutegravir- (DTG-) based antiretroviral therapy (ART) as the preferred regimen for most people with HIV. Most African countries have thus shifted from non nucleoside transcriptase inhibitor- (NNRTI-) to DTG-based ART, often without requiring prior viral suppression and without access to resistance testing in case of viremia. National programs report higher rates of viral suppression since changing to DTG, including among people with unsuppressed viremia before the change. To date, few DTG resistance-associated mutations (RAMs) have been reported from African routine care cohorts. Methods: This study aims to assess emerging DTG RAMs among participants of the Viral Load Cohort North-East Lesotho (VICONEL). Eligibility criteria were i) written informed consent, ii) having changed from NNRTI- based to DTG-based ART, and iii) subsequently having ≥2 viral loads ≥50 copies/mL (c/ mL), including at least one available sample ≥500 c/mL and taken ≥18 months after changing to DTG (data closure: April 20, 2023). For each participant, the last-available sample with a viral load ≥500 c/mL, as well as previous samples if DTG RAMs were detected, were analysed near full-length HIV sequencing for genotypic resistance testing (GRT). RAMs were interpreted using the Stanford HIVdb (9.5.0). Results: Among 14'881 VICONEL participants who had changed to DTG ≥18 months before data closure, 75 (0.5%) fulfilled the inclusion criteria (median age at change 27 years, 57% female). GRT were available for 54/75 (72%). Among these 54 participants (median age at change 24 years, 54% female), high-level and low-level resistance to DTG was detected in five and one, respectively. None of these six had a documented viral load <50 c/mL <6 months before changing to DTG (Figure). DTG RAMs detected were H51Y (participant 6 in Figure), E92Q (6), G118R (1,2,3,5), E138A (3), E138K (1,2,3,5), N155H (4), and R263K (1,4,5). GRT data from before the change to DTG were available for three of these six participants (participants 1, 3, 6 in Figure): in all cases, RAMs against the nucleoside reverse transcriptase inhibitor backbone but no RAMs in the integrase region were recorded before change. Conclusion: Among participants who changed from NNRTI- to DTG-based ART with sustained viremia ≥18 months after change, DTG resistance was more frequent than expected, highlighting the need for national programs to ensure close follow-up with access to GRT for this specific subgroup.

677

DTG Resistance in Patients with Previous ARV Experience and Viremia in Kenya Receiving DTG-Based ART Leonard Kingwara 1 , Vera M. Onwonga 1 , Rukia S. Madada 1 , Peter Lokamar 1 , John N. Kiiru 1 , James Wagude 1 , Barbara Mambo 1 , Caroline Mwangi 1 , Rose Wafula 1 , Kerri Penrose 2 , Urvi M. Parikh 2 , Bhavna Chohan 3 1 Ministry of Health, Nairobi, Kenya, 2 University of Pittsburgh, Pittsburgh, PA, USA, 3 University of Washington, Seattle, WA, USA Background: Kenya began rolling out DTG-based ART in late 2017 as both 1st- and 2nd-line treatment for adults and children living with HIV (PLHV). HIV drug resistance (HIVDR) data is limited in PLHIV failing DTG-based ART. We used the cyclical-acquired HIVDR (CADRE) methodology to assess the frequency of HIVDR mutations in PLHIV with detectable viremia on DTG-based ART between January and March 2023 in Kenya. Methods: The National AIDS and STI control program(NASCOP) collected remnant plasma from HIV viral load testing between January and March 2023 from PLHIV in 15 high/moderate HIV prevalence counties receiving DTG-based ART through the Kenya HIV Care and Treatment Program. We received 191 samples from PLHIV out of the expected CADRE-calculated sample size of 622. Plasma was genotyped using Thermo-Fisher Sanger pro/RT/int sequencing on samples >200 cp/mL and mutations were identified using Stanford HIVdb v9.5. Clinical and demographic data on treatment history and duration was obtained from viral load request forms. Results: Samples were available for 138 of 332 (42%) adults, median age 36 [IQR 26-45] years, and 52 of 290 (18%) children (median age 15 [IQR 12-16] years) with 1 of unknown age. 146 of 191 total (76%) received DTG as 2nd-line, with 141 on NNRTI-based ART and 5 on PI-based ART for a median of 5 [IQR 2-8] years before switching to DTG-based ART; the remaining PLHIV (45 of 191; 24%) received DTG as 1st-line. 56 of 191 (29%) had HIV-1 VL >200 cp/mL; 44 of 56 (79%) were successfully genotyped. 7 of 32 (22%) ART-experienced PLHIV had INSTI resistance with E138K alone or with up to three additional major INSTI mutations including T66I, G118R, G140A, S147G, Q148KNR, and/or N155H. All 7 also had multiple NNRTI and NRTI DRMs including 5 with thymidine analogue mutations. 1 of 12 (8%) PLHIV on 1st-line TLD had VL 296 c/mL after 17 months on ART and the INSTI DRM R263K with only K70Q and M184V in RT (Table). Conclusion: The frequency of INSTI HIVDR was high (22%) in ART-experienced PLHIV on DTG-based ART used as 2nd-line ART and lower (8%) in ART-naïve adults using DTG for 1st-line ART, suggesting the risk of failing DTG may be higher in a background of pre-existing mutations to NRTIs in the regimen. Our data emphasizes the importance of HIVDR monitoring in PLHIV on DTG-based ART given the anticipated introduction of long-acting cabotegravir for HIV prevention and the potential for transmission of INSTI-resistant virus from those on failing DTG-based ART to cabotegravir PrEP recipients.

Poster Abstracts

679

Resistance to Second-Generation InSTIs in Mexican PLWH: Emergence of the R263K Mutant Jannette A. Juárez-González, Emiliano Ivan Sanchez Cruz, Luis A. Angulo Medina, Roberto A. Rodriguez-Díaz, Elsa Y. Vidal-Laurencio, Sofía Sierra Vásquez, Luis Enrique Soto Ramírez Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico Background: Clinical trials and real-life experience have shown limited resistance development after use of second generation INSTIs, specially in first line. One of the mutants found in this scenario is the R263K, a nonpolymorphic mutation that alone reduces DTG, BIC, and CAB susceptibility about 2-fold. This mutation has been described in first line failure to second generation INSTIs.

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