CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

988

Emerging Integrase Resistance in the Perinatal Virtual Clinic: The Need for Protease Inhibitors Caroline Foster 1 , Ayolola Eni-Olutu 2 , Angela Bailey 3 , Alasdair Bamford 4 , Hermione Lyall 1 , Julia Kenny 5 , Leon Levin 6 , Katherine R. Simon 7 , Tiago Milheiro Silva 8 , Neil Tickner 1 , Anna Turkova 9 , Steven Welch 10 , Nicola Mackie 1 , for the Perinatal Virtual Clinic at Imperial College 1 Imperial College Healthcare NHS Trust, London, United Kingdom, 2 Imperial College London, London, United Kingdom, 3 Buckinghamshire Healthcare NHS Trust, Oxford, United Kingdom, 4 Great Ormond Street NHS Foundation Trust, London, United Kingdom, 5 Evelina London Children's Hospital, London, United Kingdom, 6 Right to Care, Johannesburg, South Africa, 7 Baylor College of Medicine Children's Foundation, Lilongwe, Malawi, 8 Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal, 9 UCL Great Ormond Street Institute of Child Health, London, United Kingdom, 10 University Hospitals Birmingham, Birmingham, United Kingdom Background: The perinatal virtual clinic (PVC); a monthly multidisciplinary forum reviews complex management decisions for children and adolescents living with HIV (CALWHIV) referred from high (HIC) and low/middle income countries (L/MIC). We investigated the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) necessitating protease inhibitor (PI) based regimens. Methods: Review of 5 years of PVC referrals; October 2018-September 2023. Demographic data included age, sex, country of residence. Clinical data included: comorbidities, antiretroviral therapy (ART) history, HIV viral load (VL) and CD4 count. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database and CALWHIV with emergent INSTI-DRMs described. Results: 341 CALWHIV were discussed; 51 (15%) from L/MIC, 106 (31%) with virological failure (VF) of which 96 (91%) had resistance sequences available. 17/96 (18%) had INSTI-DRMs, median (IQR) age 11 (6-14) years, weight 24 (17-49) kg, CD4 430 (77-805) cells/ul, and VL 35,000 (2380-132000) c/ml. Current region; Africa (7), Americas (2), Europe (5) and Western Pacific (2), with 11 (65%) from L/MIC. 12/17 (74%) were referred in 2022/23. Six had current AIDS diagnoses and 4 concomitant antimycobacterial therapy. 15/17 were on second/subsequent ART (median 2 [IQR 2-3] prior regimens) comprising nucleoside reverse transcriptase inhibitors (NRTI) with: dolutegravir (DTG) (7), raltegravir (4), DTG and darunavir/ritonavir (DRV/r) (4). One adolescent failed first line DTG/lamivudine (3TC)/abacavir (ABC) with E138K S147G Q148R N155H M184V (high-level DTG resistance (R)) after 5 years. A second suppressed on nevirapine/3TC/ABC for 11 years simplified to DTG/3TC/ABC but failed 4 years later with an R263RK (intermediate DTG-R). Cumulative resistance by number of ART classes was 1 (1), 2 (5), 3 (7), 4 (4) with DRMs described in Table 1. PVC recommendations were for tenofovir (TXF) with lamivudine or emtricitabine, using split adult tablets in 5, with DRV/r (17), twice daily (BD) in 6, with BD DTG (6), and novel agents sought for 2. Conclusion: INSTI resistance is emerging in CALWHIV, most commonly in highly treatment experienced individuals from L/MIC. This highlights the global need for access to DRV/r, TXF and novel classes, including formulations for children <35kg. Pediatric HIV Hotspots: Machine Learning and Geostatistical Analysis for Enhanced Case Finding Amobia A Onovo 1 , Kathleen Handley 2 , Gonza Omoro 3 , Jonah Maswai 3 , Reuben Ngumo 4 , John Owuoth 4 , Rosemary Mrina 1 , Patricia Agaba 1 1 Henry M Jackson Foundation, Bethesda, MD, USA, 2 Walter Reed Army Institute of Research, Bethesda, MD, USA, 3 Walter Reed Army Institute of Research, Kericho, Kenya, 4 Henry M Jackson Foundation, Kisumu, Kenya Background: Global data indicates a significant disparity in HIV case finding and treatment coverage between pediatrics and adults. To enhance HIV case finding and treatment for pediatrics within the HIV care continuum, targeting significant hotspot areas may be essential. This study investigates spatial patterns of the disease in Kenya, identifying hotspots to prioritize program resources for epidemic control efforts among pediatrics. Methods: We utilized national HIV testing data for HIV-positive pediatrics under 15, combined with 2022 Kenya Demographic and Health Survey indicators, to train various supervised machine learning (ML) algorithms.

2019 participants aged ≥2 years had a change from baseline BAZ ≤1 to newly overweight or obesity-level BAZ. No AEs of weight increase were reported. Conclusion: Children and adolescents initiating DTG had a small overall increase in mean BAZ over 48 weeks in P1093 and IMPAACT 2019 and remained within mean BAZ >−1 to ≤1 at Week 48. Some participants with BAZ <−2 at baseline had a more marked increase in BAZ over 48 weeks of treatment, potentially suggesting a return to health.

Poster Abstracts

987

Pharmaco-Virological Outcome and Resistance Profiles Among Togolese Adolescents Transitioning to DTG Yao R. Konu 1 , Elom Takassi 2 , Gilles Peytavin 3 , Nina Dapam 2 , Florence Damond 3 , Adama Oumarou 1 , Meryem Zaidi 3 , Anna-Maria Franco-Yusti 3 , Quentin Le Hingrat 3 , Romain Coppée 3 , Claver Anoumou Dagnra 2 , Diane Descamps 3 , Didier Koumavi Ekouevi 2 , Charlotte Charpentier 3 1 Centre Africain de Recherche en Épidémiologie et en Santé Publique, Lomé, Togo, 2 L'Université de Lomé, Lomé, Togo, 3 Hôpital Bichat-Claude-Bernard, Paris, France Background: Very few data are available regarding efficacy of the transition to tenofovir-lamivudine-dolutegravir (TLD) among adolescents living with HIV (ALHIV) in West Africa. Here, we assessed pharmaco-virological outcome and resistance profiles among ARV-treated Togolese ALHIV. Methods: A cross-sectional study was conducted among 3 clinical centers in Lomé, capital of Togo, following ALHIV. Plasma HIV viral load (VL) was quantified and plasma ARV drugs concentrations were measured. NGS of protease, RT and integrase was performed using Oxford-Nanopore Technologies (threshold: 10%). Drug resistance mutations (DRM) were identified and interpreted using ANRS|MIE algorithm. Results: 272 ALHIV were enrolled (median age: 16 years [IQR: 13-19], 47% men), 85% were receiving a DTG-based regimen and 10% a NNRTI-based regimen. Median duration since ARV initiation was 8 years (IQR: 5-12) and median duration of DTG-based regimen was 20 months (IQR: 13-25). Using a threshold of 50, 200 and 1000 c/mL; 60%, 75% and 82% of ALHIV achieved virological suppression, respectively. Regarding the 231 ALHIV receiving a DTG-based regimen, 80% had VL <200 c/mL, and DTG concentrations were adequate (i.e. >640 ng/mL), suboptimal and 200 c/mL. The most prevalent subtype was CRF02_AG (68%). Overall, at least one DRM was detected in 66% of the samples. 57%, 81%, and 1.6%, of ALHIV harbored viruses that were resistant to any NRTI, NNRTI, and PI. The most prevalent NRTI and NNRTI mutations were M184V (85%) and K103N (40%), respectively. A TDF DRM was detected in 5 RT sequences (8.8%). An INSTI major mutation was observed in 3 of the 32 (9.4%) available integrase sequences among ALHIV receiving a DTG-based regimen: R263K, E138A-G140A-Q148R, and N155H. Two of these latter patients were receiving TLD and the remaining one was receiving ABC-3TC-DTG; two had adequate DTG concentrations; and one had a virus also harboring M184V mutation. Conclusion: In this large study of 272 ALHIV carried out in Togo, we showed a high level of virological response to TLD with high level of adherence, and a rate of DTG resistance mutations emergence of 9.4% in case of virological failure. These first findings on a large series of adolescents in LMIC advocate the need of VL monitoring and to survey HIV drug resistance to DTG in the context of transitioning to TLD with a limited access to VL monitoring.

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