CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

and integrase inhibitor-based ART, respectively, at enrolment. The composite primary endpoint was reached by 67 (46.5%) in the GRT arm and 73 (52.1%) in the usual care arm (adjusted odds ratio [95% confidence interval]: 0.79 [0.49 1.27]; adjusted risk difference: -0.06 [-0.17-0.06]) (Table). No differences were observed for secondary endpoints (Table). No deaths were recorded; one WHO clinical stage 4 event requiring hospitalisation occurred in the usual care arm (Table). Conclusion: In this randomized trial conducted in Tanzania and Lesotho, GRT-informed management did not improve viral resuppression rates or clinical treatment outcomes in children and adolescents with viremia while taking ART.

rebound (HIV-1 RNA confirmed ≥LOD). Plasma ARV drug levels were assessed retrospectively to confirm absence of ARV during ATI. Results: Six children underwent ATI at median age 5.5 years. Three of 6 achieved study-defined remission, one through 80 weeks of ATI, when viral rebound (299,538 cp/mL) occurred. The other two who achieved remission remain on ATI (>48 and >60 weeks). A fourth child remains on ATI (>44 weeks). Two children had viral rebound 3 and 8 weeks after ATI (Table). Earliest available HIV-1 RNA and DNA values ranged from 96 to >5 million cp/mL and from not detected to 130 cp/106 PBMCs. The child with 80 weeks of remission had no ARVs detected in plasma during ATI (tests pending for others). Two of 3 children with rebound (at 8 and 80 weeks) experienced acute retroviral syndrome (ARS); no other clinical or immunologic events of concern were identified during or following ATI. The children with rebound at 3 weeks (67,606 cp/mL) and 8 weeks (1801 cp/mL) had HIV-1 RNA

Oral Abstracts

186

ODYSSEY 192-Week Follow-Up Evidences Superior Efficacy of DTG for Children on First/Second-Line ART Hilda A Mujuru 1 , Ellen M. White 2 , Adeodata R. Kekitiinwa 3 , Abbas Lugemwa 4 , Cissy M. Kityo 5 , Philippa Musoke 6 , Tim R. Cressey 7 , Ebrahim Variava 8 , Avy Violari 9 , Moherndran Archary 10 , Mark F. Cotton 11 , Thanyawee Puthanakit 12 , Pablo Rojo 13 , Anna Turkova 2 , for the ODYSSEY Trial Team 1 University of Zimbabwe, Harare, Zimbabwe, 2 University College London, London, United Kingdom, 3 Baylor College of Medicine Children's Foundation, Kampala, Uganda, 4 Joint Clinical Research Centre, Mbarara, Uganda, 5 Joint Clinical Research Centre, Kampala, Uganda, 6 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 7 Chiang Mai University, Chiang Mai, Thailand, 8 Klerksdorp Tshepong Hospital Complex, Jouberton, South Africa, 9 Perinatal HIV Research Unit, Soweto, South Africa, 10 Durban International Clinical Research Site, Durban, South Africa, 11 Family Centre for Research with Ubuntu, Cape Town, South Africa, 12 HIV-NAT, Bangkok, Thailand, 13 Hospital Universitario 12 de Octubre, Madrid, Spain Background: ODYSSEY demonstrated superior 96-week efficacy for dolutegravir(DTG)+2NRTIs versus standard-of-care (SOC, 77% efavirenz first line, 96% boosted PI second-line) in children starting first-line (ODYSSEY A) or second-line ART (ODYSSEY B). During a further ~3 years' extended follow-up in Africa and Thailand, children on SOC were switching to DTG following national guidelines. Here we present efficacy and safety of DTG compared to SOC over 192 weeks and virological suppression in SOC participants post-switch to DTG. Methods: The proportion of children with treatment failure (confirmed viral load (VL) ≥400c/mL after week 36, lack of virological response by week-24 with ART switch, death or new/recurrent WHO4/severe WHO3 event) was compared between trial arms by intention-to-treat using Kaplan-Meier. Viral suppression in SOC participants was defined as VL<400c/mL in the most recent sample within 24 weeks pre-DTG switch and 48 weeks post-switch. Results: 792 children were randomised (392 DTG,400 SOC); median(range) age 11.4(0.1-18) years, and weight 29(3.4-85)kg. 383 children started first-line; 409 second-line. 683 children (349 DTG, 334 SOC) consented to extended follow-up (97% of 707 approached). Overall, median follow-up was 5.5 years (286 weeks; IQR: 234-310). At 192 weeks, only 13% of SOC had switched to DTG, without prior treatment failure. 76(19%) DTG vs. 129(32%) SOC participants experienced treatment failure by 192 weeks (treatment difference [95% CI]:-13.3%[- 19.2,-6.5]; p<0.001). Treatment effects were similar on first- and second-line [heterogeneity p=0.22]. Mean change in CD4% from baseline to week 192 was 12% in DTG versus 11% in SOC (difference (DTG-SOC) 1.4[95% CI:-0.2,3.0]; p=0.095). 11 children had died (4 DTG, 7 SOC) and 18 children had experienced a new/recurrent WHO4/severe WHO 3 event (9 DTG, 9 SOC) by week 192. By the end of follow- up, 309 (77% of randomised, 99% of those completing extended follow-up) of SOC arm had switched to DTG; 297(95%) of DTG arm remained on DTG. 248/275(90%) SOC participants switching to DTG were virologically suppressed post-switch (ODYSSEY A 96%, B 86%), including 179/193(93%) of those suppressed pre-switch (A 99%, B 89%) and 29/35(83%) with pre-switch VL≥400c/mL (A 87%, B 80%). Conclusion: Superior efficacy of DTG-based ART versus SOC was maintained up to 192 weeks in children starting both first- or second-line ART. On average,

185

GIVE MOVE: Randomized Trial on Genotype-Informed Management of Viremia in Children and Adolescents Jennifer A Brown 1 , Isaac K. Ringera 1 , Ezekiel Luoga 2 , Buoang Mothobi 3 , Brenda Simba 4 , Kasasi Mayogu 4 , Mosa Molapo Hlasoa 5 , Buntshi P. Kayembe 5 , Josephine Muhairwe 3 , Thomas Klimkait 1 , Tracy R. Glass 6 , Maja Weisser 1 , Niklaus D. Labhardt 1 , for the GIVE MOVE Research Group 1 University Hospital Basel, Basel, Switzerland, 2 Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania, 3 SolidarMed, Maseru, Lesotho, 4 Management and Development for Health, Dar es Salaam, United Republic of Tanzania, 5 Baylor College of Medicine Children's Foundation, Maseru, Lesotho, 6 Swiss Tropical and Public Health Institute, Basel, Switzerland Background: Children and adolescents with HIV experience high rates of treatment failure. Genotypic resistance testing (GRT) to inform onward antiretroviral therapy (ART) is often inaccessible, and its effect on clinical outcomes in the context of viremia is unknown. Methods: The Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE) open-label randomized clinical trial enrolled children and adolescents <19 years who were receiving ART and had a recent (<16 weeks before enrolment) viral load (VL) ≥400 copies/mL. Participants were randomised 1:1 to receive either GRT with expert recommendation (GRT arm) or repeat VL testing and empiric decision-making (usual care arm) to inform onward treatment. The composite primary endpoint was the occurrence of i) death, ii) hospitalisation, iii) a new World Health Organization (WHO) clinical stage 4 event, or iv) no documented viral resuppression (<50 copies/mL) at 36 weeks. Secondary endpoints included separate analyses of the primary endpoint components and 36-week VL ≥50 copies/mL among those with a 36-week VL result. Adjusted odds ratios and adjusted risk differences were estimated in the modified intention-to-treat (mITT) population. The trial was conducted at ten sites in Lesotho and Tanzania. Trial registration: ClinicalTrials. gov (NCT04233242). Results: Between March 2020 and July 2022, 286 participants were enrolled of whom 284 were included in the mITT analyses (144 GRT arm; 140 usual care arm). Of these, 158 (55.6%) were female (versus male); 116 (40.8%) were aged 0-11 years (versus 12-18 years); and 13 (4.6%), 101 (35.6%), and 170 (59.9%) were taking non-nucleoside reverse transcriptase inhibitor-, protease inhibitor-,

50

CROI 2024