CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

155

InSTI Switch During Menopause Is Associated With Accelerated Body Composition Change Rebecca Abelman 1 , Yifei Ma 1 , Cyra C. Mehta 2 , Qian Yang 2 , James Brock 3 , Maria L. Alcaide 4 , Anjali Sharma 5 , Michelle Floris-Moore 6 , Elizabeth F. Topper 7 , Kathleen Weber 8 , Seble Kassaye 9 , Deborah Gustafson 10 , Cecile D. Lahiri 2 , Phyllis Tien 1 1 University of California San Francisco, San Francisco, CA, USA, 2 Emory University, Atlanta, GA, USA, 3 University of Mississippi Medical Center, Jackson, MS, USA, 4 University of Miami, Miami, FL, USA, 5 Albert Einstein College of Medicine, Bronx, NY, USA, 6 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 7 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 8 Cook County Health & Hospitals System, Chicago, IL, USA, 9 Georgetown University, Washington, DC, USA, 10 State University of New York Downstate Medical Center Downstate Medical Center, Brooklyn, NY, USA Background: Integrase strand transfer inhibitors (INSTIs) have been associated with greater weight gain in women with HIV (WWH) than men with HIV. The transition to menopause is also associated with body composition changes. Whether INSTI initiation during the menopausal transition affects waist circumference (WC) and BMI trajectories is unknown. Methods: From 2006-2019, 1159 non-pregnant virally-suppressed WWH [(424 who switched to an INSTI (INSTI+); 735 who did not switch (INSTI–) during a similar time window] and 904 women without HIV (WWOH) from the Women's Interagency HIV Study were included. The visit at which WWH reported switching to an INSTI was defined as the index visit. Mixed effect models including quadratic terms were used to evaluate change in WC and BMI by menopausal phase defined using anti-Müllerian hormone, a biomarker of ovarian reserve, at the index. Models were adjusted for demographics, baseline WC or BMI, behavioral factors, comorbidities, and HIV-related factors. Results: Overall, 66% identified as Black and 28% were premenopausal, 10% early peri-, 28% late peri-, and 34% postmenopausal at the index. INSTI+ were older than INSTI- and WWOH (median 52 vs 49 vs 47 years) with median BMI 30 vs 29 vs 31.5kg/m 2 , respectively. 64% of INSTI+ and 79% of INSTI- were on tenofovir DF prior to the index visit. Figure shows the WC trajectory for INSTI+, INSTI-, and WWOH who were premenopausal and late perimenopausal at index visit. In premenopausal women, INSTI+ and INSTI- was associated with a 0.06cm per 6 month (mo) (95%CI:-0.27,0.38) and 0.08cm per 6mo (95%CI:- 0.11,0.28) faster linear increase in WC respectively, compared to WWOH; INSTI+ had a 0.05cm per 6mo (95%CI:-0.31,0.40) faster increase than INSTI-. In late perimenopausal women, when compared to WWOH, INSTI+ was associated with significantly faster increases in WC which peaked at 41mo and then declined, while INSTI- had smaller increases in WC (0.14cm per 6mo;95%CI:- 0.55,0.33); INSTI+ had a 0.39cm per 6mo (95%CI:0.15,0.63) faster linear increase in WC than INSTI-. In postmenopausal women, INSTI+ was associated with faster WC increases up to 39mo then declines compared to INSTI-. BMI trajectories were similar for late peri- and postmenopausal women. Conclusion: Switching to an INSTI-based regimen during late peri- and postmenopause is associated with early accelerated increases in WC and BMI when compared to women who did not switch. Our findings suggest that menopausal status should be considered when switching to an INSTI.

156

Simultaneous Initiation in ART-Naive PWH of DTG-Based ART & 3HP Maintains Efficacious DTG Levels Ethel D Weld 1 , Belén Perez Solans 2 , Isadora Salles 1 , Bareng Aletta Nonyane 3 , M Sebe 4 , Trevor Beattie 4 , Manasa Mapendere 4 , Tanya Nielson 4 , Jayajothi Moodley 4 , Violet Chihota 4 , Rada Savic 2 , Kelly E. Dooley 5 , Richard E. Chaisson 1 , Gavin Churchyard 4 , for the UNITAID IMPAACT4TB Consortium 1 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 University of California San Francisco, San Francisco, CA, USA, 3 The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 The Aurum Institute, Johannesburg, South Africa, 5 Vanderbilt University, Nashville, TN, USA Background: People with HIV (PWH) living in areas of high TB endemicity have high potential to benefit from short-course tuberculosis (TB) preventive therapy (TPT) with weekly isoniazid and rifapentine for 3 months (3HP). 3HP given to virally suppressed PWH on dolutegravir (DTG)-based regimens has been found to be safe and to maintain virologic suppression with adequate DTG levels. No data yet supports simultaneous 3HP with DTG-based ART initiation among ART-naïve people. Methods: A phase 1/2 comparative trial of simultaneous initiation of 3HP or 6 months isoniazid (6H) with DTG-based ART was performed among antiretroviral (ART)-naïve adults with HIV in South Africa. Participants were sequentially enrolled and assigned to 6H (N=25) and 3HP (N=50). PK sampling for DTG trough was performed at: day 1 (prior to first HP dose), day 17 (3 days after 3rd HP dose), and day 52 (3 days after 8th HP dose) in both groups. Primary endpoints were safety and DTG pharmacokinetics during 3HP/DTG coadministration. Safety and the secondary endpoint of HIV viral load at TPT completion were previously reported. Results: By week 8, viral suppression (VL < 50 copies/mL) was achieved in 100% of participants in both groups. At week 12, viral suppression (VL < 50 copies/mL) was present in 44/50 (88%) and 23/25 (92%) participants in the 3HP and 6H groups, respectively. Nonlinear mixed-effects modeling showed that there was a 72% induction effect of rifapentine on DTG clearance, from 0.95 L/ hr to 1.64 L/hr. DTG trough concentration was above the PA-IC 90 (64 ng/mL) in all participants at all timepoints, and >158 ng/mL (the lower 5th percentile confidence bound of concentrations achieved with fully suppressive 10 mg daily dosing in the SPRING-1 trial) in all but 2 individuals at week 3 and in all individuals at week 8. The 2 individuals w DTG concentrations below 158 ng/mL at week 3 both suppressed by week 8. Conclusion: Simultaneous initiation of 3HP for LTBI treatment and DTG-based ART resulted in rapid viral suppression among ART-naïve PWH. Despite a 72% induction of DTG clearance in the 3HP group, DTG concentrations enabled viral suppression < 50 copies/mL in all individuals in both groups at 8 weeks. This information is critical to informing global guidelines around LTBI treatment in ART-naïve individuals.

Oral Abstracts

38

CROI 2024