CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

at the time of conception, support using DVR and TDF/FTC as HIV prevention options for pregnant people at risk of HIV.

disoproxil fumarate (F/TDF) pre-exposure prophylaxis (PrEP) have informed adherence-concentration-efficacy relationships for men who have sex with men, derived from observed dosing studies in US populations. Similar thresholds for African cisgender women have not been defined. Methods: Between April 2022 and June 2023, we conducted a prospective, randomized, pharmacokinetic study of TFV-DP in DBS and peripheral blood mononuclear cells (PBMCs) among 54 non-pregnant Kenyan women without HIV taking 2, 4, or 7 oral F/TDF PrEP doses per week and 18 pregnant women without HIV taking 7 doses per week (clinicaltrials.gov: NCT05057858). Dosing was directly observed until 8 weeks to achieve 90% steady-state in DBS. TFV-DP was quantified in DBS and PBMCs using validated LC-MS/MS assays at University of Colorado. TFV-DP concentrations were compared between groups using Wilcoxon test. Results: Median (IQR) age was 23 (20–25) years for nonpregnant and 23 (20–27) years for pregnant participants; baseline gestation age was 16 (14-20) weeks. TFV-DP was dose proportional in DBS and PBMCs. Observed median (IQR) week 8 TFV-DP concentrations in DBS in non-pregnant women were 359 (266–464), 749 (504–923), and 1389 (1151–1551) fmol/punch for 2, 4, and 7 doses/week, respectively (Table 1). During pregnancy, observed median (IQR) week 8 TFV-DP in DBS from daily dosing was 792 fmol/punch (759–946), similar to concentrations arising from 4 doses/week in non-pregnant women, but 55% lower than corresponding concentrations from daily dosing in non-pregnant women (p<0.001). Importantly, pregnant women achieved similar median (IQR) steady-state TFV-DP concentrations in PBMCs versus those observed in non-pregnant women on daily dosing [50 (35–58) versus 49 (36–63) fmol/10 6 , p =0.71]. TFV-DP concentrations in PBMCs for both pregnant and non-pregnant women were lower than levels (>80 fmol/10 6 ) previously observed in US populations. Conclusion: In this adherence benchmark study among African women, TFV-DP in DBS was more than one-half lower in pregnant versus non-pregnant women, but PBMC concentrations were similar. Concentrations were lower than levels observed in US cohorts. These benchmarks will help to define women specific concentration- efficacy relationships and accurate interpretation of HIV prevention trials in African women. HIV Incidence in the INSIGHT Cohort of African Women: Recency Testing and Prospective Follow-Up Deborah Donnell 1 , Irene Mukui 2 , Brenda G. Mirembe 3 , Sue Peacock 2 , Harriet Nuwagaba- Biribonwoha 4 , Sinead Delany-Moretlwe 5 , Katherine Gill 6 , Pippa MacDonald 6 , Philip Kotze 7 , Alastair van Heerden 8 , Remco Peters 9 , Manjeetha Jaggernath 10 , Phillip du Preez 11 , Renee Heffron 12 , Connie Celum 2 1 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 2 University of Washington, Seattle, WA, USA, 3 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 4 ICAP at Columbia University, New York, NY, USA, 5 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa, 6 Desmond Tutu HIV Foundation, Cape Town, South Africa, 7 Qhakaza Mbokodo Research Clinic, Ladysmith, South Africa, 8 Human Sciences Research Council, Pretoria, South Africa, 9 Foundation for Professional Development, East London, South Africa, 10 University of the Witwatersrand, Johannesburg, South Africa, 11 University of Cape Town, Cape Town, South Africa, 12 University of Alabama at Birmingham, Birmingham, AL, USA Background: For efficacy trials of novel agents with an active control, cross-sectional recency testing could estimate HIV incidence in the population screened. There is limited experience with use of recency testing to estimate HIV incidence for this purpose. Methods: From Aug-Dec 2022, women ages 16-30 were enrolled into the prospective INSIGHT cohort from South Africa (15 sites), eSwatini, Kenya, Malawi, Uganda, and Zambia. Women who screened HIV+ had samples collected for LAg avidity and HIV RNA testing, those with LAg avidity ≤1.5 and viral load (VL)≥1000 copies/ml were classified as recent infections. Women who were HIV-negative were offered enrollment into an open-label PrEP cohort

Oral Abstracts 169

Phone Calls for PrEP Persistence in Kenyan Women in Postabortal Care: A Cluster Randomized Trial Renee Heffron 1 , Lydia Etyang 2 , Bernard Nyerere 2 , Inviolata Wanyama 3 , Yasaman Zia 4 , Torin T. Schaafsma 4 , Katherine K. Thomas 4 , Margaret Mwangi 2 , Lavender A. June 2 , Felix Mogaka 2 , Catherine Kiptinness 2 , Michael Kamiru 5 , Kenneth Ngure 6 , Elizabeth Bukusi 2 , Nelly R. Mugo 2 1 University of Alabama at Birmingham, Birmingham, AL, USA, 2 Kenya Medical Research Institute, Nairobi, Kenya, 3 Marie Stopes Kenya, Nairobi, Kenya, 4 University of Washington, Seattle, WA, USA, 5 Children's Investment Fund Foundation, Nairobi, Kenya, 6 Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya Background: In Kenya, women of reproductive age face dual epidemics of HIV and unintended pregnancy yet persistence with HIV PrEP is low when initiated in reproductive health settings. Methods: PrEP delivery was launched in 15 postabortion care (PAC) clinics in Kenya and data were abstracted on women seeking care for 6 months post PAC. Six months after all clinics began to deliver PrEP, we initiated a cluster randomized trial (CRT) and clinics were randomized to conduct either a phone call program (4 calls during the first month, 2 calls in month 2, and 1/month thereafter) or standard of care (SOC) to support PrEP retention and adherence. Data on PrEP refills were abstracted from medical charts. Additionally, women were offered participation in research procedures through which women were tested for tenofovir (TFV) detection using a point-of-care urine assay. Results: From April 2021 to March 2023, 8362 women sought PAC from participating clinics: median age 24 years (IQR 22-27), 53% married/cohabiting. Of the 15 facilities included, 40% were public and 40% were high volume. The PrEP cascade highlights that 55% received PrEP information, 73% of those had HIV testing, and 36% of those received counseling and initiated PrEP. After the CRT launch, 4112 women sought PAC and 655 (15.9%) initiated PrEP. Overall, 11.8%, 4.9%, and 1.8% of 655 received a PrEP refill at 1, 3, and 6 months after initiation. At month 1, 14/247 (5.7%) women in facilities randomized to SOC and 63/408 (15.4%) of women in the phone call program received a PrEP refill (RR=2.7, 95% CI 0.90–8.2). At month 1, TFV was detected in 4.9% of the SOC arm and 11.8% of the phone call arm (RR = 2.4, 95% CI 0.73–8.0), assuming those who did not return were undetectable. Conclusion: In the PrEP cascade, we observed large gaps in the provision of PrEP information and PrEP counseling that contributed to low PrEP uptake. Among women who initiated PrEP, persistence and adherence was very low even in the context of research visits. However, follow up via phone calls resulted in substantially more frequent PrEP refills, a finding that warrants further investigation. Adherence Benchmarks for TFV-DP in DBS and PBMCs for African Women Using FTC/TDF PrEP Kenneth K Mugwanya 1 , Nelly R. Mugo 2 , Deborah Donnell 3 , Matilda Saina 2 , Clare E. Brown 1 , Torin T. Schaafsma 1 , David Chege 2 , Elena A. Rechkina 1 , Bhavna Chohan 1 , Sarah Mbaire 2 , Elex Hill 1 , Kenneth Ngure 4 , Lane Bushman 5 , Jared Baeten 6 , Peter L. Anderson 5 , for the Women Benchmark Study Team 1 University of Washington, Seattle, WA, USA, 2 Kenya Medical Research Institute, Nairobi, Kenya, 3 Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 4 Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya, 5 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 6 Gilead Sciences, Inc, Foster City, CA, USA Background: Intracellular tenofovir-diphosphate (TFV-DP) concentration benchmarks in dried blood spots (DBS) from oral emtricitabine-tenofovir

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CROI 2024