CROI 2025 Abstract eBook

Abstract eBook

Oral Abstracts

194

Adherence to F/TAF in Cisgender Women Prevents HIV With Low Risk of Resistance or Diagnostic Delay Flavia M. Kiweewa 1 , Khatija Ahmed 2 , Gonasagrie Nair 3 , Stephanie Cox 4 , Alexander Kintu 4 , Christoph Carter 4 , Moupali Das 4 , Ravindre Panchia 5 1 Makerere University–Johns Hopkins University Research Collaboration, Kampala, Uganda, 2 Setshaba Research Centre, Tshwane, South Africa, 3 Desmond Tutu HIV Foundation, Cape Town, South Africa, 4 Gilead Sciences, Inc, Foster City, CA, USA, 5 University of the Witwatersrand, Johannesburg, South Africa Background: PURPOSE 1 (NCT04994509) is a Phase 3, double-blind, randomized, controlled trial assessing the efficacy of lenacapavir (LEN) and emtricitabine plus tenofovir alafenamide (F/TAF) for pre-exposure prophylaxis (PrEP) in adolescent girls and young women. Although LEN was 100% efficacious at the primary analysis, F/TAF HIV incidence was similar to the background HIV incidence rate. Case-control analysis within the F/TAF group demonstrated a 9-fold lower likelihood of HIV acquisition in participants with medium or high adherence compared with those with low adherence. Here, we provide an in-depth laboratory analysis of incident HIV cases in the F/TAF group, including adherence, resistance, and timing of seroconversion. Methods: HIV testing at each study visit included rapid and central laboratory 4th-generation antibody/antigen tests. HIV-1 RNA testing was conducted from the visit prior to seroconversion using archived samples. Adherence was assessed by measuring tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS). Genotypic resistance testing was performed for participants with HIV-1 RNA concentration > 200 copies/mL. Results: DBS adherence data were available for 37/39 incident cases in the F/TAF group. Among these, 35/37 had DBS TFV-DP concentrations indicating suboptimal or nonadherence. Longitudinal adherence patterns are shown in the Figure. Of the participants with high adherence, one had no resistance associated mutations (RAMs) at the time of diagnosis and the other had M184I reverse transcriptase (RT) inhibitor RAM, K65R RT inhibitor RAM, and Y188L non-nucleoside RT inhibitor RAM at diagnosis, consistent with transmitted drug resistance (TDR). HIV-1 RNA was positive one visit prior to seroconversion in seven F/TAF participants; DBS indicated suboptimal adherence at the time of RNA detection for six of these. Conclusions: Nearly all incident HIV cases in participants receiving F/TAF in PURPOSE 1 were attributable to low oral PrEP adherence, with one additional case likely explained by TDR. Emergence of antiretroviral resistance was rare. A minority of participants had brief delays in seroconversion. Taken together, these results suggest that HIV infections in PURPOSE 1 occurred almost always in the context of nonadherence to F/TAF, with rare emergence of HIV resistance and low risk of HIV diagnosis delay. Thus, F/TAF could be important for women who prefer a daily oral HIV prevention option.

Oral Abstracts

195

Performance of HIV RNA Screening in the Context of Long-Acting Injectable Cabotegravir in HPTN 084 Sinead Delany-Moretlwe 1 , Michael Holt 2 , Brett S. Hanscom 3 , Estelle Piwowar Manning 4 , Aida Asmelash 5 , Nyaradzo Mgodi 6 , Patricia N. Ntege 7 , Jennifer Farrior 5 , Lydia Soto-Torres 8 , James F. Rooney 9 , Alex Rinehart 10 , Myron Cohen 11 , Mina C. Hosseinipour 12 , Susan H. Eshleman 4 , for the HPTN 084 Study Team 1 University of the Witwatersrand, Johannesburg, South Africa, 2 Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA, 3 Fred Hutchinson Cancer Center, Seattle, WA, USA, 4 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5 FHI 360, Durham, NC, USA, 6 University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe, 7 Baylor College of Medicine Children's Foundation-Uganda (BFU), Kampala, Uganda, 8 Division of AIDS, Bethesda, MD, USA, 9 Gilead Sciences, Inc, Foster City, CA, USA, 10 ViiV Healthcare, Durham, NC, USA, 11 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA, 12 University of North Carolina Project–Malawi, Lilongwe, Malawi Background: Long-acting injectable cabotegravir (CAB-LA) is highly effective as PrEP but may delay detection of HIV infection using conventional diagnostics. HIV RNA testing may assist with early detection of HIV infection and prevent the emergence of resistance. We evaluated the performance of HIV RNA screening in the HPTN 084 open-label extension (OLE). Methods: HPTN 084 evaluated the effectiveness of long-acting injectable cabotegravir (CAB-LA) compared to daily oral TDF/FTC for PrEP in individuals born female aged 18-45 years in eastern and southern Africa. Sites performed one or two rapid tests, a laboratory-based antigen/antibody (Ag/Ab) test, and an HIV RNA test at each visit in the OLE. Final HIV status was adjudicated based on site-based test results and retrospective testing at a central laboratory. We calculated the sensitivity of RNA screening with other tests, and the positive predictive value (PPV) and false positive rate (FPR) of isolated positive HIV RNA results. Results: Overall, 2,462 participants with 24,178 visits through November 30, 2023 were included in the analysis. HIV infection was confirmed in 8 (90.1%) of 88 participants with ≥1 reactive HIV test result (one at OLE entry, seven after OLE entry). Of these, 4/8 (50%) were detected by a positive isolated HIV RNA test (true positive cases). Fourteen additional participants had a positive isolated HIV RNA test but were adjudicated HIV negative (false positive cases). The overall sensitivity of RNA screening was 75% (34.9%-96.8%). The PPV and FPR for detection of HIV infection by isolated HIV RNA test were 22.2% (95% CI 6.4%-47.6%) and 77.8% (95% CI 52.4%-93.6%) respectively. When stratified by recent CAB use within the prior 6 months, the PPV was 20.0% (95% CI 4.3%- 48.1%) with recent CAB compared to 33.3% (95% CI 0.8%-90.6%) without. False positive tests led to CAB injections delays of >70 days in 6 (42.9%) of 14 false positive cases. Conclusions: HIV RNA testing performed poorly for detection of confirmed HIV infections. High CAB effectiveness and subsequent low prevalence of true infection in this population may explain the low PPV for HIV RNA screening. Although infrequent, most positive isolated HIV RNA tests were false positive with the potential for negative clinical consequences in some cases. Future HIV

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CROI 2025