CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

1228 Diagnosis, Resistance, and ART Outcomes After HIV Acquisition on CAB-LA PrEP in Routine Care in US Catherine A. Koss 1 , Monica Gandhi 1 , Elias Konstantine Halvas 2 , Hideaki Okochi 1 , Lisa Georgetti Gomez 1 , Amy Heaps 2 , Amit (Mickey) Dhir 3 , Aniruddha Hazra 4 , Jessica A. Altamirano 5 , Prerak Shukla 5 , Hussein Safa 6 , Christopher Bositis 1 , Carolyn Chu 1 , John W. Mellors 2 , Urvi M. Parikh 2 , for the SeroPrEP Study Team 1 University of California San Francisco, San Francisco, CA, USA, 2 University of Pittsburgh, Pittsburgh, PA, USA, 3 The Johns Hopkins University, Baltimore, MD, USA, 4 University of Chicago Medical Center, Chicago, IL, USA, 5 CAN Community Health, Fort Lauderdale, FL, USA, 6 Einstein Medical Center, Philadelphia, PA, USA Background: Reports of HIV acquisition among persons on cabotegravir (CAB) PrEP are rare thus far in routine clinical care but have occurred. We report the largest analysis to date of diagnostics, pharmacokinetics, resistance, provider selected ART and treatment outcomes following HIV acquisition on CAB PrEP in routine care. Methods: The SeroPrEP study examines HIV acquisition on PrEP in routine care in the U.S. Clinical test results (including HIV RNA) were obtained from medical records. HIV RNA was also quantified by automated single-copy assay. Resistance-associated mutations (RAMs) in plasma HIV RNA were identified by single-genome sequencing (SGS) of full-length integrase. Plasma CAB concentrations were quantified by LC/MS/MS. Results: Among 7 participants (ppts; 6 cisgender male, 1 nonbinary) diagnosed with HIV after CAB PrEP use, median age was 38 years (range 23-67), median BMI 27 kg/m 2 (range 18-36). HIV was first detected in 6 ppts after median 7 (range 2-13) on-time injections and in 1 ppt 9 mos. after last injection. At first HIV detection, HIV RNA was <500 c/ml in 3/7 (43%) ppts; median HIV RNA 4410 c/ml (range 100-2,400,000); Ag/Ab (lab-based or POC) was reactive in 3/7 (43%). Plasma CAB levels measured median 49 days (range 14-102) after last injection were median 0.99 mcg/ml (range 0.24-3.4). One ppt had major INSTI RAMs (E138EK/Q148QK/N155NH) on population sequencing. Among 4/6 other ppts, SGS identified low-frequency major INSTI RAMs: N=1 ppt with Q148R (2/24 sequences [seq]); N=1 with E138K (1/56 seq)/G140R (1/41 seq); N=1 with Q148R (12/40 seq)/R263K (1/40 seq)/G118R (2/15 seq); N=1 with S147G (1/45 seq). All 7 ppts started DRV-based ART; among 6 on ART >6 wks, all had HIV RNA <50 c/ml through median 28 wks (range 7-74). Three ppts with low-frequency INSTI RAMs later switched to provider-selected INSTI-based ART due to ARV intolerance/interactions or pt preference, with subsequent HIV RNA <50 c/ml at 31 wks (BIC/F/TAF), 20 wks (BIC/F/TAF to CAB/RPV), and 13 wks (CAB/RPV). Conclusions: Among 7 persons in the U.S. who acquired HIV despite CAB PrEP use, over half required RNA for initial HIV detection and had low-frequency INSTI RAMs detected by a sensitive assay. All started DRV-based ART (3 later switched to INSTI-based ART) and all achieved viral suppression to date. Longer-term follow-up is needed to assess the clinical significance of low-frequency INSTI RAMs detected by sensitive assays, and the durability of viral suppression on INSTI-based ART after HIV infection on CAB PrEP. 1229 The Cost-Effectiveness and Optimal Price Level of Injectable PrEP With Lenacapavir in South Africa Lise Jamieson 1 , Leigh F. Johnson 2 , Linda-Gail Bekker 3 , Hasina Subedar 4 , Gesine Meyer-Rath 1 1 University of the Witwatersrand, Johannesburg, South Africa, 2 University of Cape Town, Cape Town, South Africa, 3 Desmond Tutu HIV Foundation, Cape Town, South Africa, 4 South African National Department of Health, Pretoria, South Africa Background: Injectable lenacapavir (LEN) has been shown to be 100% effective in protecting African women from HIV infection, but its acceptable price and cost-effectiveness is unknown. We estimated the impact of LEN compared to daily oral tenofovir disoproxil fumarate and emtricitabine (TDF/ FTC) and injectable cabotegravir (CAB) for HIV prevention in South Africa, and the threshold price at which LEN or CAB would be as cost-effective as further TDF/FTC scale up. Methods: We used Thembisa, a deterministic HIV transmission model, to evaluate the impact and cost-effectiveness of PrEP provision to women (incl. female sex workers), heterosexual men, gay men and other men who have sex with men over current TDF/FTC use over 20 years (2024-2045) of a) LEN; b) CAB; and c) TDF/FTC scale up. We estimated the average cost of provision in 2024 USD using ingredients-based costing and current South African market prices for TDF/FTC and CAB drugs. For LEN we assumed a price of $40 or $100 per injection. We estimated the threshold price of LEN and CAB, with a credible interval informed by probabilistic sensitivity analysis sampling 50 parameter

combinations (incl. PrEP effectiveness, duration on TDF/FTC, tail protection for LEN/CAB, and condom use reduction on PrEP). We assumed higher uptake and longer effective use duration of LEN or CAB compared to TDF/FTC throughout, with two scenarios each defined by average duration of use across populations (LEN: 6-12 or 12-24 months, CAB: 4-8 or 8-16 months). Results: Despite similar effectiveness, LEN leads to higher impact throughout compared to CAB, due to higher uptake and longer effective use. LEN could avert 27-41% of new HIV infections and 4-6% of deaths, and CAB 21-35% and 3-5%, resp., compared to 8% and 1% averted by TDF/FTC scale-up, resp. (see Table). Under high uptake, LEN could reduce incidence to below 0.1% by 2032 instead of 2042, thus helping to eliminate HIV in South Africa 10 years earlier. Because of this higher impact, LEN can be accepted at a higher price than CAB, with a threshold price of $32-59/injection (range $19-115) or $117-225 per person year, pppy (range $74-469) for LEN, compared to $14-22/injection (range $9-30), and $88-$144pppy (range $45-343) for CAB. Conclusions: Injectable lenacapavir could be more cost-effective than scaling up oral PrEP, and much more cost-effective than injectable cabotegravir, even at a drug price of $100 per injection. However, CAB should be rolled out now to cover the time to large-scale LEN manufacture (3-4 years).

Poster Abstracts

1230 PURPOSE 1: Preference for Twice-Yearly Injection vs Daily Oral Pills for HIV PrEP in Cisgender Women Leila E. Mansoor 1 , Joanne Batting 2 , Noah Kiwanuka 3 , Elizabeth Spooner 4 , Dylan Mezzio 5 , Pamela Wong 5 , Alexander Kintu 5 , Christoph Carter 5 , Thesla Palanee Phillips 6 1 Centre for the AIDS Programme of Research in South Africa, Durban, South Africa, 2 Foundation for Professional Development Community Research Site, Ndevana, South Africa, 3 Makerere University, Kampala, Uganda, 4 South African Medical Research Council, Cape Town, South Africa, 5 Gilead Sciences, Inc, Foster City, CA, USA, 6 Wits Reproductive Health and HIV Institute, Johannesburg, South Africa Background: Although oral pre-exposure prophylaxis (PrEP) is effective for HIV prevention, its routine use in cisgender women remains low. Effectiveness is contingent on high adherence and persistence post initiation, which many cite as a barrier for daily oral pills. In the Phase 3 PURPOSE 1 trial, twice yearly subcutaneous (SC) lenacapavir (LEN) was safe and 100% efficacious in preventing HIV infection in cisgender women in South Africa and Uganda. We examined the PrEP administration preferences of PURPOSE 1 participants. Methods: In PURPOSE 1 (NCT04994509), cisgender women aged 16-25 years were randomized 2:2:1 in a blinded fashion to receive SC LEN every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF). Participants also received the alternate SC/oral placebo. During injection visits, participants completed an electronic questionnaire on their PrEP administration preference (twice-yearly injection or daily pills) and the potential impact of administration type on their feelings about HIV risk and PrEP adherence. These data were collected at baseline (prior to injection), Week (W) 26, and W52. Categorical responses were analyzed descriptively. Results: Of 5368 randomized participants, 5218 completed the questionnaire at baseline. At the time of this interim analysis, 2561 participants had completed the W52 questionnaire. Approximately two-thirds of participants preferred twice-yearly injections over daily pills, few had no preference, and less than one-third preferred daily pills (Fig). Among those with a preference for either injection or pills, slightly more than half reported their preference as “strong”.

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