CROI 2024 Abstract eBook

Abstract eBook

Oral Abstracts

due to discontinuation or missing visits. No between-group differences were seen in changes in CD4+ T-cell counts or ALC at W24 (Table). AEs occurred in 39 participants (75.0%) on ISL+LEN and 38 (73.1%) on B/F/TAF. The most common AEs in ISL+LEN participants included diarrhea (n=7; 13.5%), upper respiratory infection (n=6; 11.5%), and arthralgia, pain in extremity, and fatigue (each n=3; 5.8%). No grade 3 or 4 AEs related to study drug were reported. Two participants discontinued ISL+LEN due to AEs unrelated to drug (large intestine perforation/ renal colic; hepatitis B). Conclusion: In this Phase 2 study, the first QW oral ARV regimen of ISL+LEN maintained viral suppression at W24 and was well tolerated. The ISL 2 mg dose showed no clinically significant decreases in CD4+ T-cell counts or ALCs as were seen previously with higher daily, weekly, and monthly doses of ISL.

with a rapid treponemal test on site to guide treatment, followed by laboratory testing (TPHA confirmed with RPR). Maternal and infant data were abstracted from antenatal care (ANC) files, neonatal clinical records and laboratory testing data. We evaluated risk factors of maternal syphilis using logistic regression, adjusted for maternal age. Results: Of 500 pregnant women attending routine primary care clinics on oral PrEP, 496 (99%) were tested for syphilis at least once in ANC: median age was 25 years, median gestation was 28 weeks. At first ANC visit, 413 women received a rapid Treponemal test (83%); 26 tested positive (6.3%). Of 496 women lab tested, 51 were TPHA+ (10.3%) and 23 RPR+ (overall prevalence of current infection=4.6%, 95% CI=3.1, 6.9). After the first ANC visit, 281 women (59% of 473 who did not have prevalent syphilis) were retested at least once during pregnancy; of these, 8 had incident syphilis detected (incidence, 2.9%; 95% CI=1.5, 5.5). Overall, 31 of 496 pregnant women tested were RPR+ (6.3%, 95% CI=4.3, 8.8). In those RPR+, 16 (52%) were 'adequately treated' with 3 doses of penicillin >30 days before delivery, and 15 of 31 (48%) had 4-fold RPR titer decrease. Two congenital syphilis cases were identified (RPR titer 4x mother's RPR; 6.4% vertical transmission and 0.4% population prevalence) both with maternal diagnosis and treatment <30 days before delivery. Age-adjusted risk factors associated with maternal syphilis included younger age, reporting no sex partners, experiencing recent intimate partner violence and alcohol use (Table). Conclusion: These novel data demonstrate a remarkably high occurrence of syphilis in pregnancy among women enrolled in antenatal PrEP services, with half of women not fully treated in pregnancy leading to preventable congenital syphilis. There is a clear and urgent need to integrate syphilis prevention and treatment into antenatal PrEP services. Efficacy and Safety of Weekly Islatravir Plus Lenacapavir in PWH at 24 Weeks: A Phase II Study Amy Colson 1 , Gordon Crofoot 2 , Peter J. Ruane 3 , Moti Ramgopal 4 , Alexandra W. Dretler 5 , Ronald G. Nahass 6 , Gary Sinclair 7 , Mezgebe Berhe 8 , Chris Deaton 9 , Angela S. Liu 10 , Eva Mortensen 10 , Martin S. Rhee 10 , Elizabeth G. Rhee 11 , Jared Baeten 10 , Joseph J. Eron 12 1 Community Resource Initiative, Boston, MA, USA, 2 Crofoot Research Center, Houston, TX, USA, 3 Ruane Clinical Research Group, Inc, Los Angeles, CA, USA, 4 Midway Immunology and Research Center, Fort Pierce, FL, USA, 5 Infectious Disease Specialists of Atlanta, Atlanta, GA, USA, 6 ID Care, Hillsborough, New Jersey, , 7 Prism Health North Texas, Dallas, TX, USA, 8 North Texas Infectious Diseases Consultants, Dallas, TX, USA, 9 Gilead Sciences, Inc, Cambridge, United Kingdom, 10 Gilead Sciences, Inc, Foster City, CA, USA, 11 Merck & Co, Inc, Palo Alto, CA, USA, 12 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, and lenacapavir (LEN), a capsid inhibitor, have potent anti-HIV-1 activity and pharmacokinetic profiles permitting once-weekly (QW) oral dosing. We investigated efficacy and safety of ISL+LEN in virologically suppressed people with HIV-1. Methods: In this Phase 2, randomized, open-label, active-controlled study (NCT05052996), virologically suppressed adults on bictegravir/emtricitabine/ tenofovir alafenamide fumarate (B/F/TAF) were randomized to either oral ISL 2 mg + LEN 300 mg QW or to continue daily B/F/TAF. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA ≥ 50 copies/ mL (FDA-defined Snapshot algorithm) at Week 24 (W24). Safety parameters, including CD4+ T-cell and absolute lymphocyte counts (ALC) and adverse events (AEs), were also evaluated. Results: A total of 104 participants were randomized and dosed (52/group); median age (range) was 40 (26–76) years, and 19 (18.3%) were female at birth. One (1.9%) participant in the ISL+LEN group (whose baseline HIV RNA was 251 copies/mL) had HIV-1 RNA > 50 copies/mL at W24, then suppressed on ISL+LEN (64 copies/mL at W24, < 50 copies/mL at W30); no participant in the B/F/TAF group had HIV RNA > 50 copies/mL at W24. Forty-nine (94.2%) and 48 (92.3%) participants maintained viral suppression in the ISL+LEN and B/F/TAF groups at W24, respectively; 2 (3.8%) and 4 (7.7%) participants had no data at W24

Oral Abstracts

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HepB-CpG Vaccine Is Superior to HepB-alum in People With HIV and Prior Vaccine Nonresponse: A5379 Kristen Marks 1 , Minhee Kang 2 , Triin Umbleja 2 , Andrea Cox 3 , Karen J. Vigil 4 , Ngan T. Ta 5 , Ayotunde Omoz-Oarhe 6 , Jennifer C. Price 7 , Josphat Kosgei 8 , Leolin Katsidzira 9 , Hugo Perazzo 10 , Kevin Knowles 11 , Beverly L. Alston-Smith 12 , Kenneth E. Sherman 13 , for the ACTG 5379 (BEe-HIVe) Study Team 1 Weill Cornell Medicine, New York, NY, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 The Johns Hopkins University School of Medicine, Baltimore, MD, USA, 4 University of Texas at Houston, Houston, TX, USA, 5 Hanoi Medical University, Hanoi, Vietnam, 6 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 7 University of California San Francisco, San Francisco, CA, USA, 8 Walter Reed Project–Kericho, Kericho, Kenya, 9 University of Zimbabwe, Harare, Zimbabwe, 10 Oswaldo Cruz Foundation - Fiocruz, Rio de Janeiro, Brazil, 11 Frontier Science & Technology Research Foundation, Inc, Amherst, NY, USA, 12 National Institute of Allergy and Infectious Diseases, Rockville, MD, USA, 13 Massachusetts General Hospital, Boston, MA, USA Background: Conventional Hepatitis B surface antigen (HBsAg)-based vaccines achieve seroprotection response (SPR, HBsAb≥10 mIU/mL) in 35-80% of people with HIV (PWH) with 3 doses. HepB-CpG (vaccine with a TLR-9 agonist adjuvant) achieves high SPR in PWH, but limited data exist for non-responders to conventional vaccines. Methods: ACTG A5379 is an ongoing, open-label study to evaluate immunogenicity of HepB-CpG in PWH. Prior vaccine non-responders were on ART with CD4 ≥100 cells/mm 3 and HIV-1 RNA <1000 copies/mL without past or present serologic evidence of HBV or HBV vaccine response. Participants were randomized 1:1:1 to: 2 doses of HepB-CpG intramuscularly (IM) (20 mcg recombinant HBsAg, 3000 mcg CpG 1018® adjuvant) at Wks 0 and 4 (2-CpG); 3 doses of HepB-CpG IM at Wks 0, 4, 24 (3-CpG); or 3 doses of HepB-alum IM (20 mcg recombinant HBsAg) at Wks 0, 4, 24 (3-alum). Primary SPR was defined at Wk12 for 2-CpG and Wk28 for 3-CpG and 3-alum. We assessed noninferiority (NI) of 2-CpG vs 3-alum with a 10% margin and superiority of 3-CpG vs 3-alum. Predefined primary analysis set excluded missed sample collection. Safety was also assessed. Results: Of the 561 eligible participants enrolled at 41 sites from 10 countries: 64% were male, 42% Black, 35% White, 17% Asian, 22% Hispanic. Median age was 46 years (range 18-70), 56% enrolled in the US, 21% Africa, 17% Asia, 6% S. America. Median CD4 was 638 cells/mm 3 , 94% had HIV-1 RNA <40 copies/ mL, 29% BMI >30, and 13% diabetes. 96% completed all prescribed doses. The analysis included 505 participants (99% of 508 in the primary analysis set). SPR was achieved in 93% of 2-CpG (n=174), 99% of 3-CpG (n=169), and 80% of 3-alum (n=162). SPR difference between 2-CpG and 3-alum was 13% (97.5% CI: 5%, 22%), achieving NI and indicating superiority. SPR of 3-CpG was superior to 3-alum with a difference of 19% (97.5% repeated CI: 11%, 27%). By Wk12, >90% of participants who received HepB-CpG achieved SPR (Figure 1). Three doses of HepB-CpG achieved a higher proportion with titers >1000 mIU/ ml compared to two, and to 3 doses of HepB- alum. One or more AEs related to

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CROI 2024