CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

and 60 mg of ISL were evaluated for their pharmacokinetics (PK) in pigtailed macaques. We further investigated the efficacy of a 60 mg, 90-day ISL IVR against vaginal SHIV infection in macaques. Methods: IVRs containing 15, 30, and 60 mg ISL were inserted for 28 days into pigtailed macaques (n=8) in a crossover design. The 15 and 60 mg ISL IVRs were subsequently investigated for 90-day PK studies (n=3 macaques each). Plasma, PBMC, and mucosal fluid were collected for drug quantitation by AB Sciex API-5000 triple quadruple mass spectrometer. Based on the total amount of ISL released over the 90-day period, we initiated a vaginal SHIV challenge study in sexually mature, normal cycling pigtailed macaques (n=8). Six ISL (60 mg) IVR treated macaques received weekly SHIV162p3 inoculations starting 3 days after IVR insertion. Two untreated controls received the same weekly challenges. Infection was monitored by RT-PCR. Results: Systemic ISL concentrations were within the levels seen with the safe 0.25 mg once-daily oral human dose (Table). It was determined that the 15 mg rings released 94% of ISL over 90 days while the 60 mg had released 56%. The 60 mg IVR maintained ISL triphosphate (ISL-TP) at or above established ISL-TP benchmark concentration needed for protection (50 fmol/10 6 cells) for over 90 days and was investigated for its efficacy against vaginal SHIV infection. All ISL IVR-treated macaques remain SHIV RNA negative after 8 weekly SHIV challenges while the two controls became infected at 2 and 3 exposures. Conclusions: We demonstrate that a 60 mg 3D-printed ISL IVR provides sustained vaginal release of ISL over 90 days and results in systemic ISL dosing. Systemic ISL concentration remained below the clinical toxicity threshold and prevented SHIV acquisition in macaques. These results warrant further development of the 3D printed IVR as a three-month MPT for prevention of HIV and unintended pregnancy using an already optimized hormones dose. 1239 Syphilis Screening in Hospitalized People With HIV: A Key Strategy to Tackle HIV and STI Epidemics Mayara Secco Torres da Silva, Isabel C. Ferreira Tavares, Carolina Coutinho, Thiago Torres, Eduardo Mesquita Peixoto, Brenda Hoagland, Ingebourg Georg, Leonardo Rosadas, Estevão Portela Nunes, Emilia Moreira Jalil, Rodrigo O. Silva Escada, André M. Japiassu, Sandra Wagner Cardoso, Valdilea Gonçalves Veloso, Beatriz Grinsztejn Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil Background: Active sexually transmitted infections (STI) elevate the risk of HIV acquisition, highlighting the need for timely diagnosis and treatment to address the intertwined HIV/STI epidemics. Latin America bears a disproportionate burden of STIs, with sexual and gender minorities most affected. In recent years, Brazil has experienced a concerning rise in acquired/congenital syphilis cases, particularly among people with HIV (PWH), evolving into a major public health challenge. This study aims to evaluate the prevalence of active syphilis and its associated factors among hospitalized PWH within the framework of a universal syphilis screening strategy. Methods: A retrospective analysis was conducted on all PWH hospitalized at INI-Fiocruz, an infectious diseases’ referral center in Rio de Janeiro, Brazil from October 2021 to April 2024. Participants hospitalized for neurosyphilis were excluded. All participants were screened for syphilis, with active syphilis defined as a VDRL titer ≥1/8. Sociodemographic and clinical characteristics were compared based on syphilis diagnosis (yes vs no), using Chi-squared/Fisher’s exact tests (categorical variables) and the Wilcoxon test (continuous variables) to assess group differences. Results: A total of 1,881 PWH were admitted, with an overall syphilis prevalence of 13.8%. Participants with active syphilis were younger and more frequently cisgender men, with no significant differences observed in race/color or educational level (Table). Those diagnosed with syphilis were more likely to have HIV-RNA viral loads (VL) >1,000 cps/mL (38.1% vs 32.8%) and CD4+ cell counts ≤200 cells/mm³ (61.3% vs 55.7%). Opportunistic diseases were diagnosed in 61.4% of participants with active syphilis. Coinfections with mpox, hepatitis B, and hepatitis C were diagnosed in 3.5%, 3.1%, and 5.4% of cases,

respectively. Hepatitis C seroprevalence was higher among participants with active syphilis (5.4% vs 1.8%). Conclusions: Routine syphilis screening for hospitalized PWH is crucial for tackling the growing syphilis epidemic in Brazil, particularly for those who are disengaged from regular HIV care. Likewise, it mitigates the heightened risk of HIV transmission associated with active STIs in individuals with elevated viral loads. Integrating syphilis screening into standard care is essential for managing the interconnected HIV and STI epidemics, particularly in high-burden settings.

Poster Abstracts

1240 Differences in Presentation and Outcome of Subsequent Episodes of Syphilis in People Living With HIV Leticia Espinosa 1 , Jorge Peris 1 , Ana Moreno 2 , Isidro Hernandez 1 , María Ezquerra Marigómez 3 , Ana Abad 2 , Jose L. Casado 4 1 Hospital Universitario San Juan de Alicante, Alicante, Spain, 2 Hospital Juan Ramón Jiménez, Huelva, Spain, 3 Hospital Sierrallana, Torrelavega, Spain, 4 Hospital Ramón y Cajal, Madrid, Spain Background: The impact of a first episode of syphilis on the course of subsequent episodes in people living with HIV (PLH) is somehow controversial and of clinical interest. Methods: Prospective cohort study of 348 episodes of syphilis observed in 175 PLH with regular follow up (12.5 person-years) in a HIV Unit in a tertiary hospital. Syphilis testing was routinely performed every 6-12 months in all the cases, and unscheduled visits were included in case of suspicion of syphilis or other sexually transmitted diseases. Results: At the first diagnosis, median age was 48 years, predominantly were male (99%), nadir CD4+ count was 303 cells/μL, and 99% were receiving suppressive antiretroviral therapy. Of note, a fall in CD4+ count (-10 cells/μL) and CD4/CD8 ratio (-0.04) was observed at the diagnosis of syphilis. During median follow up of 35 months (3.6 person-years), nearly half of included PLH had more than 1 syphilis episode (two, 91, 26%; three or more, 82 PLH, 24% of episodes of syphilis). The form of presentation changes according to number of episodes (primary syphilis from 17 to 9%; secondary syphilis from 17% at the first, to 8% at those with a third episode). However, the proportion of individuals whose 1st episode was early latent stage was similar, probably related to the close follow up. Also, serological presentation was similar according to successive episodes (median RPR 1/32 from the 1st to 3rd episode, but with a trend to higher RPR titer subsequently), as well as the decrease in the CD4+ count (-9 vs -11 cells/μ in 1st and 2nd), CD4/CD8 ratio, time to initial serological response (5.5 vs 5.9 months), or time to negativization of RPR titer (with a trend to decrease, 19 vs 16 vs 12 months; p=0.12). Of note, the rate of serofast status was similar in subsequent episodes (37% vs 46% vs 50%) whereas the time of persistence in the serofast status was significantly shorter in the third or successive episodes (p=0.012, log-rank). Conclusions: A previous episode of syphilis could change the clinical picture of successive episodes, but importantly it does not alter the serological presentation and outcome of subsequent infections with T. pallidum . A shorter time of persistence of serofast status reinforce the role of immunity in this outcome.

CROI 2025 409