CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

807

2 vs 3 Doses of HPV9-Valent Vaccine in Women With HIV: Safety & Immunogenicity From Randomized Trial Debora R. Konopnicki 1 , Christine Gilles 1 , Yannick Manigart 1 , Patricia Barlow 1 , Anca Reschner 1 , Coca Necsoi 1 , Marc Delforge 1 , Davy Vandenbroeck 2 , Nicolas Dauby 1 , Stephane De Wit 1 1 Saint-Pierre University Hospital, Brussels, Belgium, 2 AML BV, Antwerp, Belgium Background: WHO recommends 2 doses of human papillomavirus (HPV) vaccine for adults without HIV and 3 doses among persons with HIV. There are currently no immunogenicity data on 2 doses schedule in women with HIV (WWH). Methods: This monocentric prospective study (NCT03391921) compares 2 (month 0,6) versus 3 (month 0,2,6) doses of 9-valent (9v-) vaccine (Gardasil9®MSD) in WWH aged 15-40 years, on antiretrovirals (ART) with HIVRNA<400cp/ml; enrollment 2018-2021. An initial open-label phase assessed safety in 45 participants receiving 3 doses. As no safety signal was identified, we further randomized participants between 2 or 3 doses. Primary outcome was non-inferiority of 2 doses (=at least 80% of seroconversion against all vaccine genotypes at Month7, alpha=0.05, 1-beta=0.8) compared to 3 doses (expected seroconversion rate: 90%). Due to COVID-19 pandemic, 102 WWH, instead of initially planned 120, were randomized. Due to budget constraints, the trial was further amended to give 2 doses to all participants enrolled thereafter Feb 2021 (n=22). Results were analyzed in intention-to-treat (ITT, missing = failure) on the randomized (n=100; 2/102 consent withdrawals) and on-treatment (OT) on the whole cohort (n=151; 16/167 missed Month7 visit) according to number of doses received. Results: Among 167 WWH enrolled, 81% were from sub-Saharan Africa, median age 35 years, median CD4 count 649/µL. Before vaccination among the 167 participants, the mean antibody titers against each of the 9 vaccine genotypes were below the detectable cutoff and detectable antibodies were found in respectively 26% for HPV6, 8% for HPV11, 7% for HPV16, 12% for HPV18, 13% for HPV31, 14% for HPV33, 9% for HPV45, 7% for HPV52 and 10% for HPV58. After vaccination, rates of seroconversion against all vaccine genotypes were non-inferior for 2 doses in both ITT (84% versus 94% for 3 doses, p=0.19) and OT (96% versus 98.8% for 3 doses, p=0.57). In both ITT and OT analysis, GMCs significantly increased after vaccination with 2 doses (p<0.0001) or 3 doses (p<0.0001) with a magnitude of increase 17 to 259 times (1.2 to 2.4 log 10 ) compared to baseline. There was no serious adverse event; most reactions were local and mild but significantly more frequent with 3 doses in ITT (82% versus 60% for 2 doses, p=0.027) and OT (80% versus 61% for 2 doses, p=0.016). Conclusions: In women with well-controlled HIV under ART, 2 doses of HPV 9v-vaccine is non-inferior to 3 doses in terms of seroconversion rate and is associated with less reactogenicity. Optimizing Anal Cancer Screening in PWH: The Role of ADAR1 mRNA in Predicting High-Grade Lesions Melissa Bello-Perez 1 , Paula Mascarell 1 , Marta Fernández-González 1 , Jose Alberto Garcia 1 , Christian Ledesma 1 , Ana Gutiérrez-Ortiz de la Tabla 2 , Isabel Valencia 1 , Angela Botella 1 , Miguel Bardellini 1 , Marta Inclán 1 , Nieves Gonzalo-Jimenez 1 , Javier Garcia-Abellan 1 , Sergio Padilla Urrea 1 , Felix Gutierrez 1 , Mar Masiá 1 1 Hospital General Universitario de Elche, Elche, Spain, 2 University Hospital Gregorio Marañon, Madrid, Spain Background: The incidence of anal squamous cell carcinoma is significantly increased in people with HIV (PWH). Early detection of high-grade squamous intraepithelial lesions (HSIL) through high-resolution anoscopy (HRA) in individuals with abnormal anal cytology can prevent over half of these cases. However, the poor specificity of anal cytology leads to a high number of unnecessary HRAs. This poses significant challenges to anal cancer screening, considering the scarce availability of HRA. Overexpression of adenosine deaminase acting on RNA 1 (ADAR1) has been reported in several cancers, including cervical cancer. This study aimed to determine whether quantifying ADAR1 mRNA levels could improve the selection of candidates for HRA. Methods: A prospective cohort study was conducted between 2022 and 2023, involving consecutive HIV-positive adults with abnormal anal cytology (atypical squamous cells of undetermined significance or worse). All patients underwent HRA to collect anal swabs and biopsies. ADAR1 mRNA expression levels were quantified using RT-qPCR in anal swabs. The diagnostic performance of ADAR1 mRNA to discriminate HSIL from low-grade squamous cell intraepithelial lesions

(LSIL)/normal biopsies was analyzed using receiver operating characteristic (ROC) curves. Results: HSIL was confirmed by anal biopsy in 40/171 participants (23.4%) with abnormal anal cytology. Participants with HSIL had a higher median [IQR] number of HPV genotypes compared to those without HSIL (5 [4-8] vs 3 [1-5], p<0.001). ADAR1 mRNA levels were significantly higher in the HSIL group compared to the non-HSIL group (49.4 vs 4.1, p<0.001). The ROC curve for ADAR1 mRNA showed an area under the curve of 0.83 (95% CI: 0.75-0.92). Using a threshold of ≥24.8 relative units to endogenous control, the test achieved 73% sensitivity, 92% specificity, 74% positive predictive value and 92% negative predictive value. This threshold would reduce the need for HRA to 22.8% of participants with abnormal anal cytology. Among the 132 (73%) participants with ADAR1 levels <24.8, incorporating HPV genotype quantification with a threshold of >4 improved HSIL detection rates to 95%, though it would require 40 (23%) additional HRAs. Conclusions: ADAR1 mRNA quantification helps mitigate the limited availability of HRA by more accurately identifying PWH who need the procedure. By increasing specificity and reducing unnecessary HRAs, ADAR1 mRNA presents a more efficient, targeted and less invasive strategy for detecting HSIL. Anal Cancer Incidence Among Privately Insured People With and Without HIV in South Africa Eliane Rohner 1 , Nathalie Veronica Fernandez Villalobos 1 , Yann Ruffieux 1 , Chido Chinogurei 2 , Andreas D. Haas 1 , Morna Cornell 2 , Nicola Low 1 , Gary Maartens 3 , Jenni Noble 4 , Naomi Folb 4 1 University of Bern, Bern, Switzerland, 2 Centre for Infectious Disease Epidemiology and Research, Cape Town, South Africa, 3 University of Cape Town, Cape Town, South Africa, 4 Medscheme, Roodepoort, South Africa Background: People with HIV (PWH) have a higher anal cancer incidence than the general population. Although most PWH live in sub-Saharan Africa, data about the association of HIV and anal cancer in this region are scarce. We examined anal cancer incidence rates among privately insured people with and without HIV in South Africa. Methods: We did a retrospective cohort study using reimbursement claims data from a South African medical insurance scheme (01/2011-07/2020) to assess anal cancer rates among people with and without HIV aged ≥18 years. We defined anal cancer diagnoses as ≥2 claims with ICD-10 codes for anal cancer (C21). Using proportional hazards survival models, we estimated adjusted hazard ratios (aHRs) for the association of HIV and incident anal cancer. The multivariable model included sex, HIV status, age, population group, calendar year, history of genital warts, and history of other sexually transmitted infections (STIs). Among women, we also estimated aHRs for the association of past cervical precancer and an incident anal cancer diagnosis. Results: We included 1,068,915 people of whom 557,717 were women (52%) and 69,985 (7%) were PWH. The median age at the start of time-at-risk was 39.7 years (interquartile range [IQR] 33.4-47.3) in PWH and 36.3 years (IQR 26.1-49.9) in people without HIV. Over 3,933,145 person-years, 122 incident anal cancers were diagnosed for a crude incidence rate of 3.1/100,000 person-years (95% confidence intervals [CI] 2.6-3.7). PWH had a four-fold higher risk of an incident anal cancer diagnosis than people without HIV ( Table ). Anal cancer rates increased with older age, and they did not differ by sex. A history of genital warts was associated with a substantially higher risk of an incident anal cancer diagnosis, but we did not find a clear association with a history of other STIs. Among women, a prior diagnosis of cervical precancer was associated with an almost six-fold increased risk of developing anal cancer (aHR 5.70; 95% CI 1.75-18.58). Conclusions: We found that PWH in South Africa had considerably higher anal cancer rates than people without HIV. Older individuals, people with a history of genital warts, and women with a prior diagnosis of cervical precancer were also at increased risk of developing anal cancer - these groups may benefit from risk-targeted anal cancer screening, as recommended by the International Anal Neoplasia Society's consensus guidelines for anal cancer screening.

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Poster Abstracts

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CROI 2025 242