CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

the HIV-1 epidemic in KZN to describe observed HLA-B frequencies, and a counterfactual scenario where ART was never rolled out. Results: In the pre-ART era, ‘disease-susceptible’ HLA-B alleles were significantly associated with an increased risk of vertical transmission (OR 2, p=0.018), whilst ‘protective' HLA-B alleles lead to a decreased risk of vertical transmission (OR 0.51, p=0.004). Disease-susceptible HLA-B alleles were significantly enriched in transmitting mother-child pairs (p=0.006) and ‘protective’ HLA-B alleles enriched in non-transmitting mothers (p=ns). In the ART era, this process has been reversed. The model that was constructed, simulating the differential impact of HLA-B alleles on disease progression and vertical transmission, indicated that, in the absence of ART, the HIV epidemic would have reduced KZN population frequencies of ‘disease-susceptible’ HLA-B allele by 50% and increased those of ‘protective’ HLA-B alleles two-fold by 2035. Conclusions: We demonstrate that, in the pre-ART era, the HIV-1 epidemic drives reduction in the population-level frequency of HLA-I alleles mediating rapid HIV disease progression. This process of negative natural selection has been reversed by the impact of ART. 1014 LA-ART for Breastfeeding Women With HIV in Zimbabwe: Clinical Impact and Cost-Effectiveness Sujata Tewari 1 , Risa Hoffman 2 , Shahin Lockman 3 , Clare Flanagan 1 , Karen Webb 4 , Stephanie Horsfall 1 , Anesu Chimwaza 5 , Caitlin Dugdale 1 , Judith Currier 2 , Efison Dhodho 4 , Angela Mushavi 5 , Florence Ebem 1 , Kudakwashe Takarinda 4 , Sophie Desmonde 6 , Andrea L. Ciaranello 1 1 Massachusetts General Hospital, Boston, MA, USA, 2 University of California Los Angeles, Los Angeles, CA, USA, 3 Harvard TH Chan School of Public Health, Boston, MA, USA, 4 Organization for Public Health Interventions and Development, Harare, Zimbabwe, 5 Ministry of Health and Child Care, Harare, Zimbabwe, 6 Université Toulouse III - Paul Sabatier, Toulouse, France Background: Long-acting injectable ART (LA-ART) may reduce barriers to medication adherence for postpartum women with HIV (PPWH) and thus reduce vertical transmission (VT) and improve health outcomes. With CEPAC, a validated computer model of mother-child pairs, we estimated the clinical outcomes and cost-effectiveness of LA-ART for breastfeeding PPWH with adherence challenges to oral ART in Zimbabwe. Methods: At time of delivery, we simulated 2 cohorts of women who had been engaged in antenatal care, had adherence challenges while prescribed oral tenofovir/lamivudine/dolutegravir (TLD) in pregnancy, and had no prior NNRTI exposure, along with their infants: 1) women not virally suppressed at the time of delivery (NVS) and 2) women with viral suppression at delivery (VS). We modeled 2 ART approaches immediately after delivery: standard of care (SOC: continuation of TLD) and LA-ART (switching from TLD to cabotegravir/rilpivirine [LA-CAB/RPV]). Key inputs included: 6-month postpartum suppression (RNA <50c/ml) for CAB/RPV (NVS: 85%, VS: 90%) and TLD (NVS: 63%, VS: 78%); monthly ART costs (LA-CAB/RPV: $12, TLD: $3.60); 24-month postpartum engagement in care (NVS: 70%, VS: 79%); 18-month breastfeeding duration; and vertical transmission (VT) risk (0.06%-0.89%/month of breastfeeding, range by maternal RNA). Primary outcomes included VT; pediatric life expectancy (pLE); total costs, defined as maternal drug costs in breastfeeding and pediatric HIV-related lifetime care costs; and incremental cost-effectiveness ratios (ICERs: $/life-years saved (LYS), defining cost-effective as ICER <$840/ YLS (0.5xGDP). Results: LA-ART reduced projected VT compared to SOC: from 8.07% to 6.59% (NVS) and from 4.18% to 3.81% (VS), averting ~200 infections/year in Zimbabwe (Table). For NVS, LA-ART improved pLE (SOC: 65.93y, LA-ART : 66.37y) while saving money (SOC: $770/child, LA-ART : $760/child); LA-ART would not be cost-effective if CAB/RPV cost >$23/month or 6-month suppression was <68%. For VS, LA-ART led to higher projected pLE and costs (67.51y, $550/child) than SOC (67.39y, $450/child), with ICER $2,500/LYS; LA-ART would become cost effective if CAB/RPV cost <$7/month. Conclusions: LA-ART for breastfeeding women with adherence challenges to oral TLD could reduce infant infections. If efficacy is confirmed in postpartum women, LA-ART for women without viral suppression at delivery would improve outcomes and save money; for women with viral suppression, it would be cost effective in Zimbabwe if costs were ≤$7/month.

1015 Long-Acting Cabotegravir/Rilpivirine in Pregnancy

William R. Short 1 , Matty Zimmerman 2 , Mariam Aziz 3 , Jillian Baron 1 , Philip Bolduc 4 , Eric Farmer 5 , Naima Joseph 6 , Stephan Kohlhoff 7 , Florence Momplaisir 1 , Alexander Nelson 8 , Natalie Nielsen 9 , Dimple Patel 10 , Stephen Pagkalinawan 4 , Mireya Wessolossky 11 , Rachel Scott 1 University of Pennsylvania, Philadelphia, PA, USA, 2 Hospital of the University of Pennsylvania, Philadelphia, PA, USA, 3 Rush University Medical Center, Chicago, IL, USA, 4 University of Massachusetts, Worcester, MA, USA, 5 Indiana University Health, Indianapolis, IN, USA, 6 Boston Medical Center, Boston, MA, USA, 7 SUNY Downstate Medical Center, Brooklyn, NY, USA, 8 Ohio State University, Columbus, OH, USA, 9 University of Cincinnati Medical Center, Cincinnati, OH, USA, 10 Drexel College of Medicine, Philadelphia, PA, USA, 11 MedStar Washington Hospital Center, Washington, DC, USA Background: Long-acting cabotegravir and rilpivirine (LA-CAB/RPV) is a novel injectable antiretroviral therapy approved for virologically suppressed individuals with HIV-1. Data on the safety, efficacy, and outcomes for individuals receiving LA-CAB/RPV during pregnancy are limited. We evaluated HIV viral suppression, perinatal, and neonatal outcomes in pregnant persons with HIV-1 receiving LA-CAB/RPV. This is the first case series to evaluate these outcomes, offering new insight into the use of LA-CAB/RPV during pregnancy. Methods: We performed a multi-center retrospective chart review of pregnant persons prescribed LA-CAB/RPV between January 2021 and October 2024. Patient demographics, HIV RNA throughout pregnancy, and key perinatal and neonatal outcomes, including birth weight, gestational age, and rates of viral suppression at delivery were collected. Results: Twenty-two pregnant persons receiving LA-CAB/RPV were included. Baseline demographics are presented in Table 1. Sixteen (73%) initiated LA-CAB/RPV prior to pregnancy and 6 (27%) switched to LA-CAB/RPV during pregnancy. Among those who remained on LA-CAB/RPV for the remainder of pregnancy, 90% maintained HIV RNA <200 copies/mL. The majority had vaginal deliveries; caesarean deliveries were performed for obstetric indications only. Most neonates were born at term, with a median birth weight of 2,390 grams (interquartile range: 2,144, 2,816). Additionally, 81% (n=17) of the newborns received zidovudine only post-delivery. There were no cases of vertical transmission. Three cases of congenital anomalies occurred (ventriculomegaly, fetal pyelectasis, and Trisomy 21) which were not attributed to LA-CAB/RPV by an independent Maternal Fetal Medicine consultant. Conclusions: The results of this multi-center retrospective cohort suggest that LA-CAB/RPV is associated with high percentage of viral suppression in pregnant persons with HIV-1. Given the small sample size, it was not possible to conduct a meaningful analysis of any associations between perinatal outcomes and the use of LA-CAB/RPV during pregnancy. Our findings support the consideration of LA-CAB/RPV as a viable treatment option during pregnancy, though further research with larger cohorts is needed to validate these findings and ensure long-term safety.

Poster Abstracts

CROI 2025 323