CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

transplacental or gut-absorption, with cell-associated transmission, is likely implicated in these rare cases. Arteriolar Dysfunction in Placentas of HIV-Exposed, Small-for Gestational-Age Neonates Rachel K Scott 1 , Jason Umans 1 , Sean Dalby 2 , Katherine Michel 3 , Christopher Wilcox 3 , Dan Wang 3 1 MedStar Health Research Institute, Hyattsville, MD, USA, 2 George Washington University, Washington, DC, USA, 3 Georgetown University, Washington, DC, USA Background: Birthing individuals with HIV (BIHIV) are more likely to deliver small-for-gestational-age (SGA) neonates. Fetal growth restriction largely results from limited delivery of nutrients and O2 during development. We hypothesized that placental microvascular dysfunction may contribute to SGA among BIHIV. Methods: Immediately after delivery, we biopsied placentas with/without HIV exposure and with/without SGA birthweight between 36-41weeks gestation. We assessed fetoplacental arteriolar function by myograph; we measured dose-dependent contraction to U-46,619 (a thromboxane-prostanoid receptor agonist), endothelin (ET1), norepinephrine (NE), and phenylephrine (PE), as well as relaxation to acetylcholine (ACh), sodium nitroprusside (SNP), and AdipoRon (ApR, an adiponectin [ApN] agonist). ET1-induced reactive oxygen species (ROS) were measured by DHE fluorescence and apR-induced nitric oxide (NO) activity by DAF-FM fluorescence using a RatioMasterTM system. Umbilical cord and maternal plasma ApN and malondialdehyde (MDA, a marker of oxidative stress) were measured by ELISA. Dose response curves across groups were compared using two-way mixed ANOVA. Results: We collected 33 placental biopsies; we excluded 3 due to poor quality from excessive time in transit. We analyzed specimens from 9 placentas of HIV-unexposed normal birthweight (NBW) neonates, 6 HIV-unexposed SGA neonates, 11 HIV-exposed NBW neonates, and 4 HIV-exposed SGA neonates. Both U46,619 (103±4% of KClmax) and ET1 (109±5%) induced robust contractions, while vessels were unresponsive to NE (7±3%) or PE (5±2%). Contractions to ET-1 and U-46,619 were greater in placentas with HIV-exposure (p=.003; p=.03) or of SGA neonates (p=.01; p<.0001) compared to controls, and greatest in the setting of both HIV-exposure and SGA (p<.0001; p<.0001). U46,619 pre-constricted arterioles relaxed to ApR (93±4%), but only minimally to Ach (7±2%) or SNP (10±2%). Impaired arteriolar relaxation to ApR was associated with HIV-exposure (p=.01), SGA (p=.001), and combined HIV exposure with SGA (p<.0001). Likewise, ApR-induced NO was decreased and ET1-induced ROS was increased with HIV-exposure and SGA. Birthweight was correlated directly with ApR-induced relaxation (r=.48) and inversely with MDA (r=-.68). Conclusion: Fetoplacental arteriolar relaxation was impaired and contraction was enhanced among placentas of HIV-exposed and SGA neonates. These findings contribute to the limited body of research elucidating the pathophysiology of SGA among BIHIV. The figure, table, or graphic for this abstract has been removed. A Target Trial of Preconception Switch From Nevirapine- to Dolutegravir Based ART on Birth Outcomes Ellen Caniglia 1 , Rebecca Zash 2 , Modiegi Diseko 3 , Judith Mabuta 3 , Mompati Mmalane 3 , Shahin Lockman 4 , Gloria K. Mayondi 3 , Gaerolwe Masheto 3 , Joseph M. Makhema 3 , Roger Shapiro 5 1 University of Pennsylvania, Philadelphia, PA, USA, 2 Beth Israel Deaconess Medical Center, Boston, MA, USA, 3 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 4 Brigham and Women's Hospital, Boston, MA, USA, 5 Harvard TH Chan School of Public Health, Boston, MA, USA Background: Antiretroviral regimens have differential effects on adverse birth outcomes. Nevirapine (NVP) has been associated with particularly high risk of adverse birth outcomes compared with newer ART like dolutegravir (DTG). We emulated a target trial of pre-conception switch from NVP to DTG to evaluate whether switch from high-risk to low-risk regimens prior to pregnancy can favorably impact outcomes. Methods: The Tsepamo Study has performed birth outcomes surveillance at government delivery sites in Botswana since 2014. Among individuals who initiated NVP from 2002-2014 and remained on NVP in 2016, we compared those who switched to DTG (usually for programmatic reasons, after DTG became first-line ART) with those who did not switch from NVP prior to pregnancy. We estimated adjusted risk ratios (RRs) and 95% CIs for stillbirth, in hospital neonatal death (<28 days), preterm delivery (<37 weeks), very preterm delivery (<32 weeks), small-for-gestational-age (SGA) (<10%tile), very SGA (<3%tile),

of infant HIV infection were 2.6 times higher for each log 10 increase in maternal plasma RNA VL (95% CI: 1.6-4.5) and 1.8 times higher for each log 10 increase in BM RNA VL (95% CI: 1.3-2.6). BM DNA VL was not detected in 26 (84%) cases and 59 (95%) controls. Only 3/14 (21%) case mothers on a TFV-containing regimen had detectable TFV levels in their plasma or BM vs 31/37 (84%) control mothers with detectable TFV in plasma and 29/37 (78%) in BM. In case mothers, plasma TFV levels were 10-fold lower (geometric mean ratio (95% CI): 0.11 (0.04-0.26) compared with controls, and BM TFV levels were 5-fold lower 0.18 (0.08-0.43) in case mothers compared with controls. Conclusion: Odds of breastmilk HIV-1 transmission is associated with higher maternal plasma and BM VL and lower TFV levels.

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Poster Abstracts

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Could This Be Cell-Associated Perinatal HIV Transmission? Beatrice Cockbain 1 , Caroline Foster 2 , Paula Seery 2 , David Hawkins 3 , Marta Boffito 3 , Graham P. Taylor 1 , Hermione Lyall 2 1 Imperial College London, London, United Kingdom, 2 Imperial College Healthcare NHS Trust, London, United Kingdom, 3 Chelsea and Westminster NHS Foundation Trust, London, United Kingdom Background: Recent French Perinatal Cohort data demonstrated no vertical transmissions among 5482 women living with HIV fulfilling the following criteria: effective ART from conception; undetectable plasma HIV RNA viral load (VL) near delivery; infant post-exposure prophylaxis (PEP); no breastfeeding. Despite fulfilling these criteria, we present two cases of vertical transmission from one UK centre and review the literature. Methods: Retrospective case series of two infant HIV infections, without known vertical transmission risks. Review of maternal and infant notes. Literature review for cases of HIV transmission despite undetectable maternal plasma HIV RNA. Results: Cases series. Both mothers conceived on triple ART. Excellent adherence reported. With an exception of 380 HIV RNA copies/ml (cpm) at gestational age (GA) 8 weeks in case A, both had multiple VL measures <50 cpm during pregnancy and around delivery (38 weeks GA for mother A; 36 weeks GA for mother B). Mother A had 6 weeks of enoxaparin from 11 weeks GA; mother B an iron infusion at 33 weeks GA. Both deliveries were term, one vaginal with induction of labour for pre-eclampsia at 38 weeks with <1 hour ruptured membranes, and one a planned pre-labour, pre-rupture of membranes Caesarean section at 39 weeks. Both infants had negative HIV VL at birth, had standard of care zidovudine PEP for 2–4 weeks as per contemporary guidelines and were exclusively formula-fed. HIV RNA was first detected in Infant A at 12 weeks (17.6 x 106 cpm) and in infant B at 6 weeks (1.4 x 106 cpm). Literature review. One late transmission reported in Dolphin-2: Efavirenz-based ART commenced week 28 GA with HIV VL undetectable at delivery, weeks 6, 12, 24, 48 and 72 post-partum. Exclusive breastfeeding to 24 weeks, breastmilk and solids to 48 weeks when breastfeeding stopped. The infant was HIV negative on VL testing until week 72. HIV sequencing and phylogenetic analyses linked all infant and maternal viruses. Conclusion: Without detectable maternal viraemia, vertical HIV transmission is rare. Residual transmission may be from cell-associated virus, the dominant mode of transmission for other human retroviruses. ART may limit cell associated HIV transmission. Exposure to maternal ART in utero may act as foetal pre-exposure prophylaxis and infant PEP protects for a limited period postnatally. Maternal lymphocyte persistence in the infant circulation, whether

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CROI 2024 292