CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Makhema 1 , Tumalano Sekoto 1 , Goabaone Mogomotsi 3 , Shahin Lockman 4 , Roger L. Shapiro 5 , Rebecca Zash 6 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 University of Pennsylvania, Philadelphia, PA, USA, 3 Ministry of Health, Gaborone, Botswana, 4 Brigham and Women’s Hospital, Boston, MA, USA, 5 Harvard University, Boston, MA, USA, 6 Beth Israel Deaconess Medical Center, Boston, MA, USA Background: In Botswana, >90% of HIV+ women receive ART in pregnancy. An increasing proportion of MTCT may occur among women with incident undiagnosed HIV infection during pregnancy. Botswana guidelines recommend repeat HIV testing every 3 months in pregnancy, with at least 1 in the 3rd trimester. We evaluated the rate of antenatal repeat HIV testing and estimated HIV incidence during pregnancy. Methods: In the Tsepamo Study, we abstracted HIV test dates and results from obstetric records of all women who delivered in 8 maternities across Botswana between May 2017 (when abstraction of these data were added) and Sept 2018. This analysis includes women not known to be HIV+ at the start of pregnancy. We defined seroconversion as an initial negative or indeterminate HIV test in pregnancy, followed by a positive test. The incidence rate (IR) of seroconversion was calculated among women with >= 2 known testing dates during pregnancy. Missed seroconversions were estimated among women without a test in the 3rd trimester by applying the IR to the time after their last HIV test until delivery. Results: Among 28,999 women delivering, 5724 (20%) were known to be HIV+ prior to pregnancy 1,758 (6.1%) tested HIV+ at first test in pregnancy, 229 (0.8%) had no HIV test in pregnancy, 57 (0.2%) were unknown, and 21,231 (73%) tested HIV-negative at first test in pregnancy. Of women who initially tested negative, 5321 (25%) had 1 test, 12225 (58%) had 2 tests, and 3678 (17%) had 3 tests during pregnancy. The median gestational age at first HIV test was 16 weeks (IQR 12,21) and median gestational age at last HIV test was 31 weeks [IQR 26,35], with 68% tested in the 3rd trimester (Figure 1). Older women, women with more education, and primigravid women had more HIV tests. The proportion with only one test also differed by site (range 11%-50%). There were 39 seroconversions identified among 15,940 pregnancies (2.4/1000 pregnancies) with at least 2 HIV tests, yielding an IR of 6.5/1000 person-yrs. Among 5547 women without an HIV test in the 3rd trimester, we estimate approximately 10 seroconversions may have been missed because of a lack of repeat testing. Conclusion: In pregnancy, HIV incidence after an initial negative test was low and the majority of women tested in the 3rd trimester. However lack of re-testing in the 3rd trimester led to an estimated 20% decrease in detection of seroconversions. To reach the goal of zero new pediatric HIV infections, Botswana will need to intensify identification of incident HIV.

772 ABUNDANT EXPRESSION OF CCR5 ON EARLY HOFBAUER CELLS MAY INCREASE HIV-1 SUSCEPTIBILITY Dominika Swieboda , Erica L. Johnson, Ioanna Skountzou, Rana Chakraborty Emory University, Atlanta, GA, USA Background: Even with optimal adherence, maternal antiretroviral therapy reduces, but does not eliminate, vertical transmission of HIV-1. Placental macrophages (Hofbauer cells, HCs) are thought to be key mediators of in utero HIV-1 transmission to the fetus. Previous studies have demonstrated that HIV-1 replication of HCs can be regulated by cytokines and interferons (IFNs) (Cobos Jimenez, Booiman et al. 2012), and that certain maternal coinfections (such as HCMV) (Johnson, Boggavarapu et al. 2018) can enhance HC susceptibility and viral replication in vitro by altering HC polarization. Early gestation placental tissue has yet to be evaluated in the context of HIV-1 permissivity. Methods: Here, we determined the levels of expression of HIV-1 co-receptors CCR5 and DC-SIGN on HCs isolated from fresh placentae throughout gestation (12 weeks to term) and evaluated expression of HIV-1 restriction factors SAMHD1, Tetherin, Trim5α, TREX-1, and APOBEC3G. To determine if HC polarization and activation state differentially modify HIV-1 permissivity throughout gestation, HCs were subjected to polarizing conditions (LPS+IFN-γ, IL-10) or IFNs (IFN-α A/D, IFN-λ1), and changes in receptor and restriction factor expression were determined at the protein and RNA level. Results: Basal CCR5 expression levels significantly differed throughout gestation; while only 50% of term HCs expressed CCR5, 100% of early gestation HCs were positive for this receptor. Surface expression of CCR5 remained stable at the protein level and was increased at the RNA level. HIV-1 restriction factors were present at baseline and were upregulated in HCs as a result of treatment. Upregulation of restriction factors in HCs isolated from early gestation matched or exceeded that of term samples, suggesting a level of innate immune protection from vertical transmission even in early pregnancy. Interestingly, IFN-λ1, which is strongly produced by placental trophoblasts, did not affect the expression of HIV-1 restricting factors, suggesting a limited role in controlling HIV-1 replication in HCs. Conclusion: Placental macrophages in early pregnancy may be susceptible to HIV-1 infection due to abundant expression of CCR5, as compared to term samples. Co-receptor expression may be counterbalanced by robust basal and cytokine-induced expression of key HIV-1 restriction factors in HCs, offsetting in utero transmission early in gestation.

Poster Abstracts

774 HETEROGENEITY OF HIV RETESTING DURING PREGNANCY AND POSTPARTUM IN KENYA Monalisa Penumetsa 1 , Shiza Farid 1 , Daniel Matemo 2 , Barbra A. Richardson 1 , Grace John-Stewart 1 , John Kinuthia 2 , Alison L. Drake 1 1 University of Washington, Seattle, WA, USA, 2 Kenyatta National Hospital, Nairobi, Kenya Background: HIV retesting during pregnancy/postpartum is crucial for early detection and treatment of incident maternal HIV infection, and to

773 INCIDENT HIV INFECTION AMONG PREGNANT WOMEN IN BOTSWANA Gloria K. Mayondi 1 , Modiegi D. Diseko 1 , Judith Mabuta 1 , Sonya Davey 2 , Arielle Isaacson 1 , Sikhulile Moyo 1 , Chelsea Morroni 1 , Mompati O. Mmalane 1 , Joseph

CROI 2019 299