CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

Conclusions: In treated HIV-infected women, monocyte activation and inflammation decline during pregnancy and remain low postpartum. While D-dimer increases during pregnancy, likely due to venous stasis, it declines in the postpartum period and is thus unlikely to explain postpartummortality. Conversely, IDO activity increases significantly during the postpartum period for at least 6-9 months, potentially increasing the risk of infectious complications. These pregnancy-related immunologic changes may support earlier ART initiation in women of reproductive age and/or closer post-partummonitoring for those who start ART at low CD4+ T cell counts. 900 T-Cell Activation and Exhaustion in HIV-Infected and HIV-Uninfected Pregnant Women Christina Fiske ;Vlada Melekhin; Fernanda Maruri; Cindy Hager; Louise Barnett;Timothy Sterling; Spyros Kalams Vanderbilt University School of Medicine, Nashville, TN, US Background: Pregnancy alters T cell phenotype and function, but the effect of pregnancy on the immune system in the setting of HIV infection is unclear. We compared the degree of T cell activation and exhaustion and regulatory T cell (Treg) frequency in HIV-infected women pre- and postpartum. Methods: We prospectively enrolled HIV-infected (HIV+) women on HAART and HIV-uninfected (HIV-) women and assessed immunologic parameters during the third trimester and at 24 weeks postpartum. We compared immune activation (CD38+ and HLA-DR expression), immune exhaustion of CD4+ and CD8+ cells (PD-1 expression), and Treg frequency (CD4+CD25 hi CD127 low FoxP3+) and function (CD39+ expression) between the two groups. Results: We enrolled 31 HIV- and 9 HIV+women. Twenty-seven HIV- and 7 HIV+women had both pre- and postpartum data available for analysis. Two HIV+women experienced postpartum viral load rebound (increase of >0.7log 10 compared to prepartum). There was no difference in prepartum levels of CD4+ or CD8+ T cell activation between the two groups. Compared to HIV- women, HIV+women had higher postpartum levels of CD4+CD38+HLA-DR+ (0.3%(0.2,4.4) v. 0.2%(0.1,0.3), p=0.02) and CD8+CD38+HLA-DR+ (1.6%(0.5,5.7) v. 0.5%(0.3,0.9), p=0.08) T cells. These differences were no longer statistically significant when HIV+women with postpartum viral rebound were excluded, though the point estimates were the same. Compared to HIV- women, HIV+women had higher postpartum expression of PD-1 on CD4+ (1.4%(1.0,2.5) vs. 0.5%(0.3,1.1), p=0.03) cells but following exclusion of HIV+women that experienced postpartum viral rebound, this was of borderline significance (p=0.07). HIV+women had higher levels of PD-1 on CD8+ T cells both prepartum (8.1%(8,15.4) vs. 5.1%(3.1,7.6), p=0.04) and postpartum (11.3%(10.4,15.4) vs. 5.2%(3.7,8.5), p=0.01, respectively). The postpartum CD8+PD-1+ findings were significant after excluding the HIV+women that rebounded (p=0.03). There was no difference in pre- or postpartum Treg frequency, exhaustion, or function between the two groups. Conclusions: We found that HIV+ women had a higher postpartum frequency of CD4+ and CD8+ T cell activation compared to HIV- women and this may have been driven in part by postpartum viral load rebound. HIV+ women had higher levels of CD8+ exhaustion markers postpartum after controlling for postpartum viral load rebound. The mechanism of decreased CD8+ exhaustion during pregnancy in HIV-infected women should be further explored. 901 HIV and Smoking Associated with Shorter Telomere Length in a Cohort of Pregnant Women Background: Shorter leukocyte telomere length (LTL) has been reported in HIV + adults. Combination antiretroviral therapy (cART), HIV proteins, and chronic inflammation/ oxidative stress can all potentially affect telomerase activity and/or LTL, a marker of aging and predictor of lifespan, and pregnancy may modify this effect. To evaluate this we investigated LTL in HIV+ and HIV- pregnant women to distinguish between the possible effects of HIV vs cART on LTL. Methods: HIV+ (n=108) and HIV- (n=68) pregnant women were enrolled in a prospective cohort study. In most women, relative LTL was assessed at three visits during pregnancy (1 st :13-23, 2 nd : 23-31, and 3 rd : 31-40 weeks of gestation), and for HIV+women, at delivery and 6 weeks post-partum. At each visit, possible predictors of LTL were examined by linear regression models that included age, HIV/cART status (HIV-, HIV+ on-cART, HIV+ off-cART), ethnicity, hepatitis C virus (HCV) Ab+, and smoking status. Among HIV+ women, on/off cART status was also examined. Paired t-test was used for within woman comparisons. Results: The HIV+ and HIV- groups were similar in age (31 ± 6 vs. 31 ± 5 years, p=0.49) but there were fewer Black/African Canadians, and HCV Ab+ women in the HIV- group (p<0.001). At the three pregnancy visits, 48, 45 and 44 % of participants reported smoking, with no difference between groups (p=0.24). CART initiation was pre-conception for 23%, 76% started cART during pregnancy and 50% continued post-partum. At 1 st visit, smoking (p=0.002) and HIV + status (p=0.012), irrespective of cART status, were associated with shorter LTL. At subsequent visits, a similar trend continued but no longer reached significance. No change in LTL was seen between the 1 st and 3 rd visits in HIV-(p=0.84) or HIV+ women receiving cART at both visits (p=0.11). However, in women who initiated cART after the 1 st visit, LTL at 3 rd visit was significantly longer (+5.5%, p=0.001) than at the 1 st . Post-partum LTL in HIV+ women was significantly shorter (P< 0.0001) than that measured at the 3 rd visit, irrespective of post-partum cART status although the effect size was greater among those off cART. Conclusions: In the context of pregnancy, cART initiation appears to improve LTL, possibly due to reduced inflammation and oxidative stress. Whether the post-partum LTL shortening is related to pregnancy ending or HIV/cART is unclear as post-partum samples were unavailable in controls. Of importance, in addition to HIV, smoking is also independently associated with shorter LTL. 902 Low Prolactin and High 20 α HSD May Contribute to cART-Induced P4 Deficits in Pregnancy Eszter Papp; Lena Serghides AAPHTeam Toronto General Research Institute, Toronto, Canada Background: Combination antiretroviral therapy (cART) has been linked to small birth weight, preterm delivery and other pregnancy complications. Our earlier results demonstrated that cART exposure was associated with decreased levels of progesterone (P4) mid-pregnancy in HIV-positive (HIV+) cART exposed women, which correlated with Sara Saberi 1 ; Beheroze Sattha 1 ; Evelyn Maan 2 ; JulieVan Schalkwyk 3 ; Deborah Money 1 ; Hélène Côté 1 On behalf of the CIHRTeam in Cellular Aging and HIV Comorbidities inWomen and Children (CARMA) 1 University of British Columbia, Vancouver, Canada; 2 BC Women’s Hospital and Health Centre, Vancouver, Canada; 3 Women’s Health Research Institute, Vancouver, Canada

Poster Abstracts

542

CROI 2015