CROI 2016 Abstract eBook

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Poster Abstracts

772 Trends in Hospitalizations of Pregnant HIV-InfectedWomen in the USA: 2004-2011 Alexander Ewing 1 ; Hema Datwani 2 ; Lisa Flowers 1 ; Sascha Ellington 1 ; Denise Jamieson 1 ; Athena P. Kourtis 1 1 CDC, Atlanta, GA, USA; 2 CDC, Philadelphia, PA, USA

Background: Although patterns of hospitalizations of HIV-infected pregnant women in the U.S. have changed with the introduction of combination antiretroviral therapy (cART), increased rates of adverse outcomes among HIV-infected, compared with uninfected, women have persisted. There is a lack of recent evidence on the hospitalization burden among HIV-infected pregnant women in the U.S. and of estimates of deliveries among such women. Methods: Using hospital discharge data from the Nationwide Inpatient Sample’s years 2004, 2007 and 2011, we compared the numbers, demographic characteristics and morbidity outcomes of hospitalizations of pregnant women by HIV status in the U.S. Multivariate logistic regression was used to examine time trends, adjusting for confounders. Analyses were weighted to produce national estimates. Results: In 2011, there were 4,751 estimated pregnancy hospitalizations, including 3,855 delivery hospitalizations for HIV-infected pregnant women, unchanged since 2004. In 2011, compared with those of HIV-uninfected women, pregnancy hospitalizations of HIV-infected women, on average, were longer, incurred higher hospital charges, were more likely to be in the South, and to be covered by public insurance. They also had higher odds of many adverse outcomes, including preterm delivery (aOR: 1.46 [95% CI: 1.19-1.79]), preeclampsia/hypertensive disorders of pregnancy (aOR: 1.44 [1.16-1,80]), bacterial infections (aOR: 2.90 [1.88-4.47]) and viral/mycotic/parasitic infections (aOR: 5.56 [4.21, 7.35]). From 2004-2011, prevalence of hospitalizations with gestational diabetes and pre-eclampsia/hypertensive disorders of pregnancy increased for both HIV-infected and uninfected women. Prevalence of bacterial infections increased only among hospitalizations of HIV-infected pregnant women. Conclusions: The numbers of hospitalizations during pregnancy and of deliveries have not increased for HIV-infected women since 2004. Pregnancy hospitalizations of HIV- infected women remain more medically complex than those of HIV-uninfected women. An increasing trend in infections among the hospitalizations of HIV-infected pregnant women and increasing trends in gestational diabetes and hypertensive disorders of pregnancy among both HIV-infected and uninfected women warrant further attention. 773 Cost-Effectiveness of Cotrimoxazole Among HIV+ Pregnant Women in Malarious Regions Background: Malaria is a leading cause of morbidity and mortality among HIV+ pregnant women in East Africa. The pregnancies of at least 1 million women are complicated by co-infection of malaria and HIV annually. Current guidelines recommend either cotrimoxazole (CTX) or intermittent preventive treatment (IPTp) for HIV+ pregnant women to prevent malaria and its complications. While daily CTX makes its schedule simple, concerns remain over adherence and discontinuation of CTX at high CD4 counts. We assess the cost-effectiveness of CTX compared with IPTp to prevent malaria among HIV+ pregnant women. Methods: We constructed an individual-level microsimulation model of malaria and HIV among pregnant women, matched by CD4 count, and antiretroviral therapy and malaria statuses to the Malawi population. Cohorts of 10,000 HIV+ pregnant women were simulated for a 40-week pregnancy period. We compared 3 strategies:(i) 0/1-doses IPTp, (ii) 3-dose IPTp, and (iii) daily CTX. Our primary outcomes include maternal malaria episodes, anemia, low birth weight, and neonatal mortality. We estimated disability-adjusted life-years (DALYs) averted for the CTX and 3-dose IPTp strategies compared with the 0/1-doses IPTp. Costs were estimated based on data from observational studies and published literatures. Sensitivity analyses assessed the effect of adherence to CTX, its efficacy in preventing malaria, and the risk of malaria. Results: Compared with 0/1-doses IPTp, 3-dose IPTp averted 43.6 DALYs per 100 pregnant women at an estimated cost of $70.3, an incremental cost-effectiveness ratio (ICER) of $1.61. The CTX strategy was associated with additional 15.8 DALYs averted per 100 women compared with 3-dose IPTp at an incremental cost of $16.8, an ICER of $1.06. The CTX strategy was less effective than 3-dose IPTp when more than 1.8% of pregnant women dropped out of CTX every week, less than 46% of women taking CTX for the duration of pregnancy. When the risk of malaria was 40% lower than the base case scenario, the DALYs and estimated costs from CTX and 3-dose IPTp strategies were not significantly different: both averted 43.4 additional DALYs compared with 0/1-doses IPTp. One-way sensitivity analyses on CTX efficacy, down to 50% of base case efficacy, did not substantially affect the primary findings. Conclusions: In malarious regions, daily CTX to HIV+ pregnant women regardless of CD4 count is more effective than IPTp, and highly cost-effective by standard measures as long as more than half of women adhere to daily dosing. 774 Intracellular Atazanavir Concentrations Remain Stable During Pregnancy in HIVWomen Emanuele Focà 1 ; Andrea Calcagno 2 ; Andrea Bonito 1 ; Marco Simiele 2 ; Elisabetta Domeneghini 1 ; Antonio D’Avolio 2 ; Maria Antonietta Forleo 1 ; Giovanni Di Perri 2 ; Eugenia Quiros Roldan 1 ; Stefano Bonora 2 1 Univ of Brescia, Brescia, Italy; 2 Univ of Torino, Torino, Italy Background: Several physiological changes occurring in the third trimester may impact the pharmacokinetics of administered drugs. Significant reductions in protease inhibitors (PIs) plasma concentration have been described and the correct dose in unclear in HIV-positive pregnant patients. Acting at the intracellular level, PIs intracellular (peripheral blood mononuclear cells, PBMC) concentrations may be relevant and they have not been studied during pregnancy. Methods: HIV-positive pregnant patients treated with atazanavir/ritonavir (300/100 mg, ATV/r) plus either tenofovir/emtricitabine or abacavir/lamivudine were prospectively enrolled after signing a written informed consent. ATV and ritonavir (RTV) plasma and intracellular (IC, intra PBMCs) were measured at every visit [second (2T) and third trimester (3T) and within 3 months post-partum (PP)] using validated HPLC/MS-MS methods (with direct evaluation of cells volume). Data are described as medians (interquartile ranges) and through non-parametric tests. Results: 20 patients were enrolled; median age and body mass index were 31.4 years (25.8-35.6) and 24.7 Kg/m 2 (23-32.5). All patients were on treatment with plasma HIV RNA <50 copies/mL; CD4+ T-lymphocytes were 738 /uL (529-833). ATV plasma concentrations were 526 ng/mL (334-1066), 474 ng/mL (317-969) and 740 ng/mL (589-1132) during 2T (n=12), 3T (n=14) and PP (n=15); respective ICs were 723 ng/mL (569-1615), 762 ng/mL (382-1141) and 555 ng/mL (364-1930). RTV plasma concentrations were 35 ng/mL (29-57), 25 ng/mL (12-53) and 65 ng/mL (23-137) during 2T, 3T and PP; respective ICs were 1146 ng/mL (964-1676), 804 ng/mL (526-1511) and 986 ng/mL (613-1461). ATV intra/plasma ratios were 1.25 (1.12-1.89), 1.36 (0.61-2.68) and 1.05 (0.52-2.37); RTV intra/plasma ratios were 33.19 (22.75-46.39), 29.21 (14.80-63.12) and 16.6 (7.19-1.36). ATV ICs concentrations and intra/plasma ratios showed non-significant changes over time (Wilcoxon’s p>0.05) while RTV intra/plasma ratios were lower during the third trimester and postpartum (p=0.03 and p=0.05). Conclusions: Intracellular ATV exposure was unchanged during second and third trimester supporting the standard ATV/RTV 300/100 mg dosing throughout pregnancy. 775 Pharmacokinetics of Increased Dose Darunavir During Late Pregnancy and Postpartum Alice Stek 1 ; Brookie M. Best 2 ; Edmund Capparelli 2 ; JiajiaWang 3 ; David E. Shapiro 4 ;Tim R. Cressey 5 ; Elizabeth Smith 6 ; Regis Kreitchmann 7 ; Nahida Chakhtoura 8 ; Mark Mirochnick 9 1 Univ of Southern California, Los Angeles, CA, USA; 2 Univ of California San Diego, San Diego, CA, USA; 3 Harvard Sch of PH, Boston, MA, USA; 4 Cntr for Biostatistics in AIDS Rsr, Harvard Sch Of PH, Boston, MA, USA; 5 Harvard Sch of PH, Boston, MA, USA; 6 NIAID, NIH, Bethesda, MD, USA; 7 Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; 8 Eunice Kennedy Shriver NICHD, Bethesda, MD, USA; 9 Boston Univ Sch of Med, Boston, MA, USA Background: IMPAACT P1026s previously demonstrated that during pregnancy darunavir (DRV) exposure was reduced by 26% compared to postpartumwith DRV/ritonavir (RTV) 600/100 mg bid. We hypothesized maternal plasma DRV exposure during pregnancy would increase with DRV/RTV 800/100 mg bid. Methods: IMPAACT P1026s is an ongoing, non-blinded study of antiretroviral pharmacokinetics (PK) in pregnant women that includes a cohort in the USA taking DRV/RTV 800/100 mg bid. Intensive steady-state 12 hour PK profiles were performed during the 2 nd trimester (2T), 3 rd trimester (3T) and 2-6 weeks postpartum (PP). DRV and RTV plasma Sung Eun Choi ; Eran Bendavid Stanford Univ, Stanford, CA, USA

Poster Abstracts

322

CROI 2016