CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

concentrations were measured using HPLC; DRV detection limit was 0.09 mcg/mL. Target DRV exposure was 43.6 mcg*hr/mL, > 70% of median AUC in non-pregnant adults on 600/100 mg. Results: PK data are available for 17 women (10 Black, 7 Hispanic). At 3T, median age (range) was 28.3 (18.5-41.8) yr, weight 80.7 (53.3-133.5) kg, gestational age (GA) 33.3 (30.1-34.9) wk, median duration of DRV/r use was 123 (3-316) wk. Median CD4 was 451/mm 3 (128-1140) in 3T and 469/mm 3 (220-1164) PP. VL was <400 in 3T and delivery in 15/16 women and in 12/15 women PP. Median (range) GA at delivery was 39.0 (32.6-41.0) wk; birthweight 3390 (1950–3970) g. 8 infants are confirmed HIV negative; for 9 status is pending. Table presents DRV and RTV PK data for these subjects and, for comparison, DRV PK data from our previous P1026s cohort receiving DRV/RTV 600/100 mg. Median DRV AUC with 800 mg dose during 3T was 36% lower than with 600 mg dose PP (not statistically significant, p=0.14). Geometric mean of the individual women’s 3T/PP ratios was 0.65 (90% confidence interval (CI) 0.54-0.78; p<0.001). C max and C last were significantly lower, and oral clearance was higher, in 3T compared to PP. While 63% (95% CI 35-85%) of the women met our AUC target in 3T, 93% (95% CI 68-100%) met the target PP, but this difference was not statistically significant. Conclusions: These data confirm that DRV exposure is decreased during the third trimester of pregnancy. Increasing the DRV dose to 800 mg during pregnancy failed to increase DRV exposure compared to 600 mg. While viral suppression was good in our subjects, if achieving DRV exposure during pregnancy equivalent to that in nonpregnant adults is desired, other strategies, such as increasing the RTV dose or using an alternative booster, will need to be investigated.

776 High Risk of Liver Enzyme Elevation in Pregnant Women Receiving Protease Inhibitors Jeanne Sibiude 1 ; JosianeWarszawski 1 ; RolandTubiana 2 ; Jérôme Le Chenadec 3 ; Françoise Meier 4 ; Eliane Galiba 5 ; Albert Faye 6 ; Stéphane Blanche 7 ; Laurent Mandelbrot 8 ; for the ANRS CO1/CO11-EPF French Perinatal Cohort Study Group 1 CESP, INSERM U1018, Le Kremlin-Bicêtre, France; 2 Sorbonne Univ, Paris, France; 3 INSERM, Le Kremlin-Bicêtre, France; 4 APHP, Hosp Louis Mourier, Colombes, France; 5 CHU de l’Archet, Nice, France; 6 Univ Diderot Paris 7, Sorbonne Paris-Cité, Paris, France; 7 Hosp Necker Enfants Malades, Paris, France; 8 Hosp Louis Mourier, Colombes, France Background: Antiretroviral therapy (ART) is recommended for all HIV-infected pregnant women and is highly effective in preventing vertical transmission of HIV. High rates of liver enzyme elevation (LEE) during pregnancy and some cases of severe hepatotoxicity have been reported, but the causes remain unclear. Surveillance including sequential liver function tests is recommended for all HIV+ pregnant women in France. Our objective was to estimate the prevalence, causes and risk factors of LEE in the national prospective French Perinatal Cohort. Methods: We studied the 6264 HIV+ pregnant women treated with ART, enrolled in the French Perinatal Cohort between 2005 and 2014, who had >1 normal measure of liver enzymes during pregnancy. Adjusted hazard ratio (aHR) for the association of LEE with ART were estimated using multivariate Cox models with ART as time-dependent variable, separately for women on ART at conception and for those starting ART during pregnancy. Results: Liver enzyme elevation (grade >1) was observed in 17.4% (n=1087), grade 3-4 in 2%. Two third occurred in the third trimester. Among women with LEE, 13% had active hepatitis B or C, 7% preeclampsia, 11% intrahepatic cholestasis of pregnancy, and less than 1% other identified causes (sickle cell disease, malaria or bile duct obstruction). More than 2/3 of LEE were unexplained: some of themwere the reason for hospitalizations (n=53), cesarean sections (14), inductions of labor (3), and changes in ART regimens (36). Unexplained LEE was significantly associated with higher risk of preterm births; p<0.001. In the women already on ART at conception, the risk of unexplained LEE was lower with NNRTI-based regimens (n=633) than with ritonavir-boosted protease inhibitors (PI/r n=1557): aHR=0.48 [0.29-0.79]. The risk was similar with boosted and non-boosted PIs (n=127): aHRs = 0.80 [95%CI 0.37-1.72] with no difference among the various PI drugs. Among the women initiating ART during pregnancy, most regimens included PIs (89%). Compared with lopinavir/r (the most prescribed PI), LEE were less frequent for nelfinavir, tended to be higher for darunavir/r, and similar for atazanavir/r (Table1). The few women who initiated NNRTI, NRTI monotherapy or dual therapy as first treatment were excluded from this analysis. Conclusions: The rate of LEE among HIV-infected women is high and impacts obstetrical care management. In most case, the cause remained undetermined. Our results suggest a possible role of PIs which needs further investigation.

Poster Abstracts

323

CROI 2016