Safety and Pharmacokinetics of Nelfinavir During the Second and Third Trimesters of Pregnancy and Postpartum

Purpose: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women. Methods: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. Results: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. Conclusions: Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy

The Impact of Race/Ethnicity on Mother-to-Child HIV Transmission in the U.S. in Pediatric AIDS Clinical Trials Group Protocol 316

The present analysis was designed to determine whether race/ethnicity was independently associated with mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intra-partum nevirapine in combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity, predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression models were fit to evaluate possible association of factors with HIV transmission and with viral load at delivery. Variables associated with the outcome at P \u3c 0.05 level were retained in the final models. Of 1052 women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206 (23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic (11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant (0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women were more likely than white women to start therapy during their current pregnancy but did not initiate prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P \u3c or = 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P = 0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have significant implications for the health of these women and their newborns. Race/ethnicity is significant in predicting viral suppression at the time of delivery

Maternal Toxicity and Pregnancy Outcome According to Antiretroviral Therapy during Pregnancy: An analysis of the PACTG 316 Study

BACKGROUND: Antiretroviral therapy (ART) during pregnancy reduces the risk of perinatal transmission of HIV-1 but may increase the risk of pregnancy complications. Pregnancy may enhance toxicity of ART. We evaluated rates of maternal toxicity, adverse pregnancy outcomes, and maternal peripartum morbidity according to the type and duration of ART taken during pregnancy. METHODS: PACTG 316 evaluated if the addition of intrapartum/neonatal nevirapine to established ART during pregnancy reduced perinatal transmission of HIV-1. Detailed data were collected on maternal ART use throughout pregnancy. For this analysis, women were categorized into 1 of 6 groups based on type of therapy during pregnancy (monotherapy [monoRx], combination without protease inhibitor [PI], combination with PI) and start date (early = before pregnancy or during first trimester, late = begun second or third trimester). Outcomes were determined from signs/symptoms, diagnoses, laboratory results forms prospectively completed on study at enrollment, delivery and 6 wks postpartum. RESULTS: A total 1,409 women were included in the analysis: 290 monoRx early, 34 monoRx late, 175 combo no PI early, 327 combo no PI late, 263 combo PI early, and 320 combo PI late. The most common symptoms anytime during pregnancy (moderate grade or higher) were vaginal bleeding 5.5%, nausea/vomiting 2.7%, and headache 2.2%. The most frequent lab abnormalities were anemia ( 2.5 x ULN) 1.1%. Mean gestational age at delivery was 38.1 wks and mean birth weight was 3078 g. Stillbirth occurred in 0.4%. Bacterial pneumonia occurred in 3% of women and AIDS-associated pneumonia in 2% during pregnancy or the postpartum period. Peripartum complication rates were low and depended on delivery mode. Event rates did not differ by antiretroviral group or study treatment assignment. CONCLUSIONS: In this population of HIV-infected women receiving prenatal care and ART, adverse events were uncommon and did not differ by type and duration of ART. Pneumonia occurred relatively frequently during pregnancy