PROTEASE INHIBITORS TO REDUCE MALARIA MORBIDITY IN HIV-INFECTED PREGNANT WOMEN
ClinicalTrials.gov Identifier: NCT00993031
Screening and enrolling into the study began in December, 2009 and closed in September 2012. Study activities are expected to continue until April, 2013.
This study is designed to compare a PI containing antiretroviral regimen (zidovudine, lamivudine, and lopinavir/ritonavir) to a non-PI regimen (zidovudine, lamivudine, and efavirenz), with the goal of reducing the morbidity of HIV and malaria among women at all CD4 counts and their children. Malaria represents a significant cause of morbidity and mortality for pregnant women and their offspring in Africa. Indeed, our primary goal will be to build on current knowledge to improve upon standard care to reduce the burden of HIV and malaria and to improve maternal and infant outcomes. Our study will also provide a unique opportunity to learn more about the interactions between HIV and malaria in pregnant and breastfeeding women in a high malaria transmission setting by testing the hypothesis that HIV PIs will reduce malaria-related morbidity in pregnant and breast feeding women.
The study aims are:
Specific Aim 1. To determine if the use of PI-based ART versus non-PI ART among HIV-infected pregnant women leads to reduced placental malaria and malaria related complications. We will test the hypothesis that HIV-infected pregnant women treated with a PI-based ART regimen will have reduced risk of placental malaria compared to women treated with a non-PI ART regimen. To address this hypothesis, 500 HIV infected pregnant women 12-28 weeks gestation will be randomized to a LPV/r vs. a non-PI ART regimen. All women will receive TS prophylaxis and an ITN. The primary endpoint of the study will be placental malaria. Secondary endpoints will include maternal anemia, maternal malaria and a composite clinical outcome of a) infant low birth weight, b) stillbirth and c) second-trimester spontaneous abortion.
Specific Aim 2. To compare the maternal and infant safety and tolerance profile of PI versus non-PI based ART during pregnancy and breastfeeding. We hypothesize that risk of adverse events for the LPV/r vs. non-PI based ART will not be significantly different among women and their exposed infants. To address this hypothesis, safety and tolerance will be compared between the two arms from study entry until 24 weeks postpartum. The primary endpoint will be Grade 3 or 4 toxicity in mothers and infants. Secondary endpoints will be obstetrical complications of preterm delivery and pre-eclampsia.
Specific Aim 3. To compare the virologic and immunologic efficacy of PI versus non-PI based ART in pregnant and breastfeeding women. We hypothesize that virologic and immunologic outcomes will not be significantly different between women receiving PI-based and non-PI-based ART. To address this hypothesis, virologic and immunologic outcomes will be compared at birth and after 24 weeks of ART. The primary endpoints will be prevalence of HIV RNA <400 copies/ml and CD4 cell counts at birth and at 24 weeks. Secondary endpoints will include development of HIV drug resistance, and maternal to child transmission of HIV (MTCT) at 24 weeks post partum.