Improving maternal child health among HIV-infected pregnant women and their children in Africa requires strategies that effectively address HIV and co-morbidities. Success of antiretroviral therapy is resulting in a growing population of HIV -exposed uninfected (HEU) children, still suffering poor outcomes. A high malaria burden among pregnant women and children, despite insecticide treated nets and trimethoprim- sulfamethoxazole (TS), contribute to these poor outcomes. Dihydroartemisinin-piperaquine (DP), an artemisinin combination therapy (ACT) with a long post treatment prophylactic effect, is highly effective and safe for malaria treatment in pregnant women and children but has not been evaluated for malaria prevention. We propose to test the hypothesis that enhanced malaria chemoprevention (DP +TS) vs. TS in pregnant women and their children during the first 2 years of life will reduce the incidence of malaria during the first 2 years of life. This hypothesis is based on observations that maternal and placental malaria increase the risk of infant malaria and that DP chemoprevention of HEU reduces malaria incidence. Additionally, we will evaluate the safety and pharmacokinetics of DP including interactions with efavirenz and examine malaria incidencein HEU after malaria chemoprevention discontinuation at 2 years of age. We plan to test our hypotheses in a double-blind, placebo-controlled, randomized tnal of HIV-infected pregnant women in Tororo, Uganda, an area of high malaria transmission. The primary study endpoint is malaria incidence in children from birth to 24 months. Our 3 aims are: 1) To determine if enhanced (DP+TS) versus standard malana chemoprevention (TS) during both pregnancy and infancy reduces malaria during the first 24 months of life. W e will randomize 200 HIV-infected pregnant women to monthly DP+daily TS vs monthly placebo+daily TS during pregnancy. Infants will receive the same prevention regimen as their mother for 24 months. 2) To evaluate safety of monthly DP given for malaria prevention during pregnancy and early childhood. We will compare grade 3 and 4 toxicity and birth outcomes between the arms 3) To evaluate the pharmacokinetic exposure of concomitant DP and efavirenz during pregnancy. We will perform intensive PK for DP and EFV during the 3"^ trimester and compare DP between HIV infected and uninfected pregnant women.

Public Health Relevance

This study seeks to advance the current public health framework of maternal child health from reduction of perinatal HIV transmission to elimination of perinatalHIV transmission and malaria at the most vulnerable time period-the first 2 years of life.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
2P01HD059454-06A1
Application #
8614265
Study Section
Special Emphasis Panel (ZRG1-AARR-D (42))
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-06-30
Support Year
6
Fiscal Year
2013
Total Cost
$350,403
Indirect Cost
$72,624
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Ruel, Theodore D; Kakuru, Abel; Ikilezi, Gloria et al. (2014) Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to lopinavir/ritonavir or nonnucleoside reverse transcriptase inhibitor therapy. J Acquir Immune Defic Syndr 65:535-41
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