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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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University of California San Francisco
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Prahl, Mary; Jagannathan, Prasanna; McIntyre, Tara I et al. (2016) Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation. Malar J 15:497
Jagannathan, Prasanna; Bowen, Katherine; Nankya, Felistas et al. (2016) Effective Antimalarial Chemoprevention in Childhood Enhances the Quality of CD4+ T Cells and Limits Their Production of Immunoregulatory Interleukin 10. J Infect Dis 214:329-38
Boivin, Michael J; Sikorskii, Alla; Familiar-Lopez, Itziar et al. (2016) Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children. Malar J 15:210
Kakuru, Abel; Natureeba, Paul; Muhindo, Mary K et al. (2016) Malaria burden in a birth cohort of HIV-exposed uninfected Ugandan infants living in a high malaria transmission setting. Malar J 15:500
Achan, Jane; Kakuru, Abel; Ikilezi, Gloria et al. (2016) Growth Recovery Among HIV-infected Children Randomized to Lopinavir/Ritonavir or NNRTI-based Antiretroviral Therapy. Pediatr Infect Dis J 35:1329-1332
Kakuru, Abel; Jagannathan, Prasanna; Muhindo, Mary K et al. (2016) Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy. N Engl J Med 374:928-39
Farrington, Lila A; Jagannathan, Prasanna; McIntyre, Tara I et al. (2016) Frequent Malaria Drives Progressive Vδ2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood. J Infect Dis 213:1483-90
Marquez, Carina; Chamie, Gabriel; Achan, Jane et al. (2016) Tuberculosis Infection in Early Childhood and the Association with HIV-exposure in HIV-uninfected Children in Rural Uganda. Pediatr Infect Dis J 35:524-9
Odorizzi, Pamela M; Feeney, Margaret E (2016) Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity. Trends Mol Med 22:877-888
Muhindo, Mary K; Kakuru, Abel; Natureeba, Paul et al. (2016) Reductions in malaria in pregnancy and adverse birth outcomes following indoor residual spraying of insecticide in Uganda. Malar J 15:437

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