Project Summary/Abstract Pregnant women with HIV in Africa have high rates of coinfection with malaria and sexually transmitted infections (STIs) that contribute to adverse maternal and birth outcomes including stillbirth, preterm delivery, low birth weight and vertical transmission of HIV. Malaria prophylaxis improves maternal and perinatal outcomes but current regimens are limited by emerging resistance and serious interactions with medications that are used in patients with HIV. The identification of a novel drug regimen with dual prevention for both malaria and curable bacterial STIs in pregnancy would be an important innovation toward improved outcomes in this vulnerable group of women and infants. To address this pressing problem, this K23 application describes the background and experience of the applicant, Jodie A. Dionne-Odom, MD and her plan to acquire the knowledge and training necessary to become an independent, leading scientist in the prevention and treatment of coinfections in HIV-infected pregnant women in sub-Saharan Africa. Her K23 training objectives are to: (1) develop expertise in the design and conduct of clinical trials in resource-limited settings (2) gain advanced training in epidemiology and biostatistics including perinatal epidemiology, drug safety monitoring and infection modeling techniques; (3) acquire skills in measuring malaria and STI endpoints and (4) gain additional training in performing human subjects research and grant and manuscript preparation. To meet these objectives, a comprehensive training plan has been developed in concert with an interdisciplinary team of mentors and consultants who are established senior research experts. The plan includes hands-on learning, coursework leading to an MSPH in Clinical and Translational Science and supplemental short courses and conferences. Equipped with this training, Dr. Dionne-Odom will conduct research to test whether a novel combination prophylactic regimen of trimethoprim-sulfamethoxazole (TMPS) and azithromycin (AZ) is superior to the current standard malaria prophylaxis (TMPS) and whether it has the added benefit of reducing STI prevalence. In Specific Aim 1, a phase II randomized controlled trial will be performed to test the efficacy of the combination prophylaxis regimen TMPS-AZ compared to TMPS in HIV-infected pregnant women. The primary efficacy outcome will be a decrease in the peripheral malaria parasite load at delivery. In Specific Aim 2, the prevalence of treatable bacterial STIs after 35 weeks gestation (or delivery) will be measured and compared between both arms. In Specific Aim 3, the fetal/neonatal safety and adherence/tolerability of the combination regimen will be determined. Data from this phase II trial will be used to support an R-01 phase III multicenter randomized controlled trial in sub-Saharan Africa. The training acquired from this award in combination with results from this project will facilitate the successful transition of Dr. Dionne-Odom to research independence and success.

Project Narrative More than 3 billion people worldwide are at risk of acquiring malaria and HIV-infected pregnant women in Africa are at particular risk. An effective prophylaxis regimen capable of preventing malaria and other common perinatal infections would have great potential to improve adverse birth outcomes. The proposed study is to evaluate a new combination prophylaxis regimen in pregnant women with HIV in Cameroon to determine its efficacy and safety.