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Prevention of Malaria and HIV Disease in Tororo,Uganda

Contact person: Diane Havlir, MD; dhavlir@php.ucsf.edu

The PROMOTE program establishes new approaches to reduce HIV and malaria burdens in sub-Saharan Africa, and enhances the public health approach to both diseases. The PROMOTE program is funded by NIH and protease inhibitor (PI) drugs donated by Abbott Labs and consists of 5 projects. Three of the projects are interlinked hypothesis-based intervention cohort trials. The other 2 projects are linked to all of the clinical trials and utilize data and specimens from each of these trials to characterize nutrition and drug resistance. The PROMOTE program is being conducted in Tororo District, Uganda, a rural area with HIV seroprevalence of 8% and malaria transmission intensity of 562 infective bites per person year, and started accruing participants in October 2009. The five projects of this program are:


A randomized open label trial of HIV protease inhibitors for the prevention of malaria in HIV-infected children will enroll 300 HIV-infected children with the aim of determining if the use of PI-based (LPV/r) ART versus NNRTI-based ART among HIV-infected children will reduce the incidence density of malaria in children.

PROMOTE-Pregnant Women and Infants (PIs)

Protease inhibitors to reduce malaria morbidity in HIV-infected pregnant women will enroll 500 HIV-infected pregnant women with the primary objective of determining if the use of PI-based ART versus non-PI ART among HIV-infected pregnant women leads to reduced rates of placental malaria as measured by Giemsa-stained smear or polymerase chain reaction (PCR) of placental blood.


A randomized trial of monthly dihydroartemisinin-piperaquine versus monthly sulfadoxine-pyrimethamine versus daily trimethoprim-sulfamethoxazole versus no therapy for the prevention of malaria will enroll 400 HIV-unexposed infants and 200 HIV-exposed infants with the aim of comparing the incidence of malaria among these infants enrolled at 4-5 months of age and randomized to one of the four arms listed above until they reach the age of 24 months.


This project evaluates the nutritional status of PROMOTE program participants, identifying factors which increase the risk of nutritional deficiency and subsequent poor clinical outcomes, correlating levels of malnutrition and ART pharmacokinetic exposure and response, and pilots a nutritional supplementation strategy tailored to routine practice in resource limited settings.

PROMOTE-Drug Resistance

This program project includes three randomized clinical trials to test whether long-term use of chemopreventive antimalarial therapies in children or of antiretroviral protease inhibitors in children or pregnant women will decrease the incidence of malaria and related malarial morbidity. These interventions offer the opportunity to significantly decrease the incidence and morbidity of malaria, the most important infectious disease in children and pregnant women in Africa. However, repeated or chronic therapy for infectious diseases routinely entails a risk of selection of drug-resistant parasites. This is a particular concern for malaria, as drug resistance already limits treatment options, and control efforts based of intermittent therapy have relied heavily on antifolates, against which resistance is increasing.

Key Publications
  1. A trial of lopinavir/ritonavir-based versus non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy for the prevention of malaria in HIV-infected Ugandan children. Achan J, Kakuru A, Ikilezi G, Ruel T, Clark TD, Nsanzabana C, Charlebois ED, Aweeka F, Dorsey G, Rosenthal PJ, Havlir DV, Kamya MR. In review.
  2. In vitro activity of antiretroviral drugs against Plasmodium falciparum. Nsanzabana C, Rosenthal PJ. Antimicrob Agents Chemother. 2011 Nov;55(11):5073-7. Epub 2011 Aug 29.
  3. Maternal nutritional status predicts adverse birth outcomes among HIV-infected rural Ugandan women receiving combination antiretroviral therapy. Young SL, Murray K, Mwesigwa J, Natureeba P, Osterbauer B, Achan J, Arinaitwe E, Clark TD, Ades V, Charlebois ED, Ruel T, Kamya MR, Havlir DV, Cohan DL. PLoS One, In press.