HIV drug combo Trimethoprim-sulfamethoxazole highly effective at preventing malaria

A drug combination used to prevent pneumonia and opportunistic bacterial infection in persons with HIV/AIDS has unexpectedly been found to be highly effective at preventing malaria, according to a study published in the November 15 issue of The Journal of Infectious Diseases, now available online.

The combination, trimethoprim-sulfamethoxazole (TS), is known to reduce morbidity and mortality from certain opportunistic infections in HIV-infected individuals, and is widely recommended for individuals with advanced disease, both in developed and developing countries. In addition, TS shares many properties--including resistance patterns--with a leading anti-malarial therapy, sulfadoxine-pyrimethamine (SP), causing concern that widespread use of TS prophylaxis might increase the number of malarial parasite strains resistant to SP treatment, thereby increasing the risk that SP treatment may fail in HIV-infected individuals who contract malaria.

These concerns prompted Christopher V. Plowe, MD, MPH, and colleagues at the University of Maryland School of Medicine and the Malaria Research and Training Center at the University of Bamako to conduct a study to determine whether TS prophylaxis impairs SP efficacy for treating malaria. The investigators studied 160 children (aged 5-15 years) given TS prophylaxis and 80 children in a control group receiving no preventive treatment in Mali, where malaria is endemic and rates of HIV infection in children are low. Plowe and colleagues were expecting to compare the success of SP treatment on malarial episodes in both groups. What they encountered, however, was just a single clinical episode of malaria in the TS group, and the infected individual had an adequate clinical and parasitological response to SP. In the control group, there were 72 episodes of malaria and three instances of SP failure.

Lack of malarial episodes in the TS group precluded meaningful comparison of SP efficacy in the TS and control groups, but, importantly, TS was shown to be a highly effective prophylactic agent against malaria in this population, reducing the incidence by 99.5%.

In addition to being protected against malaria, children in the TS group also experienced fewer gastrointestinal illnesses and had slightly higher hemoglobin levels than those in the control group. The authors pointed out that such benefits did not mean that routine TS prophylaxis should be used in healthy children but that they did "mitigate concerns about TS use in HIV-exposed children whose HIV status is not yet known."

Although the authors cautioned that studies of SP efficacy in persons taking TS prophylaxis are still needed and that SP should be used only with caution in those taking TS who contract malaria, "based on the results of this study and the clear evidence that TS prevents death in persons living with HIV in a variety of African settings, concerns about spreading SP resistance do not justify further delays in implementing TS prophylaxis."