HIV treatment interferes with malaria meds

The overlapping disease burdens of HIV and malaria in sub-Saharan Africa continue to pose an enormous health threat to millions of people, many of whom are children.

While antiretroviral therapy (ART) regimens are increasingly being used to effectively suppress HIV, these same drugs can dramatically change the effectiveness of an antimalarial therapy for patients who are being simultaneously treated for both diseases.

A new study led by a researcher at the Yale School of Public Health and published in the journal Clinical Infectious Diseases finds that some ART regimens considerably alter the effectiveness of an antimalarial, known as artemether-lumefantrine, the most widely used antimalarial worldwide.

Sunil Parikh, M.D., assistant professor in the Department of Epidemiology of Microbial Diseases, co-led a team of 11 other scientists from Africa and the University of California, San Francisco, to determine the optimal treatment combination for people co-infected with the diseases.

The study focused on children in Uganda and examined three antiretroviral therapies, finding widely varying results on how they impacted the effectiveness of the antimalarial. Specifically, an ART known as efavirenz, which is recommended as first-line by the World Health Organization for individuals over 3 years of age, significantly reduced the efficacy of the antimalarial drug, while patients taking a different ART, known as lopinavir/ritonavir, first-line for children under 3 years of age, had a much lower rates of recurrent malaria. Children taking efavirnez were found to have 4-fold higher odds of recurrent malaria. These clinical changes stem from dramatic drug-to-drug pharmacokinetic (PK) interactions, coupled with a potential direct impact of lopinavir/ritonavir on killing parasites.

“The choice of which antiretroviral therapy is being used can make a tremendous difference in health outcomes,” said Parikh. “This has been a rewarding study which started with laboratory findings, that we have now translated into the field. Our next step is to see whether we can either improve outcomes in efavirenz-treated individuals by altering the antimalarial regimen, or whether we have to advocate more strongly for a different first-line regimen in co-endemic settings.”

Large PK studies of ill children are difficult to do, so the HIV-malaria study is particularly valuable, noted the editors of UNAIDS Science now.

HIV and malaria continue to be major health concerns in the region. Some 25 million people in sub-Saharan Africa live with HIV and in 2013 there were 198 million malaria cases, with the vast majority of which were in the same region of Africa. Further study in co-infected individuals is clearly needed.

Parikh specializes in malaria and has worked in Africa for years, particularly in Uganda, Burkina Faso and Nigeria, to better understand the treatment options for the disease, as well as how early host responses and genetic variation impact responses to infection. He recently participated in revising the World Health Organization’s third edition of the Guidelines for the Treatment of Malaria, released in April 2015.

While the incidence of malaria has started to decline as a result of concentrated international efforts, the disease remains a major killer. Close to 600,000 people died from the disease in 2013. In some regions of Uganda alone, people are infected on average up to six times a year by the mosquito-borne parasite.

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