Scott Greenhalgh1, Charlotte V Hobbs2,3,4, Sunil Parikh5. 1. Department of Mathematics, Siena College, Loudonville, NY. 2. Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD. 3. Department of Pediatrics, Division of Infectious Disease and Immunology, New York University School of Medicine, New York, NY. 4. Department of Microbiology, University of Mississippi Medical Center, Jackson, MS. 5. Yale School of Public Health, New Haven, CT.
Abstract
BACKGROUND: We previously used mathematical modeling to predict reduced malaria incidence in children with protease inhibitor (PI)-, compared with nonnucleoside reverse transcriptase inhibitor-, based highly active antiretroviral therapy (HAART), in moderate to high malaria transmission areas. These effects were accounted for, in part, by pharmacokinetic (PK) interactions between PIs and artemether-lumefantrine (AL). OBJECTIVE: Because of potentially reduced malaria transmission reservoirs in HIV-infected children due to PI/AL PK interactions impacting non-HIV-infected children, we estimate the antimalarial benefit of PI-based HAART in all children, and in HIV-infected children only residing in low to moderate malaria transmission areas. DESIGN: A dynamic model of malaria transmission was developed to evaluate the PK interaction of PI-based HAART with the antimalarial, AL for preventing malaria. METHODS: To evaluate the benefit of HIV PI-based HAART on malaria incidence, a malaria transmission model with varying degrees of HIV newborn prevalence was developed using recent pediatric clinical trial data in Lilongwe, Malawi. RESULTS: Comparing situations of low to high HIV newborn prevalence, and low to moderate malaria transmission intensities, our model predicts the combination of PI-based HAART with AL-treated malaria prevents 0.04-24.8 and 0.05-34.5 annual incidences of malaria overall per 1000 children, and saves 0.003-1.66 and 0.003-2.30 disability-adjusted life years per 1000 children, respectively. When incorporating seasonality, 0.01-7.3 and 0.01-5.9 annual incidences of malaria overall per 1000 children, and 0.0-0.5 and 0.001-0.41 disability-adjusted life years per 100 children, are prevented, respectively. CONCLUSIONS: In low to moderate malaria transmission intensity areas, PI-based HAART may reduce malaria events in children when AL is used.
BACKGROUND: We previously used mathematical modeling to predict reduced malaria incidence in children with protease inhibitor (PI)-, compared with nonnucleoside reverse transcriptase inhibitor-, based highly active antiretroviral therapy (HAART), in moderate to high malaria transmission areas. These effects were accounted for, in part, by pharmacokinetic (PK) interactions between PIs and artemether-lumefantrine (AL). OBJECTIVE: Because of potentially reduced malaria transmission reservoirs in HIV-infectedchildren due to PI/AL PK interactions impacting non-HIV-infectedchildren, we estimate the antimalarial benefit of PI-based HAART in all children, and in HIV-infectedchildren only residing in low to moderate malaria transmission areas. DESIGN: A dynamic model of malaria transmission was developed to evaluate the PK interaction of PI-based HAART with the antimalarial, AL for preventing malaria. METHODS: To evaluate the benefit of HIV PI-based HAART on malaria incidence, a malaria transmission model with varying degrees of HIV newborn prevalence was developed using recent pediatric clinical trial data in Lilongwe, Malawi. RESULTS: Comparing situations of low to high HIV newborn prevalence, and low to moderate malaria transmission intensities, our model predicts the combination of PI-based HAART with AL-treated malaria prevents 0.04-24.8 and 0.05-34.5 annual incidences of malaria overall per 1000 children, and saves 0.003-1.66 and 0.003-2.30 disability-adjusted life years per 1000 children, respectively. When incorporating seasonality, 0.01-7.3 and 0.01-5.9 annual incidences of malaria overall per 1000 children, and 0.0-0.5 and 0.001-0.41 disability-adjusted life years per 100 children, are prevented, respectively. CONCLUSIONS: In low to moderate malaria transmission intensity areas, PI-based HAART may reduce malaria events in children when AL is used.
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