ArticlesEffect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study
Introduction
Malaria and HIV-1 are two of the most common infections in sub-Saharan Africa.1 Malaria has been associated with a rise in HIV viral load,2, 3 and a fall in CD4-cell count,4 potentially worsening the clinical course of people with HIV infection. Malaria also seems to be more common5, 6, 7, 8 and more severe in HIV-infected adults,9 pregnant women,10 and children11 than in people without the virus.
Prevention of malaria in HIV-infected people living in endemic areas is increasingly regarded as a part of basic HIV care.12 Identification of the best methods for reducing the incidence of malaria in adults with HIV infection and better understanding of the relation between HIV disease and the incidence of malaria could improve clinical and public-health strategies, especially in areas with high HIV prevalence and malaria incidence in adults.1 Prophylaxis with co-trimoxazole (trimethoprim and sulfamethoxazole) can reduce the incidence of malaria, as well as mortality, in HIV-infected people in Africa,13, 14 and is recommended by the WHO.15 Insecticide-treated bednets also reduce the incidence of malaria and associated morbidity in children and pregnant women,16 but their benefits have not been assessed in adults with HIV. Antiretroviral therapy (ART) is linked to HIV virus suppression, reconstitution of immune response, and decreased mortality in HIV-infected people, and is increasingly available in malaria-endemic areas. To assess the effect of ART on the frequency of clinical malaria in people with HIV, and the additive effects of co-trimoxazole prophylaxis, ART, and insecticide-treated bednets, we analysed data from two prospective cohort studies, one of co-trimoxazole prophylaxis, and the other of ART in HIV-infected people in rural Uganda.
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Participants
We undertook two sequential studies in HIV-1-infected adults who were clients of the AIDS Support Organization (TASO) in Tororo and Busia Districts in Uganda—both areas with high-intensity transmission of malaria.17, 18 Interventions were prospectively introduced in phases: phase 1 no intervention; phase 2 co-trimoxazole prophylaxis; phase 3 co-trimoxazole prophylaxis and ART; and phase 4 co-trimoxazole, ART, and insecticide-treated bednets (figure). Study methods and results for phases 1 and 2
Results
466 HIV-infected participants aged 18 years or older were enrolled in phase 1; the median age was 35 years (IQR 30–41); 75% were women (figure). 399 participants survived and continued to phase 2 (co-trimoxazole prophylaxis); 138 of these participants survived, were clinically eligible for ART, and were enrolled in phase 3 (co-trimoxazole prophylaxis and ART). 897 additional participants were enrolled at the start of phase 3 to make a total of 1035. 985 of these survived and received bednets;
Discussion
The provision of co-trimoxazole, ART, and bednets was associated with a 95% fall in the frequency of malaria from 50·8 to 2·1 episodes per 100 person-years in HIV-infected adults. Two of these interventions are recommended for other reasons, including their substantial effect on preventing mortality from HIV infection and AIDS.15, 20
The addition of ART to a cohort of HIV-infected people already receiving co-trimoxazole prophylaxis was associated with a 64% fall in malaria incidence. HIV
References (28)
- et al.
Effect of Plasmodium falciparum malaria on concentration of HIV-1 RNA in the blood of adults in rural Malawi: a prospective cohort study
Lancet
(2005) - et al.
Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study
Lancet
(2000) - et al.
Effect of malaria on HIV-1 progression and transmission
Lancet
(2005) - et al.
Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial
Lancet
(1999) - et al.
Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4 cell count, and HIV viral load among persons with HIV in rural Uganda
Lancet
(2004) - et al.
Resistance in vivo of Plasmodium falciparum to co-trimoxazole in western Uganda
Trans R Soc Trop Med Hygiene
(1998) - et al.
Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial
Lancet
(2002) - et al.
Malaria attributable to the HIV-1 epidemic, sub-Saharan Africa
Emerg Infect Dis
(2005) - et al.
The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration
AIDS
(1999) - et al.
Association between malaria and CD4 cell count decline among persons with HIV
J Acquir Immune Defic Syndr
(2006)
Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults
AIDS
HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya
AIDS
HIV, malaria parasites, and acute febrile episodes in Ugandan adults: a case-control study
AIDS
HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa
AIDS
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2018, International Journal of Infectious Diseases