Interactions between HIV and malaria in non-pregnant adults: evidence and implications

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IntroductionMalaria and HIV are two of the most common and important health problems facing developing countries. It is estimated that over 40 million people are living with HIV globally [1] and there are 350–500 million clinical malaria episodes annually [2]. Even modest interactions between the two infections would have substantial public health implications in resource-constrained countries, especially in subSaharan Africa, where both infections are highly prevalent.Our current immunological knowledge suggests potential for a detrimental interaction in both directions. HIV infection impairs T-cell immunity, which is of crucial importance for antimalarial responses [3]. Therefore, in theory, HIV immunosuppression should increase the risk and severity of malarial infection. In addition, malaria infection activates T-cells, promoting HIV replication [4,5]. Since increased HIV RNA levels are associated with accelerated disease progression [6,7], malaria could potentially facilitate faster progression to AIDS and death [8].Malaria–HIV interactions have been clearly demonstrated in young children, in whom malaria-induced anaemia leads to blood transfusions, which may transmit HIV [9–11]. Also, in pregnant women, HIV contributes to higher malaria infection rates, higher parasite density, more clinical illness, more anaemia, and diminished response to treatment [12–16]. Malaria infection also contributes to higher maternal HIV viral load, but whether this leads to increased mother-to-child HIV transmission is uncertain. Most studies have not found any evidence of an effect [12,17–21], although one study found a substantial increase in HIV transmission associated with malaria infection, and another with the rainy season when malaria infection rates are high [22,23].This study reviews the evidence regarding HIV–malaria interactions in non-pregnant adults, for whom the likely overall public health impact is less clear. It focuses on how HIV alters the clinical presentation and outcome of malaria, what effect malaria may have on the natural history of HIV infection, and the implications of an interaction for surveillance systems, burden estimates and for the prediction of future trends. The implications of the interactions on policies for prevention and control of both diseases are considered as are priority areas for research.The data were obtained by searching PubMed for English publications using the keywords HIV, malaria, and adults; further information was obtained from abstracts of scientific meetings, the Internet and personal communications with scientists. Malaria in this review refers to infection with Plasmodium falciparum and HIV to HIV-1 unless otherwise specified.Effect of HIV on malariaThe effect of HIV on malaria infection and clinical illnessEarly studiesEarly studies of the interaction between HIV and malaria were reviewed in 1992 [24] and again in 1998 [25]. Many of the studies available for those reviews had several features in common: they did not report CD4 cell counts and so did not distinguish between HIV infection and the associated immunodeficiency; and most were facility-based case–control or cross-sectional designs with limited ability to assess any longitudinal population-based impact of the two infections and their interaction [26]. Only one cohort study (involving both children and adults) had been published at the time [27], and this reported increased rates of non-severe malaria and significantly higher fever rates among HIV-seropositive individuals compared with seronegative individuals in Kinshasa. However, there were no significant differences in malaria slide positivity rate or parasite densities and the authors concluded that the higher rates of malaria were a consequence of ascertainment bias. Several other studies raised the prospect of an association between malaria and HIV. A cross-sectional study in rural Tanzania reported increased prevalence of parasitaemia, and non-significant increases in rates of non-severe malaria, among HIV-seropositive adults compared with those who were seronegative [28].

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