Malaria almost doubles the concentration of HIV-1 RNA in the blood, according to researchers in the US and Malawi (Lancet 2005, 365:233–240). The jump in viral load subsides 8–9 weeks after correct malaria treatment. But the researchers suggest that even a temporary malaria-related rise in HIV-1 RNA could increase a person's chances of transmitting the virus and hasten the progression to AIDS.
Previous studies have explored the interaction between the two diseases, which are endemic and overlap geographically in many parts of the world, including much of sub-Saharan Africa. Most of the research has looked at HIV's effects on malaria, for example, finding that HIV-positive adults have an increased risk of malaria. The current study, which builds on earlier, but inconclusive, work by the authors, assessed the effect Plasmodium falciparum malaria has on HIV infection.
To do that, lead author James Kublin of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and colleagues designed a prospective study that enrolled 334 adults living in and around an agricultural estate in Thyolo District of Malawi. The participants were HIV-positive but did not initially harbor P. falciparum. For the study, which spanned one malaria season, participants were asked to make regularly scheduled clinic visits that included a baseline visit, routine visits every 8 weeks, interim visits when ill, and visits 3, 7, 14, and 28 days after taking the anti-malarial drug sulfadoxine/pyrimethamine, which requires a single dose to clear non-resistant P. falciparum from the blood. The participants were tested for presence of the mosquito-borne parasite, HIV-1 RNA concentration, and CD4 cell count.
By the end of the study, 100 people had made the visits as requested and had all the blood tests necessary for statistical analysis. Seventy-seven of the individuals had been infected with the mosquito-borne parasite. The researchers defined four categories of malaria infection: presence of P. falciparum; a parasite density of 2000/μl or greater; any parasitemia with fever; and a parasite density of 2000/μl or greater with fever.
When the researchers compared HIV-1 RNA concentration and CD4 cell counts among the different categories, they found the HIV-1 RNA concentration almost doubled from a pre-malaria average of 96 215 copies/ml to 168 901 copies/ml in the 77 people who contracted malaria during the study. Their viral load dropped back to an average of 82 058 copies/ml by 8 to 9 weeks after taking sulfadoxine/pyrimethamine.
The biggest increase in HIV-1 RNA occurred in the 13 people who had CD4 cell counts greater than 300 cells/μl and acute bouts of malaria accompanied by fever and a parasite density of 2000/μl or more. Their average viral load rose from 38 483 copies/ml at baseline to 196 098 copies/ml during malaria, then fell to an average of 75 331 copies/ml after treatment—a level 0.25 log above baseline level but not statistically significant, the scientists note. The 23 individuals who did not develop malaria showed no changes in HIV-1 RNA concentration.
The scientists speculate that malaria-induced changes in viral load result from “a series of immunological mechanisms.” For example, P. falciparum infection might promote macrophages and CD4 cells to activate viral transcription. A high parasite density likely elicits a strong immune response, leading to a high turnover of HIV-1 RNA. And fever indicates a cytokine response that might raise HIV-1 RNA concentrations. The scientists also note that a number of studies suggest more effective sexual transmission of HIV and an accelerated progression to clinical disease in people with elevated concentrations of HIV-1 RNA in the blood.
“Our findings may have even greater significance among those individuals who do not have an adequate clinical response to anti-malarial treatment, which is becoming more frequent due to anti-malarial drug resistance,” Kublin says. In those people or individuals who fail to get anti-malarial treatment, levels of HIV in the blood “could remain elevated for a longer period of time than what we’ve found in this study.”