Acute malaria episodes are associated with a marked increase in HIV viral load, according to a study by a team of Malawian and American researchers published in the January 15th issue of The Lancet.
Although the increase in HIV viral load resolves with effective anti-malarial treatment, the study researchers propose that malaria episodes could facilitate HIV transmission and accelerate disease progression — especially if the parasite burden is high and accompanied by fever.
Malaria the coinfection
Malaria is a disease caused by several species of Plasmodium, a parasite that can be transmitted by mosquito bites, primarily in tropical regions of the world. Over 300 million people contract malaria each year; one million of them die.
Most of the fatalities are children. In the areas of highest risk, exposure to the malaria parasite is so persistent that children develop a functional immunity to the parasite by the age of five - or else they simply don’t survive.
Immune’ adults are still bitten and can be infected by the parasite, however the parasite burden is lower and with few or no symptoms.
Approximately 90% of the malaria cases occur in sub-Saharan Africa where the burden of HIV is also high. Yet, while malaria is one of the most important diseases in the world, its role as an HIV coinfection has perhaps been under-appreciated. Recent studies have shown that the two diseases can have a number of harmful interactions.
For example, pregnant women with HIV are at a greatly increased risk of malaria — even if they were previously immune to the organism. HIV also increases the risk of malaria crossing the placenta and affecting the foetus. Conversely, the risk of HIV transmission to the child is increased when there is placental malaria
Other studies regions suggest an increased risk of symptomatic malaria among people with AIDS. There are indications that adults may gradually lose malaria immunity as their immune system weakens. Also, malaria diagnosis is often made using simple clinical criteria - fever - that can be mimicked or masked by HIV/AIDS and its opportunistic infections.
However, the effect of malaria on the course of HIV infection has not been as well characterised, and initial reports of any interaction have been inconclusive. While an earlier study in Malawi found higher HIV loads in patients with malaria than those without, the difference could not be clearly attributed to malaria, since the patient’s viral loads before illness were unknown.
Study in Malawi
For this prospectively designed study, researchers recruited 334 HIV positive adults who were free of malaria parasites at the start of the study.
The plan was to monitor these patients closely for acute episodes of malaria using four definitions: parasitaemia (any detectable parasite in the blood), parasite density above 2000/ L, parasitaemia with fever, and parasite density above 2000/ l and fever.
Viral loads were measured at baseline, during malaria and after anti-malarial treatment (when possible). Patients were also stratified depending upon baseline CD4 cell counts above 300 and 300 and below. Baseline characteristics, such as age, sex, and employment status, were similar across strata.
During follow-up, 148 patients had at least one malaria episode and received antimalarial treatment. Of these 77 had viral load measurements at all three key timepoints. In these patients, the median baseline viral load was 96,215 copies/ml.
When malaria was defined simply as parasitaemia, episodes were found to transiently increase viral load by 0.25 log (95% CI 0.11–0.39, p = 0.0003 within this stratum). About 8–9 weeks after treatment for malaria, the patient’s viral loads returned to levels similar to those at baseline. In a control group of 23 patients who never developed malaria, HIV viral load was generally unchanged.
The affect on HIV viral load increased with the severity of malaria. In 24 patients with fever and high parasitaemia, the mean increase in viral load was 0.51 log (0.29 to 0.73), p =
Another finding was that viral load elevations were most marked in patients with CD4 cell counts above 300; and this was true using each definition of malaria. In the thirteen patients with fever and high parasitaemia, the mean increase in viral load was 0.81 log. In this subset of patients, viral load also remained elevated 0.23 log above baseline after malaria treatment. Although this finding was not statistically significant, the researchers suggested that it was likely to become so in a larger study.
Many other concurrent infections have been shown increase HIV viral load, usually indirectly via inflammatory immune responses that in turn stimulate HIV replication. The Malawi study authors suggest that the more modest increase in viral load among people with lower CD4 counts is likely due to the weaker immune responses to malaria in these patients.
The Malawi study researchers believe their results suggest “malaria, especially if frequent, unrecognised, inadequately treated, or untreated, might lead to sufficient elevation of viral loads in HIV-infected adults to result in increased rates of HIV transmission and disease progression.”
Although viral load increases may appear small, “both infections are of such great public-health importance in tropical countries, particularly in sub-Saharan Africa, that any potential interaction should make us worry,” according to Drs. James Whitworth and Kirsten A Hewitt of the London School of Hygiene and Tropical Medicine, who authored a Lancet commentary accompanying the study. “Given the number of cases of HIV and malaria, even small increases in relative risks of HIV transmission and progression are important.”
The Malawi researchers note that population-based studies show no great increase in the rate of HIV disease progression in areas of the world with malaria. However, this author must point out, there are far too many intervening variables, including subtype of HIV, which could affect such analyses. The only valid comparisons would be within the same population - which this study does.
Also, even though the increase in HIV load is reversible with prompt and effective treatment for malaria, outside of clinical studies, parasitaemia without symptoms is likely to go undetected and untreated. And without prompt malaria treatment or with treatment failure, increase in viral load might be sustained for longer periods.
The researchers conclude that “these observations highlight the importance of coordinated efforts to prevent HIV and malaria in areas where both diseases are endemic.” Finally, “antimalarial measures might be important for HIV-infected people who are not yet eligible for antiretroviral therapy.”
Kublin, JG 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; 365: 233–40, 2005.
Whitworth JAG, Hewitt KA. Effect of malaria on HIV-1 progression and transmission. Lancet; 365: 196–197, 2005.