Malaria Increases HIV Viral Load
AIDSmap.org (1/19/05) Smart T

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 15 issue of The Lancet (365:9455,
p. 233, 2005). 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 in the 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 = <0o0001. 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.

Implications
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."