Albendazole treatment of helminth co-infection in Kenyan HIV patients raises CD4 counts

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Albendazole therapy in adult Kenyan AIDS patients co-infected with the parasitic worm Ascaris lumbricoides significantly increased CD4 cell counts, according to the results of a clinical trial published in the August 20th edition of the journal AIDS.

These findings and an accompanying editorial suggest that deworming may be an important public health intervention for delaying HIV-1 progression in resource-poor settings. This has important implications for millions of Africans living with AIDS who still have no access to antiretroviral drugs.

There are three classes of helminth parasites, namely nematodes (round worms), cestodes (tape worms), and trematodes (represented by human flukes such as Schistosoma mansoni). Experimental studies in mice have shown that different helminth parasites have distinct effects on immune functions.

Glossary

disease progression

The worsening of a disease.

placebo

A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

immune system

The body's mechanisms for fighting infections and eradicating dysfunctional cells.

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

mother-to-child transmission (MTCT)

Transmission of HIV from a mother to her unborn child in the womb or during birth, or to infants via breast milk. Also known as vertical transmission.

Helminth infections cause immune activation, resulting in increased HIV replication, and also shift the immune system to a TH2 response, which results in a loss of HIV-specific immunity.

A handful of human studies have produced conflicting results, and the impact of treating different types of helminth infection has not been compared.

In order to revisit this issue, a team of Kenyan and US investigators undertook a randomised, double-blind, placebo-controlled trial to assess the impact of albendazole therapy on HIV-1 and helminth coinfection in adult Kenyan patients.

Study participants were recruited from ten study sites dispersed throughout Kenya and were HIV-1 seropositive, at least 18 years of age, not pregnant, and not eligible for antiretroviral therapy. Those participants with active tuberculosis, on antiretroviral treatment, or receiving anti-helminthic therapy were excluded.

A total of 1551 HIV-1-infected participants who were antiretroviral treatment-naïve were screened for helminth infections. Two hundred and thirty-four adults out of the 299 participants with either ascariasis, hookworm, trichuriasis, or all three infections were randomised to receive either albendazole (400mg daily for three days) or a placebo. CD4 and HIV viral load twelve weeks after the completion of treatment were compared in the two arms.

Of the 208 participants included in the analysis, 148 (71.2 %) were infected with hookworm species, 54 (26.0 %) with A. lumbricoides, and 24 (11.5 %) with T. trichiura.

At enrolment, mean CD4 cell count was 557 cells/ml and mean plasma viral load was 4.75 log10 copies/ml. However, albendazole therapy resulted in significantly higher CD4 cell counts among individuals with Ascaris lumbricoides infection (+109 cells/ml; 95% confidence interval +38.9 to +179.0, P = 0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (P = 0.09) after 12 weeks.

No significant effect of treatment was seen in the groups of patients infected with hookworm or trichuriasis.

The authors suggest that this lack of demonstrable effect may have been due to the low worm burden among study participants, and that the positive effect of treatment detected in the Ascaris lumbricoides group may be due to the greater skewing of the immune system towards a TH-2 type response in people infected with this class of helminth. Eradication of the parasite may have led to a greater reduction in immune activation, allowing greater CD4 cell replenishment.

The authors suggest that the trend towards viral load reduction seen in the Ascaris lumbricoides group might be sufficient to slow disease progression and delay the need for antiretroviral therapy, and in an accompanying editorial Zvi Bentwich of Israel’s Ben Gurion University suggests that the modest reduction in viral load associated with deworming may also reduce the risk of mother-to-child transmission.

However, unequivocal evidence is still required for a policy advocating routine deworming in HIV-infected patients. This could be obtained, as suggested by the accompanying editorial, through large multi-centre, multi-country trials of anti-helmintics in resource-poor settings. These trials would need to enrol sufficient numbers of patients with HIV and helminth infections, have the power to detect the effect of each helminth species on markers of HIV disease progression, and follow patients for long enough to detect meaningful differences in disease progression.

References

Walson JL et al. Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial. AIDS 22:1601–1609, 2008.

Bentwich Z et al. The helminth HIV connection: time to act. AIDS 22:1611–1614, 2008.