Antiretroviral therapy is expected to have benefits both for individual patients and for public health in resource-limited settings, according to a mathematical modelling study presented in the 15^th April edition of The Journal of Acquired Immune Deficiency Syndromes.

The model predicted that HIV treatment would have greatest impact on reducing new HIV infections and AIDS deaths if it were introduced early in an epidemic. However, its effects could be diminished by patients on treatment still being infectious or experiencing disease progression, or by increases in sexual activity.

A number of studies have attempted to model the impact of antiretroviral treatment on the HIV epidemic. While most of these have concentrated on the use of single anti-HIV drugs or the epidemic in the developed world, less attention has been given to its predicted effects in resource-limited settings.

To estimate the impact of antiretroviral therapy in the developing world, investigators from Pittsburgh and London developed a model that took account of recent observations of the pattern of HIV epidemiology and transmission, sexual behaviour, and response to treatment in sub-Saharan Africa. These include observations that the risk of HIV transmission through heterosexual sex is reduced by HIV treatment.

The model revealed that implementing the World Health Organization’s guidelines of treating all patients with a CD4 cell count below 200 cells/mm³ would reduce new HIV infections by 29% and the total number of AIDS deaths by 58% over ten years. This assumes that the guidelines were implemented early in an epidemic, when 5% of the population were HIV-positive.

The investigators calculated that this is equivalent to averting 6.9 million HIV infections and 9.3 million AIDS deaths in the whole of sub-Saharan Africa, ten years after introducing antiretroviral therapy to patients with CD4 cell counts below 200 cells/mm³.

“This enormous individual and public health benefit would require sustained access to antiretroviral therapy beyond the near-term goal of the World Health Organization's ‘three by five’ programme,” they write.

Implementing these guidelines later in an epidemic, when 40% of the population were infected, would have a slightly smaller impact on HIV infections and AIDS deaths, reducing them by 28 and 37% respectively.

“Late implementation of treatment was only modestly inferior to early treatment and considerably better than no treatment,” write the researchers, “because there was a persistent and sustained decrease in cumulative deaths from AIDS at early and late intervention times.”

The investigators point out that introducing antiretroviral therapy benefits not only individuals with HIV by improving survival, but also the population of uninfected people by reducing transmissions. While the benefit to the community is small at first, representing around 1%of the total benefit after five years of treatment, it becomes more significant, reaching up to 71% of the total benefit after 25 years, depending on when treatment is started.

As expected, the investigators discovered that the benefits of antiretroviral treatment would be reduced by treating fewer patients, but would be increased by treating all infected patients regardless of CD4 cell counts.

When they adjusted other parameters in their model, they found that patients still being infectious despite treatment could also reduce the benefits of treatment. It could also be diminished by disease progression while on treatment or by patients becoming more sexually promiscuous after treatment was begun.

“Our analyses identified persistent infectivity or disease progression on treatment and sexual disinhibition as key variables that could potentially undermine the beneficial effect of therapy,” they explain. “These findings are in general agreement with earlier models.”

The investigators point out that their model, although complex, fails to take into account some possible factors that could influence the response to treatment. These include people having more than one sexual partner, the structure of sexual networks, age, gender and the availability of different types of anti-HIV treatment.

“With more complex models, parameter numbers spiral quickly as complexity increases, especially in connection with human sexual behaviour. Because of limited knowledge, the problem of making parameter assignments is thus greatly exacerbated as complexity and realism are increased,” they write.

“Our results must be interpreted with these caveats in mind, in terms of the relative merits of simplicity versus complexity,” they warn.

Reference

Abbas UL et al. Potential impact of antiretroviral therapy on HIV-1 transmission and AIDS mortality in resource-limited settings. J Acquir Immune Defic Syndr 41: 632-641, 2006.

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