Using treatment to prevent HIV

July 23, 2012

–Jessica Wapner writes on biomedical issues on her PLOS (The Public Library of Science) blog, Work in Progress. The opinions expressed are her own.–

Despite widespread knowledge of how the AIDS-causing virus HIV is transmitted, and how to prevent it, the disease is still spreading. An estimated 34 million people worldwide were living with HIV/AIDS in 2010, according to the World Health Organization. Sub-Saharan Africa is the worldwide epicenter, with 22.9 million people living with HIV/AIDS, but epidemics and areas of high concentration abound elsewhere, including in Western Europe and the southern United States. Now, an emerging concept known as treatment as prevention – where patients are given medication for the primary purpose of stopping new infections – is gaining favor as a way to decrease the spread of HIV, if not end it altogether.

Antiretroviral therapy (ART) can halt the progress of HIV in infected people, and prevent them from passing it on by reducing the amount of virus in the body. It is rarely initiated at the time of diagnosis because the disease usually isn’t causing physical deterioration at that point, but the lag between diagnosis and starting ART leaves a wide window for new infections. (WHO guidelines recommend starting ART when the level of CD4 cells – an infection-fighting component of the immune system that is gradually destroyed by the virus – plummets below 350 cells per cubic millimeter, far below the normal range of 500-1,500 cells per cubic millimeter).

For years, studies have explored whether starting ART earlier could help prevent the spread of HIV. A landmark finding published last year in the New England Journal of Medicine came from the large HPTN 052 clinical trial which found that starting ART early reduced the rate of transmission between stable, heterosexual partners by 96%.

But the concept of “treatment as prevention” is controversial and complicated. Should infection-preventing medicine be given to people who may not benefit from it themselves? Knowing that finances are limited, which individuals should be prioritized?

HPTN 052 focused on stable, heterosexual couples in which one partner was infected and the other not. Are those results applicable to the broad, diverse HIV-positive population? Considering the urgent need to thwart continued spread of the virus, how can these questions be answered in a timely, ethical manner?

A collection of articles just published by PLOS Medicine ahead of AIDS 2012, the 19th International AIDS Conference currently underway in Washington, offers an in-depth look at the problem, including mathematically modeling the cost and potential benefit of expanding access to ART. These models quantify: behaviors that lead to transmission, the biology of the infection, patterns of contact between infected and uninfected individuals, and the many other variables that make HIV so complex and difficult to study in actual populations.

A paper analyzing 12 distinct models finds that expanding ART access to 80% of the HIV-positive population, (and where 85% of those patients remain in care) could reduce the incidence of HIV by 35%-54% by 2020 (although the long-term implications are less clear).

Another looking at economic issues finds that simplifying treatment delivery – such as by not monitoring disease before ART begins, or eliminating CD4 count measurements – could offset the added expense of scaling up treatment-as-prevention efforts.

Wim Delva (University of Stellenbosch, South Africa) and colleagues note there are benefits and potential pitfalls with picking which groups of patients to prioritize. Targeting stable, heterosexual couples for treatment-as-prevention efforts makes sense in light of the HPTN 052 findings, but would be controversial among a population where such couples are relatively rare. Expanding ART access among female sex workers could dramatically reduce HIV transmission, though a lack of adherence to care may diminish that potential benefit. Prioritizing ART treatment according to viral load, rather than CD4 counts, may be a more effective approach for preventing new infections, though evidence supporting the benefit of this strategy for the infected patient is lacking.

Observations of real-world populations often contradict the findings of mathematical models, leaving researchers and policymakers perplexed about how to implement treatment as prevention strategies. The question of how to best use the tools that have been shown to reduce HIV transmission will likely dominate the field of HIV prevention for the foreseeable future.

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