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New Rationale for Treatment as Prevention

By Adina Goldberger

An analytical review of the “Cost-effectiveness of HIV treatment as prevention in serodiscordant couples”. Walensky RP et al. N Engl J Med. 2013; 369:1715-25. 

Primary disease prevention is a hallmark of our contemporary healthcare culture. From immunizations to prophylactic medication dosing to behavior counseling, researchers and healthcare providers have developed a host of interventions to thwart disease before it strikes, with the rationale that it is often easier to prevent disease than it is to treat it. This concept has been particularly important in the field of HIV therapy. Though numerous medications have been developed to treat HIV over the course of the last two decades, it is a virus with frighteningly disastrous potential outcomes that requires extremely complex antiretroviral therapies, making it an ideal target for a primary prevention strategy.

While a vaccine for HIV immunization has yet to be developed due to the rapid mutagenicity of the virus, various observational studies have suggested the potential viability of a “treatment as prevention” approach since 2009 [1-4]. Essentially, this approach entails that HIV-positive individuals receive HIV therapy early in their disease progression in order to reduce the risk of their HIV-negative partners contracting the virus. Antiretroviral therapy can reduce the HIV load in body fluids in an HIV-positive individual and can thus render him/her less likely to transmit the virus during sexual activity. While this notion is compelling in theory, observational data is limited in its ability to demonstrate reduction in HIV transmission as a result of early treatment. Reduction in transmission in these studies might instead be attributed to confounding variables, such as the higher likelihood of people receiving early treatment to use condoms regularly.

Until recently, there was only observational data to support the efficacy of “treatment as prevention” in HIV, but the HIV Prevention and Trials Network (HPTN), an international association of clinical trials focused on the prevention of HIV transmission, was the first to demonstrate “gold standard” evidence for early HIV treatment as prevention in a randomized controlled trial [5]. Conducted across nine different countries, HPTN’s study enrolled 1763 serodiscordant couples (one partner HIV-positive and one partner HIV-negative) to receive antiretroviral therapy either immediately after a decline in CD4 count (early therapy) or at the onset of HIV symptoms (delayed therapy) in the HIV-positive partner. The end point with respect to primary prevention in this study was demonstration of seroconversion in the formerly HIV-negative partners, while the clinical end point in the study was the development of a severe HIV-related complication such as pulmonary TB, other severe bacterial infection, or death. In other words, the study stopped following patients if the HIV-negative partner became HIV-positive or if the HIV-positive partner developed a severe HIV-complication or died. After finding that of the 28 virally-linked transmissions, only one occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; p<0.001)—and that subjects receiving early therapy experienced fewer clinical end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; p=0.01), the study concluded that early antiretroviral therapy reduced the rates of HIV transmission and adverse clinical endpoints.

While this HPTN study was foundational in shaping the current thinking about HIV prevention strategies on a theoretical level, a very obvious barrier to its implementation—particularly in developing countries where HIV is most prevalent—is cost. In low-resource environments, healthcare economics do not seem to justify the expense of antiretroviral medications to facilitate a “treatment as prevention” strategy at face value. However, a recent elaboration on the original HPTN early antiretroviral therapy study by the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International Group demonstrated that qualms about cost-effectiveness of treatment as prevention may be unfounded and simply erroneous [6].

In this recent cost-effectiveness study, Walensky and colleagues used the data from the original HPTN study as well as a micro simulation model of HIV progression and therapy to project the economic implications of early antiretroviral therapy in two of the original nine countries: India and South Africa. They compared early initiation of treatment with delayed treatment for HIV-infected partners in serodiscordant couples. Five-year and lifetime outcome measures included cumulative HIV transmission, life-years, cost, and cost-effectiveness. Early therapy was defined as “cost-saving,” “cost-effective,” or “very cost-effective.” “Cost-saving” denoted a decrease in total costs and an increase in life-years compared with delayed antiretroviral therapies. “Cost-effective” constituted an incremental cost-effectiveness ratio (ICER) that was less than three times the GDP. The ICER is an equation for cost-effectiveness analysis that represents the ratio of change in cost to incremental benefit—in other words, the increase in benefit from baseline—of an intervention. “Very cost-effective” constituted an ICER below the annual GDP per capita in that country.

It is especially interesting to examine the specific results in South Africa compared to those in India, as these countries represent high population loads of HIV amidst very different economic conditions: South Africa is a middle-income country (GDP $8,100 USD) and India is a low-income country (GDP $1,500 USD). The study found that in South Africa, early treatment prevented opportunistic disease and was “cost-saving” over five years, while it was “very cost-effective” ($590 per life-year saved) over a lifetime. In India, where healthcare costs are lower at baseline, early treatment was “cost-effective” ($1,800 per life-year saved) over five years, and “very cost-effective” ($530 per life-year saved) over a lifetime. Thus, in both South Africa and India, early antiretroviral therapy represents a cost-effective utilization of resources for HIV prevention, indicating that the results of this study can be applied to countries with non-identical economic profiles. In conclusion, Walensky and colleagues highlight the importance of supporting early antiretroviral therapy for serodiscordant couples even in low-resource settings, thereby lending strong support to the “treatment as prevention” concept.

  1. Cain, L.E., et al., When to initiate combined antiret- roviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study. Ann Intern Med, 2011. 154(8): p. 509-15.
  2. Writing Committee for the CASCADE Collaboration, Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med, 2011. 171(17): p. 1560-9.
  3. Donnell, D., et al., Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet, 2010. 375(9731): p. 2092- 8.
  4. Kitahata, M.M., et al., Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med, 2009. 360(18): p. 1815-26.
  5. Cohen, M.S., et al., Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med, 2011. 365(6): p. 493-505.
  6. Walensky, R.P., et al., Cost-effectiveness of HIV treat- ment as prevention in serodiscordant couples. N Engl J Med, 2013. 369(18): p. 1715-25.
About the Author

Adina Goldberger

Adina Goldberger is a third-year MD/MPH student and lifelong women’s and reproductive health enthusiast. Her role on the NPHR is staff writer and she is excited for the opportunity to tell the Northwestern community about the frontiers of public health research and practice.