Since the publication of the results of the HIV Prevention Trials Network (HPTN) 052 trial,1 “treatment as prevention” has become the new buzzword in the HIV/AIDS field. Advocates are hailing it as the beginning of the end of AIDS, researchers are talking about it at conferences, and countries are adding it to their national strategies. But there seems to be confusion as to what constitutes “treatment as prevention” and how it should be implemented programmatically.
HPTN 052, a randomized, controlled trial with HIV serodiscordant couples, in which the HIV+ partner was randomized to start on treatment when their CD4 count was between 350 and 500, or to wait until their CD4 count fell below 350. Among those in which the HIV+ partner had a CD4 count between 350 and 500, those who received Highly Active Antiretroviral Therapy (HAART) had a 96 percent lower rate of transmission to their uninfected partners compared to those who did not receive HAART.
Jia, et. al.2 recently published a study in the Lancet suggesting that in a real world setting, HIV treatment can reduce HIV transmission by 26 percent. They attempt to relate these results to the HPTN 052 trial and to the (World Health Organization) WHO recommendation that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. While the Jia, et. al. results are certainly useful, they cannot really be compared with HPTN 052, and it is debatable whether the study can claim to be an analysis of treatment as prevention.
The Jia, et. al. study was a retrospective observational cohort analysis, in which they compared the transmission rates within serodiscordant couples in which the HIV+ partner either received treatment or didn’t receive treatment. An important point to note about this study is that in this cohort, those receiving treatment were receiving it for their own health based on China’s treatment guidelines, unlike in HPTN 052, which was comparing treatment to no treatment among those with CD4 counts above 350 and no AIDS-defining events.
While treatment of an HIV+ person for their own health may also prevent an individual from transmitting HIV to others, we believe it is confusing to refer to this as treatment as prevention. To keep from comparing apples to oranges or causing confusion, we would like to propose that the term “treatment as prevention” only be used to refer to the provision of HAART to HIV+ people who do not qualify for ART for their own health based on the WHO guidelines, or country policy, if they differ. We suggest that “treatment as prevention” should not be used to refer to treating people with CD4<350, or for provision of ARV drugs to HIV-uninfected people, which is more appropriately referred to as pre-exposure prophylaxis (PrEP).
Once defined, the question remains - how should treatment as prevention be implemented, and who should be included? Some3 have suggested that all HIV+ people should be put on HAART for life as soon as they test positive. Given that treatment coverage in low- and middle-income countries is still at 54 percent,4 it seems for now that scaling up treatment for those who need it urgently for their own health should remain the priority. For countries struggling with limited resources, it is a human rights issue to ensure that the excitement about treatment as prevention does not end up siphoning resources away from providing treatment to people with advanced HIV disease. Keeping the focus on treating those in urgent need will still result in prevention benefits, as suggested by the Jia, et. al. paper. A recent study published early online by Bärnighausen, et. al.5 finds that the combination of scaling up voluntary medical male circumcision along with ART for those who need it for their own health is more cost-effective than a treatment as prevention approach, both in terms of infections averted and mortality.
Additionally, the health effects of treating people with CD4>500 are still unknown. While HPTN 052 demonstrated a clear clinical benefit to patients of initiating treatment between CD4 350-500, it is yet unknown whether the effects of starting treatment sooner will be helpful or harmful. The START trial,6 whose results are expected in 2015, seeks to answer this question. In the meantime, it is prudent to avoid claims that providing treatment to all HIV+ people is better for their health.
In light of the uncertainties, policy- and decision-makers may be best advised to carefully interrogate the risks and benefits as they consider implementing treatment as prevention strategies as part of programs. For countries that have succeeded in scaling up ART for those already eligible, spending additional resources to pilot treatment as prevention approaches may be a wise investment. However, there are numerous complex issues they will have to consider before moving ahead. They will need to determine how they want to target these programs: discordant couples? Pregnant women? Will they stratify by CD4 counts below 500? How will they allocate prevention resources to these programs compared with other prevention approaches? Will they consider cost-effectiveness of treatment as prevention programs compared with other prevention interventions? They will also need to consider how to measure the outcomes and impact of these programs. What kinds of surveillance will help them understand if such a strategy is working? Tracking HIV incidence is challenging for most countries but can be done using cross-sectional methods such as the “detuned” assay. Do measures such as “community” viral load have a role is such assessments, as has been shown in parts of North America?7
The emerging evidence about treatment as prevention is potentially a game changer and has helped to diminish the polarization between treatment and prevention within the HIV field. To remain on track to eliminate HIV as quickly and cost-effectively as possible, countries should take a measured approach based on their own unique circumstances, such as prevalence, ART scale-up, and resources available and required. As evidence continues to emerge, the HIV community will be wise to avoid the temptation to jump on the bandwagon of the next big thing and carefully consider the programmatic, economic, and human rights implications of treatment as prevention.
Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. The New England journal of medicine. Aug 11 2011;365(6):493-505.
Jia Z, Ruan Y, Li Q, et al. Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study. Lancet. Nov 30 2012.
Granich R, Crowley S, Vitoria M, et al. Highly active antiretroviral treatment for the prevention of HIV transmission. Journal of the International AIDS Society. 2010;13:1.
Bärnighausen T, Bloom DE, Humair S. Economics of antiretroviral treatment vs. circumcision for HIV prevention. Proceedings of the National Academy of Sciences. December 6, 2012 2012.
Babiker AG, Emery S, Fätkenheuer G, et al. Considerations in the rationale, design and methods of the Strategic Timing of AntiRetroviral Treatment (START) study. Clinical Trials. April 30, 2012 2012.
Das M, Chu PL, Santos GM, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco. PloS one. 2010;5(6):e11068.