Shira Berman, Salim S. Abdool Karim, MBChB, PhD
DisclosuresMay 03, 2013
Editor's Note: In 2011, the HIV Prevention Trials Network (HPTN) 052 study of serodiscordant couples demonstrated that lowering viral load through the use of antiretroviral therapy (ART) in an infected partner could lower the risk for HIV acquisition by the uninfected partner. In early 2013, using data on more than 16,000 people in the Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal, South Africa, investigators demonstrated a real-world setting application of this principle: Individual HIV acquisition risk in KwaZulu-Natal declined significantly with increasing ART coverage in the surrounding local community.
In an interview with Medscape, Salim S. Abdool Karim, MBChB, PhD, Professor at the Centre for the AIDS Programme of Research in South Africa (CAPRISA) at the University of KwaZulu-Natal in Durban, South Africa, reviewed the findings from this study and considers what more we need to learn about treatment as prevention strategies moving forward.
Medscape: The report in Science focused on the real-world application of how increased ART coverage changes the demographics of HIV acquisition. Why was a study like this important?
Dr. Karim: When the HPTN 052 results were published, we had, for the first time, a clear idea of the very high efficacy that is possible with the use of ART to suppress viral load and lower the risk for HIV transmission to HIV-negative partners. But even before the HPTN 052 results, there was a study by Donnell and colleagues published in The Lancet that showed a very low incidence of HIV infection in serodiscordant couples in which the HIV-positive partner was receiving ART. Mathematical models have also provided some indication of the potential impact of "treatment as prevention." However, it was not known what the impact would be if this strategy were implemented in the real world.
The data from the study published in Science provide, for the first time, a compelling picture of the effects that ART scale-up within a community can have not only in terms of its treatment impact but also in terms of its prevention potential.
Why is it that they were able to show this in this particular community?
The circumstances are unique in that population. The first and very important issue to understand is that ART was simply not available for many years in that community. It was official government policy not to provide ART during South Africa's "denialist" era. Eventually, when the government did decide to provide antiretrovirals, it took them quite a while to establish health systems capabilities to initiate therapy. So, in this community, the researchers were dealing with a huge backlog of patients who needed treatment.
In essence, then, this Hlabisa community was experiencing a rapidly advancing HIV epidemic associated with a very high mortality rate because of the absence of treatment. With the increasing prevalence and the concomitant large number of infected individuals in this community, it was also experiencing a very high HIV incidence rate within the population.
In this kind of situation, introducing ART and providing it to scale puts a spotlight on the substantial impact it can have on such areas as the huge improvement in life expectancy. The HIV epidemic wiped out almost 10 years of life expectancy; with the introduction of ART, we're now regaining those lost years of survival. So what we're seeing in this community in Hlabisa in northern KwaZulu-Natal is a return in life expectancy to the pre-HIV era. That's a very substantial impact. If you add 10 years of life expectancy in that community of nearly 100,000 people, you've got a million new years of peoples' lives. These are potentially productive life-years gained to be able to contribute toward society. It's just amazing when you think about that scale of impact.
But it was not only that those who were treated who benefited -- those who were HIV-negative also benefited from HIV-infected people getting treatment. In communities in which the rollout of ART was highest, we saw a substantial impact on HIV transmission and declines in HIV incidence.
This demonstrates the real-world impact of treatment as prevention -- where HIV-positive people are getting the intervention, but HIV-negative people are benefiting from the intervention.
To me, it highlights how we've come full circle. On the basis of data from the Rakai Project Study Group, we thought that if someone doesn't have a detectable viral load, they would probably not transmit HIV. The Rakai study provided the initial discovery of the central role of viral load in HIV transmission when its data showed that transmission among couples was dependent on viral load. The next step in the sequence was the observation of the effects of ART in cohorts. In this secondary analysis of serodiscordant couples, the data provided observational evidence of the potential impact of ART on HIV transmission. Then came the HPTN 052 randomized controlled trial in discordant couples that showed convincingly that treatment of HIV-infected partners is highly efficacious. Now we've gone to the final step, where we have evidence of an impact in the real world.
On a note of caution, these data do not mean that the effect observed in Hlabisa will be necessarily present in every community. Owing to the unique circumstances in that community, where they were deprived of ART for such a long period and the epidemic was able to progress to such an advanced stage, when ART was introduced and scaled up, you could see a substantial impact. But it has shown us that with real-world implementation, treatment both to improve the HIV-infected patient's health and as prevention for the partners of HIV-infected patients is of benefit.
Medscape: On that point about the applicability of these findings to other communities, the investigators showed this tremendous impact in communities that had coverage rates of 30%-40%. That's a fairly low coverage rate, but obviously, in this community, that was a huge step forward.
Dr. Karim: Absolutely. When coverage goes from 0% to 30%, a big difference can be observed. But when there is a slow incremental growth of coverage, it is much less likely to lead to this kind of impact.
But there's another factor that is affecting outcomes: We're identifying key populations and treating them at the earliest stages. In other words, the 30%-40% that are being treating in that community are the important 30%-40% -- the ones with the low CD4 counts and the highest viral loads. So they're not just lowering each individual's viral load, but also lowering the overall mean community-level viral load. That's probably one of the mechanisms leading to the impact that was observed.
It is not clear whether such dramatic and large benefits would be readily observed in other communities where ART scale-up has been more incremental. Observing a large effect within this specific community was feasible due to its unique circumstances.
Medscape: Moving forward, having measured such a dramatic impact in this community, is it reasonable to think that we might see continued benefit if coverage is higher but increases at a slower, incremental rate?
Dr. Karim: These kinds of interventions can reach a point where substantial increases in coverage may be required for smaller additional benefits. So although the initial intervention had a very substantial effect at relatively low coverage rates, to improve on that and to get a marginal increase above the currently observed effect may require substantially higher coverage rates.
One way to assess the potential impact of increased coverage is to model the different coverage levels and the impact on the community base on the Hlabisa data -- to essentially ask such questions as, "If you achieved 80% coverage, what would that do?"
Three community-based randomized controlled trials being conducted by the National Institutes of Health, USAID, and the Centers for Disease Control and Prevention with the President's Emergency Plan for AIDS Relief (PEPFAR) funding are asking a more direct question: If we can scale up ART from the current coverage rate, which is around 30%, and achieve 60% or 80% coverage, what is the magnitude of the impact on survival and on HIV transmission to HIV-negative people?
These 3 studies will help us determine how incremental increases in treatment coverage through active scale-up strategies may or may not continue to show a prevention benefit.