The Promise of Antiretrovirals: When Treatment and Prevention Converge

The TREAT Asia Report Interview: Quarraisha Abdool Karim, Ph.D.

TREAT Asia Report: Almost a year ago, you and your colleagues announced the results of the CAPRISA microbicide trial, which found that a tenofovir-based vaginal gel cut a woman's risk of HIV infection by roughly half—the first good news about HIV prevention for women in a long time. Hopes were expressed that a product would be available to women within three years. Can you tell us where that process stands now?

Dr. Quarraisha Abdool Karim: The results of the CAPRISA 004 trial have injected much more energy and hope into the fields of microbicides and HIV prevention. The process of moving from proof of concept—demonstrating that a product or intervention works—to public access is long and complicated. There are three broad streams of activity. The first is licensure; the second relates to access and encompasses normative guidance, manufacture, and marketing; and the third concerns implementation, i.e., how do you make it available to those who need it?

Within a month of the CAPRISA results, UNAIDS and WHO hosted a meeting with scientists, donors, advocacy groups, and regulatory bodies to review the results and map out systematically what we need to do to get this product into women's hands. Based on progress being made on confirmatory studies, we anticipate that by late 2013 we could have a licensed product. A public-private partnership has been developed to establish manufacturing capabilities in South Africa based on a royalty-free agreement.

A key challenge to implementation is understanding the consequences for those women who acquire HIV while being exposed prophylactically to ARVs. We need to monitor drug resistance patterns and disease progression, and understand the implications for treatment options, particularly in regard to tenofovir-containing antiretroviral treatment (ART). All of these efforts require funding, but this remains a challenge. At this point USAID, the US National Institutes of Health, and the South African Ministry of Science and Technology remain the key sponsors of tenofovir gel research. For the first time we have an intervention for women, one that empowers young women who have had no strategy to protect themselves from infection when condoms and monogamy are not feasible. You would think smart investors would be rushing in to advance its development, but shockingly we are not seeing this.

TA Report: What do you see as the most promising directions for HIV prevention?

Dr. Abdool Karim: The future of HIV/AIDS prevention is very bright. In the past year, with the advances in using ART for prevention, our options have expanded substantially. For many years we relied on a variety of prevention strategies—the abstinence message, monogamy, behavior change, partner change, circumcision, treatment of sexually transmitted infections, and others—but HIV infection has continued to spread. Last year our microbicide study showed a 39 percent reduction in HIV infections among women who used a tenofovir gel, and 54 percent among high adherers. That was followed by the iPrEx trials, which demonstrated that a combination of two antiretrovirals could significantly reduce the likelihood of HIV infection, by 44 percent, among men who have sex with men. More recently the HPTN 052 trial demonstrated that treating an infected person in a discordant couple can reduce transmission by 96 percent. So overall the news around the prophylactic and preventive use of ART—either in gel or oral formulations or as treatment—is very encouraging.

TA Report:  These new prevention methods involve the use of antiretrovirals in some way—at a time when global donors are increasingly unwilling to expand their distribution. How can we shift the momentum back toward investing in these potentially game-changing medicines?

Dr. Abdool Karim: The question really comes down to how we can reconcile using ART for prevention while we are unable to meet the treatment demand. We need to look at the cost of the continuing spread of HIV and also the cost of treating those who are already infected and need treatment. Plus, we now have evidence that early initiation of treatment can significantly lower transmission. While this makes expanded treatment desirable and moral, even a human-rights obligation, the question is at what additional cost? How much earlier should we start and what are the trade-offs?

I don't think the dialectic is between having to choose drugs for prevention on the one hand, or treatment on the other. Our goal has to be stopping the HIV epidemic globally and deciding how to do this. We certainly have the tools to achieve this goal, it's a question of how we choose to utilize our resources. I think it's important that we contextualize HIV as part of a broader development agenda, and recognize that HIV is single-handedly undermining our efforts to reach our goals.

TA Report: In addition to your microbicide research, you have studied sustainable ways to introduce anti-HIV treatment in resource-limited countries. What insights have you gleaned from this research that could be meaningful in Asia?

Dr. Abdool Karim and colleagues in the CAPRISA lab.

Dr. Abdool Karim: I can share my understanding of HIV care in South Africa and the centrality of nurses for healthcare delivery. The provision of ART has brought attention to longstanding issues in healthcare delivery, including weak infrastructure, understaffing, inadequate information systems for monitoring progress, and problematic procurement and supply chain systems. If we are going to depend on a clinician-managed system, we are going to shortchange a lot of people who need treatment. There are now several nurse-treatment-driven programs that demonstrate that nurses are as effective in treatment as doctors. We have also learned that treatment can be reliably provided in rural, primary-care settings. Engagement with the community enhances adherence rates. Significantly, we are reaching substantially higher rates of therapeutic success with first-line drug regimens than are many industrialized countries. This is quite phenomenal!

Achieving treatment coverage rates beyond 30–40 percent remains a challenge. One option for increasing coverage and maximizing the survival benefits of ART is to identify and prioritize key groups. In Africa this includes pregnant women and HIV-TB co-infected patients. We know that HIV-positive pregnant women in Africa have high mortality rates in the first 42 days post-partum, as well as in the first two years post-partum. By prioritizing pregnant women for treatment initiation and using the opportunity of antenatal visits for HIV care, programs to prevent mother-to-child transmission and post-partum visits can make a substantial impact on survival outcomes in mothers and infants.

Tuberculosis is one of the most common opportunistic infections associated with advancing HIV in resource-con-strained settings. You can reduce mortality substantially by initiating ART and TB treatment simultaneously. Investments in infrastructure, human resource development, supply chains and systems, and good partnerships with communities are important, but actively addressing TB is a key to maximizing the benefit of ART.

We have reached a defining moment in our response to the pandemic. Stopping the epidemic is a real possibility, but the false dichotomy between treatment and prevention has to be broken. And there is a great deal to do. We need to overcome stigma, discrimination, and fear so that people are willing to learn their HIV status, which is the most important gateway to prevention and treatment. We must understand how to optimize the available treatment and prevention options to meet the needs of different epidemic settings. We need investments by governments, philanthropic organizations, and multilateral agencies, and partnerships between communities, service providers, and public and private sectors. Finally, if we are to realize an AIDS-free world, we must continue our efforts to develop new prevention modalities, including vaccines.

(Photos: CAPRISA)