Research Roundup: A Decade of Seminal HIV Studies
The landscape of HIV prevention, treatment and care has changed drastically since the virus was first discovered in 1983. Even in the past decade, there have been tremendous advances in HIV research, arguably more so than for any other infectious disease. While all research furthers our understanding of how to respond to the virus, certain studies have had a particularly powerful impact. Some have influenced policies and programs and services for people living with HIV, while others have contributed to reducing HIV-related stigma and breaking down the divide between HIV-positive and -negative people.
Here we take a quick tour through some of the most influential findings of the past 10 years.
Treatment as Prevention
At the 2006 International AIDS Conference in Toronto, the HIV community was introduced to the concept of "HIV treatment as prevention" -- the idea that increasing the number of people living with HIV who are on treatment can reduce the number of HIV transmissions. Dr. Julio Montaner, director of the BC Centre for Excellence in HIV/AIDS and the driving force behind this concept, published a paper entitled "The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic" to coincide with the conference. In it, Montaner and colleagues summarized the research findings supporting treatment as prevention, including preliminary results from B.C., where new HIV diagnoses had decreased following a large increase in the number of people on HIV treatment.
It wasn't until 2010 that Montaner and his colleagues would publish their full findings: Between 1996 and 2009 the number of people on antiretroviral therapy (ART) had increased by more than 500% and the number of new HIV diagnoses had dropped by 50%. While the findings were not yet conclusive evidence that treatment as prevention works -- because other interventions, such as needle exchanges and Vancouver's supervised injection site likely played an important role in the decrease -- the seed was sown. Treatment as prevention is now a household name for those working in the world of HIV and it has had an undeniably profound impact on HIV policy and programs, both in Canada and internationally.
The HIV Care Cascade
As the idea of treatment as prevention began gathering momentum, there was uncertainty about exactly how it should be brought to bear on the ground. While there were global calls to scale-up testing and treatment, there were also concerns that some people might be coerced into getting tested and treated for HIV. The emergence of the HIV care cascade, a concept first widely disseminated in a paper by Edward Gardner and colleagues in 2011, offered insights into how treatment as prevention could be implemented.
The HIV cascade concept highlights the fact that efforts to fully realize the health and prevention benefits of HIV treatment will fail unless they go beyond simply improving access to testing and treatment. The researchers estimated that only 19% of people living with HIV in the United States had achieved an undetectable viral load. This wasn't only because of gaps in testing and treatment but also due to deficiencies in HIV care -- including linking people to care after their diagnosis, retaining people in care, and supporting people to stay on and adhere to their HIV medications. A visual model of this series of steps -- from HIV testing to engaging in care and starting treatment to achieving an undetectable viral load -- became known as the HIV care cascade.
Policies are emerging that put the cascade at its centre, such as UNAIDS' ambitious 90-90-90 strategy, which calls for 90% of people living with HIV to be diagnosed, 90% of diagnosed people to be on treatment, and 90% of people on treatment to achieve viral suppression (or have an undetectable viral load) by the year 2020.
HPTN 052 and PARTNER
The interest and excitement in using ART to reduce HIV transmissions first peaked with the release of the "Swiss Statement" in 2008. It declared that HIV-positive people with an undetectable viral load have a negligible to non-existent risk of passing HIV as long as they have been undetectable for at least six months, are adherent to ART, receive regular care and have no other sexually transmitted infections.
While some applauded the statement, others were critical of it due to the lack of evidence supporting its position. But fast-forward to a few years later: Compelling evidence arrived in the form of HPTN 052 and PARTNER. The landmark HPTN 052 study found that ART reduced the risk of HIV transmission by 96% among heterosexual serodiscordant couples, with no HIV transmissions occurring when the HIV-positive partner's viral load was undetectable. Findings from the PARTNER study came to a similar conclusion for both gay male and straight serodiscordant couples, with no HIV transmissions occurring when the HIV-positive partner's viral load was undetectable despite more than 58,000 condomless sex acts.
New consensus statements are now emerging, including that of the "Undetectable=Untransmittable" campaign, providing important guidance for people who want to use ART and an undetectable viral load as a prevention strategy.
Strategic Timing of Antiretroviral Treatment (START)
With so much focus on the use of treatment as prevention, it is important that the primary purpose of ART not be forgotten -- improving the health of people living with HIV. In the past decade, as we have learned more about the importance of starting treatment early for HIV prevention, evidence has also demonstrated its importance for one's health. In turn, treatment guidelines have gradually changed to recommend that people start treatment sooner after diagnosis.
The first guidelines recommending treatment as soon as possible after diagnosis, regardless of CD4 count, were released in the U.S. in 2012, despite the lack of conclusive evidence of a health benefit at the time. In 2015, the START study filled this evidence gap with its finding that starting treatment when your CD4 count is greater than 500 significantly reduces the risk of serious infections, cancer and death. Starting treatment early is also associated with improved quality of life. What's more, the vast majority of people who started treatment early did not experience serious side effects. With the evidence in, many other guidelines have followed suit to recommend starting treatment as soon as possible after diagnosis.
CAPRISA 004 and iPrEX
At the 2010 International AIDS Conference in Vienna, the presentation of the CAPRISA 004 study results received a standing ovation. The ongoing use of ART in HIV-negative people, a concept known as pre-exposure prophylaxis (PrEP), was shown to work for the first time. While various types of PrEP may eventually become available, the CAPRISA 004 strategy involved the use of a vaginal gel (containing the antiretroviral drug tenofovir) before and after sex. It was found to reduce the risk of HIV infection among women by 39%.
The excitement generated by CAPRISA quickly grew with the release of the iPrEX findings later that same year. The iPrEX study found that the use of a daily pill sold as Truvada reduced the risk of HIV by 44% among HIV-negative men who have sex with men. Impressively, the level of HIV protection was over 90% among those who used the pill consistently. A series of other PrEP studies released in the following years showed that the daily pill also worked for people at risk of HIV infection through vaginal sex and sharing needles.
While the vaginal gel remains unavailable, the use of a daily pill (Truvada) to prevent HIV infection has been approved by Health Canada and endorsed by the World Health Organization. Efforts are now underway to make this pill more available to people who need it.
James Wilton is an epidemiologist at the Ontario HIV Treatment Network (OHTN) who previously worked as CATIE's Biomedical Science of HIV Prevention Coordinator for six years.