When the AIDS epidemic first took hold in the United States more than 30 years ago, doctors were at a loss for how to treat or prevent this mysterious and deadly illness that seemed to primarily affect gay men. Today, HIV/AIDS is a worldwide global health crisis that has claimed the lives of more than 38 million men, women, and children.
In recent years, much progress has been made on the HIV treatment and prevention fronts. Antiretroviral therapy (ART) is helping people with HIV live longer, healthier lives while also reducing the risk of passing the virus to others. Pre-exposure prophylaxis (PrEP) offers antiretroviral medications to uninfected people in high-risk communities as a way to prevent HIV infection. And, pregnant women and mothers who take ART can virtually eliminate the chance of passing the virus to their babies. As a result of interventions like these, global pediatric HIV infections have been reduced by more than half since 2001.
But, despite the milestones, an HIV cure remains elusive. And as we commentate World AIDS Day 2016, the research done around the world, including ongoing work here at Penn, continues to search for clues that can offer new insights into a possible cure.
“There are many reasons why we haven’t been able to find a cure for HIV,” said Pablo Tebas, MD, director of the Therapeutic Clinical Trials Unit at Penn. “HIV is a virus that attacks the immune system’s t-cells and white blood cells – the very cells that are supposed to fight infections. It also has the ability to quickly replicate and mutate, making it very hard to find a cure that would work for everyone who is infected with HIV.”
Timothy Brown, also known as the Berlin patient, is the only person in the world who appears to have been cured of HIV. In 2007, Brown, who was living with HIV, was also diagnosed with leukemia. To treat his leukemia, Brown needed a stem cell transplant. Doctors in Berlin were able to locate a donor with a rare gene mutation known as delta 32 CCR5, which makes human cells immune to HIV because they lack the receptor that HIV uses to enter them.
The resulting stem cell transplant meant that Brown’s entire immune system was replaced, which also removed HIV from his body. To this day, Brown shows no signs of the virus in his system.
“The Berlin Patient is an example of someone who has been cured of HIV,” Tebas said. “But this was a unique case and it’s extremely unlikely this method could be replicated on a mass scale.”
In 2013, researchers got a fresh dose of hope when it was announced that a baby girl, known as the “Mississippi Baby,” who contracted HIV from her mother, had been “cured” after receiving antiretroviral medications shortly after birth. After 15 months, she stopped taking the medication and the virus did not come back. Her doctors thought that she may have been cured because she was treated immediately after becoming infected. However, a little more than a year later, researchers discovered that the virus rebounded in the little girl’s system and that she needed to restart her HIV treatment.
“In the case of the Mississippi Baby, as well as a few similar cases of children being born with HIV and seeming to be cured, the immune system was able to control the virus for a while, but it was not completely eradicated. This is what we call a ‘functional cure,’” Tebas said.
A functional cure means HIV may still exist in extremely small amounts, requiring long-term follow-up to ensure that the virus doesn’t return to high levels, but the person shows no detectable signs of the virus even without taking daily medications.
A functional cure is probably the most realistic path toward a cure for people currently living with HIV, explained Katharine Bar, MD, director of Viral and Molecular Core of the Penn Center for AIDS Research (CFAR).
“HIV it is extremely challenging to fully eradicate once the virus has locked onto the cells. One promising strategy is to find a way to suppress the virus to an undetectable level and give people living with HIV a ‘virus-free remission’ without taking medication,” Bar said.
Tebas and Bar are working with researchers across the country to find an effective immunotherapy approach to treating HIV that could eventually lead to a functional cure. The study, which was recently published in the New England Journal of Medicine, examined chronically HIV-infected participants and found that injections of one broadly neutralizing HIV antibody (bNAb), known as VRC01, were safe, generated high levels of the antibody, and modestly delayed the time of HIV viral rebound compared to historical controls. However, suppression did not surpass eight weeks in the majority of participants. By demonstrating that HIV-specific antibodies could be successfully administered as long-acting agents to suppress or even kill HIV-infected cells, this method is a first step toward the ultimate goal of durable suppression of HIV in the absence of ART.
Any functional cure for HIV would only be one component of a global, multi-pronged effort to end AIDS. That also includes efforts to prevent new infections and eliminate the ones that have already happened. Prevention measures, including a vaccine, will also be needed in order to meet UNAIDS’ ambitious goal to end the entire epidemic by 2030.
“An effective preventive vaccine is a completely separate but incredibly important intervention. Approximately 2 million people — including 45,000 Americans — are projected to become infected with HIV in the coming year. Thus, we need advances in preventing new infections and in improving the health of those who are currently living with HIV," Bar said. “Strategies based on powerful antibodies, like the one we studied, are being applied to both cure and vaccine research by many groups around the world. We are optimistic that the field can develop both an effective vaccine and a successful functional cure in the near future.”
Both a cure and a vaccine would need to work in tandem with preventive measures already in place, such as PrEP, condom use, and prevention of mother-to-child transmission to curb the epidemic.
Even if a vaccine or other highly effective prevention intervention could stop new infections right now, there would still be more than 36 million people worldwide who are living with HIV and will need treatment and other services for the rest of their lives.
“Ending AIDS by 2030 is an incredibly ambitious goal, but it’s the type of goal we need to have as scientists in order to continue to push for the well-being of all people, and we will only be able to do that by advancing research, treatment, and prevention measures,” Tebas said. “We have the tools to end the AIDS epidemic and I am hopeful I will see that happen in my lifetime.”
Follow #WAD2016 on Dec. 1 to learn about all the World AIDS Day events and news happening around the globe.