Big advances in treatment can’t make up for an inability to stop new infections, which number 5,000 per day worldwide.
The trajectory of HIV has changed dramatically in just a few decades. Back in the early days of the epidemic, contracting HIV basically meant progressing to full-blown AIDS and death. Now, thanks to antiretroviral drugs and other therapies, individuals with HIV often can keep the virus at bay, avoid infecting others and live a normal lifespan. But while HIV has moved from a guaranteed death sentence to a chronic condition that can be kept at bay, a permanent cure has, thus far, eluded researchers.
The first step toward figuring out how far we’ve progressed toward a cure, according to experts, is to define it. “What do you mean by a cure?” asked Anthony Fauci, MD, the director of the National Institute of Allergy and Infectious Diseases. “If by cure you mean eradicating the virus, there hasn’t been much progress made.”
However, Dr. Fauci spoke encouragingly about the gains that have been made just this past year in terms of long-term virus suppression. Researchers continue to develop long-acting therapeutics, such as broadly neutralizing antibodies, that enable those living with HIV to keep the virus undetectable and untransmissible for longer periods of time. Referencing ongoing animal studies that demonstrate long-term suppression, these results “get into the cure range,” he told Contagion®.
One recent study at Beth Israel Deaconess Medical Center in Boston involved rhesus monkeys infected with simian-human immunodeficiency virus (SHIV), which is related to HIV, and then put on antiretroviral therapy (ART) for roughly 2 years. Toward the end of this period, the monkeys were split into 4 groups: One group was given the broadly neutralizing antibody known as PGT121, another was given a selective TLR7 agonist known as GS-9620, the third was given both, and the fourth was given a placebo.
After a period of time, the animals stopped receiving ART, so the researchers could observe whether they experienced a viral rebound. Every monkey taking the placebo rebounded, with an average rebound time of 3 weeks. Nine out of the 11 taking only PGT121 rebounded, and 10 of the 11 taking only GS-9620 rebounded. However, of the 11 monkeys taking the combination therapy, 5 experienced no rebound after 168 days of monitoring. The other 6 did rebound but then experienced suppression of the virus.
This is an encouraging response that can hopefully be replicated in continuing animal trials and, one day, in humans. “We are organizing an ambitious human trial that should start this year,” Paul Volberding, MD, a professor at UCSF School of Medicine in San Francisco, told Contagion®. “The field remains an exciting one to watch."
Gene Therapy Shows Promise
Roughly a decade ago, the so-called “Berlin patient” was given a stem-cell transplant to treat his leukemia, which had the unintended side effect of curing his HIV. He remains the only person in the world to have been cured, and scientists are trying to figure out how to replicate this success in other patients.
“These cells likely underwent graft-versus-host disease,” Scott Kitchen, PhD, associate professor of medicine at the David Geffen School of Medicine at UCLA, told Contagion®. Graft-versus-host disease, which can occur after a bone-marrow transplant, involves the new donor cells attacking not only the cancerous cells but healthy cells as well. Dr. Kitchen explained that in the case of the Berlin patient, the donor was one of a very small number of individuals who are naturally resistant to HIV because of a mutation in the CCR5 gene. This donor’s cells may have targeted a dormant reservoir of HIV in the patient, killing it off and rendering him free of the disease.
Unfortunately, researchers have been unsuccessful in replicating this treatment in other HIV-positive subjects due to an extremely small pool of naturally HIV-resistant donors and severe side effects in the subjects. Going forward, scientists likely will focus on treatment that “involves combining approaches like ART with bone marrow transplantation,” said Dr. Kitchen. “Another approach is to use gene therapy and basically take the person’s own stem cells and modify them in a way that knocks out the CCR5 gene.”
Dr. Kitchen is currently working on gene therapy as a treatment for HIV. “There’s some promise, but at this point the studies are ongoing,” he said. “What we can say is that there are increasing signals that are being found in nonhuman primate studies. We are eager to evaluate whether these interventions may have an effect in humans.”
Treatment Breakthroughs, but Infection Rates Still High
“Can we and will we end the HIV epidemic?” asked Quarraisha Abdool Karim, PhD, associate scientific director of the Centre for the AIDS Programme of Research in South Africa (CAPRISA), speaking at a National Institutes of Health symposium earlier this month. “We really have no more excuses, because we have the tools.”
However, the reality is that the infection continues to spread worldwide, negating the very real advances in treatment. According to Dr. Karim, 5,000 new infections occur each day, 70% of them in sub-Saharan Africa. In many African communities, a significant portion of the residents have HIV. “A key driver of the epidemic is high rates of infection in young women,” she said, adding, “We’re talking about this in a continent where 65% of the population is under age 35.”
Several other symposium attendees agreed that infection in young women often occurs because of sexual contact—possibly nonconsensual—with older men who either don’t know they’re infected or are noncompliant with their medication regime. “We see young people in great danger,” said Linda-Gail Bekker, MBChB DTMH DCH FCP(SA) PhD, deputy director of the Desmond Tutu HIV Foundation at the University of Cape Town in South Africa. “Youth in Africa have a high rate of communicable diseases.”
It’s not just underdeveloped nations in Africa and Latin America that are dealing with out-of-control HIV: According to Dr. Bekker, the United States experiences 30,000 to 40,000 new infections yearly.
Sten Vermund, MD, PhD, dean of the Yale School of Public Health in New Haven, said, “We have some very profound structural inhibitions that make it very challenging.” He referred to difficulties such as financial problems and social stigma faced by those of color, individuals in lower socioeconomic groups, and the LGBTQ community when he said, “These structural underpinnings of risk are a backbone of why we’re kind of stuck in America.” There are bright spots, however: A report by the Centers of Disease Control and Prevention noted that new infections in the United States declined from 45,700 yearly to 37,600 yearly between 2008 and 2014. At the same time, HIV rates have risen in recent years in certain communities in Europe, Asia, the Caribbean, and Africa
HIV experts note that it’s important for the medical community to pay attention to sexual and mental health issues to try to stem the tide of infection worldwide. Also critical is the need to provide job incentives for individuals so they don’t turn to sex work, which is a driver of HIV.
Finally, it’s incumbent on political leaders to prioritize a society’s health and well-being by making funds available for prevention and treatment as well as reducing poverty and its ill effects. “If you don’t have housing, if you’re starving, if you’ve got other things going on, you’re not going to stay in a[n HIV treatment] program,” Dr. Fauci said.
Ms. Saloman is a health writer with more than 20 years of experience working for both consumer- and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.