Putting AIDS 2018 Into Perspective: Clinical Implications

The 2018 International AIDS Conference in Amsterdam, the Netherlands, brought a plethora of new clinical implications for HIV care, reflecting ongoing investments in research efforts and optimism across all clinical domains, including vaccines, prevention, and new treatment approaches.

However, with the excitement also came caution in other areas, such as incidence rates, where rates of new infection among adolescents and adults are not decreasing enough to gain control of the epidemic.

Following the conference, experts in the space convened in Washington, DC, to recap the meeting’s findings and discuss what they mean and what’s next.

To read more on news coming out of AIDS 2018, click here.

Vaccine Potential

While we’re still in the era of trying to nail down an effective HIV vaccine, there’s no shortage of researchers assessing new approaches and vaccine paradigms, according to Chris Beyrer, MD, professor, Johns Hopkins Bloomberg School of Public Health and past president of the International AIDS Society.

These novel approaches include new small molecules that mimic the CD4 receptor medical compounds and new immunogens known as SOSIPs. “The challenge is that we’re learning more and more about neutralizing antibodies, but we want to do is make the human immune system generate the kind of antibodies and cellular responses that can really neutralize a variety of wildtype viruses,” said Beyrer.

Beyrer highlighted the phase 2 APPROACH trial, which included nearly 400 participants. The trial assessed the safety, tolerability, and immunogenicity of vaccine regimens that included 2 doses of a prime vaccine to stimulate an initial immune response and 2 boost vaccinations using various combinations of Adv.Mos.HIV, or modified vaccinia Ankara, with or without 2 different doses of clade C HIV gp140 envelope protein containing an aluminum adjuvant.

He also highlighted the large-scale South African phase 3 HVTN702 trial, which is testing the safety, tolerability, and efficacy of a vaccine using a prime boost strategy.

New Approaches to a Cure

The AIDS conference put a large focus on HIV reservoirs—a group of immune cells in the body that are infected with HIV but are not actively producing new HIV. With this, the method of action has shifted from a sterilizing cure to a functional remission, with the goal of getting numbers so low that people may be able to function off treatment for some time, explained Beyrer

A number of presentations focused on the shock-and-kill approach, where researchers wake up the reservoir with an activating agent and then kill the virus. While studies have shown they can wake up the reservoir, there has been no success in effectively killing the virus. Beyrer noted the RIVER trial, which experimented with adding a vaccine boost. Unfortunately, he said, it was not effective.

During the conference, there was the introduction of a new approach: shock and block, where researchers are able to lock down the reservoir and keep it quiescent.

Prevention

“The pre-exposure prophylaxis (PrEP) implementation era finally has begun,” said Beyrer. Following years of focus on treating existing diagnoses, there is now increased attention on preventing new cases.

Notable study results at the AIDS conference came from the French PrEP trial. The French have pioneered the idea of on-demand PrEP—taking the pill when needed rather than daily. In the open-label study, participants were able to choose on-demand or daily PrEP, which resulted in half in each cohort. During follow-up, there has not been a single incident of infection in either group.

“This is important because this means a new option,” said Beyrer. This means taking 18 doses a month, rather than 30, which results in cost-savings.

Evidence coming from Sydney, Australia; London, United Kingdom; and the United States all point to a direct association between increased PrEP use and a decrease in HIV incidence, added Greg Millett, MPH, vice president and director, public policy, amfAR. He also noted that a study presented at the AIDS conference showed that declines in HIV incidence were particularly pronounced in areas in the cities, with not as much of a decline in the suburbs. Researchers hypothesized that this could be attributed to more community cohesion and networking in cities.

Dolutregravir

Prior research has shown that the integrase inhibitor, in combination with other agents, induces rapid suppression of HIV, has high barriers to resistance, and is well-tolerated, representing a promising treatment option.

However, the treatment made headlines in May as the FDA issued an alert on neural tube births affecting babies born to women with HIV being treated with dolutegravir at the time of conception or early in the first trimester. During the AIDS conference, researchers presented new data on another 170 births in the cohort, which resulted in no neural tube deaths, bringing down the proportion from 0.9 to 0.67.

Viral Suppression

Study results from the 2014 PARTNER study touted the idea that those who are virally suppressed are less likely to transmit HIV to their partner. However, critics of the study pointed out that same-sex couples were underrepresented and that the data wasn’t as accurate as once thought in terms of viral suppression equaling untransmittable.

From this came the PARTNER 2 study, whose results were presented at the 2018 AIDS conference. Including 635 same-sex couples, the study analyzed more than 78,000 unprotected sex acts and found no HIV transmissions.

“This is amazing news, but we have a long way to go to make sure PARTNERS 2 is even a reality for some of the places most impacted by HIV globally,” explained Millet. According to Millett, key populations accounted for 44% of global HIV infections in 2017.

Among men who have sex with men in sub-Saharan Africa, only 25% are aware of their HIV status, of which only 10% are on antiretroviral therapy and 8% are virally suppressed.