Charles Flexner, MD, on HIV Management

Every year, we raise awareness for World AIDS Day on December 1. This year, we caught up with Dr Charles Flexner about HIV prevention, treatment, and progression during the aging process.

Charles Flexner, MD, is director of Johns Hopkins University AIDS Clinical Trials Group and professor of medicine at Johns Hopkins University School of Medicine.

Infectious Disease Consultant: Because of advances in antiretroviral therapy, people with HIV are living longer. But how do diseases associated with aging affect HIV infection?

Charles Flexner: Aging-related conditions are becoming more common as the HIV-infected population ages. This includes cardiovascular disease, hypertension, stroke, kidney disease, and diabetes. Although a number of observational studies suggest that HIV-infected patients on successful suppressive antiretroviral therapy (ART) develop aging-related comorbidities earlier than age-matched controls (perhaps 5 to 10 years earlier), most studies suggest that aging-related diseases do not affect the course or severity of HIV-associated illness. Of course, concurrent medications and polypharmacy also can increase with aging, and the possibility of adverse drug interactions involving those medications and antiretrovirals should be considered. 

ID CON: What role do long-acting antiretrovirals play in HIV care? How are they different from other HIV therapies?

CF: There are several long-acting injectable or implantable formulations in clinical development for treatment and prevention of HIV, although none are yet approved. The most advanced are long-acting formulations of cabotegravir and rilpivirine, which are in Phase 3 clinical trials. These formulations are given as intramuscular injections every 8 weeks, although implants are being developed that could be given as infrequently as once per year.

ID CON: Do at-risk populations have easy access to long-acting antiretrovirals? Are these medications increasing adherence rates?

CF: Long-acting formulations are designed to improve adherence, fight pill fatigue, and reduce HIV-related stigma. Adherence and persistence rates with these formulations in clinical trials have generally been excellent—90% or greater after 1 year of treatment with long-acting cabotegravir and rilpivirine. On the other hand, the patients who are participants in these clinical trials are highly motivated to receive these formulations, and they may not accurately reflect product performance in more “real-world” populations.

ID CON: What challenges need to be overcome in order to eliminate HIV in the United States?

CF: The greatest hurdle for controlling transmission of HIV in the United States is to get all at-risk individuals tested for infection. Then those who are seropositive could be treated, and those who are seronegative could be counseled to reduce transmission risk and/or advised about taking pre-exposure prophylaxis (PrEP). These are the only tools available to effectively block the continued spread of this virus.

ID CON: What HIV therapies are on the horizon in 2019?

CF: In addition to long-acting formulations of cabotegravir and rilpivirine described previously, there are several broadly neutralizing anti-HIV antibodies (bnAbs) in clinical trials. These agents are exciting because they can be modified molecularly to achieve very long half-lives in plasma and could be given to patients and at-risk individuals every 3 to 6 months, possibly less frequently. So far, these antibodies appear to be very well tolerated in clinical trials and have clear anti-HIV activity in infected individuals. However, they must be used in combination to avoid selecting resistant viruses. Other agents on the horizon from pharmaceutical companies include a very potent and long-lived HIV capsid inhibitor, GS-CA1, as well as a potent and long-lived nucleoside reverse transcriptase inhibitor, EFdA, that could be a good candidate for implant formulation.