MEXICO CITY — For Wendy Armstrong, MD, who still sees patients die from complications of AIDS, news of monthly injectable HIV treatment, simplified regimens, and better tolerated antiretroviral drugs are exciting. But they're also frustrating.
"All these ideal populations don't help us at all think about how we actually treat real-world patients," said Armstrong, from the Emory University School of Medicine in Atlanta, Georgia.
These "ideal populations," as seen in clinical trials, are often white, male, cisgender — people whose identity matches the sex they were assigned at birth — and have ready access to healthcare. It's a group representative of those devastated by the early AIDS epidemic.
But even as they eagerly await the upcoming International AIDS Society (IAS) 2019 Conference on HIV Science, Armstrong along with other physicians, scientists, government agencies, and companies are questioning whether the way they've always recruited for clinical trials still serves patients.
“We have products that haven’t been tested in all types of people, even though they are going to be used in all types.”
"This gets back into what we need to do to end the epidemic," said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Health's National Institute of Allergy and Infectious Diseases (NIAID). "These questions are critical. We can't just answer them with cohorts from the 80s."
It wasn't that long ago that the participants of an HIV drug trial would have had the following demographic characteristics: 15% women, 15% non-white, and 0% transgender. Those are the demographics for the 2013 SPRING-2 trial that proved the effectiveness of dolutegravir (DTG) (Tivicay, GlaxoSmithKline).
For the 2015 IPERGAY trial of on-demand preexposure prophylaxis (PrEP) for gay men, the demographics was 0% women, 8.5% non-white, and 0% transgender. To date, it's the only trial for on-demand PrEP.
For pharmaceutical companies, the goal has been to "complete the study as quickly as possible," said Vani Vannappagari, PhD, MBBS, MPH, global head of epidemiology and real-world evidence at ViiV Healthcare. "That means, historically, that white MSM [men who have sex with men] populations really were the participants in clinical trials."
At last year's International AIDS Conference, Rebecca Zash, MD, of Beth Israel Deaconess Medical Center in Boston, Massachusetts, reported that there was evidence of an increase in neural tube defects in infants born to women who were taking the drug dolutegravir at the time of conception. She will present updated data on that evidence at the upcoming conference.
Ironically, when women who were participating in the trial became pregnant, they were excluded from the study, as happens with all clinical trials.
"It's something that I hope to hear at every trial of a new ARV [antiretroviral], long-acting ARV, an antibody or immune strategy — basically, what's the plan to figure out whether this is safe for women who could become pregnant?" Zash said.
And it's not just women of reproductive potential. It's people in sub-Saharan Africa, women, adolescents and, Bekker added, "especially transgender people who get left out but then in whom we want to use these products."
This exclusion from trials has had real-world impact.
A 2017 NIAID study found that transgender women have shied away from using PrEP because of fear that it interacts with hormone therapy.