As psychedelic drugs near FDA decisions, people with HIV remain absent from trials, commentary says

Health plans could soon face coverage decisions on the first FDA-approved psychedelic medicines, yet the trials behind them have almost entirely excluded people with HIV, a population with outsized rates of depression, PTSD and substance use, two authors write in a commentary in the Lancet HIV.

Parya Saberi, Pharm.D., MAS, MFA, University of California, San Francisco professor and director of the UCSF Center for AIDS Prevention Studies Development and Mentoring Core, and Nelson Vergel, MBA, an HIV survivor and advocate, call on funders and HIV research networks to make sure people with HIV are enrolled in the next wave of psychedelic-assisted therapy studies.

Why mental health is an HIV care issue

Modern antiretroviral therapy (ART) lets most people with HIV live with the virus long term, but keeping viral load down is only part of staying well, the authors contend. Both depression and PTSD are linked to patients skipping appointments, taking ART less consistently, losing viral suppression and dying earlier and substance use can pull patients out of care.

Pooled results from a global systematic review put PTSD at approximately 28% among people with HIV, several times higher than general population estimates. Depression care also breaks down at each step. A 2023 U.S. modeling study estimated that 45% of people with HIV have a depression diagnosis, a little over half of them get treatment and one-third of those treated reach remission, or approximately 8% overall.

Standard options have limits, the authors wrote. Psychosocial interventions tend to lose effect over time and are constrained by workforce shortages, while medications usually require daily dosing and can take weeks or months to work and add to a patient’s drug burden.

What the psychedelic pipeline means for HIV payers

The stakes are concentrated in Medicaid, the single largest source of coverage for adults with HIV, covering approximately 4 in 10, according to KFF. Medicaid enrollees with HIV are more likely than other enrollees to have mental health conditions and substance use disorders, and average Medicaid spending per adult enrollee with HIV was approximately $24,500 in 2021, nearly three times the figure for adults without HIV, KFF found.

“To our knowledge, only one published study has specifically evaluated a psychedelic-assisted intervention among people with HIV,” Saberi and Vergel write in the study. “In an open-label pilot study of older men who were long-term AIDS survivors, psilocybin-assisted group therapy was feasible, appeared safe and was associated with significant reductions in demoralization several months after treatment.”

Evidence for psilocybin and MDMA so far

Psychedelic-assisted therapy combines a drug, most often psilocybin or 3,4-methylenedioxymethamphetamine (MDMA), with structured psychotherapy. Randomized studies in the general population have found that psilocybin-assisted therapy lowers depressive symptoms quickly and durably, while MDMA-assisted therapy has produced large improvements in moderate to severe PTSD.

Compass Pathways completed its new drug application for COMP360 psilocybin in treatment-resistant depression this week, and the FDA is now reviewing three psychedelic applications, including Usona Institute’s psilocybin for major depressive disorder and a resubmitted MDMA application for PTSD. If psilocybin or MDMA is approved, state Medicaid programs would have to cover it, though low reimbursement rates and annual budgets would complicate rollout, according to a Health Affairs Forefront analysis.

What psychedelic trials in people with HIV should measure

Because HIV clinics already follow patients’ clinical markers over time, investigators could see whether mental health gains after treatment show up in hard outcomes, the authors argue. How psychedelics interact with ART, and whether diverse communities with HIV find the therapy acceptable, remain open questions.

The authors are explicit that they want evidence, not rollout. Next steps they list include pharmacokinetic and safety studies, randomized efficacy trials and hybrid implementation-effectiveness studies. Trials should track whether patients stay in HIV care, take ART as prescribed, and keep the virus suppressed and should deliberately enroll groups that both fields have historically underrepresented. Implementation studies, they added, should test how the therapy fits with HIV, behavioral health and addiction services without disrupting ART or retention.

“As psychedelic-assisted therapies move from the margins toward the clinical mainstream, people with HIV should not be left waiting for evidence generated with other populations,” Saberi and Vergel conclude.