HIV infection

Long-Acting Injectables for HIV Prevention: Insights From IAS 2019

The 10th International AIDS Society Conference on HIV Science focused on many aspects of HIV care, prevention, and management. Among the sessions that discussed prevention was “Long-acting injectables for HIV prevention,” presented by Myron Cohen, MD, who is professor of epidemiology and director of the UNC Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill in Chapel Hill, North Carolina.1

“I discussed injectable agents such as cabotegravir long-acting (CAB-LA) and other long-acting oral drugs and implants in development,” Dr Cohen said. “Also discussed (by my colleagues) were intravaginal rings and broad neutralizing antibodies. I am supervising several ongoing studies in this space.”

Dr Cohen first discussed rilpivirine as an intramuscular injection. The HIV Prevention Trials Network (HPTN) 076 study2 evaluated the safety and acceptability of rilpivirine in healthy, HIV-uninfected women. Results showed that 2 mL injections every 8 weeks were well-tolerated and safe among participants.

He then went on to discuss trials involving cabotegravir, including HPTN 0773, 0834, and 0845: “HPTN 083 (men in the Americas) and 084 (women in Sub-Saharan Africa) are ongoing trials of CAB-LA every 8 weeks.”

Results of HPTN 077 showed that CAB-LA, 600 mg, every 8 weeks was well-tolerated and met pharmacokinetic targets among men and women in the trial cohorts. HPTN 083 and 084 are ongoing. HPTN 083 is a phase 2b/3 trial of injectable cabotegravir compared with daily oral tenofovir disoproxil fumarate/emtricitabine for pre-exposure prophylaxis (PrEP) in cisgender men and transgender women who have sex with men.

HPTN 084 is a phase 3 double-blind safety and efficacy study of long-acting injectable cabotegravir compared with daily oral tenofovir disoproxil fumarate/emtricitabine for PrEP in HIV-uninfected women.

“CAB-LA and rilpivirine long-acting are on the horizon of treatment in 2020; CAB-LA for prevention depends on clinical trial results,” Dr Cohen said. “Long-acting drugs for prevention are potentially an important new biological tool, but efficacy must be demonstrated; user preference, cost, and supply chain logistics are unknown.”

Researchers are hopeful that the ongoing trials will answer these questions so that much-needed PrEP medications can reach the market and, ultimately, prevent the spread of HIV.

“HIV prevention research is dynamic; tools for treatment, prevention, and cure are completely entwined. So, advances in one area represent opportunities in the others,” Dr Cohen concluded.

References:

  1. Cohen M. Long-acting injectables for HIV prevention. Talk presented at: 10th International AIDS Society Conference on HIV Science; July 21-25, 2019: Mexico City, Mexico. http://programme.ias2019.org/PAGMaterial/PPT/17_85/Cohen%20Long%20ACTING%20PrEP%20%20IAS%202019.pptx. Accessed August 26, 2019.
  2. Phase II Safety and Acceptability of an Investigational Injectable Product, TMC278LA, for Pre-Exposure Prophylaxis (TMC278LA). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02165202. Accessed August 26, 2019. ClinicalTrials.gov identifier NCT0216520.
  3. Landovitz RJ, Li S, Grinsztejn B, et al. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected individuals: HPTN 077, a phase 2a randomized controlled trial. PLoS Med. 2018;15(11):e1002690. https://doi.org/10.1371/journal.pmed.1002690.
  4. Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), for Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women Who Have Sex With Men. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02720094. Accessed August 26, 2019. ClinicalTrials.gov identifier NCT0272009.
  5. Evaluating the Safety and Efficacy of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03164564. Accessed August 26, 2019. ClinicalTrials.gov identifier NCT03164564.