A huge global trial has begun of a long-acting injectable form of the investigational antiretroviral cabotegravir as pre-exposure prophylaxis (PrEP) against HIV.
The Phase III trial, which will ultimately enroll 4,500 HIV-negative transgender women and cisgender men who have sex with men (MSM), will determine whether long-acting injectable cabotegravir given every eight weeks protects against HIV as well as daily oral Truvada (tenofovir disoproxil fumarate, or TDF/emtricitabine).
“We urgently need more HIV prevention tools that fit easily into people’s lives,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), said in a press release. “Although daily oral Truvada clearly works for HIV prevention, taking a daily pill while feeling healthy can be difficult for some people. If proven effective, injectable cabotegravir has the potential to become an acceptable, discreet and convenient alternative for HIV prevention.”
NIAID is cosponsoring the trial with cabotegravir’s manufacturer, ViiV Healthcare.
Daily Truvada, which was given the green light by the FDA as an HIV prevention tool in 2012, is currently the only approved form of PrEP and likely will remain so throughout the decade.
Another Phase III trial recently began comparing the safety, tolerability and efficacy of daily oral Descovy (emtricitabine/tenofovir alafenamide, or TAF) with Truvada as PrEP. Descovy is an updated version of Truvada that includes a new take on the drug tenofovir that is safer for the bones and kidneys. The first results from that trial are expected in 2019.
Called HPTN 083, the long-acting cabotegravir PrEP trial will be conducted at 45 sites in eight countries in the Americas, Asia and Africa and will include participants 18 years or older who are at high risk for HIV. Results are expected in 2021.
“The annual number of new HIV infections among young people, especially young men who have sex with men and transgender women who have sex with men, has been on the rise despite nearly flat HIV incidence among adults worldwide,” HPTN 083 protocol chair Raphael J. Landovitz, MD, MSc, said in the press release. “It is essential to develop multiple effective HIV prevention modalities so the most vulnerable populations have a choice of preventive options.” Landovitz is an associate professor of medicine at the David Geffen School of Medicine at University of California, Los Angeles.
The HPTN 083 participants will be randomly assigned to receive long-acting cabotegravir or daily Truvada and will remain in the study for an average of four and a half years. The study design uses placebos to keep both the participants and the investigators in the dark about which form of PrEP the participants receive. For the first five weeks of the study, the participants will receive two daily oral tablets, including either an oral version of cabotegravir or Truvada plus a placebo pill. At the six-week point, those in the cabotegravir group will receive injections of the long-acting injectable version of cabotegravir plus placebo tablets to be taken orally each day. Those in the Truvada group will receive injections of a placebo and daily Truvada tablets. The study staff will administer the injections.
The first two injections will be given four weeks apart. Thereafter, the injections will be given every eight weeks for an average of nearly three and a half years. Once the injections end, the participants will be provided 48 weeks of daily oral Truvada.
The reason for switching the participants back to daily oral Truvada as PrEP is to provide protection against the potential for emerging drug resistance while cabotegravir slowly dissipates from the body. Long-acting cabotegravir has a very long “tail”; recent research found that the drug may linger in the body for more than a year in some people after they stop receiving the injections. After the drug has dropped below levels in the body that provide maximum protection against HIV, an individual could potentially contract the virus; at that time, there may still be enough drug in the body to give rise to virus that is resistant to it. Drug resistance can limit future HIV treatment options.
The participants will receive HIV prevention counseling, condoms, lubricant and counseling to encourage adherence to the daily oral pill. They will receive regular sexually transmitted infection testing and referral to STI treatment if necessary. Routine HIV testing is also part of the study protocol. Those who test positive will stop receiving the study drug and placebo and will be referred to care and treatment for the virus.
Another study, HPTN 084, will test the safety and efficacy of long-acting injectable cabotegravir as PrEP among young women in sub-Saharan Africa starting in 2017.
For more information on the HPTN 083 trial, including the contacts of those running the trial sites in 15 U.S. cities for individuals interested in participating, click here.
To read a press release about the study, click here.