Five Surprising Seroconversions
Eleven of the 15 HIV infections in the cabotegravir group occurred in people who had received at least one injection. Three of these infections actually occurred during the first 5 weeks of the study when participants were taking oral cabotegravir, two occurred when participants chose to discontinue the injection and return to daily oral Truvada, and one occurred after a participant missed the injection for a prolonged period of time.
But five of the transmissions occurred in participants who appeared to be perfectly adherent.
Landovitz offered a number of possible reasons for this surprising finding.
“Number one could be that there’s something about these five particular individuals such that they grind up and eliminate the cabotegravir faster than other people, so an 8-week interval is too long for them,” he explained. “Another possibility, although pretty rare, is that there is a rare circulating virus that is intrinsically resistant to cabotegravir.”
Breakthrough HIV transmissions have been rare in people taking oral PrEP.
Disruptions caused by the COVID-19 pandemic have meant that the researchers don’t yet have the data on drug-resistant mutations or drug levels for these five participants, but they will.
“I suspect the truth is that there will never be a 100% failsafe HIV prevention mechanism,” said Landovitz.
“Impressive” Findings
The findings were greeted with excitement, although questions remain.
They are “impressive,” especially the data on black and Hispanic participants, said Paul Sax, MD, medical director of the Division of Infectious Diseases at Brigham and Women’s Hospital in Boston.
However, he said he is interested in the data showing that although participants in both groups gained weight during the study, there was early weight loss in the Truvada group, meaning that those in the cabotegravir group weighed more at the end of the study than those in the Truvada group.
“I’ve been watching the data on weight with integrase inhibitors,” he explained, including weight data specific to Truvada and to the combination of emtricitabine and tenofovir alafenamide (Descovy, Gilead). It looks like Truvada “has some sort of weight-suppressive effects. That’s going to be a thing we’re going to have to watch.”
Coleman said she is already thinking about patients at Whitman-Walker who might do well on cabotegravir and those who can start PrEP for the first time with this option.
“Not only would people probably switch to this option, but maybe people would be interested in starting a biomedical prevention approach that isn’t a pill every day,” she said. “It’s just exciting to have another option. Hopefully, in a few years, we’ll have implantable devices and rings; I can’t even imagine what all those brilliant minds are coming up with.”
But that’s still a ways off. First, cabotegravir has yet to be approved for HIV prevention, and ideally, eventually, there will be a way to determine if cabotegravir is safe for each patient that doesn’t involve a month of daily pills.
“We need to solve that problem because it’s so complicated to do an oral lead-in for a month or so,” said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. “Otherwise it’s not going to be feasible.”
We need to make sure this gets licensed for men and women and transgender individuals.
Even with these positive data, Dieffenbach and other officials are not keen to have ViiV apply for licensing right away. Last October, Descovy was the second oral PrEP pill approved for HIV prevention, but only for use by gay men and transgender women — it hadn’t been well studied in cisgender women — causing an outcry. Now, officials are suggesting that ViiV not make the same mistake.
They are urging the company to hold off until data from the sister study of the medication in women — HPTN 084 — is completed in 2022.
“We need to make sure this gets licensed for men and women and transgender individuals,” Dieffenbach told Medscape Medical News. “We just need to give this a little more time and then build a plan with contingencies, so that if something happens, we still have collected all the safety data in women so we can say it’s safe.”