A bimonthly injection of Cabotegravir (ViiV Healthcare) increases the blocking effect. HIV With tenofovir disoproxil fumarate Emtricitabine (Tolvada, Gilead Sciences), new data from HPTN 083 Trial show.
The findings “can change the HIV prevention status for so many people,” said Megan Coleman, DNP at Whitman Walker Health in Washington, DC, who regularly prescribes Truvada as Pre-Exposure Prevention (PrEP). I am.
In Whitman Walker alone, about 3000 people were taking the drug in early 2020, but “for some, taking it daily is not a viable option,” Coleman said. “It’s amazing to have a patient’s ability to have something that can help them make their choices and reduce their risk of HIV.”
The final results of the trial — investigating transgender drugs for men and women having sex with men — were presented at the International AIDS Conference 2020.
Early test completion
Half of the 4,566 study participants from 43 sites in Africa, Asia, Latin America, and the United States were under the age of 30, 12.4% were transgender women, 29.7% were black, and 46.1% were Hispanic.
The research sponsor, ViiV Healthcare, was designed to allow 50% of US participants Population at risk Regarding HIV in the United States, Dr Rafael Landwitz, MD of UCLA David Geffen School of Medicine in Los Angeles, said he was chairman of HPTN 083. In fact, 49.7% of the American cohorts were black and 17.8% were Hispanic.
Patients randomized to the cabotegravir group received cabotegravir and oral placebo daily for 5 weeks to assess safety, followed by cabotegravir injections for 5 and 9 weeks, then 153 every 2 months. Oral placebo was given weekly and daily. Patients randomly assigned to the Truvada group received oral oral Truvada and placebo for 5 weeks on the same schedule for up to 153 weeks, followed by daily oral Truvada and placebo.
After the last injection, all participants continued to take Truvada orally daily for 48 weeks.
The researchers expected to wait for 172 participants to become infected with HIV. They initially determined that this number would be sufficient to determine if cabotegravir injection was superior to daily oral tolvada. However, by May 2020, when 52 study participants were infected with HIV, the results were biased in favor of Cabotegravir, The trial was canceled.. At that time, all participants were given cavotegravir injections every two months.
Of the 52 new HIV infections, 39 (75%) occurred in the Truvada group. In fact, people in the cabotegravir group were less likely to acquire HIV than people in the tolvada group (hazard ratio, 0.34).
“This clearly establishes the superiority of Cabotegravir,” Randwitz said.
He and his colleagues were legitimately concerned that at trial, HIV infection was so low that they could not show how effective injections were. With the success of Truvada PrEP, Difficult to design Preventive test.
“We know that Torvada works very well, so the fact that we were able to show that this group of cabotegravir works better is a powerful observation,” Randwitz said. It was This is especially true because the prevalence of sexually transmitted diseases, which are considered to increase the risk of HIV infection, is very high. Overall, 16.5% of the participants syphilis During the trial, 13.3% were positive for gonorrhea and 21.1% were positive for chlamydia.
5 amazing cello conversions
Eleven of the fifteen HIV infections in the cabotegravir group occurred in people who received at least one injection. Three of these infections actually occurred during the first five weeks of the study in which participants were taking oral cabotegravir, and two chose to have participants discontinue injections and return to Truvada daily. Occurred when one of the hours occurred after the participant neglected the injection for a long period of time.
However, five of the infections occurred in participants who appeared to be in full compliance.
Landovitz provided some possible reasons for this amazing discovery.
“The number one reason is that the eight-week interval is too long, because there are things like crushing and eliminating cabotegravir for these five specific individuals faster than others,” he explains. Did. “Another possibility, though quite rare, is that there are rare circulating viruses that are intrinsically resistant to cabotegravir.”
Breakthrough HIV infections are rare in people taking oral PrEP.
The disruption caused by the COVID-19 pandemic meant that researchers would not yet have data on drug resistance mutations or drug levels in these five participants, but they would.
“I think the truth is that there will never be a 100% fail-safe HIV prevention mechanism,” Landovitz said.
“Impressive” discovery
Despite the doubts, the results of the survey were excited.
They are “impressive,” especially data about black and Hispanic participants, says Paul Sachs, MD, MD, Medical Director of Infectious Diseases at Brigham and Women’s Hospital in Boston.
However, he said he was interested in data showing that participants in both groups gained weight during the study, while there was initial weight loss in the Truvada group, with the Cabotegravir group studying more. At the end of the Tolbada Group meant that he was heavier.
“I have seen the data above Weight with integrase inhibitorHe explained and included weight data specific to the combination of tolvada, emtricitabine, and tenofovir alafenamide (Descovy, Gilead). Tolvada seems to have “some weight-reducing effect. That will be something we must be careful of.”
Coleman said he was already thinking about Whitman Walker patients who might work well with Cabotegravir and those who could start PrEP for the first time with this option.
“People will probably be interested not only in switching to this option, but also in starting a nonmedicinal biomedical prophylaxis approach,” she said. “Another option is very exciting. Hopefully we’ll have implantable devices and rings within a few years. I can’t even imagine what all these wonderful minds would come up with.”
But it’s still a way to go. First, cabotegravir has not yet been approved for HIV prevention, and ideally there is a way to ultimately determine if cabotegravir is safe for each patient who does not need one month of pills. There will be.
“We need to solve that problem, because having a verbal introduction for a month or so is very complicated,” says Karl, director of AIDS at the National Institute of Allergy and Infectious Diseases. Dr. Diefenbach said. health. “If not, that is not feasible.”
We need to make sure this is licensed for men and women and transgender individuals.
Despite these positive data, Diefenbach and other officials do not want ViiV to apply for a license immediately. Last October, Descovy was the second oral PrEP tablet approved for HIV prevention, but only for use by gay men and transgender women. Protest.. Now authorities are suggesting that ViiV not make the same mistake.
They have asked the company to postpone data from sister studies of drug treatments for women. HPTN 084 — Completed in 2022.
“We need to ensure this is licensed for men and women and transgender individuals,” Dieffenbach said Medscape Medical News.. “We just have to give this a little more time and plan for the contingencies, so if something happens, we’ll have all the safety data of a woman so we can say it’s safe. We are collecting.”
ViiV seems to have such a plan.
“Our goal is to seek approval for all genders, and we work with the FDA and other regulators to plan for achieving this goal,” said ViiV Healthcare Head of Research and Development. Dr Kimberly Smith says.
On the other hand, the World Health Organization (WHO) does not expect to change guidelines on HIV prophylaxis until data from HPTN 084 is reported.
“What’s important when looking at the guidelines is that we also look at the population as a whole,” said Meg Doherty, Coordinator of Treatment and Care in the HIV/AIDS department at WHO. “I want to know more about how cabotegravir works in women. We certainly want men and women of different ages to have preventative medications that can be used ideally during pregnancy. Because.”
International AIDS Conference 2020: Abstract OAXLB01. Announced on July 8, 2020.
