The long-acting HIV prevention medication cabotegravir led to an an estimated 66% lower HIV incidence versus oral tenofovir/emtricitabine (TDF/FTC), according to interim results from the .
"The hazard ratio between the two arms was 0.34 -- that is 66% fewer incidents in the people receiving cabotegravir compared to those receiving tenofovir/emtricitabine [95% CI 0.18-0.62], which excludes the pre-specified non-inferiority margin of 1.23," explained Raphael Landovitz, MD, of the David Geffen School of Medicine at the University of California Los Angeles in a presentation at the International AIDS Conference virtual meeting.
"The superiority boundary was unity of 1.0; the protocols pre-specified alternative hypothesis of 0.75 -- definitively establishing superiority of cabotegravir compared to tenofovir/emtricitabine," he stated, adding that the trial was truncated on recommendation of the data monitoring and safety board because of dramatic reduction in infections in the cabotegravir arm.
"At that time we had enrolled 4,570 participants," Landovitz said at a press conference. "We found 52 incident infections or an incident rate of 0.81% overall. In the cabotegravir arm, we found 13 infections for an incidence rate of 0.41%; in the tenofovir/emtricitabine arm, we found 39 incident HIV infections for an incidence rate of 1.22%."
He noted that trial disruptions due to the COVID-19 pandemic prevented him from presenting resistance analysis on the HIV pre-exposure prophylaxis (PrEP) failures. Among the 13 individuals who acquired HIV in the cabotegravir arm, five were generally compliant in receiving treatment, he reported. Five others were diagnosed after a prolong hiatus in taking medication, while three were diagnosed during the oral lead in period.
"These results are exciting," press conference moderator Monica Gandhi, MD, MPH, of the University of California San Francisco, told 鶹ý, "The results show that prevention works, but we need to know what happens if the drugs fail and there is a development of resistance. That data will be forthcoming. What we have seen is incredibly important data."
HPTN083 is an ongoing phase IIb/III randomized, double-blind, double-dummy, clinical trial conducted at 43 sites in North and South America, Asia, and Africa. Interim results were also reported in May.
Landovitz said they enrolled adult cisgender men and transgender women who had sex with men at increased risk of HIV infection. The primary endpoints were HIV efficacy, prevention, and safety.
"The study population was diverse by intention," he said. "Two-thirds were under the age of 30; almost 13% were transgender women; and 50% of the U.S. enrollment were Black or African-American."
The participants were randomized to either cabotegravir as an oral daily dose for about 1 month to establish safety and tolerability, then injectable dosing every 8 weeks, or active oral TDF/FTC daily.
Landovitz said the plan was that the blinded, randomized component would last 3 years so that all patients were on one active and one placebo drug at all times. Patients who were forced to stop taking the injections were given 48 weeks of open-label TDF/FTC to cover the pharmacokinetic tail of the long-acting injectable cabotegravir.
The study was reviewed regularly after its initiation in December 2016 by the NIH data monitoring and safety board at pre-specified intervals. "The first analysis occurred in May 2020, and at that data monitoring and safety board meeting, they recommended that the blinded comparison be terminated, the results be made public, and all participants be offered long-acting cabotegravir if they so chose as soon as sufficient drug supply was available," Landovitz said.
He reported that injection site reactions were common, with 81% of cabotegravir recipients and 31% of TDF/FTC recipients reporting any injection site reactions, but most were mild to moderate. Only 2.2% of those receiving cabotegravir injections stopped due to side effects.
Decreases in kidney function were observed in the TDF/FTC group, while nasopharyngitis, blood glucose increase, and fever were more frequent in cabotegravir. Sexually transmitted infections were similar in both groups he said.
A companion trial in cisgender women is ongoing, according to the researchers.
Disclosures
The study was supported by Gilead Sciences and ViiV Health Care. Some co-authors are employees of the companies.
Landovitz disclosed relevant relationships with Gilead Sciences, Merck, Roche, and ViiV.
Gandhi disclosed no relevant relationships with industry.
Primary Source
International AIDS Conference
Landovitz R, et al "HPTN 083 interim results: Pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir is safe and highly effective for cisgender men and transgender women who have sex with men" IAC 2020; Abstract 10750.