The 11th IAS Conference on HIV Science (IAS 2021), which takes place virtually this year from July 18 through July 21, features hundreds of presentations highlighting the latest science on a huge array of HIV-related subjects. Here we share bite-sized summaries of several studies selected by our team of editors and correspondents that provide new data pertaining to antiretroviral therapy (ART) and HIV medications in development, with a particular focus on U.S.-centric findings.
We will continue to update this article throughout the month. You can also check out our bite-sized summaries of research on complications and comorbidities among people living with HIV.
The following data bites are covered in this article:
- Long-Acting Cabotegravir/Rilpivirine Maintains Strength Through Week 124
- Twice-Yearly Lenacapavir Impresses in Phase 2 Study—But Its Real Test Is Yet to Come
Long-Acting Cabotegravir/Rilpivirine Maintains Strength Through 124 Weeks
The latest set of findings from the ongoing FLAIR study largely support prior results regarding the use of long-acting injectable cabotegravir/rilpivirine (LA-CAB/RPV, Cabenuva) for HIV treatment. IAS 2021 featured 124-week data from this Phase 3 study, which build off 96-week results presented at CROI 2020 last March.
Of course, one major development between those March 2020 study results and these July 2021 results is that LA-CAB/RPV won approval by the U.S. Food and Drug Administration; in January 2021, the combo got the nod as a maintenance regimen with a monthly dose. That approval was based in part on results from FLAIR, an open-label phase 3 non-inferiority study in which participants who initiated treatment with oral abacavir/dolutegravir/lamivudine were randomized to continue that therapy or switch to monthly intramuscular injections of LA-CAB/RPV.
Chloe Orkin, M.D., of Queen Mary University of London, presented a subset of the 124-week FLAIR findings at IAS 2021. Her presentation focused specifically on the arm of the study in which participants had been randomized from the start to switch to LA-CAB/RPV. (This presentation did not touch on study’s other arm, in which participants initially continued oral abacavir/dolutegravir/lamivudine for about two years, then switched to LA-CAB/RPV.)
Of the 283 people who were initially randomized to the LA-CAB/RPV arm, 229 remain in the study at Week 124 in the “extension phase,” Orkin reported. Since the 96-week analysis, five new participants had a viral load of 50 copies/mL or higher and one participant had confirmed virologic failure (i.e., back-to-back viral loads of 200 copies/mL or higher), bringing the total number of confirmed virologic failures since Week 1 to five.
When including other study discontinuations for any reason, the overall virologic success rate (in an intent-to-treat analysis) among participants in the LA-CAB/RPV arm dropped from 86.6% at Week 96 to 80.2% at Week 124.
Seven new patients experienced a drug-related adverse event (not including injection site reactions, which were common) between Week 96 and Week 124; none were Grade 4, and the sole Grade 3 event was a paracetamol overdose. In total through 124 weeks, 3,732 individual injection site reactions were reported among 17,392 injections, with pain the most frequent symptom (18% of all injections, usually subsiding in about three days) and indurations or nodules each occurring less than 1% of the time. Overall, injection site reactions have led to 7 study discontinuations among the 283 original study arm participants.
“These results demonstrate the durability of cabotegravir/rilpivirine LA dosed monthly as a well-tolerated, effective maintenance therapy for people with HIV,” Orkin said.
*For conference registrants: watch the study presentation
For everyone else: read the study abstract, “Week 124 results of the randomized, open-label, Phase 3 FLAIR study evaluating long-acting cabotegravir + rilpivirine for treatment in adults with HIV-1 infection (ITT-E population)”
Summary by Myles Helfand; posted July 19 at 1:51 p.m. ET.
Twice-Yearly Lenacapavir Impresses in Phase 2 Study—But Its Real Test Is Yet to Come
The experimental HIV-1 capsid inhibitor lenacapavir, when taken in combination with a daily oral NRTI backbone, yields high virologic suppression rates in treatment-naive people, early Phase 2 study results show.
The findings, presented at IAS 2021 by Samir Gupta, M.D., of the Indiana University School of Medicine, primarily spotlight 28-week results from one of a handful of ongoing HIV prevention and treatment studies currently underway involving lenacapavir. This particular study, called CALIBRATE, is a randomized, open-label trial exploring the safety and efficacy of a few induction-maintenance treatment approaches utilizing the nascent drug.
Gupta and colleagues randomized 182 HIV treatment-naive individuals into one of four groups:
- Subcutaneously injected lenacapavir every six months plus daily oral emtricitabine/tenofovir alafenamide (F/TAF, Descovy) for 28 weeks (i.e. the induction phase), followed by oral therapy simplification from daily F/TAF to daily TAF (i.e., the maintenance phase)
- Subcutaneously injected lenacapavir every six months plus daily oral F/TAF for 28 weeks, followed by oral therapy simplification from daily F/TAF to daily bictegravir
- Daily oral lenacapavir plus daily oral F/TAF
- Daily oral bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, Biktarvy), which effectively serves as a control group
Through the end of the induction period at 28 weeks, the proportion of people with a viral load below 50 copies/mL was 94% in the first group, 92% in the second group, 94% in the third group, and 100% in the control group. These figures were per an intent-to-treat analysis; the only documented cases of potential virologic failure (i.e., a viral load of 50 copies/mL or more) were seen among four participants the second group. (The other instances of non-suppression were due to a lack of available viral load data for some participants.)
The speed with which participants achieved an undetectable viral load was similar across all four study groups.
Injection site reactions (ISRs) were common among participants in the first two study groups, but not ubiquitous; 63 of 103 individuals (61%) reported no ISRs. The most typical ISRs were swelling (18%, usually resolving in 10 days), erythema (17%, usually resolving in 5 days), and pain (16%, usually resolving in 4 days). About 11% of subcutaneous lenacapavir recipients reported nodule development (of which one was considered Grade 3 and the rest Grade 1); another 11% reported injection site induration, with two of these participants discontinuing the study as a result (though Gupta noted they were both Grade 1). Gupta said these two were the only individuals who ended their participation in the study due to adverse events.
Other adverse events among people receiving any form of lenacapavir generally occurred at similar rates to those in the control group, with headache and nausea the most common (11% each among lenacapavir recipients). Rates of gastrointestinal distress appeared similar between injectable and oral lenacapavir recipients. Gupta stated that no Grade 4 or serious adverse events occurred that were attributable to lenacapavir.
Lab abnormalities were generally similar between the three groups taking lenacapavir and the control group, with no clinically relevant Grade 3/4 abnormalities and no related discontinuations reported.
The CALIBRATE study continues onward into its maintenance phase, while separate studies are exploring the use of lenacapavir in a number of other treatment and prevention scenarios, including its potential as part of a regimen consisting entirely of long-acting medications.
For conference registrants: watch the session in which this study was presented, entitled “Modern ART and COVID-19 in PLHIV” (the presentation begins at 9:48)
For everyone else: read the study abstract, “Long-acting subcutaneous lenacapavir dosed every 6 months as part of a combination regimen in treatment-naïve people with HIV: interim 16-week results of a randomized, open-label, phase 2 induction-maintenance study (CALIBRATE)”
Summary by Myles Helfand; posted July 20 at 4:50 p.m. ET.