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Research Director (HIV and Infectious Diseases)
Hospital La Paz. IdiPAZ.
José R. Arribas, MD, has disclosed that he has received consulting fees from Aelix, Janssen, MSD, Serono, and ViiV; funds for research support from Gilead Sciences and ViiV; and fees for non-CME/CE services from Gilead Sciences.
As usual, the 2022 Conference on Retroviruses and Opportunistic Infections (CROI) had many exciting presentations. Two studies of particular interest for healthcare professionals and people with HIV (PWH) in Western Europe involved long-acting (LA) injectable antiretroviral medications for the treatment of HIV.
Q8W Injectable Cabotegravir (CAB) Plus Rilpivirine (RPV)
The 3-year update of the ATLAS-2M study addresses a question of interest to patients and healthcare professionals alike—namely, whether Q8W LA CAB plus RPV is as effective as the Q4W regimen. Encouraging data presented by Overton and colleagues showed that LA CAB plus RPV in the Q8W regimen was noninferior to the Q4W regimen when considering the prespecified endpoints of percentage of patients with HIV-1 RNA ≥50 copies/mL and HIV-1 RNA <50 copies/mL. No new safety signals were observed, and—not surprisingly—treatment satisfaction ratings significantly favored the Q8W regimen at all timepoints.
And what about resistance? Between Weeks 96 and 152, 2 additional patients (in the Q8W arm) met confirmed virologic failure (CVF) criteria, bringing the CVF total in both arms to 13/1045 (1%). Of these 13 patients with CVF, 11 (2%) were in the Q8W arm compared with 2 (<1%) in the Q4W arm, and no patients were >7 days late on their injections. Of note, only 6 of the 13 patients with CVF had ≥2 of the baseline risk factors (ie, proviral RPV resistance-associated mutations, HIV-1 subtype A6/A1, BMI ≥30 kg/m2) previously associated with virologic failure on LA CAB plus RPV when ≥2 are present. This demonstrates that there is more to learn about this infrequent problem of resistance.
Therefore, when we talk to patients in clinics, we should inform them that, although the risk of virologic failure with antiviral resistance selection is small with both LA CAB plus RPV regimens, based on this study, it does seem to be higher with Q8W dosing than Q4W dosing. This is important, because the Q8W dosing is naturally going to be appealing to patients for its benefits of convenience and avoiding stigma.
Lenacapavir Every 6 Months for Multidrug-Resistant HIV
In Western Europe, we generally have strong linkage to care rates for PWH and, hence, not many virologic failures. However, having effective treatment options for multidrug-resistant HIV is still important across the globe, both for the welfare of the individuals affected and to prevent transmission of HIV. Having a promising drug from a new class—the capsid inhibitor lenacapavir (LEN)—is very encouraging.
The phase II/III CAPELLA trial enrolled heavily treatment–experienced patients with resistance to ≥2 agents from 3 of the 4 main antiretroviral classes. We have previously seen data demonstrating LEN efficacy after 14 days in the functional monotherapy phase. At CROI 2022, Ogbuagu and colleagues presented the 52-week data from the randomized cohort in the maintenance phase, in which patients received SC LEN every 6 months plus an optimized background regimen (OBR).
After 52 weeks of follow-up, 30/36 (83%) patients attained HIV-1 RNA <50 copies/mL, and the percentage was even higher (94%) in patients with ≥2 active agents in their OBR. There was a very good CD4+ cell count recovery at 52 weeks, and no additional cases of LEN resistance were observed in the randomized cohort after Week 26. (Among the 8 patients with emergent LEN resistance up to Week 26, 4 had no fully active drugs in their OBR, and 4 had inadequate adherence to OBR.)
No serious adverse events were attributed to LEN. Most injection site reactions were grade 1 or 2 and relatively well tolerated. There was interest in the injection site reactions because LEN is the first LA agent planned to be self-administered by PWH. Ogbuagu and colleagues reported that the LEN injections may produce SC nodules that are palpable but not visible but that can, in some cases, persist for a prolonged time (median duration of 180 days).
Self-administration is another empowering advance in antiretroviral therapy (ART) that enhances patients’ privacy, but LA ART may present a trade-off—the risk of emergent resistance compared with the oral drugs with a high genetic barrier, such as dolutegravir or bictegravir. Going forward, important questions remain about optimal implementation and management on LA antiretrovirals.
What challenges have you encountered with implementation of LA injectable ART? Join the discussion by posting a comment. For more details on this and other key HIV issues from CROI 2022, review more CCO Conference Coverage, including Capsule Summary slidesets and other ClinicalThought commentaries highlighting US and global perspectives.