Long-Acting HIV Shot Works Just Fine for Patients With Adherence Issues

— IMPALA study builds on research showing long-acting therapy is similar to daily oral therapy

Long-acting injectable therapy was similar to daily oral therapy for maintaining viral suppression in people with HIV and adherence challenges in Africa, according to an open-label phase IIIb trial.

At 48 weeks, 91% of participants who were receiving long-acting cabotegravir/rilpivirine (Cabenuva) had a viral load less than 50 copies/mL compared with 89.2% of those who were receiving oral dolutegravir (Tivicay)-based therapy, which met the criterion for noninferiority, reported Fiona Cresswell, MBChB, PhD, of the Uganda Virus Research Institute and the London School of Hygiene and Tropical Medicine Uganda Research Unit in Entebbe, and colleagues.

Confirmed virologic failure occurred in five participants in the long-acting therapy group and in no participants in the oral therapy group, also meeting noninferiority, they noted in the New England Journal of Medicineopens in a new tab or window.

"These findings add to the growing body of evidence supporting long-acting therapy for persons who face challenges with adherence to treatment, engagement in care, or both," Cresswell and colleagues wrote. The results also support the inclusion of the long-acting injectable therapy in World Health Organization treatment guidelines, they added.

Inconsistent adherence to highly effective oral antiretroviral therapy can put patients at two to four times' greater risk of death, the authors explained, and resulting viremia spikes can increase the risk of HIV transmission.

By their very nature, injectables could make adherence more certain. Unlike patient-administered oral therapy, clinicians administer long-acting injectable therapy and track adherence directly. Injectables have trade-offs, however, including more frequent clinic visits, more complex storage requirements, and a greater risk of integrase strand transfer inhibitor resistance.

The results of this study, known as IMPALAopens in a new tab or window, build on research showing that long-acting injectables can deliver similar effectiveness to daily oral treatments, even in people with adherence challenges. In the CARES trialopens in a new tab or window, 96.9% of participants receiving injectable cabotegravir/rilpivirine had a viral load of less than 50 copies/mL at 48 weeks compared with 97.3% of those receiving standard first-line oral antiretroviral therapy.

In addition, the U.S.-based LATITUDE trialopens in a new tab or window showed that fewer patients on long-acting cabotegravir/rilpivirine experienced treatment failure compared with those who stayed on standard oral treatment (24.1% vs 38.5%). However, LATITUDE's results can't be extrapolated to African public health approaches, Cresswell and colleagues cautioned, given a scarcity of resistance testing and infrequent viral load monitoring.

IMPALA enrolled 540 adults with HIV across seven sites in Kenya, South Africa, and Uganda, and 537 were included in the primary analysis. Median age was 40 years, 60% were women, and 99.6% were Black. About half of patients who had sequencing data had subtype A1 virus.

Adherence challenges were defined as an HIV viral load greater than 1,000 copies/mL or being more than 4 weeks late for a clinic visit or drug refill during the prior 2 years.

Patients were randomized to either long-acting injectable cabotegravir/rilpivirine every 8 weeks or to continue a once-daily, single-tablet regimen of tenofovir, lamivudine, and dolutegravir.

Noninferiority of the primary outcome -- a viral load of less than 50 copies/mL at week 48 -- was assessed with a margin of -10 percentage points.

Excluding injection-site reactions, adverse events occurred in 84.1% of the long-acting therapy group and 76.6% of the oral therapy group. Ten adverse events resulted in treatment discontinuation, two of which, one in each treatment group, were deemed to be drug-related.

Adverse events of grade 3 or higher occurred in 12.2% of participants who received long-acting therapy and 8.9% of those in the oral therapy group, while serious adverse events were reported in 4.1% and 3%, respectively.

More than a third of long-acting therapy patients (37.3%) reported an injection-site reaction, all of which were grade 1 or 2, and none of which led to treatment discontinuation.

Despite the injection-site reaction risks, most patients who received long-acting injectable therapy preferred the approach over their prior oral regimen (93.6%).

Study limitations included its open-label design. In addition, the structured nature of a clinical trial may overestimate adherence and engagement rates compared with routine care.