Long-Acting HIV Therapy in African Adults with Adherence Challenges.

Background

In eastern and southern Africa, approximately 1 million people living with human immunodeficiency virus (HIV) and receiving oral therapy do not have viral suppression because of adherence challenges.

Methods

We conducted a phase 3b, open-label, randomized trial to compare long-acting injectable cabotegravir plus rilpivirine with oral dolutegravir-based therapy among adults with virally suppressed HIV type 1 (viral load, <200 copies per milliliter) and suboptimal adherence or care engagement. The participants were assigned in a 1:1 ratio to receive intramuscular injections of cabotegravir (600 mg) plus rilpivirine (900 mg) every 8 weeks, with the first two injection visits occurring 4 weeks apart, or to continue daily oral dolutegravir-based therapy; baseline drug-resistance testing was not performed. The primary end point was a viral load of less than 50 copies per milliliter at week 48; noninferiority was assessed with a margin of -10 percentage points. Confirmed virologic failure (two consecutive viral loads of ≥200 copies per milliliter) was a key secondary end point.

Results

A total of 540 participants were enrolled across seven sites in Kenya, South Africa, and Uganda; 537 were included in the primary analysis. At 48 weeks, 244 of 268 participants (91.0%) in the long-acting-therapy group had a viral load of less than 50 copies per milliliter, as compared with 240 of 269 participants (89.2%) in the oral-therapy group (risk difference, 1.9 percentage points; 95% confidence interval [CI], -3.1 to 6.9), which met the criterion for noninferiority. The results of a per-protocol analysis were consistent with those of the primary analysis. Confirmed virologic failure occurred in 5 participants (1.9%) in the long-acting-therapy group and in no participants in the oral-therapy group (risk difference, 1.9 percentage points; 95% CI, 0.3 to 3.5). Serious adverse events were reported in 11 of 271 participants (4.1%) who received long-acting therapy and in 8 of 269 participants (3.0%) who received oral therapy (risk difference, 1.1 percentage points; 95% CI, -1.1 to 4.2).

Conclusions

Among persons with HIV in Africa who have adherence challenges, long-acting cabotegravir plus rilpivirine was noninferior to oral dolutegravir-based therapy for maintaining a viral load of less than 50 copies per milliliter. (Funded by Johnson & Johnson; IMPALA ClinicalTrials.gov number, NCT05546242; Pan African Clinical Trials Registry number, PACT202301600757432TMC278LAHTX3005.).