Background:
Long-acting injectable therapy (LA) is a recommended option for individualized treatment of human immunodeficiency virus type 1 (HIV-1) infection in resource-rich settings. Additional evidence is required to determine the role of LA for treatment programs in Africa, where demographic factors, viral subtypes, prior treatment exposure, prevalence of pre-existing antiviral drug resistance and standardized approach to treatment delivery and monitoring differ.
Methods:
This ongoing phase 3b randomized, multicentre, open-label trial evaluates efficacy, safety, and tolerability of switching from oral antiretroviral therapy (ART) to LA. HIV-1 positive adults, stable on first-line ART (TDF +3TC/FTC+EFV/NVP/DTG) with VL <50 copies/ml at screening were enrolled at 8 African sites. Main exclusion criteria were past virologic failure, pregnancy and HBV infection. Participants were randomized (1:1) to continue oral ART (OT group) or switch to cabotegravir (CAB) and rilpivirine (RPV) intramuscular injections every 8 weeks (LA group). VL was monitored every 24 weeks. Primary outcome was the proportion of participants with VL <50 copies/ml at week 48, by FDA snapshot algorithm (non-inferiority margin 10%). Confirmed virologic failure (CVF, secondary outcome) was defined as 2 consecutive VL ≥200 copies/ml. Resistance testing was done retrospectively on archived DNA at baseline in all participants, and at CVF.
Results:
512 participants were enrolled (median age 42y; 58% female; 92% on DTG-based ART; 74% with prior NNRTI exposure; 14% baseline archived RPV resistance mutations; 57% viral subtype A1; 21% baseline BMI ≥30kg/m2). Four withdrew by week 48 (2 LA, 2 OT group). At 48 weeks, 248/255 (97.3%) in LA and 252/257 (98.1%) in OT group had VL<50 copies/mL (difference -0.8%; 95%CI -3.4 to 1.8%); demonstrating non-inferiority (Table). One participant in LA group met the definition of CVF. Adverse events of grade ≥3 severity occurred in 24 (9%) in LA and 10 (4%) in OT group; only one adverse event in LA led to treatment discontinuation (injection-site abscess).Treatment satisfaction increased after switching to long-acting therapy.
Conclusions:
At 48 weeks, CAB and RPV LA showed non-inferior efficacy to standard oral ART when used in the public health approach with sparse VL monitoring and where pre-existing RPV resistance, subtype A1 virus and obesity are common. CVF and acquired resistance was rare. LA was effective and safe and may be considered for use in treatment programs in sub-Saharan Africa.
