Long-acting injectable treatment superior to daily pills for adolescents in African trial

Eight-weekly injectable treatment with cabotegravir and rilpivirine proved superior to oral daily treatment with dolutegravir and two other drugs in maintaining viral suppression among adolescents in Africa, researchers from the LATA study reported at the 26th International AIDS Conference (AIDS 2026) in Rio de Janeiro on Wednesday.

Adolescents often experience difficulties in adhering to daily oral antiretroviral treatment and have poorer treatment outcomes than adults. Several studies have shown that adolescents who switch from oral to injectable antiretroviral treatment prefer injections and do not experience virologic rebound.

The LATA trial is the first randomised comparison of injectable treatment and oral antiretroviral treatment in adolescents. The study compared standard oral antiretroviral treatment with dolutegravir, tenofovir disoproxil and lamivudine to injections of cabotegravir and rilpivirine every eight weeks.

The study

The study recruited 476 adolescents aged 12-19 years in Kenya, South Africa, Uganda and Zimbabwe. Participants were eligible to join the study if they had a viral load below 50 copies/ml on antiretroviral treatment for at least 12 months and no history of treatment failure.

The study population was 54% female, had a median age of 16.5 years and had been taking antiretroviral treatment for a median of 11.7 years. Almost all participants (99%) had taken dolutegravir and 83% had taken a non-nucleoside reverse transcriptase inhibitor.

Injectable cabotegravir and rilpivirine were given as intramuscular injections; 40% of participants assigned to the injectable arm opted for oral lead-in dosing with the two drugs. Oral lead-in dosing for one month has been used in clinical trials and clinical practice to monitor for drug reactions, to establish stable blood levels of each drug before the first injectable dose and to check for the maintenance of viral suppression before the first injectable dose.

Results

The primary endpoint of the LATA study was the proportion in each study arm who experienced viral rebound above 50 copies/ml by week 96. Two out of 235 participants in the long-acting injectable arm (0.9%) experienced virologic rebound compared with 15 (6.4%) in the oral antiretroviral arm.

The long-acting injectable regimen was non-inferior to oral treatment (-5.5%, 95% confidence interval -10.3%, -1.5%). A separate superiority test showed that long-acting injectable treatment proved to be superior to oral treatment in this adolescent population (p=0.001).

Although the trial wasn't powered to detect differences at higher levels of viral rebound, the researchers carried out post-hoc analyses of the rates of viral rebound above 200 copies/ml and 1000 copies/ml. They found no significant differences in the performance of the two regimens when higher thresholds were used to define viral rebound.

One of the two participants in the long-acting injectable arm who experienced viral rebound developed drug resistance (high-level resistance to cabotegravir and rilpivirine). In the second case, the participant received cabotegravir and rilpivirine at week 4 but switched to dolutegravir-based oral treatment due to an adverse reaction. Viral rebound occurred at week 44 and did not result in the development of drug resistance.

Among the eight participants in the oral treatment arm who experienced viral rebound and who had viral loads sufficiently high to carry out resistance testing, two developed non-nucleoside reverse transcriptase inhibitor resistance and one developed the M184V mutation associated with resistance to lamivudine and emtricitabine.

Seven participants discontinued long-acting injectable treatment, one due to viral rebound above 200 copies/ml, one by choice, one due to tuberculosis, two due to plans for pregnancy and two due to drug-related adverse events (a hypersensitivity reaction and a drug-related skin eruption). No participant discontinued oral treatment. The frequency of injection site reactions was similar in adolescents in the LATA study to rates seen in adult studies (91% reported an injection site reaction, three of grade 3 severity).

There were 18 pregnancies in the long-acting injectable treatment arm and 17 in the oral treatment arm. Twelve of the 18 young women in the long-acting injectable arm who became pregnant opted to stay on injectable treatment, of whom four experienced miscarriages, four have given birth, one underwent an abortion and three are still pregnant.

Almost all participants in both study arms (99%) reported that taking HIV medication had not been a burden and had not made it difficult to live a normal life. But 94% of those in the long-acting injectable arm said that injectable treatment made things “a lot easier” for them than taking daily medication.

Dr Mutsa Bwakura Dangarembizi of the University of Zimbabwe Clinical Research Centre concluded that the study findings support the WHO recommendation that injectable cabotegravir/rilpivirine should be made available as an alternative to oral treatment to reduce the burden of adherence for adolescents.

But she warned that access to long-acting injectable treatment remains limited in the regions where need is greatest. Although ViiV Healthcare has licensed injectable cabotegravir to the Medicines Patent Pool and three generic manufacturers have signed agreements to develop injectable cabotegravir for lower-income countries, an injectable generic form of rilpivirine is not available.