Young people living with HIV manage their condition better when their antiretroviral therapy is given by injections every eight weeks, rather than in the form of daily tablets, according to the results of a trial in Africa led by UCL (University College London) researchers.
In a paper published in The Lancet, the team found that the injections were more effective at keeping the virus suppressed than the tablets and called for efforts to make this treatment more accessible worldwide.
Although HIV is incurable, antiretrovirals can help people live long, healthy lives and greatly reduce the risk of the virus being transmitted to other people. About 1.6 million adolescents (aged 10 to 19 years of age) live with HIV.
Professor Sarah Pett (UCL Innovative Clinical Trials Unit), Chief Investigator of the LATA trial, said: "HIV-positive adolescents as a group have historically done worse on antiretrovirals compared to adults. There is bullying and stigma associated with taking pills every day. Long-acting injectables taken every two months can help young people to lead a more normal life.
"The benefits of this form of treatment for adolescents is stronger than we have seen for adults. Previous trials in adults have shown only that injectables are no less effective than tablets.
"Our results support making injectables more widely available to groups such as adolescents who may not do so well on daily tablets. Nine out of 10 adolescents with HIV live in Africa yet currently this treatment is not accessible to them."
The LATA (Long-Acting Treatment in Adolescents) trial was conducted in five clinics in Kenya, South Africa, Uganda and Zimbabwe. It involved 476 adolescents aged 12 to 19 who were randomly assigned either a daily tablet, which is standard care, or a long-acting injectable (cabotegravir and rilpivirine), a relatively new way to treat HIV.
Those participating in the trial had been on tablet treatment for more than a year, had HIV that was fully suppressed (undetectable), and had not previously experienced treatment failure. Almost all the participants in LATA had had HIV since birth.
The research team found that, after just under two years (96 weeks), only two adolescents (1%) on injectables experienced confirmed viral rebound (two viral load measurements, measured at least seven days apart), where the amount of virus in the blood increases, compared to 15 (6%) in the daily tablets group. Increases in viral load can harm people's long-term health, increasing the number of dormant cells infected with HIV, and in some cases can lead to the infection being passed on to partners or offspring.
Nearly all (94%) adolescents in the long-acting injectables group said the eight-weekly injections were a lot easier than taking medicines daily.
A few challenges need careful consideration regarding the use of long-acting injectables in lower resource settings. The injectables are more expensive than standard daily tablets because the drugs are still on patent, and are more costly to make. In addition, rilpivirine needs to be kept refrigerated during its supply and storage. Skilled nursing staff are also required to administer the injections every eight weeks, whereas appointments for people taking tablets may be as infrequent as every three or six months. There is no agreement yet about a generic version of the injectable treatment.
Presently, adolescents aged 12 years and older as well as adults can be prescribed the injectables in the US, Europe and other high-income settings but in Africa, bar a few clinics, the treatment is not yet available.
The World Health Organization currently recommends the injectables as an "alternative" option for adults and adolescents on daily tablets who are successfully suppressing their virus and do not have active hepatitis B. This stance may be strengthened as a result of the LATA trial findings.
Corresponding author Dr Deborah Ford (UCL Innovative Clinical Trials Unit) said: "The lack of availability of injectable treatments in Africa risks increasing inequalities in HIV care, leaving most people living with HIV without access to treatments that are available in high-income settings.
"This gap may widen further with second- and third-generation injectables being trialled that may require doses just twice a year."
Dr Mutsa Bwakura-Dangarembizi, trial physician and Principal Investigator of the site in Harare, Zimbabwe, said: "The LATA trial finding that the eight-weekly injections were much better for keeping the virus undetectable, were well tolerated and strongly preferred by adolescents, is really exciting news. But we have a major problem right now in Africa and in other low-and-middle income settings, where these long-acting injectables are simply not available for use. This problem needs to be addressed to enable us to use these injectables in the groups that need them the most, i.e. adolescents living with HIV."
The trial received funding from the European Union through EDCTP-2 (the second European and Developing Countries Clinical Trials Partnership) and Johnson & Johnson Innovative Medicines. Johnson & Johnson Innovative Medicines provided the injectable rilpivirine and ViiV Healthcare provided injectable cabotegravir. The sponsor was UCL.
The LATA trial scientific collaboration included researchers from all four participating countries and participants were enrolled and followed from five trial sites: Baylor College of Medicine Children's Foundation, Uganda; Joint Clinical Research Centre (JCRC), Uganda; University of Zimbabwe Clinical Research Centre (UZCRC), Zimbabwe; Moi University Clinical Research Centre, Kenya; and Durban International Clinical Research Site - Enhancing Care Foundation, South Africa.
The study also involved social science, pharmacology and health economic researchers at the London School of Hygiene and Tropical Medicine, Radboud University Medical Center, and the University of York respectively.
