LATA Trial: Eight-Weekly Cabotegravir/Rilpivirine Injections Beat Daily Pills in African Adolescents
核心洞察
In the LATA trial, 1 per cent of adolescents on eight-weekly cabotegravir and rilpivirine injections had confirmed viral rebound at 96 weeks versus 6 per cent on daily tablets.
The trial randomised 476 adolescents aged 12 to 19 across five clinics in Kenya, South Africa, Uganda and Zimbabwe, all previously suppressed on oral antiretrovirals.
Ninety-four per cent of participants in the injectable arm said treatment every eight weeks was much easier than taking daily medicines.
Eight-weekly injections of the long-acting HIV (搜索) medicines cabotegravir and rilpivirine suppressed the virus more effectively than daily antiretroviral tablets in adolescents, according to results from the LATA (Long-Acting Treatment in Adolescents) trial published in The Lancet.
The trial, led by researchers at University College London, found that only two adolescents, or 1 per cent, receiving the injectable treatment experienced confirmed viral rebound after 96 weeks, compared with 15, or 6 per cent, among those taking daily tablets. Viral rebound refers to an increase in the amount of HIV (搜索) in the blood after the virus had been suppressed. The researchers noted that rising viral loads can affect long-term health and, in some cases, increase the risk of transmission.
Trial Design and Population
LATA randomised 476 adolescents aged 12 to 19 across five clinics in Kenya, South Africa, Uganda and Zimbabwe. Participants were assigned either standard daily tablet treatment or injections containing cabotegravir and rilpivirine. All had been taking tablet treatment for more than a year, had fully suppressed HIV (搜索) and had no previous treatment failure. Almost all had acquired HIV at birth.
Nearly all participants in the injectable group, 94 per cent, said receiving treatment every eight weeks was much easier than taking medicines every day.
"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," said Professor Sarah Pett of the UCL Innovative Clinical Trials Unit, chief investigator of the LATA trial.
Pett framed the adherence problem in social terms. "HIV (搜索)-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."
Access Gap in Low-Resource Settings
Pett said the findings supported wider availability of injectable treatment for adolescents. "Nine out of 10 adolescents with HIV (搜索) live in Africa, yet currently this treatment is not accessible to them," she said. About 1.6 million adolescents aged 10 to 19 are living with HIV. Although there is currently no cure for HIV, antiretroviral treatment can enable people to live long, healthy lives and substantially reduce the risk of transmission.
In the US, Europe and other high-income settings, the injections can currently be prescribed to adolescents aged 12 and older and adults. In Africa, they remain unavailable outside a small number of clinics. The World Health Organisation currently recommends long-acting injectables as an "alternative" option for adults and adolescents who are taking daily tablets, have successfully suppressed HIV (搜索) and do not have active hepatitis B (搜索).
Researchers said expanding access in Africa and other lower-resource settings faces several challenges. The medicines are more expensive than standard tablets because they remain under patent and cost more to manufacture. Rilpivirine also requires refrigeration during supply and storage, while trained nursing staff are needed to administer the injections every eight weeks. By comparison, people taking daily tablets may have treatment appointments only every three or six months. There is also currently no agreement on a generic version of the injectable treatment.
"The lack of availability of injectable treatments in Africa risks increasing inequalities in HIV (搜索) care, leaving most people living with HIV without access to treatments that are available in high-income settings," said Dr Deborah Ford of the UCL Innovative Clinical Trials Unit, the study's corresponding author. She added that the gap may widen further with second- and third-generation injectables being trialled that may require doses just twice a year.
Dr Mutsa Bwakura-Dangarembizi, the trial physician and principal investigator of the Harare site, said the finding that the eight-weekly injections were much better for keeping the virus undetectable, were well tolerated and strongly preferred by adolescents is 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 (搜索)."
Funding and Collaboration
The trial was funded by the European Union (搜索) through EDCTP-2 and Johnson & Johnson Innovative Medicines (搜索). Johnson & Johnson Innovative Medicines provided injectable rilpivirine, while ViiV Healthcare provided injectable cabotegravir. UCL was the study sponsor. Researchers from Kenya, South Africa, Uganda and Zimbabwe contributed to the trial, with participants enrolled at five sites across the four countries. The study also involved social science, pharmacology and health economic researchers from the London School of Hygiene and Tropical Medicine, Radboud University Medical Center and the University of York.