Long-acting HIV treatment may be a game-changer for Uganda's HIV response

The long-acting therapies reduce the number of pills people need to take, making it easier to manage treatment and reduce pill fatigue.  Photo/Beatrice Nakibuuka

What you need to know:

  • Long-acting injectable therapy not only has equivalent efficacy to daily oral regimens but is also more convenient for patients, which may improve adherence and quality of life.

About 1.4 million people in Uganda are living with HIV/Aids. The prevalence of HIV among adults aged 15 to 64 in Uganda dropped from 6.2 per cent to 5.2 per cent.
 Uganda is committed to ending Aids as a public health concern by 2030. The World Health Organisation (WHO), the Global Fund, and UNAIDS all have global HIV strategies that are aligned with SDG target 3.3 of ending the HIV epidemic by 2030.

While HIV infection is a serious disease, it is important to remember that it is treatable. Since 1995, there have been medications known as anti-retroviral treatment that effectively combat the disease. The treatment is so effective that those who regularly and consistently take their medications do not even have a detectable level of virus in their system. This means that they can live longer and healthier lives without fear of transmitting HIV.

 Although there is no cure for the disease, there have been several groundbreaking studies in the fight against it over the years. For example, the prevention of mother-to-child transmission significantly reduced the number of babies that are born with HIV. 
However, the most recent research has revealed that the bi-monthly injectable HIV treatment is as effective as the daily oral pill. 

Solving the challenges of a daily pill
One of the biggest challenges faced by people living with HIV in Uganda according to Dr Andrew Kazibwe, the head of medical services at TASO Uganda, is social stigma, discrimination, and prejudice from family and community.
There is limited access to HIV testing, treatment, and care, due to stigma, and in rural areas, people have to walk long distances to get their refills of the daily pill. 
“This, therefore, makes adherence difficult since there is usually little or even no support at all from the family members. It is against this background that research innovations are now being geared towards long-acting therapies for HIV,” Dr Kazibwe says.

What are long-acting therapies?
The once-monthly CABENUVA (cabotegravir/rilpivirine) was approved by the FDA in 2021 as the first long-acting, complete HIV regimen. In 2022, it was also approved to be given once every other month.
The injectable therapy has a long half-life, meaning it can stay in the body for much longer than the pills. This makes long-acting treatment possible: injections every one or two months are enough to maintain high enough blood levels of the medication to suppress HIV.

Since its approval in 2021, habenula has not been used in Uganda and many African countries since research supporting its use had only been done outside Africa.
 Earlier this month, the Joint Clinical Research Centre (JCRC) released a 48-week report showing that the bi-monthly injectable HIV treatment with cabotegravir and rilpivirine is as effective as the standard daily oral HIV treatment combination in African patients.

Dr Cissy Kityo, the chief investigator and executive director of JCRC says the results support consideration of long-acting therapy for African treatment programmes as a viable alternative to daily oral medicines for HIV-1.
 She remarks on the transformative potential of the trial findings, especially for patients who struggle with adherence to daily medication. Long-acting therapy is a promising solution for improving adherence and quality of life among HIV-1 patients in the region.

"The findings from the trial are a huge step forward in HIV therapy in Africa. Long-acting injectable therapy not only has equivalent efficacy to daily oral regimens but is also more convenient for patients, which may improve adherence and quality of life. This could be a game changer for our treatment plans as we move to achieve the UNAIDS 95;95; and 95 targets," says Dr Kityo.
She emphasises that the long-acting injectable regimen of Cabotegravir and Rilpivirine offers a significant advantage by reducing the frequency of dosing from daily to bi-monthly, thus addressing one of the major barriers to effective HIV treatment and consistent medication adherence. This convenience would be expected to lead to better health outcomes and greater viral suppression rates.

“Our strategies for managing and treating HIV in Africa must evolve with the needs of the HIV community and we are excited to have these promising results from CARES,” she says.
The study recruited participants in Kenya (162), South Africa (106), and Uganda (244) with a median age of 42 years.  About 57.6 percent were female and one in five participants had a body mass index of 30 or above indicating a potential risk of suboptimal drug absorption. Participants had been taking antiretroviral treatment for a median of eight years but had no history of treatment failure.

Dr Ivan Mambule, the project leader, says the populations in the regions where previous registration studies were performed differ greatly from the people living with HIV (PLWH) in Africa. 
“We needed additional evidence to determine the role of long-acting therapy in treatment programmes with a public health approach in sub-Saharan Africa. There was a need to determine how effective this therapy would be against the wide range of circulating HIV subtypes and recombinants in the region,” he says.

The majority of people with HIV in Africa are women who may have differences in body fat distribution compared to men. Higher levels of body fat can affect absorption of the drugs when injected into the buttock muscle and this may affect responses to cabotegravir and rilpivirine.

From research, long-acting therapies are said to reduce the burden of daily medication, making it easier for people to stick to their treatment regimen. This in the end addresses adherence challenges, which are critical for achieving viral suppression and preventing drug resistance. 

 “The long-acting therapies reduce the number of pills people need to take, making it easier to manage treatment and reduce pill fatigue. By reducing the frequency of medication, long-acting therapies improve the overall quality of life for people living with HIV,” Dr Kityo says.
The intramuscular injection of long-acting habenula is a long-acting antiretroviral therapy (ART) combination approved for use as a fully suppressive regimen for people living with HIV not only in Uganda but also globally.

Dr Kityo adds that longer-term follow-up on the study is continuing to week 96. This demonstration of the safety and efficacy of the bi-monthly treatment is the essential first step to discussing a potential role for long-acting treatment programs in sub-Saharan Africa using the public health approach.

This new era of long-acting ART, which includes other antiretrovirals and formulations in various stages of clinical development, holds tremendous promise to change the standard of HIV treatment. 

However, although long-acting ART has high potential to be revolutionary in the landscape of HIV care, prevention, and treatment cascade, more data is needed to substantiate its efficacy and cost-effectiveness among patients at risk of non-adherence and across age groups, pregnancy, and postpartum.
Dr Kazibwe remarks that “these therapies are currently available under research studies and are not yet on a large scale primarily because of the cost of the therapies and safety concerns among pregnant and breastfeeding women.” 

A single dose of CAB-LA for HIV prevention costs $3,000 (about Shs11.2m) while the habenula costs from $4,300 (about Shs14m) up to $6,500 (about Shs23m) for a single dose.

Dr Andrew Kazibwe, the head of medical services at TASO Uganda, warns that the long-acting therapies for HIV treatments do not cure HIV or eliminate the virus from the body but are meant to effectively manage and control the virus. They should be continued within the specified time to maintain viral suppression.

Therefore, he says, the best method of preventing the spread of HIV is abstinence, being faithful to your partner, and using condoms.