The big switch to injectable HIV treatment

Nine years ago, Jacinta’s * world was turned upside down. She had discovered she had contracted HIV. At first, she was in denial. Soon, the discovery started to devastate her physically and mentally. For two months, she was hospitalised as she fought to come to terms with her changed circumstances. 

“My viral load was very high. I had also developed tuberculosis. I was wasted and could barely walk or do anything by myself. I was in such a bad shape that I was willing to give up my life,” she says. 

It took weeks of counselling and psychosocial support for her to accept her condition and start treatment. Afraid of upsetting her elderly mother, Jacinta informed only her sister. To date, she is the only family member aware of her HIV status. 

During a routine clinic appointment in 2022, her doctor impressed upon her to take part in a clinical trial for the efficacy of an injectable Antiretroviral (ARV), to which she agreed.

 Healthy Nation met Jacinta at Aga Khan University Hospital, where she was participating in the trial.

She, like others on the trials, only needed to pass an inclusion criterion. Participants must be at least 18 and must have been taking an ARV oral regimen for at least six months. Their viral load must have been undetectable for more than six months. 

Their liver and kidneys must have been functioning normally. The participants are also required to be free from infections such as tuberculosis and pneumonia.

The study took two years and featured 40 patients in Kenya, Uganda and South Africa, which have a high HIV burden. Participants were randomly assigned to a long-acting regimen — cabotegravir and rilpivirine —  or oral therapy through a digital system. 

Those selected for the injectable ARV would get an injection after two months while those on oral tablets either maintained their current regimen or chose a different one. None was charged to participate. “The injections are convenient and time-saving. Sometimes patients delay or completely forget to take the tablets,’’ says Jacinta.

She adds: ‘‘I get my injection on the first week of every second month. This is easier for me. It allows me to plan well in advance, especially when I am travelling,” she explains.

For her, the only major side effect is the discomfort from the injection. The pain could last up to 48 hours. ‘‘I only wish the interval between the injections were longer. But I lead a fairly normal life. Sometimes I forget I am positive.’’

Prof Reena Shah, who was running the trial, explains that the injectable ARV provides another form of care for those who do not want to take tablets. The infectious diseases specialist at Aga Khan University Hospital says ARVs have significantly evolved since the 1980s. 

“Back in the day, a patient would take sometimes 16 tablets daily. Now patients take two tablets a day. The injectable ARV also works as effectively as the tablets,” says Prof Shah.

She says women are advised to take up contraception before enrolling in the trial. ‘‘We do not know the effects of the drug on the baby. So, we don’t take women who are planning to conceive during the period of the trial.’’

According to the doctor, the safety of the mother and baby is paramount. ‘‘We monitor patients more closely than those on normal pills. Any development of side effects is referred to the hospital,’’ notes Prof Shah, adding that 99.9 per cent of patients had no alarming side effects.

“The only issue we had was soreness after the injection, which is normal. There have not been any infections, swelling or induration.’’ 

The efficacy of the injectable was assessed by monitoring the viral loads (the amount of virus in an infected person’s blood) of patients on tablets and comparing it to that of patients taking injectables after 24 weeks. 

‘‘The viral load was the same for patients on tablets and those on injectables. This gives patients treatment options. The result is more adherence to the treatment and suppression of the virus,” she reveals, saying most patients who were put on the injectable do not want to go back to the tablets. 

The study also sought to obtain evidence to support the use of long-acting injectable in African treatment programmes, where demographics, viral subtypes of HIV and previous treatment and delivery approaches differ. The injections are already available for use in the West as part of the standard of care. The clinical trial in Africa sought to interrogate how African patients would respond to the medication.

‘‘The main challenge was the limited number of patients on the trial. We had to lock out many interested patients due to limited capacity. We had to train nurses to administer the injections. This took some time,” she adds. 

The study took two years, from April 2022 to June 2024, and it involved 40 people living with HIV, who  had all been on tablets before.

The hospital says some participants in the trial will continue to the post-trial access or rollover study, fully sponsored for four more years. In total, the patients will have experienced six years of injectable medication.

“We hope the injectables will be available in the country when the four-year post-trial ends.. There are a lot of processes ongoing behind the scenes by the sponsor, the government, regulatory bodies such as the pharmacy and poisons board and others to see how quickly to make this available to our patients at an affordable price,”  she says.

For doctors and caregivers, the frequency of taking the medication remains a significant concern. “If we can get a six-month injection, it will be a game changer. There are ongoing studies in the world.  Providing the treatment available for babies is, however, likely going to take some time,” Prof Shah says. 

A study about the trial published in The Lancet states that the main advantage of long-acting therapy for people living with HIV is ‘increased treatment satisfaction’ that is driven by increased convenience’ as patients don’t need to carry or remember to take daily pills. 

There is also reduced fear of disclosure ‘upon discovery of pills.

“Long-acting therapy provides a unique opportunity to maintain very high population levels of viral suppression, without dependence on individuals to adhere to daily pill consumption—which is uncertain and difficult for programmes to monitor and support remotely,” says the study.

The study notes that patients highly adhered to the injection schedule, attributed to the programme supporting visit attendance through reimbursing travel costs for all participant visits and reminding participants of forthcoming appointments.

Outside clinical trials, the study authors note that the higher levels of treatment satisfaction observed may be sufficient to maintain high motivation and attendance rates for injections. ‘‘This trial provides crucial evidence for the efficacy, safety, acceptability and potential feasibility of switching from standard oral therapy to long-acting therapy in the public health approach.’’

It adds: “Careful evaluation of risks and benefits for individuals and programmes will determine whether long-acting therapy ultimately finds a place in the public health approach to HIV treatment in Africa.”

This might trigger a paradigm shift in HIV treatment globally as the viral disease continues to be major public health concern. According to UNAIDS, 39 million people were living with HIV in 2022 in the world. That year, 1.3 million people were newly infected with HIV while 630000 died from AIDS-related illnesses.

Since the start of the pandemic in the 1980s, 40.4 million people have died from AIDS-related illnesses, says USAID. 

Globally, women and girls accounted for 46 per cent of all new HIV infections in 2022. In sub-Saharan Africa, adolescent girls and young women made up more than 77 per cent of new infections among people aged between 15 and 24. This demographic is three times more likely to acquire HIV than men in this age group. 

Shockingly, only about 42 per cent of regions with high HIV incidence in sub-Saharan Africa in 2021 had dedicated HIV prevention programmes for adolescent girls. 

While the injectable ARV is used to manage the disease, the development of a HIV vaccine is already underway at the Kenya Medical Research Institute (Kemri) and the Kericho-based Walter Reed Project. The vaccine research is funded by USAID for Sh7 billion.

Prof Walter Jaoko,  director of KAVI Institute of Clinical Research at the University of Nairobi, notes that developing a preventive HIV vaccine has remained difficult to date and that only one vaccine tried in Thailand has shown some efficacy. He, however, says this is proof that a vaccine can prevent HIV. 

“We had hoped one study conducted in the US would be successful. The results were, however, not positive. Consequently, scientists have had to go back to the drawing board to improve the quality of the vaccine,” he adds.

Of the many setbacks in the HIV vaccine development, scientists say the main concern is the fact that HIV is a highly mutable virus, with multiple subtypes circulating globally. This makes it harder to develop a vaccine that provides durable protection against all HIV strains.

Prof Jaoko says proving that a vaccine is preventive is difficult since study participants may be required to use Prep medication to prevent infection. 

“To demonstrate that a vaccine prevents people from becoming infected, you need to provide the participants with other preventive methods. You don’t expose people to HIV intentionally,” he argues. 

He adds: “You must always pass preventive messages to all the people taking part in HIV vaccine clinical trials. This is essential especially with more prevention modalities like the use of PrEP emerging.’’

Even after developing and testing a vaccine, it will only become more complicated to show it is preventive, according to Prof Jaoko.

For a vaccine intended to prevent new infections, delays in developing it means the number of new cases will continue to rise. The risk of infection will also continue for pregnant, infected mothers who may pass the disease to their babies. Victims of sexual abuse and sexual violence are also at higher risk.

“Vaccination will mean no risk of infection. This will be particularly useful in situations of conflict. The wars in the DRC and South Sudan where women continue to be sexually assaulted are a case in point,” says Prof Jaoko.

Doctors also believe that when it is available, the vaccine will be administered once to provide lifetime immunity. They also hope the uptake will be high. ‘‘We can’t tell for now. It may require boosters in the beginning.’’

The doctor says that ultimately, a vaccine is the best solution to ending the HIV epidemic. Its development, however, is dependent on the availability of resources. 

‘‘It is critical that funders commit money to this cause. Over the years, funding for HIV vaccine research has either remained the same or retreated. This has made it difficult to predict when a vaccine will be ready.’’

Without funds, HIV vaccine research stalls. Without research, a vaccine remains a fancy. Without a vaccine, HIV continues to claim lives globally.  

[email protected]