After several research findings establishing that injectable antiretrovirals are effective in preventing HIV infection, the Government will next month launch a policy to guide their use in the country.

The revelation was made by health ministry director of the AIDS Control Programme Dr Joshua Musinguzi.

He said the Government had cleared the use of the bi-monthly injectable cabotegravir for PrEP (pre-exposure prophylaxis) and the policy to guide the implementation will be approved in a month’s time ahead of roll out next financial year.

“We are supplementing the oral PrEP with an injectable option called cabotegravir. It is a bi-monthly injection that concentrates the medicine in the body to prevent HIV infection. The injection is easier to adhere to. We have been working with our partners to update the guidelines and policy. These will be approved by the end of next month so that in the next financial year, we roll out the intervention through facilities that reach the high-risk groups,” Musinguzi told New Vision on the sidelines of the function to mark 20 years of The United States President's Emergency Plan For AIDS Relief (PEPFAR) in Kampala recently.

Discordant couples will also use it. The drug, cabotegravir is used together with rilpivirine. Cabotegravir was developed by ViiV Healthcare, while rilpivirine was by Janssen.

He said the policy heavily borrows from the World Health Organisation's (WHO) guidelines on the use of the injectable that were released in June last year.

“WHO guidelines will act as the blueprint for the national policy that is due to be approved in about a month’s time. The policy is in line with WHO guidelines, but has been tailored to suit the Ugandan settings,” Musinguzi said.

He said before the rollout, health workers will be trained on how to administer the injections as per the WHO guidelines.

Already, the injectable has been approved for use in North America and Europe.

Charles Brown, an activist who has also been on the team of experts that has been reviewing the policy guidelines on the injectables, says the policy mainly guides health workers on the administration of the injections.

Brown, who is also the executive director of Preventive Care International, a non-government organisation involved in the fight against the spread of HIV, says they expect many people to embrace the drug. 

He said research indicates that it is in high demand because of its advantages over the orals.

What if the drug fails in the human body?

About the safety of the drug, Brown says there is no need for worry because it has been thoroughly tested through research and is not harmful to the human body.

“What is important is to know that the drug is safe and efficacious. If you are injected with the drug and the body reacts, we have recommended that if this is a two-month injection, the person is given for one month to study and test the reaction of the body. If they take the injection and the side effects continue, we shall tell them to stop the injection and they choose other options. Even if it reacts in your body, we do not expect somebody to die. This is because the drugs are safe and have been tested through vigorous research,” he said.

Brown said what applied to the previous interventions against HIV will apply to the injectable drugs.

“If we can talk about condoms. You know they can prevent HIV, but if you use them badly, you can acquire HIV and will not blame the policy. They tell you to check the expiry date and keep it safe before use. If you use an expired condom, there are chances you can get infected. This is the same case with the injectable Prep. People will be told how it should be taken,” he says.

For pregnant mothers, the drug was also found to be safe, according to Dr Andrew Mugurusi, a researcher with the Infectious Diseases Institute.

“It was initially tested in women who were not pregnant, but some of them became pregnant during the studies and it was found to be safe. Further studies are being done to evaluate their safety among breastfeeding women. The other group we are testing it are adolescents. We need to find out if this drug works well in adolescents so that we protect vulnerable girls,” he said.

Reducing gender-based violence

Dr Brenda Okech, the head of the International AIDS Vaccine Initiative (IAVI) based at the Uganda Virus Research Institute in Entebbe, said the injectable is good for women because the previous prevention tools such as male circumcision and condoms depended on the men.

“Women have been longing for a product that is discreet, where nobody else knows that they are using it. The injectable is something that is better than the previous products. During our studies, the women who were found with tablets got into trouble with their men and relatives. The immediate thought was that they were HIV positive and yet the tablets were for prevention. So women have been longing for a product that is discreet,” she said.

Brown on the other hand said the injectable will help in preventing gender-based violence because a woman can take it without arousing the suspicion of the men.

“Injectable PrEP will reduce issues of gender-based violence. Oral pills have sometimes resulted in gender-based violence because when people saw their partners swallowing them, they would become suspicious and end up fighting them. But for the injection, someone can take it without the partner knowing, hence arousing no suspicion,” Brown says.

Sarah (other names withheld), a resident of Kalangala, who took part in one of the studies, said she would like to continue with the injection because it will reduce the burden of swallowing pills every morning.

“I require this drug because I don’t trust my sexual partners. I find the injection easier to adhere to than the oral pills,” she said.

Cost

Currently, the injectable drug is expensive and may require the intervention of donors for a countrywide rollout.

Dr Mugurusi said on the US market, the drug costs $22,000 (over sh80m) per year, which is out of range for many people. 

It is too expensive when compared to the oral version that is just $54 (about shillings 198,000). 

It is hoped that just as the case was with the oral antiretrovirals that were made affordable by big donors and developed countries, the same will apply to the injectables.

Emilio Dirlikov, the CDC Uganda health services branch chief said under the PEPFAR, they were considering adding HIV injectables to the list of innovations to control the spread of HIV.

“We work with the NIH, the United States Food and Drug Administration National Institutes of Health and to make sure that we are using drugs that we know are effective when we support them through PEPFAR. As part of the country operational plan that we will be using with the government of Uganda, we are considering many options including the long-acting injectables,” he said.

Six months injection on the way

Dr Ali Ssetala, the head of the community studies programme at IAVI, says in addition to cabotegravir, they are working on studies for lenacapavir, an injection that will be taken by people once in six months to prevent them from getting HIV.

“We doing the purpose 1 study which is looking at the efficacy of the twice-yearly injection for PrEP among adolescent girls and young women at risk of getting HIV. Lenacapavir is a capsid inhibitor that affects the shell of the HIV virus, preventing it from multiplying or replicating. 

The purpose 1 study is being funded by GRLD Sciences, a pharmaceutical company in the US. We have participating agencies in Uganda and mainly South Africa. In Uganda, we have IAVI- Makerere Kalangala site, Makerere University – John Hopkins University (MUJHU) Research Collaboration in Mityana and AMSOL in Masaka. Once this drug is known to be effective among these high-risk groups, it will be a good addition to the already-approved cabotegravir. Lenacapavir will reduce the doctor’s visits from once in two months to twice a year. It is promising work we are looking forward to,” he says.

Dr Ssetala says Lenacapavir is being tested among young girls because it has already been proven to be effective among men.

Research on cure

Through the Joint Clinical Research Centre (JCRC), Uganda plans to start clinical trials on the HIV cure using gene therapy in 2024.

The director of clinical services, Dr Daniel Muyanja, said this will be the first trial for the HIV cure using gene therapy in Africa. Specifically, HIV gene therapy involves removing blood cells using apheresis; the same machine used to pick blood cells for sickle cell disease gene therapy.

A vector (which is a transporter of specific genes) is introduced in the cells in the laboratory. The cells are allowed to multiply and then, re-infused back into the patient. The newly introduced gene takes over and overrides HIV.

“The gene that is introduced is aimed at preventing the infection of HIV into other cells. So, when you have enough cells of that gene, the HIV stops replicating because then, the gene makes proteins that go on the surface of the cells, consequently preventing HIV from entering the cells. In so doing, an individual is cured of HIV,” Dr Muyanja said. 

Globally, several people have been cured of cancer using gene-therapy treatment modality. The trials have been based in western countries. Scientists are optimistic that the same science can be replicated to cure other diseases such as HIV.

WHO guidelines on injectable prep 

• HIV testing is required before offering CAB-LA and should also be done before each injection while using CAB-LA and, ideally, regularly after CAB-LA discontinuation. HIV testing can be conducted according to the WHO testing strategy in people above 18 months of age, using the national testing algorithm composed of quality-assured serology assays (rapid diagnostic tests and enzyme immunoassays). 
• PrEP, including CAB-LA, should be provided in combination with other effective and well-established prevention approaches and health services. Depending on the local context and the needs and preferences of the populations that could benefit from PrEP, this may include the provision of condoms, post-exposure prophylaxis (PEP) for HIV, testing and treatment of STIs and viral hepatitis, sexual and reproductive health services, mental health support, services that prevent and protect against gender-based violence, gender-affirming care and harm reduction services for people who use drugs (including for chemsex). Where feasible, providing voluntary partner services should also be considered. 
• Only individuals who are HIV-negative should be initiated on PrEP. Individuals with one or more reactive test results prior to initiating CAB-LA or while taking CAB-LA need further testing to confirm their HIV diagnosis. Anyone with inconclusive results should be referred to return for further testing to confirm HIV status after 14 days. Brief messages, support and linkage to treatment should be provided for anyone with a confirmed HIV diagnosis. 
• As CAB-LA is a new PrEP product, few PrEP providers will have experience delivering CABLA. However, there is extensive experience with delivering oral PrEP. National programmes should provide training and support to a range of providers in services that may be able to offer CAB-LA to clients. Training for providers will include capacity building on discussing HIV prevention needs and preferences with clients; assessing the appropriateness of the different HIV prevention options available, including CAB-LA, the DVR and oral PrEP regimens; correct administration of CAB-LA; support for safe and effective use; and provision of or referral to other services. 
• Countries need to consider the feasibility of using nucleic acid technologies (NAT) before CAB-LA initiation, and while taking CAB-LA. While NAT before CAB-LA initiation, and while taking CAB-LA, might prevent a small number of cases of drug resistance, countries need to consider the feasibility of NAT.  
• Liver function testing (such as measuring alanine transaminase) can be considered before and during CAB-LA use. CAB-LA should not be initiated in people with advanced liver disease or acute viral hepatitis and should be discontinued if hepatoxicity is confirmed. CAB-LA injections should not be delayed while waiting for the results of liver function tests, however. 
• To date, clinical trial data on and implementation experience with CAB-LA among people with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are very limited. Testing for HBV and HCV and further assessment for those with reactive test results are strongly encouraged. CAB-LA may be inappropriate for those requiring treatment for HBV. More research is needed on implementation of CAB-LA for people with HBV or HCV 
• If a hepatitis C (HCV) serology test is reactive and chronic infection has been confirmed, HCV treatment should be offered as per WHO guidelines, and PrEP and HCV treatment providers should (where possible) jointly manage these cases. CAB-LA is not active against HCV. There are no known drug–drug interactions between CAB-LA and treatment drugs for HCV, but data are scarce. Alternative PrEP and HIV prevention options should be considered. As no kidney toxicity is anticipated during the use of CAB-LA, kidney function testing and monitoring are not required for CAB-LA use. 
• Special consideration will be needed to make sure that CAB-LA services for members of key populations and young people are acceptable and safe for them 
• People who could benefit from PrEP have diverse HIV prevention needs and preferences, and these may change over time. A range of PrEP options should be available to provide choices to people who could benefit from PrEP, including TDF-based oral PrEP, the DVR and CAB-LA. People interested in PrEP should be provided information on the available options and their relative efficacy and safety and counselled to make an informed decision regarding the best option for them. 
• Meeting the needs of populations at substantial risk of HIV infection and providing PrEP services, including CAB-LA, requires the full participation of communities in developing and implementing programmes] 
• As CAB-LA is a new PrEP product, many communities and providers have limited or no awareness of it. Countries wanting to introduce CAB-LA as an additional HIV prevention option should conduct an awareness programme for communities and providers before and during the introduction as a first step towards creating demand and enabling people to make informed choices. 
• PrEP products, including CAB-LA, should be used during periods of substantial HIV risk and may be stopped if an individual is no longer at risk or decides to use an alternative PrEP product or HIV prevention strategy.