HPTN084 study: The promise of HIV prevention injections

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The HPTN084 study being conducted in six African countries holds out the promise of a bi-monthly injection for women as an empower new way to prevent HIV  infection, writes Siyabonga Kamnqa for Spotlight.

Kamnqa writes that arguably the most eagerly awaited study findings in HIV are from research on an antiretroviral (ARV) injection that may prevent HIV infection in women. If it works, the option of getting an injection every two months could provide women with a new way to prevent HIV infection – something that could be empowering for women who are not in a position to negotiate condom use or who cannot take pills to prevent HIV infection.

Hopes for the study (called HPTN084) are high with recent news that the same injection was effective in cisgender men who have sex with men and transgender women (that study was called HPTN083).

HPTN084 is being conducted by the HIV Prevention Trials Network (HPTN) in sexually active women in South Africa, Kenya, Malawi, Botswana, Zimbabwe, and Uganda. About 3,200 women aged between 18 and 45 will participate in the trial, with results expected in 2021 – although it is possible that results will be ready earlier, if interim reviews of the data find that the injection clearly does or does not work.

Professor Linda-Gail Bekker is the director of the Desmond Tutu HIV Centre at the University of Cape Town in Cape Town. The centre is one of seven sites in South Africa taking part in HPTN084.

“It is a fact that many people find it tricky to take pills every day without fail,” Bekker says. “Having an alternative to daily pills is a breakthrough and can be a relief for those individuals who cannot take pills daily because of stigma or privacy or other issues.”

The ARV used in the injection is called cabotegravir and in its slow release injectable form is referred to as Cabotegravir LA (or CAB LA for short – the LA stands for long-acting). In HPTN 084 it is being compared to pills combining the two ARVs tenofovir disoproxil fumarate and emtricitabine (TDF/FTC). Everyone in the study takes an intervention (pill or injection) and a placebo pill or injection. Based on current evidence, TDF/FTC pills are the most effective form of preventive treatment, or pre-exposure prophylaxis (PrEP) for both men and women.

“Integrase inhibitors act early in the HIV life cycle and have a low risk of incurring resistance mutations. Cabotegravir could also be reformulated as a depot agent – all of this made it a good choice for an injectable PrEP agent,” explains Bekker. “Eventually, the 600mg injection is given eight weekly once the dosing is established. It sits in the depot and slowly dissipates over the eight-week period,” says Bekker.

When used for prevention, the injection only contains CAB LA, Bekker points out. There is also a dual injectable in development, CAB LA with the ARV Rilpivirine that can be used to treat HIV.

Whether used for prevention or for treatment, ARVs are not vaccines, nor do they cure HIV. They do, however, suppress HIV and prevent the virus from replicating in the body. In the case of prevention this prevents the virus from taking hold if someone is exposed, in the case of people who are already infected it helps keep them healthy by suppressing viral replication.

CAB LA is injected into the gluteal muscle since it can tolerate a relatively large volume of fluid.

Should the injections be found to work and become available in the public sector, these injections will have to be given by health professionals and probably could not be self-administered.

CAB LA injections can last for four or eight weeks, depending on the dose of the injection. In the HPTN 084 study participants first get CAB in pill form, then a monthly injection, and only then every two months.

“Eventually, the 600mg injection is given eight weekly once the dosing is established. It sits in the depot and slowly dissipates over the eight-week period,” says Bekker.

“Side effects are very few: Most are around some mild injection site pain and inflammation, which settles down very quickly and [were] well tolerated by trial participants,” she says.

While safe and effective injections would be an important step forward, there are hopes that products might be developed that last even longer. Some birth control implants last for up to five years – a similar product that prevents infection without notable side effects could be a game-changer.

Bekker is upbeat about the possibility of similar ARV implants. “I think there is hope that the new agent called Islatravir which is a very potent antiviral agent could be formulated as an implant,” she says. “We saw the first PK (pharmacokinetic) data from it at IAS Mexico 2019 (International Aids Society conference) last year. I believe TAF (tenofovir alafenamide) is also being reformulated as an implant and there are even more newer agents, some with interesting new viral targets (Lenacpavir).”

She explains that antiviral agents need to be potent enough so that sufficient active ingredients can be included stably in an implant. “We are now hopeful that these novel properties are feasible and the first efficacy trials should be starting in the next few months to years,” she adds.

But while ARV implants are, at best, still years away, ARV injections that may protect women from becoming HIV-positive may be in production sooner.

HIV Prevention Trials Network (HPTN) principal investigators Myron Cohen and Wafaa El-Sadr say the network is committed to global efforts to try to identify new drugs and new ways of trying to prevent HIV /Aids “particularly for women in Sub-Saharan Africa”.

“If it (CAB LA) proves to be safe, it will be a major step forward in the fight against this pandemic,” reads a statement from HPTN. They do, however, urge people to keep using condoms.


Spotlight report


HPTN084 study

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