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 particularly empowering for those who are not in a position to negotiate condom use or who, for whatever reason, cannot take pills to prevent HIV infection.
Hopes for the HPTN084 study 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 next year.
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.
Sites in South Africa
Professor Linda-Gail Bekker, director of the Desmond Tutu HIV Centre at the University of Cape Town, says: “It is a fact that many people find it tricky to take pills every day without fail.
“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,” Bekker says.
The centre has one of seven sites in South Africa that are taking part in HPTN084.
The ARV used in the injection is called cabotegravir and in its dept form is referred to as cabotegravir long-acting. In HPTN084 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 dummy pill or injection.
Based on current evidence, TDF/FTC pills are the most effective form of preventive treatment, or pre-exposure prophylaxis (PrEP) for men and women alike.
Cabotegravir is in a relatively new class of ARVs called integrase inhibitors (which also includes dolutegravir – a drug that now forms part of South Africa’s standard first-line HIV treatment combination).
“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.
The term “depot” refers to a slow-release injectable formulation of a medicine.
When used for prevention, Bekker says the injection only contains cabotegravir long-acting. There is, however, also in development dual injectables – cabotegravir long-acting with the ARV rilpivirine that can be used to treat HIV.
Whether used for prevention or for treatment, ARVs are not vaccines, and neither 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 keeping viral replication very low.
How the injection works
According to Bekker, cabotegravir long-acting is injected into the buttock muscle since the muscle 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.
Cabotegravir long-acting injections can last for four or eight weeks depending on the dose of the injection.
In the HPTN084 study participants first get cabotegravir in pill form, then a monthly injection, and only then the two-monthly injections. Again, this may not be needed once we move beyond the efficacy trials.
“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 was well tolerated by trial participants.”
What about implants?
While a safe and effective two-monthly injection 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 HIV infection without notable side effects could be a game-changer for HIV prevention.
When we ask Bekker about the possibility of similar ARV implants, she is upbeat: “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 pharmacokinetic data from it at the International Aids Society conference last year. I believe tenofovir alafenamide is also being reformulated as an implant and there are even more newer agents, some with interesting new viral targets.”
She says antiviral agents need to be potent enough so that sufficient active ingredient 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.”
But while ARV implants are still many years away, the prospect of ARV injections that may protect women from becoming HIV-positive may be just months or a few years away.
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 [cabotegravir long-acting] proves to be safe, it will be a major step forward in the fight against this pandemic,” reads a statement from HPTN.
They, however, urge people to keep using condoms.
Read more about the HPTN084 study on HPTN.org.
*This article was produced by Spotlight – health journalism in the public interest.