One size does not fit all when it comes to preventing HIV

The recently concluded 11th International IAS Conference on HIV Science shed light on important progress in HIV prevention, treatment and cure efforts despite major disruptions caused by the Covid-19 pandemic.

Keeping in mind that there were 1.7 million new HIV infections in 2020 (which is three times higher than the UNAIDS 2020 targets), HIV prevention must remain a key focus.

Prof Linda Gail Bekker, who is director of Desmund Tutu HIV Centre at the University of Cape Town, South Africa, and former president of the International AIDS Society (IAS), said HIV prevention options should be in line with humanity and its many shapes and forms.

This article showcases an array of prevention options that are either already at our disposal or are in various stages of development.

Pre-Exposure Prophylaxis (PrEP): Once daily pill

It has been 10 years since it was proved that adherence to antiretroviral-based oral PrEP provides robust protection against HIV.

But, in some users, the daily oral PrEP can be a barrier to adherence and can lead to pause or discontinuation. This has led to the next discovery of taking the pill on-demand at the time of exposure and not daily. So we have PrEP 1.5, TDF/FTC as oral HIV prevention on-demand. The dosing for PrEP on Demand is 2-1-1, that is, two tablets taken two to 24 hours before engaging in sex, one tablet taken 24 hours after the first two, and another tablet 24 hours after that. But it can be used only by men who have sex with men.

While nearly 1 million people have accessed the PrEP prevention option globally, the oral daily or on-demand PrEP is not feasible for everyone. Many people may find it difficult to remember to take the pill daily or at the right time. If it is taken off and on, there is a risk of poor coverage of exposure, as substantiated by a study on Global Evaluation of Microbicide Sensitivity, which found high rates of HIV drug resistance in some individuals who were diagnosed with HIV while participating in HIV PrEP rollout programmes in Eswatini, Kenya, South Africa and Zimbabwe.

The level of the drug in their blood suggested they were taking PrEP at least four times a week, which was not enough to prevent HIV infection, but enough for the resistant virus to emerge. The moral of the story is to take PrEP every day as prescribed, to stay free of HIV.

So for those who cannot adhere to a daily regimen, the solution lies in having long-acting agents in different formulations – like the once-a-month pill or a long-acting injection or the vaginal ring.

Dapivirine Ring: Once a month vaginal ring

This monthly vaginal ring, developed by the International Partnership for Microbicides, is the first woman-controlled, topical long-acting HIV prevention method to reduce the risk of acquiring HIV through vaginal sex. It is a silicon ring that contains the antiretroviral drug, dapivirine, and when worn inside the vagina, it releases the drug slowly for 28 days, after which it should be replaced by a new ring. The dapivirine ring offers a discreet and long-acting alternative to daily oral PrEP.

Interim results from the REACH study show encouraging levels of adherence to dapivirine ring and oral PrEP among adolescent girls and young women in Africa. High adherence was observed in 50 per cent of users as against 22 per cent of oral PrEP users. Moreover, 88 per cent of the participants preferred the ring.

The European Medicines Agency and the World Health Organization have already approved the ring for use as an additional prevention choice for women in high HIV burden settings.

Zeda Rosenberg, CEO of International Partnership for Microbicides, said Zimbabwe has already given the go-ahead for its use and many other African nations are expected to follow suit. Rosenberg also said that studies are underway for its use in pregnant and breastfeeding women and for those who are 15-18 years old.

A 90-day dapivirine ring has successfully completed Phase-1 clinical study in which it was found to be well-tolerated and delivered target levels of the drug over three months, showing the potential to provide long-acting and sustained HIV protection. Next phase studies are to begin this year and Rosenberg is hopeful that results would be available by 2023.

Long-acting Cabotegravir: Once every eight weeks injection

This belongs to a new class of HIV drugs called integrase inhibitors and is delivered once every eight weeks via intramuscular injection. Long-acting Cabotegravir has been found to be safe and well-tolerated. Two studies (HPTN 084 and HPTN 083) done in sub-Saharan Africa have found it to be statistically superior to daily oral PrEP in preventing HIV infection among cisgender women, cisgender men and transgender women who have sex with men.

This much-awaited prevention method is now in the implementation phase and is moving towards licensing.

However, neither the long-acting dapivirine ring nor Cabotegravir offers contraceptive benefits. Women of reproductive age need multipurpose prevention technology products to address two or more overlapping health risks, such as unintended pregnancy and HIV. The dual prevention pill is an answer to their prayers.

Dual Prevention Pill: A daily oral pill for women for protection against HIV and pregnancy

Dual prevention pill, a co-formulated tablet containing oral PrEP and a combined oral contraceptive, is currently being developed for daily use to prevent both HIV and pregnancy and is likely to be a new multipurpose prevention technology to go to market. Since both the ingredients of dual prevention pill are already approved for individual use, their combination pill just needs to undergo a bio-equivalence study to determine if they are as safe and effective in combination. Regulatory timelines suggest that dual prevention pill could receive US FDA approval by 2024.

Several other multipurpose prevention technologies for HIV and pregnancy prevention are in various stages of development but are still many years away from market launch.

Islatravir: Once a month oral PrEP

Islatravir is the first nucleoside reverse transcriptase translocation inhibitor currently being evaluated across a variety of dosing regimens, for both treatments as well as prevention of HIV infection. It has a novel mechanism, as it can persist in the body for a long time and is being developed as a monthly pill and also as a subdermal implant for prevention that could provide protection for one year.

Interim data from a Phase-2a study show that it is safe and generally well-tolerated through 24 weeks. Monthly doses of Islatravir also achieved the pre-specified efficacious pharmacokinetic threshold for PrEP.

Two Phase-3 clinical studies to evaluate its efficacy and safety in cisgender women, men, and transgender women who have sex with men, have already begun. But it could be another two to three years from now until we have it. Phase-2 studies for the once-a-year removable Islatravir implant are also underway.

Lenacapavir Long-Acting: twice-yearly injectable for HIV prevention

Lenacapavir as a once every six months injectable for HIV prevention is in the early stages of development. Two studies to evaluate its efficacy and safety are to take place – one in South Africa and Uganda (in adolescent girls and young women) and the other in the US, Brazil, Peru and South Africa (in cisgender men, transgender women, transgender men and gender non-binary individuals). It is also being developed as a long-acting treatment and implant.

Broadly neutralising antibodies

Broadly neutralising antibodies provide a new approach to HIV-1 prevention and treatment. But they are still in very early stages of development.

HIV Vaccine

There is currently no vaccine available to prevent or treat HIV infection. However, scientists are working on one. Research efforts undertaken by the US National Institutes of Health include two late-stage, multinational vaccine clinical studies called Imbokodo and Mosaico.

Basket of choices to prevent HIV

We need a basket of HIV prevention options. It is about choices and preferences depending on where people are in their life cycle, local realities, and contexts. Moreover, prevention options should be accessible, affordable, simple to use, and easy to adhere, for everyone! It is only then that we may expect better coverage of all people and of all exposures, rightly said Bekker.

Shobha Shukla is the founder of CNS (Citizen News Service) as well as a feminist, health and development justice advocate. Follow her on Twitter @shobha1shukla or read her work on www.bit.ly/ShobhaShukla