Will this new injection change the course of HIV?

An injection every two months is three times more effective in preventing HIV infection among men and transgender women than a daily prevention pill. 

New research released on Tuesday at the 23rd International Aids Conference, being  held virtually this year, revealed that participants who were injected with the antiretroviral (ARV) drug, cabotegravir, were 66% less likely to get infected with HIV than volunteers who took a daily pill, consisting of two ARVs — emtricitabine and tenofovir — known as Truvada. 

The HPTN 083 study enrolled just over 4500 men who have sex with men and transgender women who have sex with men across 43 sites in South Africa, Argentina, Brazil, Peru, the United States, Thailand and Vietnam.

The South African site was at Groote Schuur Hospital in Cape Town. 

In May, a review board analysing the research data found the cabotegravir injections to be so effective that it recommended that the blinded phase of the study should be stopped. During that phase, one group of participants received a long-acting cabotegravir injection every two months and another a daily Truvada pill, without them or researchers knowing who got which product, to prevent bias.

The new data presented this week revealed that cabotegravir injections weren’t just as effective and safe to use as Truvada pills, but in fact outperformed them.  

Several studies over the past decade have shown that taking Truvada once a day can dramatically reduce someone’s chances — between 92% and 99% — of contracting HIV through sex.

Once there is a high enough level of the medication in an HIV-negative person’s vaginal or anal tissues, the drugs are mostly able to shield the immune system cells from being infected by HIV when exposed to the virus.The World Health Organisation recommends Truvada as a form of HIV prevention, or pre-exposure prophylaxis (PrEP).

In 2015, South Africa became the first African country to register the drug for this purpose. Soon thereafter, Truvada, as well as generic versions of the pill, became available in the private sector and at selected government clinics to high risk groups. 

But daily adherence to the pill has often proven a problem in studies, particularly among young women. How often you use it impacts on how effective the pill is – the less often Truvada is taken, the less protection against HIV it provides.

The new evidence from the HPTN 083 study now provides an option that may, for some people, be easier to adhere to. “We know some people find it difficult to take pills and the long-acting cabotegravir infections provide them with a choice of product that doesn’t require daily adherence,” explains the study’s chief author, Raphael Landovitz.

“Although Truvada is also an excellent choice of PrEP, it might not be the best choice for everyone. Or the right choice for the same person at different stages of their life.” Sexually transmitted infections — an indication of low condom use and relatively risky sexual behaviour – was common among participants at the start of the study: 5.3% of participants had syphilis, 6.5% rectal gonorrhea and 11% had chlamydia.  “This was a very elevated risk population by design and by demographic.

Yet both arms [the Truvada and long-acting cabotegravir injection arm] had dramatically low incidence rates of HIV infection,” Landovitz says. “So both Truvada and cabotegravir would be expected to work extremely well to reduce HIV incidence.” 

The incidence rate of the cabotegravir group was 0.41% (13 HIV infections over the course of the trial) per 100 person years and 1.22% (39 HIV infections over the course of the trial) in the Truvada group. In easy speak: three times more individuals in the Truvada group got infected compared to the cabotegravir group. 

These results meet the statistical criteria for superiority of two-monthly cabotegravir infections to Truvada. Injectable cabotegravir is also being tested among women in Southern Africa – with sites in Cape Town, Johannesburg and Durban – and preliminary results of the HPTN 084 trial are expected around November.

Needs approval

The long-acting injection needs to be approved by the United States Food and Drug Administration before it can become widely available. 

“We have no idea what the price for an injection would be, but we need to make sure that it doesn’t cost more than oral PrEP,” says Mitchell Warren from the New York-based HIV advocacy organisation, Avac. “A year’s supply of oral PrEP in South Africa costs about $54 [R923] in the public sector, which is actually pretty inexpensive.”

In the private sector, a month’s supply of HIV prevention pills can be bought for between R200 and R300 – that excludes the costs of regular HIV tests and lab tests to make sure the drugs don’t have adverse effects. South Africa’s national HIV plan aims to provide just over 104 000 new users from high-risk groups – such as sex workers, injecting drug users, men who have sex with men and young women — with PrEP by 2022.But the country’s uptake of PrEP has been slow. 

According to Avac’s international PrEP tracker, PrEP Watch, between 44 000 and 45 000 people in South Africa  currently use oral PrEP.   Some of the reasons people have stated in studies for not using PrEP is that they don’t see themselves as being at risk of HIV infection, that it’s stigmatised and that the pills are not easily available.

Warren says: “If we can’t deliver PrEP to people, it doesn’t matter how fabulous it is, it’s useless. And that’s been our problem in PrEP programmes. We’ve gotten too focused on the product that we haven’t invested in how to get it to people.”Warren argues countries, including South Africa, need to take PrEP delivery outside of medical settings.

“Ideally, we’d like to be in a place where community health workers could go from home to home with prevention options, of which one is oral or injectable PrEP, and that the worker can give an injection to clients. We need to task shift and task share. In South Africa, he says, we can learn from the social marketing of condoms in the 90s.

“It wasn’t about making condoms available in pharmacies. It was about spaza shops, the shebeens and other community settings. We need to deliver health products to where and when people want them.”  https://m.health24.com/Medical/HIV-AIDS/News/will-this-new-injection-change-the-course-of-hiv-20200708