Long-Acting Shot More Effective Than Daily Pill at Preventing HIV

Three years into a study comparing the effectiveness of two HIV preventative treatments, research scientists affiliated with the National Institutes of Health (NIH) have concluded that the rookie, cabotegravir, is functionally superior to the veteran, Truvada, by a significant margin.

Researchers stopped the study early after finding that a shot of cabotegravir every two months worked better than daily Truvada pills to help keep women from catching HIV from an infected sex partner. They announced last week that this shot was 89% more effective than the pills.

These results fall in line with results announced by the company earlier this year from a companion study testing cabotegravir among men who have sex with men and transgender women who have sex with men.

Cabotegravir belongs to a class of drugs known as integrase strand transfer inhibitors, Jonathan Appelbaum, MD, a professor of internal medicine and director of the clinical sciences department at the Florida State University College of Medicine who was not involved in the study, tells Verywell.

In order to understand how cabotegravir operates, you first have to understand the way HIV does. Whenever you share needles, have unprotected sex, or otherwise come into contact with another person’s bodily fluids, you are potentially putting yourself at risk of contracting the virus. Once an HIV molecule enters the bloodstream, it sets about targeting, attacking, and subduing T-helper cells—white blood cells that help stave off infection by surrounding and killing foreign matter—for the purpose of harnessing the cell’s reproductive machinery to produce clones of itself. These clones are then released into the bloodstream to continue the cycle of infection in what is essentially a biological snowball effect. 

“Cabotegravir works by preventing the integration of the HIV virus genetic material into the host’s genes," he says. "Without this happening, the virus cannot replicate."

Traditional HIV Treatment and Prevention

Since the beginnings of the HIV pandemic in the 1980s, an estimated 75.7 million people have been infected with the virus, and 32.7 million people have died because of it. 

The first ray of hope for HIV treatment arrived in 1987, when the Food and Drug Administration (FDA) approved the use of the antiretroviral therapy zidovudine (AZT) to treat the virus. Zidovudine and its successors revolutionized HIV care, turning the virus from a death sentence into a chronic condition.

One of those successors was Truvada, which is taken in pill form to either treat HIV or prevent HIV. Besides Truvada, the only other pre-exposure prophylaxis (PrEP) treatment available is Descovy, Volberding and Appelbaum tell Verywell. Descovy is only approved for use in gay men and transgender women, although “studies are currently being done on women to determine if it works for prevention of HIV through vaginal sex,” Appelbaum says. 

But as anyone who has ever been on medication knows, adhering to a daily regimen is easier said than done. Who hasn’t forgotten to take a pill once or twice? 

That’s the advantage of an injectable drug such as cabotegravir, Paul Volberding, MD, professor of epidemiology and biostatistics at the University of California San Francisco School of Medicine and a pioneer in the development of antiretroviral therapy, tells Verywell. 

“PrEP (oral) works well, but non-adherence—forgetting to take the pill—is a common problem,” Volberding says. If you opt for cabotegravir, there’s “less obligation to remember to take the medication every day,” Appelbaum adds. 

The Benefits of Cabotegravir

The NIH study was conducted in 3,223 sexually active women between the ages of 18 and 45 at 20 sites in the sub-Saharan African countries Botswana, Kenya, Malawi, South Africa, Eswatini, Uganda, and Zimbabwe. Sub-Saharan Africa was presumably chosen because it has long had the highest concentration of HIV-positive individuals of any region in the world, a statistical fact that prompted the Population Review to dub it “the world’s epicenter of HIV/AIDS” in 2002. In 2019, there were 730,000 new HIV infections and 300,000 AIDS-related deaths, according to the most recently available data. 

The women were assigned to either receive an injection of cabotegravir once every two months or take Truvada daily. (To ensure objectivity, those receiving cabotegravir injections took placebo pills daily and those taking Truvada received placebo injections once every two months.) Over the course of the study, 38 women contracted HIV, of whom 34 were taking Truvada and 4 were injecting cabotegravir. From those numbers, the researchers determined that there was an HIV incidence rate of 0.21% in women injecting cabotegravir and 1.79% in women taking Truvada, meaning that cabotegravir was 89% more effective at preventing HIV than Truvada. 

“While oral PrEP is highly effective in preventing HIV in women when taken as prescribed, some women find it difficult to take a daily tablet and inconsistent use of oral PrEP reduces the prevention effect,” the World Health Organization wrote of the findings. “A long-acting injectable formulation has the potential to improve the prevention effect without relying on adherence to a daily oral PrEP regimen, and to increase prevention choices and acceptability among women.” 

Indeed, many women in the study seemed to prefer cabotegravir to Truvada for its ease of use. 

“Many participants in the trial of the injection said they preferred it over taking a pill,” Volberding says. 

Side effects of both cabotegravir and Truvada were few and far between, although some women reported nausea, gastrointestinal distress, and skin reactions at the injection site. None had to discontinue participation, however. If all goes well, cabotegravir will likely be approved within a matter of months, Volberding and Appelbaum say.