PrEP’s promise to change the course of HIV worked – but only for white gay men

A decade into the era of the HIV prevention pill, called PrEP, efforts to leverage its advertised power to curb new infections have stalled in the United States.

This shortfall is a key reason the country is lagging far behind many others in the fight against HIV, with a national epidemic long plagued by racial inequality and a modestly declining rate of new infections.

“We are reaching a scientific crisis in HIV prevention,” said LaRon Nelson, associate professor of nursing and public health at Yale University, last month at the Conference on Retroviruses and Opportunistic Infections in Seattle. . Nelson lamented the gap between PrEP’s impressive performance in major studies and its moderate impact in the real world.

On the bright side, PrEP, which is short for pre-exposure prophylaxis and involves taking prescription oral or injectable antiretrovirals before potential exposure to HIV, has indeed gained considerable popularity – but only among gay men. and white bisexuals, who have long seen a decline in HIV rates.

Such inequity persists despite the efforts of a national public health army and countless millions of dollars spent to promote and facilitate the use of PrEP among black and Latino gay and bisexual men. Of all the major intersectional demographics, these groups are contracting HIV at the highest rates, and transmissions between them have stabilized or barely declined in recent years.

And so, even amid national judgment on racial inequality, PrEP has only served to widen racial disparities in HIV transmission among men who have sex with men.

According to the Centers for Disease Control and Prevention, gay and bi men account for 70% of new cases of the virus. Whites in this demographic accounted for 15% of the 34,800 HIV transmissions in 2019, while the much smaller populations of their black and Latino peers accounted for 26% and 23% of new cases, respectively.

Moreover, more than a year after the approval of a long-acting injectable form of PrEP, ViiV Healthcare’s Apretude, few are receiving it. Insurers have mostly refused to cover the expensive drug. Therefore, even after clinical trials found injectable PrEP to be significantly superior to oral PrEP in preventing HIV at a public health level, particularly among black gay men, the potential of Apretude will likely remain untapped in a foreseeable future.

Disturbing statistics

Gilead Sciences’ two-drug combination pill, Truvada, was approved as PrEP in 2012 and was followed in 2019 by a similar drug, Descovy. When either drug is taken daily, it reduces the risk of HIV by at least 99% in gay and bisexual men and transgender women, according to several studies.

PrEP has helped lower HIV rates in cities where it has reached a critical mass of popularity, such as New York, San Francisco and Seattle. But nationally, PrEP has failed to move the needle by much.

The CDC estimates that annual HIV transmissions fell by only 8% between 2015 and 2019. Cases are even rising in some states where investment in HIV prevention is lacking, such as Tennessee, where Republican Governor Bill Lee recently compounded the factors aggravating his state’s epidemic by withholding $8.3 million in annual CDC prevention funding.

Approximately 814,000 gay and bisexual men in the United States are good candidates for PrEP, the CDC believes. Between 2017 and 2022, the number of people using PrEP, who have always been predominantly gay and bisexual men, increased from 155,000 to 382,000 at some point each year. However, a CDC study presented in Seattle found that as of September 2022, only 187,000 people were on PrEP within that 30-day window, suggesting many people aren’t taking it for long.

The growing popularity of PrEP likely could have significantly reduced the national HIV rate if its use more closely mirrored viral transmission demographics, HIV prevention experts say. Of the CDC’s estimate of 21,900 new HIV cases in 2019 (the most recent year for which the agency produced a transmission estimate) in the three largest racial groups among gay and bisexual men, respectively 23%, 41% and 36% were white, black and Latino. But 69% of PrEP users last year were white, while only 9% and 18% respectively were black and Latino.

Appretude’s approval promised progress

Approved in December 2021, Apretude requires receiving an injection by a health worker every two months. Compared to providing Truvada to transgender women and men who have sex with men as PrEP, giving Apretude was associated with a 66% lower overall HIV diagnosis rate in a major clinical trial.

The superior effectiveness of Apretude was due to participants adhering better to the injection schedule than to the daily pill regimen.

Dr. Hyman Scott, an HIV prevention expert with the San Francisco Department of Public Health, reported at the Seattle conference that of the 844 black Americans participating in the trial, those randomized to receive the injectable drug had a 72% lower HIV than those who got Truvada.

His analysis suggests that if 10,000 similar black gay and bisexual trans men and women were followed for a year, about 50 would contract HIV if given Apretude, while 200 would test positive if given Truvada.

Such sobering findings about Truvada’s shortcomings are consistent with previous studies that found relatively low adherence rates to the daily PrEP regimen among black gay men. These data suggest that even if HIV prevention advocates were successful in dramatically increasing access to oral PrEP in this population, it may have only limited impact among them.

Referring to Apretude, Scott told NBC News, “The real question is if we can roll this out to communities.”

Cost is a major snag. As of 2021, Truvada has been available from several generic manufacturers and now often costs as little as $25-35 per month, although in some cases as high as $600. ViiV lists Apretude at $1,878 per month, and few insurers cover it.

The recent CDC study of PrEP use presented in Seattle found that only 1 in 200 PrEP prescriptions were for Apretude in September.

“There are patients who are getting Apretude now, but these are people who have access to healthcare, who have healthcare knowledge, who call their insurance companies and shout about the right people,” said Dr. Anu Hazra, a physician at LGBTQ-focused Howard Brown Health in Chicago.

As of 2021, nearly all insurers are required under the Affordable Care Act to cover oral PrEP without out-of-pocket medications or quarterly clinic visits and lab tests needed to maintain a prescription. Indeed, in 2019, an advisory body known as the US Preventive Services Task Force gave PrEP an “A” grade for being a valid prevention tool.

In December, the task force released a draft decision awarding Aprétudes its own “A” rating. If this rating is formalized this year, insurers will be required to cover Apretude, and without cost sharing – but not before January 2025.

Apretude Updates

In addition to the associated burden of having to come six times a year for injections, Apretude has a notable shortcoming: HIV breakthrough cases are apparently much more likely among those taking injectable PrEP compared to oral PrEP.

Of the 25 people who acquired HIV in the 2,282-person Apretude arm of the injectable versus oral PrEP trial in gay and bisexual men and trans women, six did so after receiving their injections on time, according to a presentation in Seattle by Dr. Susan Eshleman, professor of pathology at Johns Hopkins Medicine.

Eshleman’s team has yet to calculate Apretude’s per capita breakthrough infection rate, but when these researchers initially reported last year that the trial had seen seven breakthrough infections (before revising this number six), their calculations suggested that if 10,000 transgender men and women alike were followed for a year, 15 would acquire HIV despite scheduled Apretude injections on schedule.

At the same Seattle conference, Hazra reported the first case of breakthrough HIV in an Apretude patient outside of a clinical trial. By comparison, nearly four years passed after Truvada’s approval as PrEP before a breakthrough infection was first documented in someone faithfully taking the drug.

To date, there have been a handful of other case study reports of breakthrough HIV in people taking oral PrEP. However, there has only ever been one clear case of this in major clinical trials, including Truvada or Descovy as prevention.

All of this suggests that for those with a history of taking daily oral PrEP on time, switching to Apretude would actually increase their risk of HIV; although the absolute risk of infection would remain low.

Optimism in the pipes

HIV prevention experts say they are excited about the PrEP pipeline and expect that, over the next decade, more convenient, longer-acting forms will be approved.

“I’m extremely optimistic,” said Sharon Hillier, a leading HIV prevention researcher at the University of Pittsburgh. “We just need to figure out how to implement these interventions and how to be less burdensome on health systems.”

The Seattle conference heard promising early-stage research findings regarding drug-infused suppositories that could be placed in the rectum or vagina for up to 48 hours after sex and likely prevent HIV. And researchers are developing implants that could be placed under the skin and deliver preventative drugs for many months.

Gilead is also conducting major PrEP trials of the drug lenacapavir, which only requires an injection every six months. Dr. Jared Baeten, who leads Gilead’s HIV strategy, said the company hopes to deliver the first results of the study by 2025.

But if Apretude’s pace is any guide, it could be 2030 before lenacapavir is both approved and widely covered by insurers.

In the meantime, PrEP advocates continue to express their commitment to working with the options currently on the table, albeit in a complex and fractured healthcare system that is proving alienating for many of those most at risk. to contract HIV.