A decade into the era of the HIV prevention pill called PrEP, efforts to harness its heralded power to curb new infections have stalled in the United States.
This shortage is a major reason why the country lags far behind many others in the fight against HIV, with a national epidemic long plagued by racial disparities and only modest declines in new infections.
“We are reaching a scientific crisis in HIV prevention,” LaRon Nelson, an associate professor of nursing and public health at Yale University, said last month at Seattle’s Conference on Retroviruses and Opportunistic Infections. Nelson lamented the gap between PrEP’s impressive performance in large studies and its lackluster impact in practice.
On the positive side, PrEP, which is short for pre-exposure prophylaxis and involves taking prescription or oral antiretroviral drugs prior to potential exposure to HIV, has indeed gained significant popularity – but only among white gay and bisexual men, who have long seen a declining HIV rate.
Such inequality persists despite the efforts of a nationwide public health army and countless millions of dollars spent promoting and facilitating the use of PrEP among black and Latino gay and bi men. Of all the major intersectional demographics, these groups have the highest rate of HIV transmission, and transmission among them has remained flat or barely declined in recent years.
And so, despite the national reckoning on racial inequality, PrEP has only served to widen the racial disparities among men who have sex with men.
According to the Centers for Disease Control and Prevention, gay and bisexual men are responsible 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.
In addition, 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. Consequently, Apretude’s potential will likely remain untapped for the foreseeable future, even after clinical trials have shown that injectable PrEP was dramatically superior to oral PrEP in preventing HIV at the public health level, especially among black gay men.
Disturbing statistics
Truvada, the two-drug combination birth control pill from Gilead Sciences, 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% among gay and bisexual men and transgender women, according to multiple 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 hasn’t been able to move the needle much.
The CDC estimates that annual HIV transmission decreased by only 8% between 2015 and 2019. Cases are even rising in some states lacking investment in HIV prevention, such as Tennessee, where Republican Gov. Bill Lee recently exacerbated factors exacerbating his state’s epidemic by blocking $8.3 million in annual CDC prevention funding .
About 814,000 gay and bisexual men in the US are good PrEP candidates, the CDC estimates. Between 2017 and 2022, the number of people using PrEP, who have always been predominantly gay and bi men, increased from 155,000 to 382,000 at any point in any year. However, a CDC study presented in Seattle found that in September 2022 only 187,000 people used PrEP within that 30-day period, suggesting that many people don’t use it for long.
According to HIV prevention experts, PrEP’s increasing popularity could likely have made a major dent in the national HIV rate if its use had been more closely aligned with virus transmission demographics. Of the CDC’s estimate of 21,900 new HIV cases in 2019 (the most recent year for which the agency made a transmission estimate) in the top three racial groups among gay and bisexual men, 23%, 41%, and 36%, respectively, were in whites, blacks and Latinos. But a lopsided 69% percent of PrEP users last year were white, while only 9% and 18% were black and Hispanic, respectively.
Apretude’s approval promised progress
Apretude is approved in December 2021 and must receive an injection every two months from a health professional. Compared to offering Truvada to trans women and men who have sex with men as PrEP, giving Apretude was associated with a 66% lower overall HIV diagnosis rate in a large clinical trial.
Apretude’s superior efficacy was driven by the fact that participants adhered to the injection schedule better than the daily pill regimen.
Dr. Hyman Scott, an HIV prevention expert at the San Francisco Department of Public Health, reported at the Seattle conference that of the 844 black American participants in the trial, those who were randomized to receive the injectable drug had one had 72% lower HIV rates than those who received Truvada.
His analysis suggests that if 10,000 similar black gay and bi men and trans women were followed for a year, about 50 would contract HIV if they received Apretude, while 200 would test positive if they received Truvada.
Such sobering findings about Truvada’s deficiencies are in line with previous studies that found relatively low adherence rates to the daily PrEP regimen among black gay men. Such data suggest that even if HIV prevention advocates were successful in massively increasing access to oral PrEP in this population, it could have only a limited impact on them.
Referring to Apretude, Scott told NBC News, “Whether we can roll this out in communities is the real question.”
The cost is a big bump. As of 2021, Truvada is available from multiple generic manufacturers and now often costs as little as $25 to $35 per month, though in some cases as much as $600. ViiV lists Apretude at $1,878 per month, and few insurers cover it .
The recent CDC PrEP usage study presented in Seattle found that in September only about 1 in 200 PrEP prescriptions were for Apretude.
“There are patients who are getting Apretude now, but it’s people who have access to healthcare, who are healthcare literate, who are calling their insurance companies and yelling at the right people,” said Dr. Anu Hazra, a physician at the LGBTQ-focused Howard Brown Health in Chicago.
As of 2021, almost all insurers are required under the Affordable Care Act to cover oral PrEP at no out-of-pocket cost for the drugs or the quarterly clinic visits and lab tests required to maintain a prescription. This is because in 2019, an advisory body known as the US Preventive Services Task Force gave PrEP an “A” rating for being a worthy preventative tool.
In December, the task force released a draft decision giving Apretude its own “A” rating. If this rating is made official this year, insurers will be required to cover Apretude, and with no cost sharing – but not until January 2025.
Apretude updates
Besides the associated burden of having to come in for injections six times a year, Apretude has one notable shortcoming: Breakthrough HIV cases are apparently much more likely among those using injectable versus oral PrEP.
According to a presentation in Seattle by Dr. Susan Eshleman, professor of pathology at Johns Hopkins Medicine.
Eshleman’s team hasn’t yet calculated Apretude’s per capita breakthrough rate, but when these researchers first reported last year that the trial saw seven breakthrough infections (before they whittled this figure down to six), their calculations suggested that if 10,000 similar men and trans women were followed for a year, 15 would contract HIV despite receiving Apretude injections on schedule.
At the same conference in Seattle, Hazra reported the first HIV breakthrough in an Apretude patient outside of a clinical trial. By comparison, almost four years passed after Truvada’s approval as a PrEP before a breakthrough infection was first documented in someone using that drug faithfully.
To date, there are a handful of other case study reports of breakthrough HIV in people taking oral PrEP. However, there has only been one clear case in the major clinical trials, including Truvada or Descovy as prevention.
All this suggests that for people with a history of daily scheduled oral PrEP intake, switching to Apretude would actually increase their HIV risk; although the absolute risk of infection would remain low.
Optimism in the pipeline
HIV prevention experts report excitement about the PrEP pipeline and expect easier and longer-acting forms to be approved in the next decade.
“I’m extremely optimistic,” said Sharon Hillier, a leading HIV prevention researcher at the University of Pittsburgh. “We just need to work through how we can deliver these interventions and how we can be less of a burden on the health care system.”
The Seattle conference heard promising early research results regarding medicated suppositories that can be placed in the rectum or vagina for up to 48 hours after sex and likely prevent HIV. And researchers are developing implants that can be placed under the skin and deliver preventive medication over many months.
Gilead is also conducting large PrEP trials with 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 initial research results 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 demonstrate their commitment to working with the options currently on the table, albeit within a complex and fractured healthcare system that is proving alienating for many of those most at risk for HIV.