Adequately PrEPping the Next Generation

Forty years in, despite reams of data, advances in testing and treatment, and the best of intentions, experts continue to grapple over the best solution for reaching and convincing millions of people — especially adolescents and young adults — to take highly effective, daily preexposure prophylaxis (PrEP) for HIV.

Adolescents and young adults are tough customers. Aside from developmental factors — physical, psychological, and emotional changes that occur during the transition out of puberty — novel data suggest that individual level of risk is often misinterpreted, misunderstood, or at times not even considered, despite the fact that roughly one fifth of new HIV diagnoses in the US are in this population.

Dr Joshua Barocas

"We're in sort of a crisis mode of being able to get people on to preventive medicine," Joshua Barocas, MD, infectious disease specialist and director of the Social Determinants of Health and Disparities Modeling Unit at the University of Colorado School of Medicine, told Medscape Medical News.

In a study published on April 25 in AIDS Care, Barocas and his team found that among almost 140,000 US adolescents and young adults who were assessed for PrEP initiation between 2015 and 2019, only 1.6% received a prescription in the year following their eligibility claim, despite having a sexual risk factor (86.9%) and/or a drug-related risk factor (21.3%).

The issue? Barocas says that it's not the numbers that matter most but rather that the medical establishment has not gotten past the "one size fits all" approach to HIV risk assessment. Poor awareness and low prescription rates reflect that.

"Our conception of HIV risk is still stuck in the 90s," he said.

High PrEP Need, Low Receipt

Although CDC data highlighted a decline in sexual frequency among high school students between 2009 and 2019, "sexual repertoire" measures (behaviors during or related to sexual events) paint a very different story.

Sexual risk factors are pervasive in this patient population. In as many as 40% of sexual encounters, condoms are not used. Moreover, 1 in 5 sexual encounters involve alcohol or drugs, and among lesbian, gay, and bisexual youth, having multiple partners is common, as is injected substance use.

Barocas and his team found similar associations when they reviewed sexual and behavioral health and prescription claims data for adolescents and young adults with a likely PrEP indication (as indicated by the presence of ≥1 sexual risk factors and/or substance use disorder with evidence of injection drug use).

Study participants ranged in age from 13 to 26 years (median, 21 years), and roughly 65% were female. Overall, 86.9% had an identified sexual risk factor (ie, sexual activity with elevated risk and/or a sexually transmitted infection), 13.0% had an opioid use disorder (OUD) with likely injection, and 8.3% had a stimulant use disorder with likely injection. Eighty-five percent had an identified sexual risk factor without a drug-related risk factor, while 5% had a drug-related risk factor without a sexual risk factor.

Participants who received a PrEP prescription (1.6%, n = 2171) were three times likelier to be older (adjusted odds ratio [aOR] for those aged 18–20 years, 5.11; 95% CI, 3.35 – 7.77; vs those aged 21–26 years: aOR, 16.90; 95% CI, 11.0 – 24.7); male (aOR, 92.42; [95% CI, 68.24 – 125)]; to engage in sexual activity with elevated risk (aOR, 7.47; 95% CI, 6.50 – 8.60); or to be diagnosed with gonorrhea (aOR, 5.61, 95% CI, 4.93 – 6.37) or syphilis (aOR, 5.22, 95% CI, 4.16 – 6.56).

Conversely, having an OUD or using stimulants was associated with fewer PrEP initiations.

"Whether it was sexual or drug use, these people had an identified risk," said Barocas.

Still, only 1 in 64 participants with a potential indication for PrEP received it.

"Once we have an identified risk factor, then there needs to be a comprehensive assessment for HIV, for PrEP," he explained.

Nowhere is this truer than among the female population, which by and large is often overlooked when it comes to both risk recognition and PrEP eligibility. This held true for the study population.

"We really need to make sure that we do a risk assessment that is tailored to the population that we are looking at, not just, 'Do you use condoms?' When we do have women sitting in our office, we need to dig into what the risk factors are for women and their HIV risk," said Barocas. These factors might include sexual or domestic violence or sexual trauma.

Time for a Paradigm Shift

Although clinicians can be challenged to do a better job at HIV risk assessment, there's still an elephant or two in the room. Data were collected on participants who presented for care, but what about those whose PrEP needs go unrecognized? Between pervasive HIV stigma and concerns about confidentiality to lack of self-perceived risk, the bar to engagement is high.

"PrEP is a significant advance in our ability to counter the 'original' pandemic of our lifetime, which is HIV," said David A. Wohl, MD, an infectious disease specialist and site leader of the HIV Prevention and Treatment Clinical Trials Unit at the University of North Carolina at Chapel Hill. "This study — like a cottage industry of studies — shows that less than 2% of eligible young people who could get PrEP got it," he said. "But it's not always because the provider was ignorant or didn't do a good job."

Wohl, who was not involved in the study, pointed to a larger issue: PrEP itself.

"PrEP looks good on paper, it looks good as a pillar for eliminating HIV, but many people do not find that this is an acceptable way to protect themselves from HIV. They (especially teens) don't want to take a pill or come back every few months and get tested," he noted.

From Wohl's perspective, contraception offers a terrific roadmap for HIV prevention, with numerous modalities and options. With the recent approval of injectable, long-activating cabotegravir, options will soon be broader, but this comes at a cost, not only financially but also with regard to the time needed to scale up in the midst of the current pandemic.

Whether the primary problem is with risk assessment or a lack of choices, one thing is clear: there is a large, at-risk adolescent and young adult population whose needs are not being met.

Barocas reports no relevant financial relationships. Wohl reports consulting relationships with Gilead, ViiV, Janssen, and receives research funding from Merck.

AIDS Care. Published online April 25, 2022. Abstract

Liz Scherer is an independent journalist specializing in infectious and emerging diseases, cannabinoid therapeutics, neurology, oncology, and women's health. @LizScherer.

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