Tenofovir/emtricitabine (TDF/FTC, Truvada) is effective for preventing HIV transmission in teenagers, but high rates of non-adherence mean that the answer for youth HIV risk can't just be biomedical, according to the findings of a study released this month in the journal JAMA Pediatrics.
"[This study] tells us that [pre-exposure prophylaxis, or] PrEP is safe and should be made available to adolescent men who have sex with men [MSM] who are vulnerable to HIV infection," Sybil Hosek, Ph.D., lead author of the study, told TheBodyPRO.com. "It also tells us that to maximize effectiveness, additional support around adherence needs to be offered to patients."
That additional support could include more frequent clinic visits, check-ins outside the clinic via text message and other methods, and talking to young men about sexual risk.
An Indication of Adolescent Need
The open-label study, the Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 (ATN 113), comes at a pivotal time in HIV prevention efforts. The number of teenagers and young adults in Africa -- where already 41% of the population is younger than 15 years old -- is expected to continue rising dramatically throughout this century, according to United Nations data. In the U.S., the demographics will not shift as dramatically, but already, young MSM, especially young black MSM, have among the fastest growing rates of HIV in the country. The Centers for Disease Control and Prevention recently estimated that half of black MSM will acquire HIV in their lifetimes.
But while this generation and their vulnerability grows, HIV prevention options aimed at them are limited. For one thing, when the U.S. Food and Drug Administration (FDA) approved TDF/FTC for PrEP in 2012, it did so only for people over 18. Studies of HIV prevention methods that might work for young people are difficult to enroll, too, since in many states researchers must receive parental approval for their teen to participate -- which requires teens to disclose both their sexual orientation and their sexual behavior to their parents. This can lead to real social harms, including teens being evicted from their homes, which can make them even more vulnerable to HIV.
It's a problem that will not be easily solved, Carl Dieffenbach, Ph.D., director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), told a group of HIV advocates and stakeholders on a recent conference call.
"Prevention for this group is going to be a tougher challenge simply because of the heat and light around the mode of transmission" -- that is, sexual activity at all, and gay sex in particular, he told the group, assembled to discuss NIAID's future funding strategies. "There's no magic bullet at this time to solve this problem."
And, finally, funding is indeed on the line. Not only is the future of the Affordable Care Act and Medicaid access under question, but the current presidential administration has questioned the value of the President's Emergency Plan For AIDS Relief and has called for drastic cuts to the National Institutes of Health, where NIAID is based, and to the U.S. Centers for Disease Control and Prevention, which initiates its own projects to address local HIV prevention needs. Dieffenbach said on the call that he hoped that he would have the same budget to work with going forward that he has now.
Flat funding, added Warren Mitchell from AVAC, is the new normal.
Effectiveness, Adherence and Results in ATN 113
In this context, Hosek and colleagues recruited 78 MSM 15-17 years old from diverse backgrounds in six U.S. cities. They followed the teens for 48 weeks, starting with a pre-initiation behavioral risk reduction session, followed by clinic visits monthly for three months. After that, they came in quarterly. In addition to being physically handed the TDF/FTC at each visit, the men received risk counseling, tests for HIV and other sexually transmitted infections, safety assessments and condoms. They also received between $50 and $75 as incentive to attend visits.
The good news is that the drug was well tolerated among participants: Only two people experienced adverse events possibly related to TDF/FTC, both of whom reported unintentional weight loss (one of the two people discontinued the study drug). And, unlike adults, there was no dose-dependent relationship between TDF exposure and bone mineral density changes.
Plus, by week 4, 54% of the 72 participants who actually received TDF/FTC had drug concentration levels consistent with HIV protection.
The bad news is that, though protective drug levels remained relatively high in the first three months -- 49% had drug levels consistent with four pills a week -- protective drug levels plunged after that: At week 24, protective drug levels were only detected in 28% of participants, and that dropped to 22% at week 48.
This drop wasn't a surprise to Hosek. Almost every study of young people using HIV prevention methods -- whether they be TDF/FTC in VOICE and FEM-PrEP or vaginal microbicide rings in ASPIRE -- has found a similar non-adherence.
"In part, this is reflective of their developmental stage, their desire not to be seen as 'sick,' their sense of invulnerability to disease and the chaotic, busy nature of their young lives," she said. "Adherence difficulties should be expected among youth and prevention interventions must account for that."
Still, as the first PrEP trial among 15-17 year old MSM, it proves that TDF/FTC can work in young people. Hosek is hoping this will be enough to convince the FDA to expand its indication of TDF/FTC for PrEP to people 15 and over. She said that her team is working with Gilead Sciences, Truvada's maker, to assemble an application for such an indication, which would make a huge difference in access for young people.
"The lack of an indication is a barrier," she said. "Some of the financial assistance programs available for adults are not available for off-label use of PrEP."
But that's not the only barrier. Hosek said that, now that we have this data, she hopes it will help physicians feel comfortable prescribing and providing adolescent-centered care to the young men at greatest risk for HIV. For a young person to initiate the TDF/FTC conversation "takes a tremendous amount of skill and confidence" -- a burden that may not be appropriate to place on young people who might have been evicted for their sexual orientation or who are coping with other real world challenges such as housing insecurity.
Helping Young People Adhere
If physicians do start prescribing for teens, she suggested a few evidence-based approaches that could improve adherence.
These include one-on-one and group risk reduction counseling, like the Many Men, Many Voices risk reduction course piloted by Hosek and team in Project PrEPare. Offering young MSM the option of daily and weekly text messages has also been found to improve adherence among young men. Other approaches that are not yet proven but which she and others are studying in young people include adherence clubs, feedback on drug levels, mobile gaming and mobile health interventions, as well as an approach from Chicago's Cook County Health and Hospital System to use ingestible sensors that provide real-time feedback on adherence.
But, beyond that, the best approach may be more frequent visits. In the study, adherence dropped dramatically after the three-month mark -- which was also when visits went from monthly to quarterly. It may be, she said, that bringing young patients back within two weeks or a month of PrEP initiation would help identify barriers that could lead to missed doses or discontinuation.
But, instead of making the decision for the young patient, Hosek said it's essential to talk it out with teens to find out what kind of support they want.
"I would then suggest that clinicians ask each young person how often they would like to come to the clinic for check-ins and if they would like any interim contact from the provider, either via phone or email or text," she said. "Allow them the opportunity to change their mind at every visit."
And then, when young men do come in, it's essential for providers to talk with them about anal sex and do rectal swabs for gonorrhea, Chlamydia and syphilis. In her study, 14 participants were diagnosed with 19 sexually transmitted infections (STIs) before the study began, and an additional 12 participants were diagnosed with 23 more STIs during the study.
"Most STIs were asymptomatic and discovered due to anal swabs, which the majority of our participants had never experienced," Hosek said.
Ultimately, though, oral PrEP might not be the best option for young people, she said. She pointed to studies underway right now in adults for long-acting cabotegravir, which could be administered every month, as well as the dapivirine ring, which data at the International AIDS Society conference in Paris this year showed was safe and acceptable to young women in the U.S.
"Right now, we can improve on PrEP effectiveness for youth by increasing access, decreasing barriers and offering developmentally appropriate supplemental interventions," she said. "In the future, we need to continue to develop and test new products, so that youth can make choices about which products will work best for them."
Heather Boerner is a health care journalist based in Pittsburgh and author of Positively Negative: Love, Pregnancy and Science's Surprising Victory Over HIV.