AIDS is the second leading cause of death among adolescents globally; approximately 1.8 million individuals aged 10 to 19 years were reported to have HIV in 2015.1 In that age bracket, it was estimated that a new HIV infection occurred every 2 minutes. According to 2014 statistics for the United States, 80% of new cases among individuals aged 13 to 24 years affected young men who have sex with men (YMSM).2
Although tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) received approval from the US Food and Drug Administration in 2012 for HIV preexposure prophylaxis (PrEP), the efficacy trials only included adults, and therefore TDF/FTC was not approved for use in minors.3-5 “Thus, a critical gap in approved prevention products exists for adolescents, a population that is highly vulnerable to HIV worldwide,” wrote the authors of a new study published in JAMA Pediatrics.6
To that end, the authors conducted the Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 (Project PrEPare) to examine the safety, tolerability, and adherence to PrEP among healthy YMSM aged 15 to 17 years, as well as patterns of adherence to the daily regimen and risky sexual behavior.
The sample included 78 individuals with a mean age of 16.5 years (SD, 0.73 years), representing a variety of races and ethnicities, who were recruited from clinics in 6 US cities. Participants had negative test results for HIV but a high risk for infection. For inclusion, they were required to participate in a behavioral intervention, in addition to accepting a 48-week PrEP intervention.
The findings show 23 sexually transmitted infections diagnosed in 12 participants during the study period, as well as 3 new cases of HIV (HIV seroconversion rate, 6.4 [95% CI, 1.3-18.7] per 100 person-years). Tenofovir diphosphate levels indicating a high degree of protection against HIV (>700 fmol/punch) were noted in 54%, 47%, 49%, 28%, 17%, and 22% of participants at weeks 4, 8, 12, 24, 36, and 48, respectively. These results “strongly support the need for an adolescent PrEP indication for TDF/FTC,” the authors concluded. “The waning adherence, especially with quarterly visits, demonstrates that more time, attention, and resources may need to be allocated to adolescents who are seeking prevention services.”
To further explore this topic, Infectious Disease Advisor checked in with 2 experts: study coauthor Bill G. Kapogiannis, MD, program director of the Adolescent Medicine Trials Network for HIV/AIDS Interventions of the Eunice Kennedy Shriver National Institutes of Child Health and Human Development; and Helen C. Koenig, MD, MPH, associate professor of clinical medicine in the Division of Infectious Diseases at the Perelman School of Medicine at the University of Pennsylvania, and director of the PrEP program at Philadelphia FIGHT.
Disclaimer: The comments and views below are of the author and do not necessarily represent the views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Infectious Disease Advisor: Dr Kapogiannis, regarding the findings from your most recent paper, what are the main takeaways for our clinical audience?
Dr Kapogiannis: In this first safety and demonstration licensure-bridging study of PrEP to prevent HIV in adolescent minors who are at risk for infection, PrEP was safe and well tolerated. Adherence to PrEP as measured by objective drug levels started off high but decreased over time, and this decline seemed to be associated with decreasing study visit frequency (monthly to quarterly). The 3 incident HIV infections that occurred among participants with very low to undetectable PrEP levels are a stark reminder that the drug cannot work if it isn’t taken. Adolescents at risk for HIV can safely use and should be offered PrEP to reduce their risk of becoming infected, but may need additional support compared with adults, such as more frequent in-person clinic contact, cell phone reminders, and peer support group, to ensure they maintain high adherence.
Infectious Disease Advisor: What are some of the top points of debate regarding PrEP for adolescents?
Dr Kapogiannis: The main point that seems to surface is whether adolescents who are at risk for HIV infection can maintain the high levels of adherence needed for PrEP to be effective. Another, albeit less common, point that comes up is whether prescriptions of PrEP to at-risk adolescents will lead to more risky behaviors or a behavioral phenomenon that is termed disinhibition, which has not been seen in studies so far. Finally, the poor access and uptake in the very communities of young people in the United States who are at greatest risk of becoming infected by HIV is concerning and needs to be addressed.
Dr Koenig: We know that the group in which the HIV incidence is rising the fastest is youth and young adults aged 13 to 24 years, and that among this group the hardest hit subpopulation is young MSM of color and young transwomen of color. Top points for debate are the following:
- How to get pediatricians to talk with youth about PrEP in a systematic and nonjudgmental way; that is, at a routine visit, to talk about exercise, diet, smoking, routine vaccines, family planning, and HIV prevention options including PrEP with all patients, not just those deemed “at risk”
- How to get PrEP offered and discussed in schools
- The difficulty of reaching out to young sexually active women: In my experience, when we have started a young at-risk woman on PrEP and she has been enthusiastic, she then goes home and talks with her friends and none of them have heard about or been offered PrEP, and so the patient stops PrEP, given the absence of peer knowledge or support of PrEP in the young female adult community
- The need for parental consent
- The fact that TDF/FTC is not approved for PrEP for those younger than 18 years
- Concern about TDF affecting bone mineral density in youth who are still growing and laying down bone matrix
- Medication coverage for minors who do not want to use their parents’ insurance
Infectious Disease Advisor: Is parental permission necessary for PrEP in minors?
Dr Kapogiannis: The answer here is a bit complex, with some important caveats, and in the United States, it is guided at the local/jurisdictional or state level. First, the requirement for parental permission may make it very difficult to nearly impossible for adolescents who are at risk for HIV infection to access PrEP because they may not be willing to disclose required information about their risk behaviors to their parents. Also, the parent-child relationships may not be optimal, or the parent may be absent: Many of the teenagers at risk are at higher risk because they lack a stable, supportive home and family environment. In such situations, there are precedents for foregoing parental consent in adolescents when it comes to protecting their health and safety. One of those sample precedents includes medical care for the diagnosis or treatment of sexually transmitted infections (STIs).
All US jurisdictions expressly allow some minors to consent to medical care for the diagnosis or treatment of STIs. These laws are intended to encourage adolescents to seek treatment for reproductive health concerns through protecting their right to privacy in reproductive health decisions. Because HIV is mainly a STI, adolescents should be allowed to consent for HIV treatment regardless of whether state law specifically mentions HIV. However, state laws may not explicitly address an adolescent’s right to consent to medical care for the prevention of STIs. One could argue, and I would, that the extension of treatment statutes to STI prevention would be consistent with the intent of such state laws to protect the health of adolescents.
Finally, I always encourage adolescents to involve their parents in making healthcare decisions whenever possible, and they feel safe and supported in doing so.
Dr Koenig: “Is” and “should” are 2 different questions, as every state has different policies on STI/HIV prevention and treatment, and different institutions within the same state vary on what they deem medico-legally acceptable. At FIGHT, as in many other places, we believe that PrEP is just like any other state-sanctioned STI prevention intervention that can be legally offered to minors without parental consent. As a parent, I believe consent can and should be obtained wherever possible, as parental involvement can be a wonderful thing that facilitates adherence and engagement in care. However, sometimes obtaining parental consent endangers a young person’s safety; for example, if parents are not aware the patient is MSM and starting TDF/FTC “outs” them in some way, jeopardizing the emotional or physical well-being of an adolescent or financial support or housing for a young adult.
Youth not wanting parents to know they are sexually active for a variety of reasons has been a barrier with the approval of the Gardasil vaccines, home pregnancy testing kits, and so on. In these cases, PrEP can and should be offered without parental consent, again in keeping with the laws of each particular state. At FIGHT, we have codified policy allowing us to prescribe PrEP to minors. However, at the Children’s Hospital of Philadelphia, PrEP cannot be prescribed to minors, given the academic center’s legal concerns, just to give you a sense of some of the variation in practice.
Infectious Disease Advisor: Should PrEP be offered on a wider scale as part of sex education?
Dr Kapogiannis: We don’t know yet whether a “school-based clinic” alternative to the more traditional clinic-based model works better at improving uptake and adherence to PrEP for adolescents at risk for HIV infection, so more research is needed to inform whether this approach is feasible and appropriate.
Dr Koenig: A resounding “Yes,” for all of the above reasons and more. It works! Also, the question, “Why not?” must be asked. Why not share a widely available, acceptable, safe, and effective technology that can prevent a lifelong life-threatening disease, a technology that also serves to engage young people in healthy ongoing care with a healthcare provider, where they can be offered continual risk reduction prevention interventions such as STI testing, family planning assistance, condoms, flu shots, nutrition guidance, smoking cessation support, and general wellness interventions? PrEP IS primary care for youth.
By Tori Rodriguez
- UNAIDS. Global AIDS update. http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-2016. Updated May 31, 2016. Accessed October 17, 2017.
- Centers for Disease Control and Prevention. HIV among youth fact sheet. https://www.cdc.gov/hiv/pdf/group/age/youth/cdc-hiv-youth.pdf. Updated April 2017. Accessed October 17, 2017.
- Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587-2599.
- Baeten JM, Donnell D, Ndase P, et al; Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399-410.
- Thigpen MC, Kebaabetswe PM, Paxton LA, et al; TDF2 Study Group. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012;367:423-34.
- Hosek SG, Landovitz RJ, Kapogiannis B, et al. Safety and feasibility of antiretroviral preexposure prophylaxis for adolescent men who have sex with men aged 15 to 17 years in the United States [published online September 5, 2017]. JAMA Pediatr. doi:10.1001/jamapediatrics.2017.2007