PrEP: Worth the Extra Effort for Those at Risk

Jessica Tomaszewski, MD
Primary Care Pediatrics, Nemours Children’s Health System, Wilmington, Delaware

Citation:
Tomaszewski J. PrEP: worth the extra effort for those at risk [published online October 1, 2017]. Consultant for Pediatricians.

The human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) drug tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) was approved by the US Food and Drug Administration (FDA) in 2012. However, none of the initial clinical trials assessed during the approval process included adolescent participants younger than 18 years of age. This is a noteworthy gap, since adolescents are a highly vulnerable population to HIV worldwide. In the United States in 2014, adolescents and young adults made up 22% of all new HIV infections, and 80% of those infections were in young men who have sex with men (YMSM).

The Adolescent Medicine Trials Network for HIV/AIDS Interventions 113 (Project PrEPare) was designed as a demonstration project and phase 2 safety study for YMSM aged 15 to 17 years to expand regulatory approvals and create appropriate PrEP implementation efforts. This trial examined the safety, tolerability, and acceptability of TDF/FTC while measuring rates of adherence and patterns of sexual risk behavior.

Participants who were HIV-negative but were at high risk for acquiring an infection were recruited from adolescent medicine clinics in 6 cities in the United States. They all received scheduled behavioral intervention and daily TDF/FTC for 48 weeks. They also underwent tests for HIV and other sexually transmitted infections (STIs). Consent was approved without parental involvement. PrEP levels were measured in serum to determine adherence. Clinical adverse events were monitored closely, as well, particularly renal safety and bone mineral density.

Of the 2800 patients who were screened for study inclusion, 78 were enrolled. Over the 48-week period of PrEP use, 23 STIs were identified in 12 participants. The HIV seroconversion rate was 6.4 per 100 person-years. Therapeutic tenofovir disphosphate levels were found in 42 (54%) participants at week 4, 37 (47%) at week 8, 38 (49%) at week 12, 22 (28%) at week 24, 13 (17%) at week 36, and 17 (22%) at week 48. Overall, 46 participants completed a full 48 weeks.

The medication was well tolerated overall, and no renal events or bone fractures were reported. The overall bone mineral density Z-score decreased from baseline to follow-up, which warrants further study in the future. There was no increase in numbers of sexual partners or condomless sex acts throughout the study.

In this study, the HIV incidence rate was high compared with other open-label clinical studies that had been completed in a slightly older population (participants aged 18-24 years). That being said, those who had seroconversion had very low PrEP levels detected at that time, which supports the use of this medication when taken correctly.

Another finding that is fairly specific to this age range centered on how dramatically the serum drug level falls as the visit schedule spaces out to some degree. It appears that closer follow-up is needed, possibly using mobile technology, to ensure proper adherence.

Tenofovir disphosphate appears to be safe and well tolerated and is worth further study with a larger sample size. With appropriate developmental support, PrEP could be offered to a very high-risk group of individuals and can make an incredible impact.

Reference:
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