The increasing efficacy of PrEP in contributing to reduced HIV incidence often highlights the limited access in populations at high risk of HIV who were not included in original studies.
Results from an adolescent PrEP study in six U.S. cities are therefore as important for highlighting the need for PrEP as they are for reporting acceptability and efficacy. The results from the ATN 113 study, published with open access on 5 September 2017 in JAMA Paediatrics, showed that PrEP reduced HIV infections in this high-risk group, but also showed many challenges.1
This was a phase 2 PrEP implementation study in young men aged 15 to 17 at high risk of HIV and willing to take PrEP, with primary endpoints of safety and acceptability.3
At the time the study was run, approximately 22% of new HIV diagnoses in the U.S. were in people aged 13 to 24 years old, 80% of which were gay men or other men who have sex with men (MSM).
The first challenge was engaging appropriate participants for this study. Out of more than 2800 young people approached for pre-screening from August 2013 to September 2014, 260 were eligible and 78 were enrolled. Mean age was 16.5 years. Ethnicity included 29% black, 21% Hispanic, 14% white and 36% mixed race or other. Most self-identified as gay (58%) or bisexual (28%), 88% lived with their families but 15% had been forced to leave their primary home because of their sexuality; 86% were still at school. Other demographics including relatively high use of alcohol and marijuana (only a third never used either).
Baseline risk for enrollment was defined as any of the following within the previous six months: condomless sex with a male partner, more than three partners, exchange sex or an STI. PrEP was included as part of a combination prevention package, with monthly visits for the first three months and quarterly visits through to week 48, with compensation per visit of $50 to $75. Participant questionnaires included acceptability and adherence related to PrEP and behaviour risk. Adherence was also evaluated by drug level testing at study visits.
Of the 78 participants enrolled, 72 (92%) started oral daily PrEP (TDF/FTC) and only 46 (64%) completed 48 weeks follow up, with most of the other participants (n=19) lost to follow up.
Most participants had detectable drugs levels at some point during the study. Although about half of participants had drug levels equivalent to taking four or more doses a week needed for protection for the first 3 months of the study, this level of adherence halved again for the remainder of the study. Tenofovir diphosphate levels consistent with >/= 4 doses a week were found in 42 (54%), 37 (47%), 38 (49%), 22 (28%) 13 (17%) and 17 (22%) participants, at weeks 4, 8, 12, 24, 36 and 48, respectively.
Common reasons for low adherence were being away from home (32%), being too busy (28%), forgetting (26%) and changing routines (18%). Lower adherence was also significantly associated with a worry that PrEP would be associated with being HIV positive (p=0.03).
Over 48 weeks of PrEP there were three new HIV infections (at weeks 32, 36 and 38): an annual rate of 6.4 (95% CI: 1.3-18.7) per 100 person-years. One of these cases had not shown detectable TDF drug levels for several months and two cases had levels associated with taking less than two doses a week at the likely time of infection.
Although tolerability was reported as good, with no PrEP discontinuations due to side effects or laboratory abnormalities, there was a small but significant decline in total body bone mineral density z-score in the 43 participants with week 48 DEXA results (0.7%; IQR, -0.3 to 0.0; p <0.001), although changes in hip and spine did not change significantly. These changes were not related to TDF-DP levels.
There were 23 sexually transmitted infections diagnosed in 12 participants, showing that this population was certainly at risk, but rates were similar to the baseline figure of 19 prevalent STIs in 14 participants. Although more STIs were diagnosed during the first six months of the study this was not statistically significant.
These results were first presented last year at AIDS 2016 conference in Durban.3
A related adolescent PrEP study (ATN 110) in a high risk group of slightly older gay men (aged 18 to 22) reported similar high level of need, with related challenges of recruitment and retention, but also a significant loss in BMD on PrEP (which returned to baseline after PrEP was stopped).4
The details of the ATN PrEP studies are important for showing not just the need for PrEP in young people at risk of HIV, but the need for PrEP that is easier to take.
Although the risk of HIV is likely to outweigh the risk of BMD reductions from short-term use of TDF/FTC, these results also highlight the need for PrEP that would not have this concern in young people.
An accompanying editorial by Renata Arrington-Sanders, an adolescent HIV specialist at Johns Hopkins University, notes that these exciting results will help young men at risk for HIV to access and use TDF/FTC. Also, the likely support needed from an "interdisciplinary, multiteam, community approach that recognises the complexity of adolescent needs".5
- Hosek SG 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. JAMA Pediatr. Published online: 5 September 2017. doi:10.1001/jamapediatrics.2017.2007.
- clinicaltrials.gov. An open label demonstration project and phase II safety study of pre-exposure prophylaxis use among 15 to 17 year old young men who have sex with men (YMSM).
- Hosek SG et al. An HIV pre-exposure prophylaxis (PrEP) demonstration project and safety study for adolescent MSM ages 15-17 in the United States (ATN 113). 21st International AIDS Conference (AIDS 2016), 18-22 July 2016, Durban. Late breaker.
- Mulligan K et al. Changes in bone mass after discontinuation of pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine in young men who have sex with men who lost bone while using PrEP: extension phase results of adolescent trials network Protocol 110. 18th International Workshop on Comorbidities and Adverse Drug Reactions in HIV, 12-13 September 2016, New York. Oral abstract 001. See HTB, October 2016.
- Arrington-Sanders R. Human immunodeficiency virus preexposure prophylaxis for adolescent men: how do we ensure health equity for at-risk young men? Editorial comment. JAMA Pediatr. 5 September 2017.
[Note from TheBodyPRO.com: This article was originally published by HIV i-Base on Sept. 5, 2017. We have cross-posted it with their permission.]