Special clinical considerations
As a part of primary health care, HIV screening should be discussed with all adolescents who are sexually active, or have a history of injecting drug use. Parental or guardian involvement in an adolescent’s health care is often desirable, but is sometimes contraindicated for the safety of the adolescent, and can compromise full disclosure.
Clinicians should carefully consider the data discussed below on the safety and efficacy of daily PrEP taken by persons under 18 years of age, including the possibility of loss of bone mineral density, and other
toxicities among youth who are still growing. Data are also available about the safety of TD*/FTC when used in treatment regimens for young people with HIV infection (35). The clinician and the patient may conclude that the short-term, proximal risk of acquiring HIV infection greatly outweighs any short-term, or as yet undetermined, long-term risk of PrEP toxicity. Clinicians are encouraged to seek expert advice in complex situations.
Adherence to PrEP in adolescents may be suboptimal: a PrEP demonstration program involving daily PrEP use for 18–22-year-old HIV-negative MSM reported that tenofovir diphosphate intracellular levels, a marker of cumulative TD* adherence, were consistent with good adherence peaking at 56% at month, but declining thereafter (36). In another open-label 48-week study of 78 adolescent MSM commencing PrEP,
Project PrEPare, highly protective levels of PrEP were observed in 54% of adolescents at week 4 but declined thereafter (37).
Following this finding that PrEP levels declined markedly in these adolescent participants after the first week 4 visit, the authors recommended that adolescents should be offered more frequent clinical monitoring to enhance their PrEP adherence.
The ASHM PrEP Guidelines Panel endorses this approach and encourages clinicians to work with adolescents taking PrEP to design an augmented clinical review schedule.
In the Project PrEPare study, there was no observed elevation in serum creatinine levels and significant increases were observed in bone mineral density for the spine, hip and total body between baseline and week 48 (37). However, there was a slight but statistically significant decline in the total body Z-score during this time (37), suggesting that bone growth may have been suboptimal in the study participants. Although not observed in this study, higher levels of PrEP adherence as measured by red blood cells levels of tenofovir diphosphate have been associated with lower hip bone mineral density in adolescents (38).
Further research is needed to determine whether there is a long-term increased risk of bone fractures in young MSM who have had PrEP.
Globally until recently, regulatory approval of Truvada (tenofovir disoproxil fumarate (TDF (FTC)) PrEP was limited to adults over 18 years of age. However, on 15 May 2018, the US Food and Drug Administration (FDA), based on data from the Project PrEPare study discussed above, expanded its approval of Truvada as PrEP against HIV to include adolescents at risk weighing at least 35 kg.
PrEP use for prevention of HIV in adolescents has not been approved by the TGA in Australia. However, clinicians are able to prescribe PrEP off-label for adolescents. In this setting, a decision to prescribe PrEP for a person under 18 years of age should be made at the discretion of the prescriber who is responsible for obtaining informed consent from their patient. Informed consent should take into account the risks and benefits of that treatment versus other available treatments or no treatment at all based on the individual circumstances. Of note, the TGA does not regulate health professionals or clinical practice. Medical practitioners are required to prescribe in accordance with Good Medical Practice, the code of conduct published by the Medical Board of Australia – this code highlights the importance of informed consent.
Adolescents may obtain PrEP via the Personal Importation Scheme of the TGA once they have received an off-label prescription from their clinician.