Adolescent pre-exposure prophylaxis for HIV prevention: current perspectives

Figures & data

Table 1 Clinical trials of PrEP in the population at risk of HIV infection

Study	Population	Age	Efficacy of TDF or TDF/FTC compared with placebo (%)	Adherence (%)
Partners PrEP (TDF + FTC or TDF)	Heterosexual men and women	18 years or older	75	82
Botswana TDF2 (TDF + FTC)	Heterosexual men and women	18 years or older	62	79
Bangkok (TDF)	Drug users	18 years or older	49	67
iPrEx (TDF + FTC)	Men who have sex with men	18 years or older	44	51
FemPrEP (TDF + FTC)	African women	18–35 years; mean: 24.2 years	6	26
VOICE (TDF + FTC or TDF gel)	Women	18–45 years; mean:25.3 years	−4.2	29

Abbreviations: FTC, emtricitabine; PrEP, pre-exposure prophylaxis; iPrEx, PrEP initiative; TDF, tenofovir disoproxil fumarate.

Table 2 Summary of the included studies

Study/country	Type of study	Population/age	Aims/outcomes	Description	Results
Project PrEPare ATN 113 (NCT01769456) and ATN 110 (NCT01772823) Country: USA (six study sites: Boston, Chicago, Los Angeles, Memphis, New Orleans, and Philadelphia)	Open-label demonstration project and Phase II safety study Situation: completed	Enrolled: 78 young HIV-negative MSM 35% Black/African American 45% Latino/Hispanic: 15–17 years (ATN 113); 18–22 years (ATN 110)	To evaluate:  Safety of daily oral TDF/FTC (Truvada^®)  Patterns of use  Rates of adherence  Patterns of sexual risk behavior	Study subjects engaged in a behavioral risk-reduction intervention before PrEP. Monthly visits for the first 12 weeks of study. Quarterly visits thereafter until 48 weeks of study	Acceptability of PrEP was high: −56% with TDF diphosphate drug levels consistent with ≥4 pills per week (at week 24) and 34% at week 48. Noticeable drop-off occurring at week 24
Project PrEPare ATN 082 (NCT01033942) Country: USA (six study sites: Boston, Chicago, Los Angeles, Memphis, New Orleans, and Philadelphia) Hosek et al^Citation21	Demonstration project and Phase II safety study Randomized three-arm design weCompleted	Enrolled: 68 youth (mean age = 19.97 years; 53% African American, 40% Latino) Randomized: 58 (18–22 years)	To compare an efficacious behavioral HIV prevention intervention (3MV) alone, 3MV combined with PrEP (TDF/FTC), and 3MV combined with placebo. Measures:  Feasibility  Acceptability of study design  Adherence to study drug  Sexual behaviors  Risk compensation	3MV intervention: conducted as a 2-day seminar throughout centrally located communities in Chicago with approximately eight participants per session. After 3MV, study participants were randomized in blocks of six within each site to one of three study arms: 1) daily combo FTC and TDF as PrEP, 2) placebo pill control (with HIV behavioral intervention), or (3) “no pill” control (subjects receive HIV behavioral intervention but no pills)	The feasibility of enrolling at-risk youth, particularly YMSM of color has been demonstrated. The acceptability of the group intervention along with counseling and testing was high. Self-reported medication adherence and corresponding plasma drug concentrations were low. Behavioral disinhibition was not seen. Decrease in sexual risk behavior was seen over time
CHAMPS PillsPlus (clinical trial: NCT02213328) Country: South Africa (Johannesburg and Cape Town)	Prospective, open-label Situation: active, not recruiting	Enrolled: HIV-negative adolescents 98 female 50 male 15–19 years Median age of 18 years (17–19 years)	To evaluate:  Safety, feasibility, acceptability of daily oral TDF/FTC (Truvada^®)	Daily oral PrEP as part of an HIV prevention package that included condoms and STI screening and treatment. Adherence support using SMS, adherence clubs, real-time feedback on drug levels	Estimated date for final data collection date for primary outcome measure: August 2017
HPTN 082 (clinical trial: NCT01033942) Country: South Africa and Zimbabwe	Randomized multisite prospective study Situation: ongoing	Enrolled: adolescent and young adult women (16–25 years)	To assess the acceptance rate, adherence, acceptability, and continuation of oral PrEP among young Southern African women	Standard adherence support versus enhanced counseling based on feedback from observed drug levels in the first 2 months after PrEP initiation. Qualitative research about factors influencing PrEP initiation and adherence (for those who initially declined PrEP)	Ongoing
Clinical trial (NCT02915367) Country: Kenya	Interventional, randomized, open-label	Young women (18–24 years)	1) To evaluate the difference in adherence to PrEP by the study arm: SMS reminders versus no reminders 2) Acceptability 3) Risk perception	Intervention: behavioral. Adherence Wisepill data and TDF concentration on dried blood spots	Ongoing
Clinical trial (NCT02810249) Country: USA	Observational, with a qualitative design	20–30 African American YMSM aged 16–24 years	1) To identify and understand African American YMSM’s cognitive and emotional processes in response to using PrEP to reduce their risk for HIV 2) To identify what factors (sociocultural, individual, experiences in health care, socioeconomic) influence African American YMSM’s likely use of PrEP	Individual interviews	Ongoing
Koechlin et al^Citation25	Systematic review	78 studies evaluated hypothetical use of PrEP (five studies were conducted among “adolescent girls and young women.” 26 studies included individuals who actually took PrEP or placebo	To describe the evidence about values and preferences among populations that might benefit from PrEP and among health care providers who may prescribe PrEP	Three electronic databases of articles and HIV-related conference abstracts (January 1990–April 2015) Type of studies: 68 quantitative 24 qualitative 12 mixed methods	Participants showed strong interest in PrEP (aged 14–24 years). They appreciated the “privacy” of a pill; some girls expressed hesitation with regard to PrEP. Participants would be willing to take PrEP if it was free. One study showed 20% of young women expecting to use condoms less frequently if they took PrEP
Substudy of Crew 450 (an ongoing longitudinal cohort study, N = 451 YMSM); Chicago, USA	Observational, cross-sectional	YMSM aged 16–20 years N = 184	To describe PrEP interests among racially and ethnically diverse YMSM aged 16–20 years using a new measure that may have utility in the future studies	Computer-assisted self-interview with audio instructions. PrEP interest scale with a score of the likelihood of using PrEP	Participants with better HIV knowledge had higher interests in PrEP. Higher level of education was related to an increased likelihood of taking PrEP. No relationship between most of the reported risk behaviors and mean PrEP interest scores. Indirectly proportional relationship between unprotected anal intercourse with PrEP interest
Fisher et al^Citation27 NY, USA	Qualitative study, using a Web-based qualitative/mixed methods analysis program	Enrolled: 60 sexually active SGMY 14–17 years	To provide empirical data on SGMY self-consent that can assist IRBs on strategies to increase their research participation	Online survey and asynchronous focus group questions after watching a video about PrEP. Discussions addressed: guardian permission, random assignment, privacy concerns, and PrEP medication adherence	Adolescents have the ability to self-consent as compared to age- and population-appropriate procedures. Guardian permission as a significant barrier to research participation
Mack et al^Citation30 Country: Kenya and South Africa	Qualitative study Kenya (adults) and South Africa (adolescents and young women)	South Africa: focus groups (N = 36 participants). Two FGs with adolescent aged 14–17 years and two with young women aged 18–24 years	To explore the potential role of choice in women’s use of HIV prevention methods. To present the analysis of groups’ attitudes toward ARV-based HIV prevention	All focus groups were audio-recorded, transcribed, and translated into English. Transcripts were coded using a codebook and QSR NVivo 9.0 (QSR International, Melbourne, Australia); generated code reports; and conducted inductive thematic analysis to identify major trends and themes	All groups expressed strong interest in PrEP products. Adolescent girls believed that it would be possible to obtain the products more privately than condoms. Some girls stated that they would be interested in using PrEP only after seeing other girls use it. Young women showed concern that it would be challenging to negotiate PrEP use with a partner
Culp and Caucci^Citation28 Country: USA	Analytic, WestlawNext, a subscription- only online legal research service	A 50-state analysis of minor consent laws and its implications for PrEP	To analyze laws related to a minor’s ability to consent to medical care, including HIV diagnostic testing and treatment, and its implications for PrEP	Staff collected all statutes and regulations about an adolescent’s ability to consent to HIV diagnosis, treatment, and prevention. On laws current as of December 31, 2011	Minors’ access to PrEP without parental consent is unclear. No state expressly prohibits minors’ access to PrEP. All jurisdictions allow adolescents to consent to diagnosis and treatment of STIs; only eight jurisdictions allow consent to prophylactic services
Clinical trial (ATN 113 substudy) Country: USA	Qualitative study	17 research personnel at 13 ATN sites considering “implementation” of ATN 113	To examine factors related to the process by which IRBs and research personnel made decisions regarding whether to approve and implement the protocol. Emphasis on the issue of adolescent consent with high-risk minor participants	Semi-structured interviews and the receipt of IRB-related correspondence and documents generated during the review process	Of 13 ATN sites in 12 states: seven received IRB approval for ATN 113, three were denied approval, and three received no formal IRB disposition

Abbreviations: ATN, Adolescent Medicine Trials Network; ARV, antiretroviral; FGs, focal groups; FTC, emtricitabine; IRBs, institutional review boards; PrEP, pre-exposure prophylaxis; SGMY, sexual and gender minority youth; SMS, short message service; STI, sexually transmitted infection; TDF, tenofovir disoproxil fumarate; 3MV, Many Men, Many Voices; YMSM, young men who have sex with men.

Figure 1 PRISMA flow diagram.

Figure 2 Factors that influence acceptability and implementation of PrEP in adolescents.

Note: Arguments in favor and the issues that should be better addressed.
Abbreviation: PrEP, pre-exposure prophylaxis.

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