Table 3.

Characteristics of Included Studies

	Citation	Country	Study design	Participants	Intervention	Control/comparison	Outcome measures and definitions	Key findings
1	Bermudez et al.24	Uganda	Longitudinal cluster randomized trial	Total sample: 702 adolescents 10–16 enrolled for ARV treatment across 39 clinics in 4 districts of Southern Uganda, participating in 3 waves of the Suubi+Adherence project between 2012 and 2017.	Bolstered standard of care and savings-led economic empowerment intervention. Economic component included (i) a CSA, matched at a rate of 1:1 and from which financial savings could be used for medical related expenses, family small business development or education related expenses; (ii) four workshops blending financial management and life skills with topics including asset building, small business development, goal setting, and risk mitigation.	Bolstered standard of care: 8 information sessions on adherence to ART, using evidence-based print cartoons.	Viral suppression, as measured through undetectable viral load (HIV RNA viral load <40 copies/mL) and the reduced mean log of VL.	Intervention adolescents had significantly lower odds of a detectable VL at both 12 months (OR 0.42; p < 0.01) and 24 months (OR 0.3; p < 0.001) postintervention initiation, whereas no significant differences were found across time for the control group. There was also a significant reduction in log10 VL at 12 months in the intervention group (mean difference = −0.36; p < 0.05).
				Intervention: 20 clinics and 358 adolescents
				Control: 19 clinics and 344 adolescents
2	Fatti et al.29	South Africa	Retrospective cohort study	Total sample: 6706 adolescents and youth 10–24 who initiated ART between January 2004 and September 2010 at 47 public ART facilities across 4 South African provinces.	Standard clinic based care and a CBS intervention provided by lay workers, including: home-based ART- and sexual and reproductive health-related education, psychosocial support, referrals for psychosocial problems and nutritional security, screening for opportunistic infections, tracing of defaulters and support accessing government grants.	Standard clinic-based care.	Primary outcomes: All-cause mortality and LTFU after ART initiation. Secondary outcomes: (i) Adherence to ART, measured using Medication Possession Ratios derived from pharmacy refill data (number of days of dispensed medication divided by the number of days between the first and last pharmacy refill during the study period); (ii) CD4 cell count increases between months 0 and 36 after starting ART; (iii) CD4 count slope (mean change in CD4 count per month) between months 0–6 and 6–60; and (iv) the proportion of patients not achieving virological suppression after 3 years and during the fifth year of ART.	CBS was associated with substantially reduced attrition, including 40% less LTFU (aHR = 0.60; p < 0.001) and reduced mortality 5 years after the intervention (aHR = 0.52; p < 0.001). The proportion of youth who failed to achieve viral load suppression at 5 years was higher in the control group (aOR 0.24; 95% CI: 0.06–1.03), although this was marginally significant. The intervention also appeared to be cost-effective, with an ∼50$ cost per year and $600 to $776 cost per patient loss averted.
				Intervention: 2100 youth
				Control: 4606 youth
3	Grimsrud et al.4	South Africa	Retrospective cohort study	Total sample: 884 youth 16–24, from a larger sample of 8150 individuals initiating ART	CACs, a community health worker led and nurse supported model of care supporting groups of 25–30. Includes group meetings every two months for group counseling, symptom screening and distribution of prepacked ART.	Patients attending a CHC, a large primary health care facility typical of urban public sector ART services across the region, based on South African national program criteria for ART.	LTFU (no visit in the first 12 weeks of 2014) and viral rebound (a single viral load measurement >1000 copies/mL after previous suppression).	For youth 16–24 years of age LTFU for CACs was not significantly different from that of CHCs (aHR = 0.68; p = 0.197). For all other age groups in the study, participation in CACs was instead associated with a decreased risk of LTFU, compared with CHC attendance (aHR = 0.33; 95% CIs: 0.27–0.40).
				Intervention: 156 youth
				Control: 728 youth
4	Ingerski et al.28	US	Retrospective study using systematic medical record review	Total sample: 62 youth 13–24 with horizontally acquired HIV, initiating HAART in a clinic setting.	Receipt of one or more placebo trials before HAART initiation. Placebo pills, containing lactose sugar, were prescribed using a regimen with the same dosing frequency, pill size, and number of pills as the anticipated HAART medication regimen.	Youth who did not receive a placebo trial before HAART initiation.	Viral load and CD4 count readings, abstracted from participants' electronic medical record.	No significant differences were found in disease markers at 12 months between youth receiving a placebo trial post-HAART initiation and youth who did not (p > 0.01). Youth receiving multiple
				Intervention: 72% (45 youth) received one or more placebo trials before HAART, and 27% (17 youth) two or more.
								trials were more likely to have lower CD4 count 9 months post-HAART initiation, suggesting this may serve as a method to identify most at-risk adolescents.
				Control: remaining 17 youth that did not receive a trial
5	Linnemayr et al.25	Uganda	Individually randomized parallel multi-site controlled trial	Total sample: 332 HIV-positive 15–22 year olds attending one of two study HIV clinics in Kampala, Uganda. Participants randomly assigned by simple randomization in a 1:1:1 ratio to control group or 1 of 2 intervention groups.	SMS reminder messages by means of one-way SMS (message only) or two-way SMS (message plus response option). Message for both groups was “We hope you are feeling well today.” For the two-way SMS group respondents were asked to reply “1 if well, 2 if unwell”; they received a call from a study coordinator within 24 h if the response was “unwell.”	Usual standard of care.	Primary outcome: mean HIV treatment adherence over a 48-week period (number of recorded bottle openings divided by the number of prescribed bottle openings, measured by means of a pill bottle with an electronic MEMS).	No significant differences in mean adherence [67% in the control group, 64% in the one-way SMS group (95% CI = 0.77–1.14), and 61% in the two-way SMS group (95% CI = 0.75–1.12) or secondary outcomes found across the 3 groups].
				Intervention group 1 (one-way SMS messaging): 110 youth
							Secondary outcomes: at least 90% adherence; self-reported adherence for the previous month; binary indicator of whether treatment was interrupted for 48 or more hours.
				Intervention group 2 (two-way SMS messaging): 110
				Control group: 112
6	MacKenzie et al.23	Malawi	Nested case–control study	Total sample: 617 adolescents 10–19, who were ART patients participating in the Zomba District Observational Cohort Study at a tertiary urban referral hospital in Zomba and started ART during or after March 2010. From this population, 135 nonretained cases and 405 retained controls were selected.	An adolescent-centered differentiated care model (“Teen Club”), comprising: dedicated weekend clinic time; sexual and reproductive health education; disclosure and ART adherence support; ART refill; individualized peer counseling and support; peer interaction through sports, art, and games.	Usual standard of care.	Nonretention in ART care, defined as patients who were lost to follow-up (patient did not return to the clinic within 2 months after (s)he was expected to have run out of ART and is not known to have transferred out or stopped treatment); “stopped” (the patient is known to have stopped treatment for any reason) or; “died” (the patient is known to have died, based on report by guardians, health facility staff, or from routine LTFU tracing by facility staff).	Adolescents exposed to Teen Club were more likely to be retained than those without exposure (aOR for nonexposure: 0.27; 95% CIs: 0.16–0.45). Attrition was higher among older adolescents (15–19) compared with the 10–14 age group (aOR 2.14; 95% CIs: 1.12–4.11).
				Intervention: 302 adolescents
				Control: 238 adolescents
7	Ojwang' et al.7	Kenya	Retrospective cohort analysis	Total sample: 924 HIV-positive patients 15–21 years of age enrolled in care at a Youth Center or Health Center in Kisumu, Kenya, between July 2007 and September 2010.	Youth-orientated prevention, care, and treatment clinic. Similarly to the family clinic, fees are not charged and defaulter tracing is conducted (NOTE: no further description of the youth-friendly clinic and its characteristics is provided).	Family oriented clinic, offering free services and including an active defaulter program to contact patients that miss appointments. Includes assisted disclosure, identification, and enrollment of other HIV-positive family members and family counseling.	LTFU (patients missed his/her last appointment by ≥4 months).	The clinic of enrolment was not associated with LTFU (aHR = 1.09; p = 0.56). LTFU was very high, over 50% (52.9/100 person-years).
				Intervention: 584 at the youth-specific clinic
				Control: 340 at the family-oriented clinic.
8	Reif et al.5	Haiti	Retrospective analysis using programmatic clinic patient-level data	Total sample: 554 adolescents 13–19 years of age (of the 1672 who tested positive for HIV) that initiated ART at a public HIV clinic in Port-au-Prince between January 2003 and December 2012.	Implementation of a dedicated adolescent clinic. Over and above standard clinic services, youth-friendly HIV services included: HIV-positive one-on-one and small group peer counseling; age-appropriate educational materials and extracurricular activities, such as projects and games to promote retention; family planning and STI testing provided at the same clinic; counseling services for mental health and gender-based violence at the clinic; clinic hours from 8 am to 5 pm to accommodate after school hours.	Standard pediatric services (for ages 10–13) or adult clinic services (for ages 14–19). Services for adolescents in the adult clinic included counseling by HIV-positive peer educators, reminder phone calls for appointments, and transport support. Family planning and treatment for STIs were provided in separate clinics at the same site.	Attrition, defined as dead or lost-to-follow-up (no clinic or pharmacy visit for 6 months with no documented transfer or death).	Retention after ART initiation was not significantly lower in the preclinic (comparison) group (aHR = 0.83; p = 0.2), although the study showed higher rates of pre-ART attrition at 12 months from testing in the preclinic group (aHR = 1.44; p < 0.001).
				Intervention: 305 who initiated post the adolescent clinic 2009 intervention.
				Comparison: 249 who initiated preclinic
9	Teasdale et al.26	Kenya	Retrospective cohort study	HIV-positive youth 10–24 enrolled for ART at a health facility participating in the Optimal Models for HIV care in Africa study in the Nyanza region of Kenya, either during the preintervention period (March to December 2011) or postintervention period (March to December 2013).	Implementation of YAFS in 6 health facilities from March 2013. The intervention comprised: (i) training and mentorship for health care providers on care for adolescents/youth; (ii) a dedicated day for adolescent/youth HIV clinic at least once monthly, which provided integrated sexual and reproductive health services; and (iii) support groups and education programs run by youth and adult peer educators.	Standard HIV services as per Kenyan national guidelines.	Incidence of LTFU in the first 12 months after ART enrolment (LTFU before ART initiation was defined as not attending visits over the 12 months and not recorded as dead or transferred to another facility; LTFU after initiation was assessed for patients who started treatment at least 6 months before the end of data collection).	No significant differences were found in post-ART LTFU before and after YAFS implementation at intervention facilities (p = 0.19). There were also no significant differences in LTFU in patients on ART between the YAFS and non-YAFS facilities in either the pre- (p = 0.73) or post-YAFS (p = 0.77) periods. The intervention did not improve retention either before ART or in the 6 months after treatment initiation.
				Intervention: 304 youth enrolled during postintervention period at 6 intervention facilities
				Control groups: 426 youth enrolled in preintervention period at 6 intervention facilities; 1017 enrolled in the preintervention period and 304 postintervention at 28 control facilities. Analysis of LTFU in the 6 months after initiation included 274 adolescents from intervention facilities (172 pre and 102 post) and 576 from the control facilities (410 pre and 166 post).
10	Zanoni et al.27	South Africa	Retrospective cohort study	Total sample: 241 perinatally HIV-infected adolescents and young adults 13–24 who received at least 1 prescription of ART at a hospital-based ART clinic in KZN, SA, between April 2007 and November 2015	Saturday adolescent clinic opened within an existing clinic. Services included ART dispensing, lunch, and scheduled group activities (e.g., dancing, soccer, education, counseling).	Standard pediatric clinic care at the same site.	Primary outcomes: retention in care (one clinic visit and/or ART dispensing in the 6 months before data extraction) and viral suppression (viral load of <400 copies/mL from the most recent test within previous 6 months). Secondary outcome: composite outcome of retention and suppression (one clinic visit, pharmacy refill, and viral load <400 copies/mL within the previous 12 months).	Retention and viral suppression (previous 6 months), respectively, were higher among youth attending the dedicated adolescent clinic versus the standard pediatric clinic (Retention: aOR 8.5; p < 0.01. Viral suppression: aOR 3.8; p < 0.01). Retention with viral suppression (past 12 months) was also higher among youth attending the adolescent clinic (aOR 8.4; p < 0.001).
				Intervention: 88 youth
				Controls: 153 youth

CHC, community health center; CSA, Child Savings Account; LTFU, loss to follow-up; MEMS, medication event monitoring system; VL, viral load.