Effects of economic interventions on pediatric and adolescent HIV care outcomes: a systematic review

Figures & data

Figure 1. PRISMA Diagram. ^†PRISMA template modified from Page et al. (22).

Table 1. Characteristics of included studies.

									Outcomes of Interest to this Review
	Citations	Study Type	Location	N	INT	SOC	Age (yrs)	Economic Intervention	VS	CD4	R/E	A
Children	Mebrahtu et al., (2019)	Cluster randomized trial	Zimbabwe	574^†	281	293	0–2	ISP	X	–	X	–
Adolescents	Cluver et al., (2019)	Prospective observational cohort	South Africa	1063	NA	NA	10–19	GCT	–	–	X	X
	Ssewamala et al., (2020) Bermudez et al., (2018) Brathwaite et al., (2022)	Cluster randomized trial	Western Uganda	702	358	344	10–16	ISA	X	–	–	X
	Galárraga et al., (2020)	Prospective cohort, pre-post intervention	Ghana	35	35	NA	13–18	FI	X	X	–	X
	Ekwunife et al., (2022)	Cluster randomized trial	Nigeria	246	119	127	10–19	FI	X	X	X	X
	Ekwunife et al., (2021)
Youth	Barnhart et al., (2022) Nshimyumuremyi et al., (2022)	Retrospective cohort with match	Rwanda	469^‡	260	209	<14->25*	FI, ISA	X	–	X	–
	Wohl et al., (2011)	Prospective cohort, pre-post intervention	California, United States	61	61	NA	18–23	FI	–	–	X	–
	MacCarthy et al., (2019)	Randomized controlled trial^§	Uganda	215	72; 73^¶	70	17–24	FI	–	–	–	X
	Foster et al., (2014)	Prospective cohort, pre-post intervention	United Kingdom	11	11	NA	16–23	FI	X	X	–	–

INT: Study Intervention, SOC: Standard of care, yrs: years, VS: Viral suppression, CD4: CD4 count, R/E: Retention/Engagement measurement or score, A: Adherence measurement or score, ISP: Internal Savings Program, GCT: Government Cash Transfer, ISA: Incentivized Savings Account, FI: Financial Incentive, NA: not applicable, –: not a reported outcome, X: reported.

^† Study included 16 infants with confirmed HIV infection within a larger cohort of HIV-exposed infants.

^‡ 324 participants in intervention, of which 287 participants able to be matched with electronic record, matched with retrospective cohorts.

^§ Study reports results only of a randomized controlled trial with a qualitative study among subset of participants.

*Study did not report age range of participants as many participants fell outside target age ranges.

^¶ Two intervention groups studied.

Table 2. Interventions and outcomes in included studies.

Citations	Economic intervention	Packaged care interventions or support	Adherence outcomes	Viral load outcomes	CD4 Outcomes	Retention/engagement
Mebrahtu et al., (2019)	Internal savings and lending program for mothers of HIV-exposed infants	18-session group intervention including: early childhood stimulation and parenting training; an internal savings and lending group microfinance program; and home visits to reinforce parenting skills and retention in HIV care offered to intervention group only.	–	Virologic failure (HIV viral load >1000 copies/mL) ^†:	–	Child retention in HIV services: HIV-exposed cohort
						INT; 201/257 (78.2%)
				INT: 4/8 patients (50.0%)		SOC: 207/249 (83.1%)
				SOC: 4/6 patients (66.6%)		OR 0.73 (0.47-1.14), p = 0.16
Cluver et al., (2019)	Receipt of government cash transfers (household receipt of any child support grant, foster child grant, pension, disability, or care dependency grant)	Cash transfers studied among 6 hypothesized development accelerators: free school (no fees or fee exemption); government cash transfer; safe school (no past-year physical violence by teachers or students); access to a support group (HIV-specific or general); free school meals; and parental support.	ART adherence >85% self-reported adherence	–	–	HIV care retention No missed visits or medicine collections in past year (Intervention vs control):
			ORa 1.34 (0.86-2.08), p = 0.21			ORa 1.87 (95% CI 1.15-3.02), p = 0.010
Ssewamala et al., (2020), Bermudez et al., (2018), Brathwaite et al., (2022)	1:1 matched incentivized child savings account for selected expenses (medical-related, family small business development, education-related)	All participants received medical SOC and psychosocial SOC consisting of information and support provided by lay counselors. “Bolstered” SOC included 8 information sessions on adherence to ART, including use of cartoon depictions. Intervention group also received 4 workshops in financial management and life skills (topics incl asset building, small business development, goal setting, risk mitigation). Microenterprise workshops offered only to intervention group.	Self-reported adherence (Brathwaite et al., 2022) Group-within-time simple effects (Intervention vs control):	Undetectable viral load (Brathwaite et al., 2022) Group within time simple effects (Intervention vs control):	–	–
			12 months: Contrast −0.02 (−0.31, 0.27), NSS	12 months: OR 0.94 (0.45, 1.99), NSS
			24 months: Contrast −0.28 (−0.55, −0.004), p value not reported	24 months: OR 0.71 (0.39, 1.31), NSS
			36 months: Contrast −0.02 (−0.26, 0.21), NSS	36 months: OR 0.57 (0.29, 1.11), NSS
			48 months: Contrast −0.12 (−0.62, 0.38), NSS	48 months: OR 0.76 (0.37, 1.55), NSS
				Proportion undetectable viral load (<40 copies/mL)
				24 months (Bermudez et al., 2018):
				INT: 10% increase, p = 0.001
				SOC: 1.1% increase, p = 0.733
				Sub-analysis High Risk Patients*
				48 months (Ssewamala et al., 2020): IRR 1.468 (1.064-2.038), p = 0.008
Galárraga et al., (2020)	Up to $20 in individual and $40 in group-based incentives, conditioned on group average attendance and average viral load	Peer groups with didactics, group-building activities, discussions, and leadership skills training	Average missed doses in last 7 days:	Viral Load Baseline to 6 months: Coefficient: −0.05 95% CI (−0.21, 0.31) NSS	CD4 count: Coefficient: −25.09 95% CI (−104.12, 53.94) NSS	–
			Baseline: 1.06
			3 months: 0.50
			6 months: 0.91
			9 months: 0.55
			Baseline to 9 months
			Coefficient: −0.19 (−0.38, −0.03)^‡, p < 0.05
			Full adherence in last 7 days:
			Baseline: 48.6%
			3 months: 67.6%
			6 months: 52.9%
			9 months: 69.7%
Ekwunife et al., (2022), Ekwunife et al., (2021)	Up to $16.80 cash incentive for viral suppression at 3, 6, 9, and 12 months	Motivational Interviewing provided to intervention only	Participants with 95% adherence by pill count	Viral Suppression (<20 copies)	Mean CD4 count +/- Standard deviation:	Retained in Care
			Baseline:		Baseline:	12 months
			INT: 61/119	Baseline:	INT: 665 +/- 685	INT: 98/119
			SOC: 35/127	INT 26/119	SOC 665 +/- 437	SOC: 102/127
			12 months:	SOC: 54/127	12 months:
			INT: 59/119	12 months:	INT: 586 +/- 379	Adjusted IRR: 1.03
			SOC: 40/127	INT: 38/119	SOC: 611 +/- 387	95% CI (0.78-1.38) NSS
				SOC: 52/127
			Adjusted IRR: 0.69		Adjusted IRR: 0.79
			95% CI (0.45, 1.07) NSS	Adjusted IRR: 1.01 95% CI (0.72-1.42) NSS	95% CI (−14.52, 16.12) NSS
Barnhart et al., (2022), Nshimyumuremyi et al., (2022)	$10 or $15 rewards deposited in group savings account for quarterly pharmacy attendance and annual viral suppression as well as matched savings for contributions of members. Rewards sporadically doubled if funding available.	Group meetings with nurse facilitated group discussions on ART adherence and challenges	–	Viral load suppression (<20 copies/mL)	–	Death free retention with active follow-up
						Baseline:
				Baseline:		INT 215/231
				INT: 97/161		SOC 166/182
				SOC: 78/135		12 months
				12 months:		INT: 190/231
				INT: 92/183		SOC 146/182
				SOC: 79/148		Coefficient for interaction −0.15, 95% CI (−1.13, 0.83), NSS
				Coefficient for interaction, −0.22, 95% CI (−0.96, 0.51), p = 0.55
						>80% appointment attendance
						Baseline:
						INT 155/231
						SOC: 99/182
						12 months:
						INT: 103/231
						SOC: 86/182
						Coefficient for interaction: −0.91, 95% CI (−1.60, −0.22), p = 0.01
Wohl et al., (2011)	$25 quarterly incentives totaling up to $200 over 24 months	Intensive youth-focused psychosocial case management, including treatment education, adherence support, and HIV risk reduction counselling. Entailed frequent case management visits (weekly for 2 months, then monthly for 22 months), development of individualized treatment plans, and referrals for needed services	–	–	–	Retention in HIV care:
						3 months: 90%
						6 months: 70%
						Sub-analysis High Risk Population (n = 33) ^§ –
						Percentage of HIV care visits attended in prior 6 months:
						Baseline: 7% 6 months: 73% p < 0.001
MacCarthy et al., (2019)	Random drawings for mobile airtime up to $2.60 USD, with incentives based on either flexible or fixed adherence targets	Motivational mobile text messages and mobile top-up funds (up to $2.60) for responding to motivational text messages.	ART Adherence, Mean Increase (measured by MEMS caps):	–	–	–
			Flexible Target: 11%^¶
			Fixed Target: 4% (NSS)
			Increase in probability of ART adherence >90%:
			Flexible Target: 12%^¶
			Fixed Target: 1.6% (NSS)
Foster et al., (2014)	Gift vouchers for HIV viral load decrease or suppression at 3, 6, and 12 months, and attendance in motivational interviewing sessions (up to £200 total)	Motivational Interviewing	–	HIV viral suppression (<50 copies/mL) at:	Increase in mean CD4 count:	–
				12 months: 5/11 24 months^††: 6/10	12 months: CD4 increased in 9/11 patients,
					90 cells/mm^3 mean increase from baseline
					24 months:
					CD4 increased in 3/10 patients
					4/10 decreased from baseline
					122 cells/mm^3 mean increase from baseline

INT: Intervention, SOC: Standard of Care, Ora: Adjusted Odds Ratio, CI: Confidence interval, NSS: Not Statistically Significant, IRR: Incidence Rate Ratio, –: Outcome not reported.

^† Sixteen infants with confirmed HIV infection represent a small subset of the HIV-exposed infants in the study.

*Subset of 288 youth with detectable viral load (> =  40 copies).

^‡ Decreasing trend evaluated at 3, 6, and 9 months not statistically significant but comparing baseline to 9 months found to be significant.

^§ Analysis of those attending <2 clinic visits in last 6 months and who were not virally suppressed.

^¶ Reported as statistically significant without analysis or p-value reported.

^†† One patient in study transferred care to another hospital.

Table 3. Narrative summary of included economic interventions.

First Author	Narrative Summary
Government Cash Transfer
Cluver	A prospective observational study in South Africa examined the effect of receipt of government cash transfers on pediatric HIV treatment outcomes. The study conducted standardized interviews with 1063 adolescents with HIV, assessing hypothesized development accelerators including receipt of government cash transfers to households, and longitudinal outcomes of ART adherence and HIV care retention, among other targets aligned with the Sustainable Development Goals. Receipt of government cash transfers was significantly associated with HIV care retention at 18 months (adjusted OR 1.87, p = 0.01), as well as with school progression and absence of emotional or physical abuse. HIV retention and other targets were enhanced when accelerators were combined: cash transfer, parenting support, and safe schools. ART adherence was not associated with cash transfers or other hypothesized accelerators. Baseline assessments from the prospective observational cohort included in this review found that adolescent self-reported retention in HIV care was associated with five factors, abbreviated as STACK: clinics Stocked with medication, staff with Time for adolescents, adolescents Accompanied to the clinic, enough Cash to get to clinic safely, and staff who are Kind
Financial Interventions
Ekwunife Ekwunife	A cluster randomized control trial in Nigeria in twelve hospitals randomly assigned to intervention or control groups with a year-long intervention and an additional year of post intervention monitoring. The intervention group received $5.60 for viral load suppression and an additional compensation for continued suppression. The intervention was paired with motivational interviewing in the intervention group. Notably, at baseline the control arm began with 42.5% viral suppression while the intervention arm had 2.18% viral suppression. The intervention group viral suppression increased by 14.6% while the control group increased by 5.7% when adjusted for a regimen change occurring during the study, a finding which was not statistically significant on multilevel regression analysis (IRR 1.01). Both CD4 count and adherence decreased in the intervention group.
Foster	A pilot intervention study in the UK evaluating pre-post intervention measures targeted severely immunosuppressed youth (CD4 < 200 cells/mm^3) with perinatal HIV who were not on ART. The pilot intervention utilized financial incentives for viral load decrease or suppression and participation in motivational interviewing sessions (up to £200 total). In this targeted patient population, 5/11 were virally suppressed (HIV viral load <50 copies/mL) on cessation of the financial incentive at one year, and 6/10 were virally suppressed at 24 months, or 12 months after the intervention. Mean increases were seen in CD4 count at 12 and 24 months (by 90 and 122 cells/mm^3, respectively), although the increase at 24 months was driven primarily by three participants with dramatic CD4 count increases.
Galárraga	A pilot study in Ghana examined pre-post intervention outcomes for a group-based economic incentive conditioned on group clinical outcomes among adolescents with perinatal HIV with detectable viral load while on ART. Thirty-five adolescents were divided into five groups and scheduled to have their quarterly HIV clinic visits on the same day, together with peer group activities. Financial incentives were conditioned on both individual behaviors (attending clinic and completing the assessment, up to $20 total over the 9-month intervention) and on group average clinic attendance and group average viral load (up to $40 total). Missed doses in the previous 7 days decreased by 0.19 when compared from baseline to 9 months, achieving statistical significance. Changes in other adherence outcome measures, viral load, and CD4 counts were not statistically significant in this pilot study.
MacCarthy	A study from Uganda reported preliminary findings and qualitative data from the Supporting Adolescents to Adhere (SATA) intervention, which randomized participants to either fixed (study-assigned) or flexible (self-determined within a given range) adherence targets to be eligible in a drawing for small mobile airtime incentives (equivalent to up to ∼$2.60 USD), or to a control group that did not receive any incentives. While the report centered on qualitative findings, authors noted that among the group with flexible adherence targets, mean adherence increased by 11%, and there was a 12% increase in probability of >90% adherence. By contrast, for the group with fixed adherence targets, mean adherence increased by 4%, and the probability of >90% adherence increased by 1.6% (not statistically significant). Focus group participants expressed a consistent preference for flexible adherence targets, and discouragement when they did not meet targets. Some also felt discouragement when in the drawing they drew a “zero card” and didn’t receive an airtime reward; authors suggested this could be mitigated in the future if the value of the lowest prize is small but not zero.
Wohl	A pilot intervention study in the US – also evaluating pre-post intervention measures – included youth African American or Latino men who have sex with men who were either newly engaging or intermittent in HIV care. Participants were enrolled in an intensive youth-focused psychosocial case management intervention and offered $25 quarterly financial incentives during the 24-month intervention period. Of 61 participants, 90% were retained in care at 3 months and 70% were retained in care at 6 months. Among the 33 participants with previous intermittent care, the proportion attending all HIV care visits in the previous six months increased from 7% to 73% (p < 0.0001).
Savings Intervention/Mixed Intervention
Ssewamala Bermudez Brathwaite	Suubi + Adherence – cluster-randomized trial in Uganda, adolescents in the intervention group were given access to a 1:1 matched child savings account which could be utilized for eligible childhood development and healthcare expenses. All families received a “bolstered” standard of care support in the study, through 8 information sessions supporting ART adherence. Those in the CSA intervention group additionally received 4 workshops with topics covering financial management and life skills. At 24 months, the proportion virally suppressed increased by 10.0% in the intervention group (p = 0.001) and by 1.1% in the control group (p = 0.733). Increased self-reported adherence was observed in the intervention group at 24 months only. At 48 months from study initiation, youth with detectable viral loads at baseline were found to have a significantly higher incidence of undetectable viral load in the intervention group as compared to the control group (IRR 1.468, 95% CI 1.064–2.038, p = 0.008). Comparison of intervention and control groups without stratification by detectable viral load did not reveal significant changes in viral suppression or self-reported adherence at 48 months. Other findings included positive educational and economic outcomes correlated with the intervention.
Barnhart Nshimyum-uremyi	A multi-site study conducted in rural districts of Rwanda examined the effect of economic incentives deposited into joint savings accounts in the setting of adolescent support groups and discussions. This study utilized iterative implementation and study protocol changed during the observation period. Vulnerable adolescents were selected by healthcare providers and cash incentives were awarded for group performance on quarterly pharmacy visits, savings targets, viral suppression, and creation of new adolescent support groups. These adolescents were matched retrospectively to a population data extracted from the shared electronic medical record. No significant difference was noted in the intervention group for death free retention, adherence, or viral load suppression. Notably, the comparison group differed in significant ways (age, gender, viral suppression and others).
Mebrahtu	Child Health Intervention for Developmental Outcomes (CHIDO) – pragmatic cluster-randomized trial in Zimbabwe recruited a cohort of 574 HIV-exposed children ages 0–2 years and their caregivers. The intervention included three components: an 18-session group parenting program on health, nutrition, and early childhood stimulation; an internal savings and lending program with group microfinance sessions held after each parenting session; and home visits from village health workers at least monthly. No effect was observed for the intervention on retention in HIV services for the broader cohort of HIV-exposed children, nor was there an effect on child development measures at 4.5 months after the intervention. The number of infants with confirmed HIV infection (n = 16) was too small for evaluation of an intervention effect. Importantly, there was an observed effect in reducing parental distress, which may be important to child health, including engagement in HIV care.

ART: Antiretroviral therapy, OR: odds ratio, IRR: incidence rate ratio, USD: United States dollars, CSA: child savings account.

Table 4. Validity characteristics.

First Author	Study Type	Time of observation	Study Attrition N (%)	NIH Corresponding Assessment Tool: Quality of Evidence Major Limitation
Ssewamala Bermudez Brathwaite	Cluster randomized trial	48 m	46 (6.5%)	Good
Mebrahtu	Pragmatic cluster randomized trial	12 m	68 (12%)	Good Limited evidence for this review given few children with confirmed HIV infection in total study sample
Ekwunife	Cluster randomized trial	12 m	46 (18%)	Fair Limited by recruited population size, baseline differences in viral suppression in cluster groups, and differentially applied concomitant drug regimen changes
Cluver	Prospective observational cohort	18 m	69 (6%)	Good
Barnhart Nshimyumuremyi	Retrospective cohort with match	12 m	31 (7%)	Poor Limited by implementation challenges, mis-recorded data, and missing data
Foster	Prospective cohort, pre-post intervention	24 m	1 (9%)	Fair Study designed as preliminary evidence, limited by very small sample size and narrow clinical population
Wohl	Prospective cohort, pre-post intervention	6 m	8 (13%)	Fair Limited by convenience sampling and inadequate sample size
Galárraga	Prospective cohort, pre-post intervention	9 m	0 (0%)	Fair Limited by sample size
MacCarthy	Randomized controlled trial^†	6 m	NR	Poor Preliminary quantitative outcomes given without reported methods for statistical analysis

N: Sample size, m: month/s, NR: Not reported, NA: Not applicable.

^† Study reports results only of a randomized controlled trial with a qualitative study among subset of participants.

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