“Payment by Results”—Financial Incentives and Motivational Interviewing,Adherence Interventions in Young Adults with Perinatally Acquired HIV-1 Infection: A Pilot Program

Abstract

Emerging evidence suggests financial incentives (FIs) improve medication adherence in select populations. A small proportion of adolescents with perinatal HIV (PaHIV) transfer to adult services with established poor adherence and advanced disease. We describe a single center adherence intervention combining FIs with motivational interviewing (MI). Eligible patients (PaHIV,16–25 years, CD4 count ≤200, off ART despite multiple attempts) received MI, and FI dependent on viral load (VL) reduction for 1 year. Outcome measures compared CD4 gain from baseline at 1 year and 12 months post cessation of FI/MI. Eleven young people enrolled; median age 19 years, 8 female. Baseline median CD4 count 30 cells/μL (IQR 10–160), VL 12,870 c/mL. Outcomes at 12 months: 9/11 ever achieved VL <50, 5 sustained undetectable VL, median CD4 140, mean CD4 gain 90 cells/μL at 1 year. Twelve months post cessation of MI/FI; six VL <50, median CD4 75, mean CD4 gain 122 cells/μL. Total FI expenditure £1,350: £68 per 50 CD4 cells at 1 year, £55 at 24 months. To prevent death, adolescents with PaHIV require novel interventions to reverse poor patterns of adherence established since childhood. FI/MI improved virological and immunological outcomes with minimal expenditure. Extension of this pilot work for vulnerable individuals is now indicated.

Introduction

Antiretroviral therapy (ART) has improved survival in pediatric cohorts, resulting in increasing numbers of adolescents with perinatally acquired HIV-1 infection (PaHIV) transitioning from pediatric to adult care.¹ In the UK, the average age of individuals with PaHIV is 15 years, and one quarter of the perinatal cohort are in adult care.² Globally, 25% of children have failed first line therapy, 1 in 8 children have triple class failure within 4 years of starting ART, with poor adherence the commonest factor.^3,4 Patterns of adherence in childhood are established early in treatment and emerging data suggests poor adherence patterns in pediatric care persist following transfer to adult services.⁵ A recent multicenter audit of PaHIV deaths following transfer to adult care in the UK demonstrated that established poor adherence in pediatrics persisting into adult care resulted in 9 of 11 deaths reported. The 2 remaining deaths were due to suicide. All had potentially suppressive ART regimens available in the year of death and had received multimodal adherence support, including clinical nurse specialists, health advisors, psychology, peer support, and directly observed therapy in both pediatric and adult care.⁶ In addition, adolescence and the period of transition to adult care are associated with poorer adherence than in earlier childhood or in adult life, both in HIV and other chronic diseases of childhood.⁵

Published randomized controlled trials (RCT) of interventions to improve adherence to ART in pediatric and adolescent populations are lacking. With around 25% of children and adolescents in all global settings failing first line therapy, such studies are essential to optimize ART enabling long term viral suppression, immunological preservation, prevention of morbidity and mortality, and onward transmission to sexual partners and future offspring as they enter adult life. In southern Africa, cash transfers, incentivizing adolescent girls to remain in education, have been shown to reduce risk behavior and HIV acquisition.⁷ In the UK, financial incentives (FIs) have been widely used in adolescent populations; from the Educational Maintenance Allowance to improving the uptake of Chlamydia screening. Emerging evidence suggests FIs benefit health outcomes in select populations with improved completion of tuberculosis therapy,⁸ drug abstinence,⁹ and smoking cessation in pregnancy.¹⁰ FIs were associated with improved adherence to ART assessed by MEMs caps in a population enrolled in a methadone program; however improvement appeared not to be sustained beyond the 12-week intervention program.¹¹ A recent systemic review of randomized controlled trials of varied ART adherence interventions in adults showed statistically significant benefit in only one of twenty-one studies.¹² Motivational interviewing (MI) is a counselling technique that aims to bring about positive behavioral change by helping clients identify and resolve ambivalence. MI has been shown to be an effective component in reducing substance abuse and in weight loss programs and MI appears to be more effective when used in conjunction with other adherence tools. Behavioral interventions such as motivational interviewing have shown some promise in improving outcomes for youth living with HIV, with modest short-term reductions in viral load, unprotected sex and alcohol use reported.^12,13

Following the deaths of two young adults with PaHIV, due to poor adherence to ART, a pilot program combining motivational interviewing, supporting behavioral change, with financial incentives was developed for young adults with PaHIV, longstanding poor adherence to ART and severe immunosuppression.

Methods

A single center pilot of structured adherence support termed the “Incentive Scheme (IS)” was developed in conjunction with established multidisciplinary adherence support that included clinical psychology, clinical nurse practitioners, specialist HIV pharmacist, and peer support within a designated young persons HIV clinic. The incentive scheme combined financial incentives in the form of gift vouchers linked to HIV viral load results and attendance for motivational interviewing with a clinical psychologist or clinical nurse specialist trained in MI techniques (Table 1). Eligibility criteria included all patients with PaHIV who had transitioned from pediatric services to a specialist young persons HIV clinic, and were age 16–25 years with severe immunosuppression (CD4 count ≤200 cells/μL), currently off ART despite multiple attempts to restart, and were willing to restart therapy and sign a patient agreement.

Table 1.

Protocol for Financial Incentives and Motivational Interviewing

Started ART	VL response and attended for MI	Voucher value
Week 2	Fall in VL	£ 25
Week 4	Fall in VL	£ 25
Week 8–16	VL <50	£ 50
3 months suppressed	Sustained VL <50	£ 25
6 months suppressed	Sustained VL <50	£ 25
12 months suppressed	Sustained VL <50	£ 50
Total	VL suppression for 12 months	£ 200

Patients received motivational interviewing at baseline and following initiation of ART and vouchers of £25 for each fall in viral load at 2 and 4 weeks, £50 when VL <50 copies/mL, £25 if the viral load remained suppressed for 3 months, and then at 6 months, and finally £50 if the viral load remained <50 copies/mL at 1 year (Table 1). All vouchers were contingent not only on viral load results but attending for motivational interviewing and the potential maximum cumulative value of reward was £200/patient if viral suppression was sustained for 12 months. Enrollment commenced from January 2010; each individual remained on the scheme until 12 months of virological suppression was achieved or 12 months from enrollment in those who failed to suppress or experienced virological rebound. Patients could withdraw from the scheme at any time point. Routine clinical data was collected and outcomes were assessed by changes in HIV viral load and CD4 count from baseline, at 12 months from enrollment and at 24 months to establish whether any benefit seen from the intervention was sustained when financial incentives and motivational interviewing ceased. IS was developed following consultation with adolescent service users demonstrating both poor and excellent adherence and was discussed with both clinical and research ethics committees and designated a service intervention. Incentives were financed through donated lecture fees from the multidisciplinary team.

Results

Of the 12 young adults with perinatally acquired HIV and advanced immunosuppression eligible for the incentive scheme, 11 young people enrolled between January and December 2010. One patient, CD4 count 40 cells/μL, declined, stating they were unwilling to start ART at the current time. A summary of the viral load and CD4 count data at baseline, and at 12 and 24 months post enrollment is presented in Table 2.

Table 2.

Virological and Immunological Response at 12 Months on the Incentive Scheme and at 24 Months Following Cessation of the Intervention

		Baseline data			Response at 12 months			Response at 24 months
Pt No	HAART commenced	CD4 (cells/μL)	VL (c/mL)	VL <50 c/mL in first 12 months	CD4 (+/-) from base line		VL (c/mL)	CD4 (+/-) from base line		VL (c/mL)	FI total received
1	ATV/r TDF FTC	30	14,000	once	40	+10	99,000	20	−10	1250	£75
2	DRV/r TDF FTC	200	630	sustained	560	+360	<50	770	+570	<50	£200
3	DRV/r ETV RAL	160	12,000	twice	160	0	64,000	Transfer of care			£100
4	EFV TDF TFC	10	3,500	sustained	200	+190	<50	190	+180	<50	£200
5	ATV/r ABC 3TC	190	2,400	twice	230	+40	6,800	110	−80	<50	£75
6	LPV/r ZDV 3TC	0	140	sustained	60	+60	<50	20	+20	240	£200
7	DRV/r TDF FTC	50	160,000	twice	140	+90	100,000	300	+250	<50	£200
8	DRV/r ETV RAL	10	47,000	sustained	120	+110	<50	330	+320	<50	£200
9	ATV/r TDF FTC	50	22,500	nil	90	+40	105	20	−30	13,200	£25
10	LPV/r TDF FTC	30	12,900	nil	10	−20	9,000	40	+10	<50	£0
11	DRV/r TDF FTC	30	26,300	Intermittent	140	+110	<50	20	−10	41,000	£75
Cohort		median CD4 30median VL 12,900			median CD4 140median VL 105mean CD4 gain 90			median CD4 75median VL <50mean CD4 gain 122			£1,350

3TC, lamivudine; ABC, abacavir; ATV/r, atazanavir/ritonavir; DRV/r, darunavir/ritonavir; EFV, efavirenz; ETV, etravirine; FTC, emtricitabine; LPV/r, lopinavir/ritonavir; RAL, raltegravir; TDF, tenofovir disproxil fumarate; ZDV, zidovudine.

Baseline data

Of the 11 enrolled; median age was 19 years (range 16–23); 8 were female; 8 were of black African origin and 3 Caucasian. Prior ART exposure included a median of three previous ART regimens (range 2–9) and all patients had a potentially suppressive regimen available. Cumulative life time recorded resistance mutations: wild type (3), single class (4), dual class (2), and triple class (2). Six patients ever had one or more prior AIDS defining illnesses: HIV wasting syndrome (3), atypical mycobacteria (3) pneumocysitis jiroveci pneumoniae (PCP) (1), VZV retinitis (1), and HIV encephalopathy (1). At enrollment the median CD4 count was 30 cells/μL (IQR 10–160), median VL 12,870 c/mL (IQR 2,382–26,300 c/mL). 9/11 patients had a viral load >1000 copies/mL. ART commenced once daily protease inhibitor based ART (8), Atripla (1), twice daily darunavir/ritonavir, raltegravir, etravirine (2). 7/11 were known to be sexually active, 4 of whom had partners who had ever tested, all of whom were HIV antibody negative.

Outcomes at 12 months post enrollment

Nine of eleven ever achieved VL <50, 5/11 achieved virological suppression at 1 year, 4/5 sustained virological suppression from 12 weeks of starting therapy to 12 months post enrollment (Table 2). Median CD4 count at 1 year was 140 cells/μL (IQR 60–200), with a mean CD4 count gain of 90 cells/μL. 9/11 patients achieved CD4 increments, one CD4 count remained stable, and one patient showed a fall in CD4 count from a baseline of 30 cells/μL to 10 cells/μL, never having achieved virological suppression. Clinical outcomes: there were no deaths, 2 new AIDS diagnoses (PCP), with 6/11 patients requiring at least one hospital admission. One young woman became pregnant, achieving a VL <50 copies/mL at delivery and an HIV uninfected healthy male infant, confirmed by 3 subsequent negative HIV PCRs.

Outcomes at 24 months post enrollment

Follow-up post completion of the scheme (Table 2) was available for 10 patients, one patient having transferred to another hospital. 6/10 patients had an undetectable viral load 24 months post enrollment, 3 had viral loads >1000 copies/mL, 2 of whom had stopped ART, a third patient with ongoing poor adherence. Three of the 5 patients with virological suppression at completion of IS remained suppressed at 24 months, 1 year following cessation of IS. One further patient had intermittent virological suppression and one patient stopped ART post delivery of her uninfected child. 3/10 patients achieved a CD4 count >300 cells/μL. Mean CD4 count gain was 122 cells/Ul. Four patients showed CD4 decline from baseline 24 months previously, mean CD4 loss 42 cells/μL. All 4 patients had shown CD4 count increments at 12 months, with a mean increment of 50 cells/μL (range 10–110). Clinical outcomes: no deaths, 1 new AIDS diagnosis (MAI), and 4 patients required at least one hospital admission during this time period. During the 24 months of follow up, no patient acquired documented additional HIV associated resistance mutations from baseline.

Finances

Total FI expenditure was £1350 for the 11 patients. Mean CD4 count gain for 11 individuals was 90 cells at 12 months, and 122 cells for 10 individuals under follow up at 24 months. Total CD4 count gain for 11 individuals was 990 cells at 12 months; cost of financial incentives £68 per 50 CD4 cells gained. Total CD4 count gain for 10 patients under follow up at 24 months was1220 cells; cost of financial incentives £55 per 50 CD4 cells gained.

Discussion

A small proportion of adolescents born with HIV persistently struggle with adherence to ART despite conventional multidisciplinary support, some of whom die from HIV-associated disease despite the availability of potentially suppressive ART regimens.⁶ In this small pilot cohort of highly treatment experienced PaHIV adolescents with severe immunosuppression, a combined intervention incorporating motivational interviewing and financial incentives linked to HIV viral load response, showed improved adherence to ART measured by CD4 count increment and virological suppression. Four patients showed sustained virological suppression and immune reconstitution 12 months post cessation of the intervention. Completion of the Incentive Scheme did not lead to poorer adherence to ART in those on suppressive therapy and suggests that for this group, adherence behaviors were consolidated during the intervention. Whilst patterns of poor adherence, ambivalence to ART overall are difficult to change, this intervention impacted the VL and/or CD4 count of all participants even if adherence could not be sustained and amongst a significant proportion adherence patterns were sustained post completion of the scheme.

There is very limited experience of motivational interviewing in young adults living with HIV, a recent Cochrane review identified only two trials; demonstrating a short term reduction in viral load and unprotected sex acts, and highlighted the need for trials of MI reporting adherence to ART, morbidity, and mortality.^13,14 Current evidence suggests that economic incentives can aid behavioral change, including in adherence to medication and that cash/coupons have better effect than gifts/lottery and that earlier payment is associated with enhanced participation.^15

–18 Financial incentives have been shown to improve adherence to antiretroviral therapy in HIV-positive methadone patients in the US, and mathematical modeling within this population suggests that adherence interventions with moderate effectiveness costing $100 per month or less are generally accepted to meet a cost-effective threshold.^10,14 Cost analysis of this small cohort showed that financial incentives linked to virological control are feasible and improve following cessation of the intervention with a total cost of £68 per 50 CD4 cells at 12 months reducing to £55 per 50 CD4 cells at 24 months. A reduction in the number of patients admitted to hospital over time further increases the cost effectiveness of the intervention. A recent retrospective analysis of sequential adherence interventions in a small Dutch PaHIV adolescent cohort (n=31), median age 13 years, showed improved adherence to ART and a reduction in hospital admissions and placement in foster homes, following the introduction of a reward based program.¹⁹ Adolescents who remained virologically suppressed for 6 months received an outdoor sports-based gift such as a football boots or a bicycle.¹⁹

High levels of adherence to antiretroviral therapy associated with virological suppression have been shown to markedly reduce onward transmission of HIV to serodiscordant heterosexual partners and in the prevention of mother–to–child transmission.²⁰ The clear correlation between plasma viral load and risk of onward transmission of HIV is an additional factor that may motivate young people living with HIV to adhere to ART. At enrollment, all study patients had a detectable plasma HIV viral load, 9 having VL >1000 copies/ml, placing their partners and offspring at risk of onward transmission. At 24 months, following cessation of the intervention, 6/10 patients had an undetectable viral load with 3 patients having VL >1000 copies/mL. Early data suggests that in both behaviorally and perinatally infected youth, the risk of unprotected sex is higher in those with poor adherence to ART and is associated with higher rates of substance abuse and mental health diagnoses.²¹ A recent analysis of pregnancies in perinatally-infected youth living in the UK found that 81% were unplanned, 79% of the cohort had a detectable viral load around the time of conception, and despite adherence interventions one-third delivered with a detectable viral load, highlighting the urgent need for effective adherence interventions in this population to prevent the onward transmission of HIV to partners and offspring.²²

There are several limitations to interpreting the efficacy of this pilot intervention. First, it is not a randomized controlled trial and has a small number of patients. The intervention was open to all PaHIV with severe immunosuppression, the small numbers of eligible participants reflecting the overall high levels of virological control within the clinic cohort. Discussion within the multidisciplinary team, with patient representatives and subsequently clinical and research ethics committees, concluded that given the severity of disease, risk of death, and extensive adherence support already given to the cohort that randomization at this stage of disease was not desirable and on grounds of optimizing clinical care a prospective RCT was not appropriate. Subsequent to this pilot, a four-arm multicenter RCT comparing standard of care (SOC), SOC with motivational interviewing, SOC with financial incentives, and SOC with both financial incentives and motivational interviewing, is planned for individuals with poor adherence but not life threatening immune suppression. Meta-analysis of published adherence interventions has been difficult due to variable definitions of improved adherence and complexities of adherence assessment.^12,13 In recent pre-exposure prophylaxis studies, patient adherence reports and pill counts showed very poor correlation to plasma ART drug levels, and suggest that measurable endpoints including virological suppression and immune reconstitution are needed to evaluate changes in ART adherence that improve clinical outcomes.²³ Due to concerns as to the sustainability of an adherence intervention, a period of follow-up post cessation of the intervention is also required.^12,13 Linkage of financial incentives to measurable change in viral load and a follow-up period for 12 months post completion of the Incentive scheme addressed these concerns.

Adolescents represent a particularly vulnerable group living with HIV and some struggle to overturn patterns of poor ART adherence set up in childhood, resulting in HIV-associated morbidity and mortality in early adult life. A combination of financial incentives and motivational interviewing improved adherence amongst a small cohort of adolescents with PaHIV but similar levels of success amongst other vulnerable groups may be anticipated. Poor adherence to ART is frequently associated with other risk behaviors, including unprotected sex, drug use, and mental health diagnoses, increasing the risk of onward transmission of HIV. Randomized controlled trials of adherence interventions with virological/immunological endpoints are required, and in populations with PaHIV should include younger children prior to established patterns of poor adherence and the consequent morbidity of advanced disease.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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