The cost-effectiveness of highly active antiretroviral therapy, Canada 1991-2001

AIM: To estimate the cost-effectiveness ratio of highly-active antiretroviral therapy (HAART) in Canada. DESIGN: A before-and-after analysis to calculate incremental cost of life year gained (LYG) between 1991 and 1995 (pre-HAART period) and between 1997 and 2001 (HAART period) for non-AIDS and AIDS groups (CDC stage of HIV infection). METHODS: For two Quebec HIV hospital clinics, mean inpatient (IP) days, outpatient (OP) visits and direct health care costs per patient-year (PPY) were calculated. Cox's proportional hazards models calculated disease progression, stratified by study periods and adjusted for gender, age at cohort entry, sexual orientation, injecting drug use and baseline CD4 cell count. RESULTS: For non-AIDS patients, mean IP days was 1.6 (pre-HAART period) compared with 0.8 PPY (HAART period); mean OP visits increased from 2.8 to 5.5 PPY. Total cost was US$ 4265 (pre-HAART period) and US$ 9445 PPY (HAART period) of which 66 and 84%, respectively were spent on antiretroviral drugs. Median progression time was 6.3 years in the pre-HAART period compared with 12.5 years in HAART period (log rank chi = 270, P < 0.0001). Incremental cost per LYG between periods was US$ 14 587. For AIDS patients, mean IP days decreased from 13.3 to 4.4 PPY between periods; OP visits increased from 8.3 to 9.2 PPY. Total costs increased from US$ 9099 to US$ 11 754 PPY, while expenditure on antiretroviral drugs increased from 29 to 72% of total cost. Median progression time was 3.8 years in the pre-HAART period, which increased to 13.3 years in the HAART period (log rank chi = 158, P < 0.0001); incremental cost per LYG between periods was US$ 12 813. CONCLUSION: HAART appeared a cost-effective intervention in Canada.     

The costs and benefits of private sector provision of treatment to HIV-infected employees in Kampala, Uganda

OBJECTIVES: The objective of this study was to determine the financial incentives that companies have to treat HIV-infected employees, in a health care services company in Kampala, Uganda. DESIGN: Cost-benefit analysis from the company's perspective of three interventions to treat HIV-infected employees. METHODS: The costs and benefits of each intervention were compared with no intervention and with each other: cotrimoxazole prophylaxis (CTX) starting at WHO stage 2; highly active antiretroviral therapy (HAART) plus CTX starting at WHO stage 2; and a 'hybrid' strategy that begins with CTX at WHO stage 2 and later includes HAART. The 5-year health and economic outcomes were calculated using a Markov model. Inputs for disease progression rates and effects of HIV on company costs were derived from published and unpublished data and a survey administered to company officers. RESULTS: The analysis showed that the 'hybrid' intervention is the most cost-effective. For 100 skilled employees it would save the company 38,939 US dollars and 73 disability adjusted life-years (DALYs). For unskilled workers 'CTX' is the most cost effective and would save 16,417 US dollars and 60 DALYs. 'Hybrid' has an incremental cost-effectiveness ratio of 45 US dollars per DALY for unskilled workers whereas HAART is far less economical at an incremental cost per DALY of 4118 US dollars. For 'CTX', net savings are preserved across the full range of input values. CONCLUSION: A 'hybrid' intervention combining CTX prophylaxis followed by HAART would generate savings to a Ugandan company. Governments and other donors may find opportunities to share costs with the private sector as part of their phase-in strategy for antiretroviral therapy.     

The impact of malnutrition on survival and the CD4 count response in HIV-infected patients starting antiretroviral therapy

BACKGROUND: The impact that malnutrition at the time of starting antiretroviral therapy (ART) has on survival and the CD4 count response is not known. METHODS: A retrospective cohort study of patients attending the national HIV referral centre in Singapore who had a CD4 count less than 250 cells/microL and a measurement of body weight performed at the time of starting ART was carried out. Demographic and clinical variables were extracted from an existing database. Body mass index (BMI) was calculated from the weight in kilograms divided by the square of the height in metres. Moderate to severe malnutrition was defined as BMI less than 17 kg/m(2). Intent-to-treat Cox models were used to determine the predictors of survival. RESULTS: A total of 394 patients were included in the analysis, of whom 79 died during a median study follow-up of 2.4 years. Moderate to severe malnutrition was present in 16% of patients at the time of starting ART, and was found to be a significant independent predictor of death [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.29-3.73, P=0.004 for those with BMI<17 compared with those with BMI>18.5] as were stage of disease (HR 2.47, 95% CI 1.20-5.07, P=0.014 for those who were at stage C compared with those at stage A) and the type of ART [HR 0.50, 95% CI 0.27-0.93, P=0.03 for highly active antiretroviral therapy (HAART) compared with non-HAART treatment]. Malnutrition did not impair the magnitude of the increase in CD4 count at 6 or 12 months. CONCLUSIONS: Malnutrition at the time of starting ART was significantly associated with decreased survival, but the effect appeared not to be mediated by impaired immune reconstitution. Given the increasing access to ART in developing countries and the high frequency of HIV-associated wasting, studies of nutritional therapy as an adjunct to the initiation of HAART are urgently needed.     

Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

ABSTRACT: BACKGROUND: For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. METHODS: In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. FINDINGS: A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p= 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p= 0.05). Rates of adverse events were similar. Interpretation: Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Clinical trial registry number CTRI/2011/12/002260.     

Effectiveness and cost-effectiveness of strategies to expand antiretroviral therapy in St. Petersburg, Russia

OBJECTIVE: To assess the effectiveness and cost-effectiveness of treating HIV-infected injection drug users (IDUs) and non-IDUs in Russia with highly active antiretroviral therapy HAART. DESIGN AND METHODS: A dynamic HIV epidemic model was developed for a population of IDUs and non-IDUs. The location for the study was St. Petersburg, Russia. The adult population aged 15 to 49 years was subdivided on the basis of injection drug use and HIV status. HIV treatment targeted to IDUs and non-IDUs, and untargeted treatment interventions were considered. Health care costs and quality-adjusted life years (QALYs) experienced in the population were measured, and HIV prevalence, HIV infections averted, and incremental cost-effectiveness ratios of different HAART strategies were calculated. RESULTS: With no incremental HAART programs, HIV prevalence reached 64% among IDUs and 1.7% among non-IDUs after 20 years. If treatment were targeted to IDUs, over 40 000 infections would be prevented (75% among non-IDUs), adding 650 000 QALYs at a cost of USD 1501 per QALY gained. If treatment were targeted to non-IDUs, fewer than 10 000 infections would be prevented, adding 400 000 QALYs at a cost of USD 2572 per QALY gained. Untargeted strategies prevented the most infections, adding 950 000 QALYs at a cost of USD 1827 per QALY gained. Our results were sensitive to HIV transmission parameters. CONCLUSIONS: Expanded use of antiretroviral therapy in St. Petersburg, Russia would generate enormous population-wide health benefits and be economically efficient. Exclusively treating non-IDUs provided the least health benefit, and was the least economically efficient. Our findings highlight the urgency of initiating HAART for both IDUs and non-IDUs in Russia.     

Long-term cost effectiveness of early and sustained dual oral antiplatelet therapy with clopidogrel given for up to one year after percutaneous coronary intervention results: from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial

OBJECTIVES: This study sought to evaluate the long-term cost effectiveness of a clopidogrel loading strategy before percutaneous coronary intervention (PCI) followed by continued treatment for one year. BACKGROUND: The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized trial of 2,116 patients, showed the effectiveness of antiplatelet therapy with clopidogrel 300 mg before PCI and 75 mg daily for one year afterward compared with placebo load and placebo days 29 to 365 in reducing the combined risk of death, myocardial infarction, and stroke. All patients received clopidogrel on days 1 to 28 and aspirin on days 1 to 365. METHODS: All hospitalizations were assigned a diagnosis-related group. Associated costs were estimated three ways (including professional costs): 1) Medicare costs, 2) MEDSTAT costs, and 3) blend with Medicare for those age > or = 65 years and MEDSTAT for those age <65 years. Clopidogrel 75 mg cost 3.22 dollars. Life expectancy in trial survivors was estimated using external data. Confidence intervals were assessed by bootstrap. RESULTS: The primary composite end point occurred in 89 (8.45%) clopidogrel patients and in 122 (11.48%) placebo patients (relative risk reduction [RRR] 26.9%; 95% confidence interval [CI] 3.9% to 44.4%). The number of life-years gained (LYG) with clopidogrel was 0.1526 (95% CI 0.0263 to 0.2838) using Framingham data and 0.1920 (95% CI 0.054 to 0.337) using Saskatchewan data. Average total costs were 664 dollars higher for the clopidogrel arm (95% CI -461 dollars to 1,784 dollars). The incremental cost-effectiveness ratios (ICERs) based on Framingham data ranged from 3,685 dollars/LYG to 4,353 dollars/LYG, with over 97% of bootstrap-derived ICER estimates below 50,000 dollars/LYG. The ICERs based on Saskatchewan data were 2,929 dollars/LYG to 3,460 dollars/LYG, with over 98% of estimates below 50,000 dollars/LYG. CONCLUSIONS: Platelet inhibition with clopidogrel loading before PCI followed by therapy for one year is highly cost effective.     

Two decades of HIV infection in a cohort of haemophilic individuals: clinical outcomes and response to highly active antiretroviral therapy

OBJECTIVES: Many haemophilic individuals infected with HIV died before receiving antiretroviral therapy (ART). Most who remain alive are chronically infected with hepatitis C virus (HCV), which has implications for their prognosis and choice of ART. The clinical status of a cohort of HIV-positive haemophilic men is reported together with their response to highly active antiretroviral therapy (HAART). DESIGN: Longitudinal cohort study. SETTING: A comprehensive care haemophilia centre. PATIENTS: A group of 111 haemophilic men who seroconverted to HIV in the period 1979 to 1985. RESULTS: The cohort has been followed since 1979. By 30 April 1999, 57 of the 111 men had developed AIDS and 65 had died: Kaplan-Meier rates of 57.0% [95% confidence interval (CI) 46.9-67.0) and 65.1% (95% CI 52.7-77.4) by 19.5 years, respectively. AIDS rates have declined since 1997 but death rates have remained high, largely owing to deaths from non-HIV-related causes. Thirty-five patients remain alive and under follow-up at the clinic. The 28 men who had received ART had lower CD4 cell counts than the seven patients who had not received ART, but the two groups were otherwise similar. In total, 21 patients are known to have started HAART while under care at the centre. By 10-12 months after starting HAART, viral loads dropped by 2.06 log10 copies/ml and CD4 cell counts increased by 60 x 10(6) cells/l. In 10 out of 18 patients with viral loads initially > 400 copies/ml, a viral load below this level was attained; four had changed therapy at the time. CONCLUSIONS: While the decision to initiate HAART in haemophilic men should be made carefully because of the possible adverse events, our results suggest that a good response rate was achieved in this group of men.     

Highly active antiretroviral therapy associated with improved anemia among HIV-infected women

Anemia is common during human immunodeficiency virus (HIV) infection and is associated with increased mortality. We conducted a study to examine the impact of highly active antiretroviral therapy (HAART) on anemia in a multicenter cohort of HIV-positive women, the Human Immunodeficiency Virus Epidemiology Research (HER) Study. Among women receiving HAART (n = 188), non-HAART monotherapy or combination antiretroviral therapy (ART) (n = 111), or who had no reported treatment (n = 62), the prevalence of anemia (hemoglobin, <120 g/L) at baseline was 38.3, 36.9, and 43.6%, respectively (p = 0.58) and at 1-year follow-up was 26.1%, 36.9%, 45.2%, respectively (p = 0.01); mean hemoglobin at baseline was 125 +/- 16, 122 +/- 16, and 122 +/- 18 g/L, respectively (p = 0.29) and at 1-year follow-up was 128 +/- 14, 123 +/- 16, and 119 +/- 20 g/L, respectively (p < 0.0001). Adjusted linear regression models showed that HAART was associated with an increase of hemoglobin of 0.20 g/L per month (p = 0.007). After 1 year of treatment, HAART was associated with a 32% reduction in anemia among HIV-infected women (p = 0.01), whereas there was no significant change in the prevalence of anemia among those on non-HAART ART or those who had no reported treatment. HAART is associated with a large reduction in anemia among HIV-infected women.     

Determinants and causes of mortality in HIV-infected patients receiving antiretroviral therapy in Burkina Faso: a five-year retrospective cohort study

In this study, we investigated the causes of death and the factors associated with mortality in a cohort of patients receiving highly active antiretroviral therapy (HAART) in Burkina Faso, an African country with limited resources. This retrospective cohort study included patients aged 15 years and older who started HAART for the first time between January 2003 and December 2008 in 14 health districts. We used survival analyses, including the Kaplan-Meier method, to examine potential predictors of death and two Cox proportional hazard models to estimate hazard ratios for death, first from baseline covariates and then from time-dependent covariates. A total of 6641 patients initiated HAART during this period; of these, 5608 were included in the analysis. By the end of the study period, 4310 of those patients were still receiving HAART, 690 had died, 207 had been transferred and 401 were lost to follow-up. The median duration of follow-up was 23.2 months [interquartile range (IQR): 12.4-36.9], and the overall incidence of mortality was 6 per 100 person-years. The clinical stage, CD4 count, body mass index (BMI), haemoglobin level, HAART regimen, gender, age, profession and year of initiation were the primary risk factors associated with death. In the multivariate analysis, BMI, clinical stage, treatment regimen and CD4 count remained significantly associated with death. The most frequent causes of death were wasting syndrome, tuberculosis and anaemia. This result highlights the already advanced stage of immunodeficiency among patients in Burkina Faso when they start HAART. Testing patients for HIV and starting antiretroviral therapy earlier are necessary to further reduce the mortality of patients living with HIV. This study provides a solid evidence base with which future evaluations of HAART in Burkina Faso can be compared.     

Coverage of highly active antiretroviral therapy among postpartum women in Malawi

The expanding services of antiretroviral treatment (ART) in sub-Saharan Africa provide unique opportunities to reduce HIV/AIDS-related morbidity and mortality. In these settings, HIV prevalence among antenatal women remains high and treating eligible pregnant or breastfeeding women with antiretrovirals can substantially reduce transmission of HIV from the mother to her infant. However, identification of women eligible for treatment and ensuring access to ART services is challenging. In this analysis, we used data from a large clinical trial (the PEPI-Malawi study, 2004-09) to prevent mother-to-child transmission of HIV through extended antiretroviral prophylaxis of infants to examine barriers for wider coverage with highly active antiretroviral treatment (HAART) of postpartum women. Maternal HAART was not part of the original PEPI-Malawi clinical trial but became available through a government programme during the course of the study. Therefore, eligible women (CD4 cell count <250) who participated in the PEPI-Malawi trial were counselled and referred to the government ART clinics to initiate HAART. Of 3335 women who enrolled in the PEPI-Malawi study, 803 (24%) were eligible for HAART based on CD4 cell count. The proportion of women newly initiating HAART at the ART clinic remained low and constant (<20%) throughout the study period. However, the cumulative proportion of women receiving HAART increased substantially over time (29% in 2005 to 69% in 2009). Similarly, counselling and referral of eligible women substantially increased and became 100% during the last two years. There were no statistically significant differences in characteristics of eligible women who received or did not receive HAART postpartum. Despite limitations of not being able to obtain detailed data, the main barriers appeared to be related to the health-care system delivery of ART services. Issues of physical space, more personnel and better delivery need to be addressed to increase access to HAART in these settings.     

Hospitalization trends, costs, and risk factors in HIV-infected children on antiretroviral therapy

OBJECTIVE:: To assess hospitalization trends in HIV-infected children on antiretroviral therapy (ART) in Thailand, an important indicator of morbidity, ART effectiveness, and health service utilization. DESIGN:: Prospective observational cohort METHOD:: Children initiating ART in 1999-2009 were followed in 40 public hospitals. Hospitalization rate per 100 person-years were calculated from ART initiation to last follow-up/death. Costs to the healthcare provider were calculated using WHO inpatient estimates for Thailand. Zero-inflated Poisson models were used to examine risk factors for early (<12 months of ART) and late hospitalization (≥12 months) and frequency of admissions. RESULTS:: A total of 578 children initiated ART, median follow-up being 64 months [interquartile range (IQR) 43-82]; 211 (37%) children were hospitalized with 451 admissions. Hospitalization rates declined from 63 per 100 person-years at less than 6 months to approximately 10 per 100 person-years after 2 years of ART, and costs fell from $35 per patient-month to under $5, respectively. Age less than 2 years, US Centers of Disease Control and Prevention stage B/C, and stunting at ART initiation were associated with early hospitalization. Among those hospitalized, baseline CD4 cell percentage less than 5%, wasting, initiation on dual therapy, late calendar year, and female sex were associated with higher incidence of early admissions (P?<0.02). There were no predictors of late hospitalization, although previous hospitalization in less than 12 months of ART was associated with three times higher incidence of late admissions (P?相似文献   

Cost of medical care for HIV-infected patients within a regional population from 1997 to 2006

Objectives

To report on the cost of medical care for HIV‐infected patients stratified by CD4 cell count for a regional population over a 9‐year period, and to examine the effect of reporting costs of HIV care only or only in antiretroviral therapy (ART)‐experienced patients.

Methods

Retrospective costing analysis on all HIV‐infected patients within the Southern Alberta Cohort from April 1997 to April 2006. Costs for all drugs (ART/non‐ART), in‐patient (HIV/non‐HIV) and out‐patient care were obtained from primary sources. Costs were aggregated by patient's CD4 cell count and ART exposure and presented as mean cost per patient per month (PPPM) in 2006 Canadian dollars.

Results

The number of patients and annual costs increased by 74% and 69%, respectively. Overall mean PPPM costs increased slightly from $1082 in 1997/1998 to $1159 in 2005/2006. PPPM costs for patients with CD4 counts ≤75 cells/μL increased from $1595 to $2687 while costs for CD4 counts >500, 201–500 and 76–200 cells/μL remained relatively stable at $979, $1057 and $1294, respectively. In‐patient hospitalization costs account for most of the cost increases. Reporting costs using only ART‐experienced patients would overestimate total costs by 2–9%. Costs for only HIV care were 10–24% lower than total care costs.

Conclusions

Care costs have remained relatively stable for most HIV patients except those with CD4 counts ≤75 cells/μL. Expensive new antiretroviral drugs have had, at present, a minimal cost impact. Enhanced testing to achieve earlier diagnosis and initiation of highly active antiretroviral therapy could potentially reduce costs of late presentation and in‐patient care.     

Naively changing HAART

Background

Few UK studies have systematically investigated which antiretroviral therapy (ART) combinations HIV‐infected people are commenced on, when they start and reasons for stopping or changing their regimens.

Objective

To describe when HIV‐infected ART‐naive patients started first‐, second‐ or third‐line triple ART, classes of drugs prescribed and whether stopping ART was associated with virological, immunological or clinical indicators of treatment failure.

Design

A multicentre prospective open cohort study, employing the National Prospective Monitoring System on the use, cost and outcome of HIV service provision in UK hospitals‐HIV Health‐economics Collaboration (NPMS‐HHC).

Setting

Five hundred and eighty‐five ART‐naive patients seen in one London and two non‐London HIV clinics between 1 January 1998 and 31 December 1999.

Results

Of 4044 HIV‐infected individuals seen, 585 (15%) were ART naive. Median time interval (interquartile range, IQR) between HIV diagnosis and starting triple ART was 800 (63–2094) days. Median CD4 count when first diagnosed with HIV infection was 278 (IQR 127–481) cells/µL which dropped to 190 (IQR 86–297) cells/µL when starting triple ART. Of these 585 patients, 162 started second‐line and 46 third‐line ART during the study period. Of those patients who stopped ART, 51% did not have evidence of virological, immunological or clinical indicators of therapy failure.

Conclusions

Reasons for the delay between diagnosis of HIV infection and starting ART are varied. The large proportion of individuals who stopped ART for reasons other than virological, immunological or clinical indicators of therapy failure, are most likely due to drug‐associated toxicity. Both of these findings need to be elucidated in greater detail through prospective studies.

     

Retrospective analysis of suspending HAART in selected patients with controlled HIV replication

We sought to determine the consequences of stopping highly active antiretroviral therapy (HAART) in a group of 41 HIV-infected individuals with undetectable HIV viral loads and CD4+ counts greater than 500 cells per microliter for 6 months or more. Clinical and laboratory parameters were monitored, as was the time to HAART reinitiation. Three months after HAART interruption, the median CD4+ count declined by 162 cells per microliter and HIV viral load increased by 24,000 copies per milliliter. Over the next year, CD4+ counts continued to decrease by an average of 11 cells per microliter per 3-month intervals. In contrast, HIV viral loads remained stable over the same period. Five of 7 patients (71%) with elevated cholesterol levels and 6 of 13 patients (46%) with elevated triglyceride levels had these values normalize after stopping HAART. After a median of 21 months follow-up, 26 of 41 patients (63%) have restarted HAART. Patients with Centers for Disease Control (CDC) HIV/AIDS C classification were more likely to restart HAART than those with A or B classification (p = 0.008). Reasons for HAART restart included clinical events in 8 patients. Fifteen patients restarted HAART for immunologic reasons: CD4+ count less than 300 cells per microliter (n = 7); HIV viral load greater than 55,000 copies per milliliter (n = 3); or both (n = 5). Three patients restarted HAART because of personal preference. Within 4 months, all 26 patients who restarted HAART achieved HIV viral loads less than 50 copies per milliliter. Although patients were able to rapidly achieve nondetectable HIV viral loads after restarting HAART, the inability to foresee clinical events among 8 patients (20%) is disconcerting. We advise caution before HAART interruption, particularly for those patients with a preceding history of significant HIV-related complications.     

Adherence to highly active antiretroviral therapy impact on clinical and economic outcomes for Medicaid enrollees with human immunodeficiency virus and hepatitis C coinfection

We examined the impact of antiretroviral treatment adherence among hepatitis C (HCV) coinfected human immunodeficiency virus (HIV) patients on survival and clinical outcomes. We analyzed Medicaid claims data from 14 southern states from 2005 to 2007, comparing survival and clinical outcomes and cost of treatment for HIV and HCV coinfected patients (N = 4115) at different levels of adherence to antiretroviral therapy (ART). More than one in five patients (20.5%) showed less than 50% adherence to antiretroviral treatment, but there were no racial/ethnic or gender disparities. Significant survival benefit was demonstrated at each incremental level of adherence to ART (one-year mortality ranging from 3.5% in the highest adherence group to 26.0% in the lowest). Low-adherence patients also had higher rates of hospitalization and emergency department visits. Relative to patients with high (>95%) ART adherence, those with less than 25% treatment adherence had fourfold greater risk of death (adjusted odds ratio 4.22 [95% CI: 3.03, 5.87]). Nondrug Medicaid expenditures were lower for high-adherence patients, but cost of medications drove total Medicaid expenditures higher for high-adherence patients. Cost per quality-adjusted life year (QALY) saved (relative to the <25% low-adherence group) ranged from $21,874 for increasing adherence to 25–50% to $37,229 for increasing adherence to 75–95%. Adherence to ART for patients with HIV and HCV coinfection is associated with lower adverse clinical outcomes at a Medicaid cost per QALY commensurate with other well-accepted treatment and prevention strategies. Further research is needed to identify interventions which can best achieve optimal ART adherence at a population scale.