Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study

Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART) [1, 2]. The Government of Zambia revised national HIV treatment guidelines for adults in 2007 to recommend the use of tenofovir as a standard component of first-line ART [3]. Guidelines were revised again in 2010 to raise the CD4 cell count threshold for ART eligibility from 200 cells/μL to 350 cells/μL and again in 2013 to remove any CD4 cell count threshold for ART eligibility for pregnant women [4, 5]. Each of these changes substantially increased either the number of patients eligible for treatment or the cost of the drugs that comprise the treatment.

As treatment scale up continues, and as the Government of Zambia considers further guidelines changes that could expand ART eligibility even more or affect the quality of care for patients already on ART, information about the actual care provided to patients after initiating ART in Zambia can help guide decision making. Published papers have reported on the positive clinical and programmatic outcomes for patients initiating ART in Zambia [6, 7] and on the costs of providing ART in Zambia [8, 9], but no published papers have described both the actual care provided by the public sector clinics and hospitals that serve the vast majority of patients and the associated costs at the patient level. Our objective was to estimate retention in care, the quantity of resources utilized, and costs for adults initiating treatment under routine clinical conditions in Zambia.

The Government of Zambia revised national HIV treatment guidelines in 2007 to recommend the use of tenofovir as a standard component of first-line ART and in 2010 and 2013 to expand eligibility criteria for patients not yet on ART [3‐5]. As the Government of Zambia considers new guidelines changes, with potentially large implications for program planning and budgets, information on the actual care provided under previous guidelines can help guide decision making. We used primary, patient-level data to estimate retention in care, the quantity of resources utilized, and the costs of providing ART to adults in routine clinical practice in Zambia after adoption of the 2007 national guidelines.

Patients initiated ART at a median CD4 cell count of 145 cells/μL; 59% initiated on a tenofovir-containing regimen. One year after ART initiation, 75% of patients were retained in care. Patients retained in care received, on average, 11.4 months’ worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. The average cost for all patients over the first year after ART initiation was $198 (95% CI, $157-$239) while the average cost per patient retained in care one year after ART initiation was $243 (95% CI, $194-$293). Both the average quantity of resources utilized and unit costs varied widely by site, resulting in average costs per patient retained in care ranging from $184 (95% CI, $172-$195) at site 1 to $304 (95% CI, $290-$319) at site 5.

Our findings have several implications for program planning. First, as has been widely reported throughout Africa, Zambian patients are initiating ART late in the course of disease progression [16]. The median CD4 cell count at initiation for patients in our study, 145 cells/μL, was considerably lower than the 200 cells/μL threshold for ART eligibility in place at the time when these patients initiated ART [3]. This suggests that many patients may have reported to care long after meeting the eligibility criteria for ART initiation. Future guidelines changes that increase the CD4 threshold for ART eligibility, and expand eligibility to a larger proportion of the HIV-infected population, may have a smaller impact than anticipated, both in terms of increased health benefits and increased program costs, if patients are not effectively identified and linked to care soon after meeting eligibility criteria.

Second, a large proportion of patients (25%) are no longer in care within one year of initiating ART and attrition continues, at a slower rate, through three years after initiating ART. The average cost per patient in our sample for the first year on ART was $198. If we were to estimate the average cost to produce a patient retained in care one year after initiating ART, calculated as the sum of all costs for all patients divided by just the number of patients remaining in care, it would be $265. If all patients remained in care, we would expect an average cost per patient of $243, greater than the average cost per patient in the study of $198, but less than the cost to produce a patient remaining in care of $265.

Third, actual resource utilization varied considerably from what would be expected if patients were receiving fully guideline-concordant care. At the time of this study, guidelines recommended initiation on a regimen containing tenofovir, emtricitabine, and either efavirenz or nevirapine. Only 59% of patients in our sample initiated ART on a tenofovir-containing regimen while the remaining 41% of patients initiated ART on regimens containing zidovudine, abacavir, or stavudine. Patients in our sample initiated ART between July 2007 and October 2008, soon after tenofovir became the recommended first-line ART regimen in Zambia. It is not known whether study sites were still in the process of adopting tenofovir at the time of this study or if a similar mix of regimens would be seen among patients initiating ART at the same sites today. Nevertheless, these deviations from expected, guideline-concordant utilization months after guidelines were changed are notable.

Regardless of ART regimen at initiation, patients retained in care one year after initiating ART received, on average, fewer than the 12 months’ worth of ARV drugs required to ensure uninterrupted treatment. These patients also received only 1.5 CD4 tests, 1.3 blood chemistry tests, and 1.4 full blood count tests during their first year on ART. Guidelines recommend two CD4 tests, at least two blood chemistry tests, and at least two hemoglobin and white blood cell count tests, components of a full blood count test, during the first year after ART initiation [3]. While patients utilized fewer drugs and laboratory tests than they would have under fully guideline-concordant care, they had more frequent clinical consultations than recommended by guidelines. Patients retained in care had an average of 6.5 visits with a doctor or clinical officer and 9.5 visits with a pharmacist during their first year on ART, compared to the five visits recommended in the guidelines [3]. All of these examples suggest that it may not be appropriate to assume that guidelines and practice will be identical for the purposes of program planning and budgeting.

The proportion of patients retained in care one year after ART initiation in our study, 75%, is comparable to other published estimates of retention in care during the first year on ART [16]. Our estimated cost of $243 per patient retained in care one year after ART initiation is lower than, but still comparable to, previously published estimates of the cost per patient-year of ART in Zambia. Tagar et al. estimated an average cost of $278 per patient-year of ART (in 2010–2011) for a 30-site sample by estimating total facility-level costs at each site during the study period and dividing by an estimated number of patient-years in care at each site during the same period [17]. Bratt et al. estimated a cost per patient-year of ART ranging from $278 to $523 (in 2008 US dollars) by estimating unit costs from a 12-site sample and applying the unit costs to a set of resources that patients would be expected to utilize during their first year on ART under idealized clinical care conditions [9]. Marseille et al. estimated a cost of $428 per patient-year of ART in on-site costs (in 2010 US dollars) for the average facility in their 45-site sample by applying unit costs to a mix of site- and patient-level data on resource utilization [8]. The cost per patient-year of ART was $638 when off-site costs were included. Our study builds on these previous cost estimates by: (1) providing insight into the actual quantity of resources utilized and services received per patient at the level of the treatment site, and (2) differentiating between patients retained in care and those not retained.

Our study has several limitations. First, results are from six sites so we cannot attribute variation in costs of care between sites to specific site-level characteristics. These sites were purposively selected to capture variation in location and size. While results from these sites provide insight into standard types of treatment sites in Zambia, they are not necessarily representative of the ART treatment program in Zambia as a whole. Second, because patients were only classified as lost to follow up if they were ≥3 months late for their last scheduled consultation or medication pickup at the study endpoint, we likely underestimate true attrition during the study follow up period. Third, patient outcomes in this analysis are limited to what could be ascertained from a retrospective review of medical records. For patients no longer attending the study clinic, we could not always distinguish between those who had transferred to another clinic, died, or been lost to follow up due to incomplete records. Third, we excluded resource utilization and costs associated with inpatient care and outpatient care received prior to ART initiation. We also excluded costs incurred by the patient and costs for program management above the facility level. Cost estimates from Marseille et al., who found that only $428 of the $638 in total costs per patient-year of treatment were incurred on site, suggest that this exclusion of costs above the facility level may lead to a significant underestimate of the total cost of providing ART at the treatment sites in our study sample. Finally, results reflect retention in care, resource utilization, and costs for patients who initiated ART in 2007 and 2008, after the adoption of tenofovir as a standard component of first-line ART in 2007 but prior to the adoption of new HIV treatment guidelines in 2010 that increased the CD4 threshold for ART eligibility from 200 cells/μL to 350 cells/μL and the announcement in 2013 that Zambia would provide life-long ART to all pregnant women regardless of CD4 cell count [4, 5]. Both changes may lead to a higher median CD4 cell count at initiation which could, in turn, result in changes in retention in care, resource utilization, and costs.

In summary, adult patients in Zambia initiate ART late in the course of disease progression and a large proportion drop out of care within one year. Unit costs for each resource and the average quantity of resources utilized vary widely by treatment site, as do the resulting average costs of care, suggesting opportunities for efficiency gains. Overall, patients utilize a different mix of resources under routine clinical conditions than if they were receiving fully guideline-concordant care. The differences between guidelines and practice highlight the importance of looking at what is actually happening, and not just what is expected to happen, to ensure effective program planning and accurate budgeting. Improving retention in care and guideline concordance, including increasing the use of tenofovir in first-line ART regimens, may lead to increases in overall treatment costs.