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

BACKGROUND: Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia. METHODS: Data on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider’s perspective using site- and country-level data and are reported in 2011 USD. RESULTS: Patients initiated ART at a median CD4 cell count of 145 cells/μL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95$194-$293), ranging from$184 (95% CI, $172-$195) to $304 (95$290-$319) depending on site. Patients retained in care one year after ART initiation 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. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site. CONCLUSIONS: Patients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were receiving fully guideline-concordant care. 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

The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa

BACKGROUND. Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. METHODOLOGY/PRINCIPAL FINDINGS. We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived =10 kilometers from the testing center (RR=1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR=1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR=1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. CONCLUSIONS/SIGNIFICANCE. Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, K23 AI068458); the Harvard University Center for AIDS Research (P30 AI42851); National Institutes of Health (K24 AR 02123); the Doris Duke Charitable Foundation (Clinical Scientist Development Award); the Harvard University Program on AID

Resource Utilization and Costs of Care prior to ART Initiation for Pediatric Patients in Zambia

Objective. We estimated time to initiation, outpatient resource use, and costs of outpatient care during the 6 months prior to ART initiation for HIV-infected pediatric patients in Zambia. Methods. We enrolled 1,102 children who initiated ART at <15 years of age between 2006 and 2011 at 5 study sites. Of these, 832 initiated ART ≤6 months after first presenting to care at the study sites. Data on time in care and resources utilized during the 6 months prior to ART initiation were extracted from patient medical records. Costs were estimated from the provider's perspective and are reported in 2011 USD. Results. For the patients who initiated ART ≤6 months after presenting to care, median age at presentation to care was 3.9 years; median CD4 percentage was 13%. Median time to ART initiation was 26 days. Patients made, on average, 2.38 clinic visits prior to ART initiation and received 0.81 CD4 tests, 0.74 full blood count tests, and 0.49 blood chemistry tests. The mean cost of pre-ART care was $20 per patient. Conclusions. Zambian pediatric patients initiating ART ≤6 months after presenting to care do so quickly, utilize fewer resources than mandated by national guidelines, and accrue low costs

Retention in Care and Outpatient Costs for Children Receiving Antiretroviral Therapy in Zambia: A Retrospective Cohort Analysis

BackgroundThere are few published estimates of the cost of pediatric antiretroviral therapy (ART) in Africa. Our objective was to estimate the outpatient cost of providing ART to children remaining in care at six public sector clinics in Zambia during the first three years after ART initiation, stratified by service delivery site and time on treatment.MethodsData on resource utilization (drugs, diagnostics, outpatient visits, fixed costs) and treatment outcomes (in care, died, lost to follow up) were extracted from medical records for 1,334 children at six sites who initiated ART at 50%) at four sites. At the two remaining sites, outpatient visits and fixed costs together accounted for >50% of outpatient costs. The distribution of costs is slightly skewed, with median costs 3% to 13% lower than average costs during the first year after ART initiation depending on site.ConclusionsOutpatient costs for children initiating ART in Zambia are low and comparable to reported outpatient costs for adults. Outpatient costs and retention in care vary widely by site, suggesting opportunities for efficiency gains. Taking advantage of such opportunities will help ensure that targets for pediatric treatment coverage can be met

Meeting human resources for health staffing goals by 2018: a quantitative analysis of policy options in Zambia

<p>Abstract</p> <p>Background</p> <p>The Ministry of Health (MOH) in Zambia is currently operating with fewer than half of the health workers required to deliver basic health services. The MOH has developed a human resources for health (HRH) strategic plan to address the crisis through improved training, hiring, and retention. However, the projected success of each strategy or combination of strategies is unclear.</p> <p>Methods</p> <p>We developed a model to forecast the size of the public sector health workforce in Zambia over the next ten years to identify a combination of interventions that would expand the workforce to meet staffing targets. The key forecasting variables are training enrolment, graduation rates, public sector entry rates for graduates, and attrition of workforce staff. We model, using Excel (Office, Microsoft; 2007), the effects of changes in these variables on the projected number of doctors, clinical officers, nurses and midwives in the public sector workforce in 2018.</p> <p>Results</p> <p>With no changes to current training, hiring, and attrition conditions, the total number of doctors, clinical officers, nurses, and midwives will increase from 44% to 59% of the minimum necessary staff by 2018. No combination of changes in staff retention, graduation rates, and public sector entry rates of graduates by 2010, without including training expansion, is sufficient to meet staffing targets by 2018 for any cadre except midwives. Training enrolment needs to increase by a factor of between three and thirteen for doctors, three and four for clinical officers, two and three for nurses, and one and two for midwives by 2010 to reach staffing targets by 2018. Necessary enrolment increases can be held to a minimum if the rates of retention, graduation, and public sector entry increase to 100% by 2010, but will need to increase if these rates remain at 2008 levels.</p> <p>Conclusions</p> <p>Meeting the minimum need for health workers in Zambia this decade will require an increase in health training school enrolment. Supplemental interventions targeting attrition, graduation and public sector entry rates can help close the gap. HRH modelling can help MOH policy makers determine the relative priority and level of investment needed to expand Zambia's workforce to target staffing levels.</p

Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections

Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic copy number variants (CNVs) with thoracic aortic aneurysms and dissections (TAAD). By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0×10−5, OR = 12.2). The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7). Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012) and to present with aortic dissections (P = 0.010) than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes

Behavioral economic implementation strategies to improve serious illness communication between clinicians and high-risk patients with cancer: protocol for a cluster randomized pragmatic trial

Background Serious illness conversations (SICs) are an evidence-based approach to eliciting patients’ values, goals, and care preferences that improve patient outcomes. However, most patients with cancer die without a documented SIC. Clinician-directed implementation strategies informed by behavioral economics (“nudges”) that identify high-risk patients have shown promise in increasing SIC documentation among clinicians. It is unknown whether patient-directed nudges that normalize and prime patients towards SIC completion—either alone or in combination with clinician nudges that additionally compare performance relative to peers—may improve on this approach. Our objective is to test the effect of clinician- and patient-directed nudges as implementation strategies for increasing SIC completion among patients with cancer. Methods We will conduct a 2 × 2 factorial, cluster randomized pragmatic trial to test the effect of nudges to clinicians, patients, or both, compared to usual care, on SIC completion. Participants will include 166 medical and gynecologic oncology clinicians practicing at ten sites within a large academic health system and their approximately 5500 patients at high risk of predicted 6-month mortality based on a validated machine-learning prognostic algorithm. Data will be obtained via the electronic medical record, clinician survey, and semi-structured interviews with clinicians and patients. The primary outcome will be time to SIC documentation among high-risk patients. Secondary outcomes will include time to SIC documentation among all patients (assessing spillover effects), palliative care referral among high-risk patients, and aggressive end-of-life care utilization (composite of chemotherapy within 14 days before death, hospitalization within 30 days before death, or admission to hospice within 3 days before death) among high-risk decedents. We will assess moderators of the effect of implementation strategies and conduct semi-structured interviews with a subset of clinicians and patients to assess contextual factors that shape the effectiveness of nudges with an eye towards health equity. Discussion This will be the first pragmatic trial to evaluate clinician- and patient-directed nudges to promote SIC completion for patients with cancer. We expect the study to yield insights into the effectiveness of clinician and patient nudges as implementation strategies to improve SIC rates, and to uncover multilevel contextual factors that drive response to these strategies. Trial registration ClinicalTrials.gov , NCT04867850 . Registered on April 30, 2021. Funding National Cancer Institute P50CA24469

The Cost-Effectiveness of Tuberculosis Preventive Therapy for HIV-Infected Individuals in Southern India: A Trial-Based Analysis

Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India.We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH).Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of$100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of$55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence.Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care