Cost-effectiveness of community-based household tuberculosis contact management for children in Cameroon and Uganda: a modelling analysis of a cluster-randomised trial.

BACKGROUND: WHO recommends household contact management (HCM) including contact screening and tuberculosis-preventive treatment (TPT) for eligible children. The CONTACT trial found increased TPT initiation and completion rates when community health workers were used for HCM in Cameroon and Uganda. METHODS: We did a cost-utility analysis of the CONTACT trial using a health-system perspective to estimate the health impact, health-system costs, and cost-effectiveness of community-based versus facility-based HCM models of care. A decision-analytical modelling approach was used to evaluate the cost-effectiveness of the intervention compared with the standard of care using trial data on cascade of care, intervention effects, and resource use. Health outcomes were based on modelled progression to tuberculosis, mortality, and discounted disability-adjusted life-years (DALYs) averted. Health-care resource use, outcomes, costs (2021 US$), and cost-effectiveness are presented. FINDINGS: For every 1000 index patients diagnosed with tuberculosis, the intervention increased the number of TPT courses by 1110 (95% uncertainty interval 894 to 1227) in Cameroon and by 1078 (796 to 1220) in Uganda compared with the control model. The intervention prevented 15 (-3 to 49) tuberculosis deaths in Cameroon and 10 (-20 to 33) in Uganda. The incremental cost-effectiveness ratio was $620 per DALY averted in Cameroon and $970 per DALY averted in Uganda. INTERPRETATION: Community-based HCM approaches can substantially reduce child tuberculosis deaths and in our case would be considered cost-effective at willingness-to-pay thresholds of $1000 per DALY averted. Their impact and cost-effectiveness are likely to be greatest where baseline HCM coverage is lowest. FUNDING: Unitaid and UK Medical Research Council.

Cost-effectiveness analysis of interventions to improve diagnosis and preventive therapy for paediatric tuberculosis in 9 sub-Saharan African countries: A modelling study.

BACKGROUND: Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention. METHODS AND FINDINGS: We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded. CONCLUSIONS: In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context. TRIAL REGISTRATION: This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).

HIV community index testing reaches proportionally more males than facility-based testing and is cost-effective: A study from Gaza province, Mozambique.

BACKGROUND: In Mozambique, 38.7% of women and 60.4% of men ages 15-59 years old living with HIV do not know their HIV status. A pilot home-based HIV counseling and testing program based on index cases in the community was implemented in eight districts in Gaza province (Mozambique). The pilot targeted the sexual partners, biological children under 14 years old living in the same household, and parents (for pediatric cases) of people living with HIV. The study aimed to estimate the cost-efficiency and effectiveness of community index testing and compare the HIV testing outputs with facility-based testing. METHODS: Community index testing costs included the following categories: human resources, HIV rapid tests, travel and transportation for supervision and home visits, training, supplies and consumables, and review and coordination meetings. Costs were estimated from a health systems perspective using a micro-costing approach. All project costs were incurred between October 2017 and September 2018 and converted to U.S. dollars ($) using the prevailing exchange rate. We estimated the cost per individual tested, per new HIV diagnosis, and per infection averted. RESULTS: A total of 91,411 individuals were tested for HIV through community index testing, of which 7,011 were newly diagnosed with HIV. Human resources (52%), purchase of HIV rapid tests (28%) and supplies (8%) were the major cost drivers. The cost per individual tested was $5.82, per new HIV diagnosis was $65.32, and per infection averted per year was $1,813. Furthermore, the community index testing approach proportionally tested more males (53%) than facility-based testing (27%). CONCLUSION: These data suggest that expansion of the community index case approach may be an effective and efficient strategy to increase the identification of previously undiagnosed HIV-positive individuals, particularly males.

Strengthening Existing Laboratory-Based Systems vs. Investing in Point-of-Care Assays for Early Infant Diagnosis of HIV: A Model-Based Cost-Effectiveness Analysis.

BACKGROUND: To improve early infant HIV diagnosis (EID) programs, options include replacing laboratory-based tests with point-of-care (POC) assays or investing in strengthened systems for sample transport and result return. SETTING: We used the CEPAC-Pediatric model to examine clinical benefits and costs of 3 EID strategies in Zimbabwe for infants 6 weeks of age. METHODS: We examined (1) laboratory-based EID (LAB), (2) strengthened laboratory-based EID (S-LAB), and (3) POC EID (POC). LAB/S-LAB and POC assays differed in sensitivity (LAB/S-LAB 100%, POC 96.9%) and specificity (LAB/S-LAB 99.6%, POC 99.9%). LAB/S-LAB/POC algorithms also differed in: probability of result return (79%/91%/98%), time until result return (61/53/1 days), probability of initiating antiretroviral therapy (ART) after positive result (52%/71%/86%), and total cost/test ($18.10/$30.47/$30.71). We projected life expectancy (LE) and average lifetime per-person cost for all HIV-exposed infants. We calculated incremental cost-effectiveness ratios (ICERs) from discounted (3%/year) LE and costs in $/year-of-life saved (YLS), defining cost effective as an ICER <$580/YLS (reflecting programs providing 2 vs. 1 ART regimens). In sensitivity analyses, we varied differences between S-LAB and POC in result return probability, result return time, ART initiation probability, and cost. RESULTS: For infants who acquired HIV, LAB/S-LAB/POC led to projected one-year survival of 67.3%/69.9%/75.6% and undiscounted LE of 21.74/22.71/24.49 years. For all HIV-exposed infants, undiscounted LE was 63.35/63.38/63.43 years, at discounted lifetime costs of $200/220/240 per infant. In cost-effectiveness analysis, S-LAB was an inefficient use of resources; the ICER of POC vs. LAB was $830/YLS. CONCLUSIONS: Current EID programs will attain greater benefit from investing in POC EID rather than strengthening laboratory-based systems.

Estimating the Cost of Point-of-Care Early Infant Diagnosis in a Program Setting: A Case Study Using Abbott m-PIMA and Cepheid GeneXpert IV in Zimbabwe.

BACKGROUND: Point-of-care early infant diagnosis (POC EID) increases access to HIV test results and shortens time to result-return and antiretroviral therapy initiation, as compared to central laboratory-based EID. However, to scale-up POC EID, governments need more information about programmatic costs. METHODS: We evaluated POC EID costs from a health systems perspective. Our primary analysis assessed the Abbott m-PIMA and 2 versions of the Cepheid GeneXpert IV platforms-with a solar battery or gel battery-used in Zimbabwe, with instrument purchase. We also included the following 2 scenarios with zero upfront equipment purchase: (1) m-PIMA using a reagent rental model, with an all-inclusive price when the buyer commits to an average testing volume, and (2) GeneXpert IV, reflecting contexts where GeneXpert is already in place for tuberculosis diagnosis or HIV viral load monitoring. We collected data from project expenditures, observations of health workers, and from government salary scales. We calculated cost per EID test based on number of EID tests performed on each machine per day. RESULTS: The cost per successfully completed test was $44.55 for m-PIMA with platform purchase and $25.89 for m-PIMA reagent rental. Costs for GeneXpert IV with platform purchase were $25.70 using a solar battery, $25.29 using a gel battery, and $23.85 under a scenario assuming no equipment costs. In our primary analyses, materials costs comprised 73%-74% total costs, equipment 14%-20%, labor 5%-8%, training 1%, facility upgrades 1%, and monitoring 1%. CONCLUSIONS: As countries consider scaling up POC EID, these data are important for budgeting and planning.

Front-Line Human Resource Time-Use for Early Infant HIV Diagnosis: A Comparative Time-Motion Study at Centralized and Point-of-Care Health Facilities in Zimbabwe.

BACKGROUND: Point-of-care (POC) assays for early infant diagnosis of HIV (EID) increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy when compared with laboratory-based assays. However, there is a significant gap in our understanding of its human resource impact at the facility level. This study evaluates front-line health workers' (HWs') time associated with EID. SETTING: Using time-motion methodology, we collected time-use data on EID tasks performed by HWs at 3 EID facility types in Zimbabwe-5 POC hubs, 9 POC spokes, and 11 facilities that used centralized laboratories. METHODS: Data collectors observed 30 EID processes and 30 HWs' provided self-reported time. Comparisons of mean differences of HWs' time-use between centralized and POC EID were performed with a 2-sample t test with unequal variances. RESULTS: Observed average total labor time per EID test at POC facilities was 28 minutes, 22 seconds [95% confidence interval (CI): 22:51 to 35:48], which was equivalent to the average preresult time at facilities using centralized EID. HWs performed other tasks while the machine processed samples. Observed average preresult time (counseling to sample preparation) was 18 minutes, 6 Supported by seconds (95% CI: 13:00 to 23:42) for POC compared with 27 minutes, 48 seconds (95% CI: 23:48 to 32:50) for facilities using centralized laboratories. The mean difference of 9 minutes, 42 seconds (95% CI: 03:04 to 16:18) was statistically significant. The differences in self-reported average total labor time per EID test between HWs at facilities using centralized laboratories or POC were not statistically significant. CONCLUSION: Use of POC assays did not incur additional human resource time compared with sending dried blood spots to a centralized laboratory for EID.

Clinical effect and cost-effectiveness of incorporation of point-of-care assays into early infant HIV diagnosis programmes in Zimbabwe: a modelling study.

BACKGROUND: New point-of-care (POC) assays for early infant HIV diagnosis are costlier than conventional total nucleic acid assays, but could increase access to testing, shorten time to results, and expedite initiation of antiretroviral therapy. We aimed to assess the clinical benefits and cost-effectiveness of incorporating these POC assays into early infant diagnosis programmes in Zimbabwe. METHODS: We used the Cost Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to examine the clinical benefits, costs, and cost-effectiveness of replacing conventional assays for early infant HIV diagnosis with POC assays at age 6 weeks in Zimbabwe. We simulated two strategies for early infant HIV diagnosis: conventional and POC. Modelled assays differed in sensitivity; specificity; time to, and probability of, return of results; and cost. Model outcomes included survival, life expectancy, and mean lifetime per-person treatment cost, which were reported separately for all HIV-exposed infants and all infants with HIV. We calculated incremental cost-effectiveness ratios with discounted (3% per year) costs and life expectancy from a health-care system perspective for all HIV-exposed infants. We judged incremental cost-effectiveness ratios of $1010 (Zimbabwe's annual gross domestic product per person) or less per year of life saved to be cost-effective. FINDINGS: When conventional assays were used for early infant diagnosis, projected undiscounted life expectancy was 22·7 years for infants with HIV and 62·5 years for all HIV-exposed infants, at a cost of $610 per HIV-exposed infant. Use of POC assays for early infant HIV diagnosis improved projected undiscounted life expectancy to 25·5 years among infants with HIV and 62·6 years among HIV-exposed infants at a cost of $690 per HIV-exposed infant. At age 12 weeks, survival among all infants with HIV was 76·1% with the conventional testing strategy and 83·5% with the POC testing strategy. The incremental cost-effectiveness ratio of POC assays versus conventional assays for early infant diagnosis was $680 per year of life saved. When conventional assay characteristics remained constant, this ratio remained under the cost-effectiveness threshold as long as the specificity and sensitivity of the POC assay were greater than 92% and 65%, respectively. Our results were robust to plausible variations in POC assay cost, the probability of ART initiation, and probability of return of the results of POC testing. INTERPRETATION: Compared with conventional assays, POC assays for early infant HIV diagnosis in Zimbabwe will improve survival, extend life expectancy, and be cost-effective for HIV-exposed infants. FUNDING: Elizabeth Glaser Pediatric AIDS Foundation, US National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Unitaid.