Elsevier

The Lancet HIV

Volume 6, Issue 3, March 2019, Pages e182-e190
The Lancet HIV

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

https://doi.org/10.1016/S2352-3018(18)30328-XGet rights and content

Summary

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.

Introduction

Each year, nearly 1·4 million children are born to HIV-infected mothers worldwide.1 Although 76% of pregnant women living with HIV now have access to antiretroviral therapy (ART) to prevent transmission to their infants, 160 000 children acquired HIV in 2016.1, 2 Without treatment, half of all children born with HIV die before age 2 years.3 However, only 43% of children with HIV received ART in 2016, falling short of UNICEF's global treatment targets.1 One of the greatest challenges in the management of paediatric HIV is diagnosis in early infancy. Although WHO recommends early infant HIV diagnosis testing at age 6 weeks for all HIV-exposed infants, less than 50% of these infants undergo such testing.4 A primary reason for this gap is that virological assays (ie, PCR-based assays) are needed to diagnose HIV in infants, and this advanced technology is often available only at central laboratories. The logistic difficulties of transporting samples to these laboratories and returning results to health facilities often leave caregivers waiting several months for the results of early infant diagnosis tests.5 Nearly half of infants tested never receive their results, and only 50–80% of those who test positive and receive results are eventually linked to care and ART.6

New point-of-care (POC) early infant HIV testing technologies are now available.5 If strategically integrated into national early infant diagnosis networks, these POC assays could both increase the number of HIV-exposed infants who are diagnosed and substantially reduce waiting times for results and time to initiation of ART, thereby decreasing infant mortality.5 POC assays are simpler and faster than laboratory-based assays, and do not require extensive training or complex infrastructure. However, the clinical effect and cost-effectiveness of these novel POC assays for early infant HIV diagnosis are largely unknown. An early infant HIV diagnosis initiative, launched by Unitaid and the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF), has expanded access to POC testing in nine African countries.7 We used a validated computer model of paediatric HIV disease, populated with programme assessment data from Zimbabwe, to examine the clinical benefits and cost-effectiveness of POC assays for early infant HIV diagnosis in Zimbabwe.

Research in context

Evidence before this study

Although WHO recommends HIV testing at age 6 weeks for all HIV-exposed infants, less than 50% of these infants worldwide have access to early infant HIV testing. New point-of-care (POC) assays for early infant HIV diagnosis are costlier than conventional total nucleic acid assays, but might increase access to diagnostic results, shorten time to return of results, and expedite initiation of antiretroviral therapy. Although trials and implementation studies have shown operational improvements in, and clinical benefits of, POC testing, the cost-effectiveness of these novel assays compared with conventional assays remains largely unknown. We searched PubMed by combining the search terms “point-of-care” and “early infant HIV diagnosis” with health economic terms (“cost-effectiveness”, “cost benefit”, and “ICER”) for studies published in English from inception up to Sept 25, 2018. We did not identify any studies in which the cost-effectiveness of POC and conventional early infant HIV testing were compared.

Added value of this study

We report the first cost-effectiveness modelling study informed by real-world data from a large-scale implementation initiative of POC early infant HIV diagnosis in Zimbabwe. We include testing costs from the Global Fund to Fight AIDS, Tuberculosis and Malaria to reflect real-time price-breakpoint negotiations and resource-utilisation data for early infant HIV testing from Unitaid and the Elizabeth Glaser Pediatric AIDS Foundation. We present novel outcomes, including projected survival over time, life expectancy, lifetime per-person costs, and cost-effectiveness, for POC testing for early infant HIV diagnosis.

Implications of all the available evidence

Incorporation of POC assays into early infant HIV diagnosis programmes at age 6 weeks in Zimbabwe will improve survival, extend life expectancy, and be cost-effective compared with conventional early infant HIV diagnosis. Results were robust across a wide range of sensitivity analyses, suggesting that they might be largely generalisable to other sub-Saharan African countries. Policy makers should incorporate POC assays into early infant HIV diagnosis programmes to optimise outcomes along the care cascade and thereby improve clinical outcomes for infants.

Section snippets

Study design and overview

We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)—Pediatric model to assess the clinical effects, costs, and cost-effectiveness of integration of POC assays into early infant HIV diagnosis programmes in Zimbabwe.8, 9, 10, 11 We modelled a population of infants born to HIV-infected mothers presenting to early infant HIV testing at age 6 weeks, and simulated two testing strategies for early infant HIV diagnosis: conventional assays and POC assays. Model outcomes included

Results

In the base-case analysis, we projected a total mother-to-child transmission risk of 5·2% for the entire HIV-exposed cohort (1·4% of infants acquired HIV in utero, 1·0% acquired HIV in the intrapartum period, and 2·8% acquired HIV post partum). Thus, 94·8% of HIV-exposed infants were not infected. The clinical effect of POC testing for the entire HIV-exposed cohort was small, with the proportion of infants surviving to 1 year increasing from 93·1% with conventional testing to 93·4% with POC

Discussion

In this model-based analysis, incorporation of POC assays into early infant diagnosis programmes at age 6 weeks in Zimbabwe substantially improved survival and life expectancy among HIV-infected infants, and was cost-effective for all HIV-exposed infants, compared with conventional testing. Our work had four main findings. First, the operational characteristics of POC testing—ie, improved time to return of results, increased likelihood of return of results, and increased initiation of

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