The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis

Abstract

Background

The specificity of nucleic acid amplification tests (NAATs) used for early infant diagnosis (EID) of HIV infection is <100%, leading some HIV-uninfected infants to be incorrectly identified as HIV-infected. The World Health Organization recommends that infants undergo a second NAAT to confirm any positive test result, but implementation is limited. Our objective was to determine the impact and cost-effectiveness of confirmatory HIV testing for EID programmes in South Africa.

Method and findings

Using the Cost-effectiveness of Preventing AIDS Complications (CEPAC)–Pediatric model, we simulated EID testing at age 6 weeks for HIV-exposed infants without and with confirmatory testing. We assumed a NAAT cost of US$25, NAAT specificity of 99.6%, NAAT sensitivity of 100% for infants infected in pregnancy or at least 4 weeks prior to testing, and a mother-to-child transmission (MTCT) rate at 12 months of 4.9%; we simulated guideline-concordant rates of testing uptake, result return, and antiretroviral therapy (ART) initiation (100%). After diagnosis, infants were linked to and retained in care for 10 years (false-positive) or lifelong (true-positive). All parameters were varied widely in sensitivity analyses. Outcomes included number of infants with false-positive diagnoses linked to ART per 1,000 ART initiations, life expectancy (LE, in years) and per-person lifetime HIV-related healthcare costs. Both without and with confirmatory testing, LE was 26.2 years for HIV-infected infants and 61.4 years for all HIV-exposed infants; clinical outcomes for truly infected infants did not differ by strategy. Without confirmatory testing, 128/1,000 ART initiations were false-positive diagnoses; with confirmatory testing, 1/1,000 ART initiations were false-positive diagnoses. Because confirmatory testing averted costly HIV care and ART in truly HIV-uninfected infants, it was cost-saving: total cost US$1,790/infant tested, compared to US$1,830/infant tested without confirmatory testing. Confirmatory testing remained cost-saving unless NAAT cost exceeded US$400 or the HIV-uninfected status of infants incorrectly identified as infected was ascertained and ART stopped within 3 months of starting. Limitations include uncertainty in the data used in the model, which we examined with sensitivity and uncertainty analyses. We also excluded clinical harms to HIV-uninfected infants incorrectly treated with ART after false-positive diagnosis (e.g., medication toxicities); including these outcomes would further increase the value of confirmatory testing.

Conclusions

Without confirmatory testing, in settings with MTCT rates similar to that of South Africa, more than 10% of infants who initiate ART may reflect false-positive diagnoses. Confirmatory testing prevents inappropriate HIV diagnosis, is cost-saving, and should be adopted in all EID programmes.

Abstract

Lorna Dunning examine the cost-effectiveness of confirmatory testing in early infant HIV diagnosis programmes in South Africa.

Author summary

Why was this study done?

• Paediatric HIV remains a substantial burden in many low-resource countries, with 170,000 infants infected with HIV in 2015. The World Health Organization (WHO) recommends virological testing of HIV-exposed infants by 6 weeks of life, with immediate referral of those who test positive for initiation of HIV care to reduce infant mortality associated with HIV.

• Despite reported specificities greater than 99%, virological assays still have the possibility for false-positive diagnoses. The use of confirmatory testing is therefore strongly recommended in early infant diagnosis (EID) programmes.

• A recent policy survey by WHO demonstrated that implementation of confirmatory testing in EID programmes is limited, with 38% (8/21) of high-burden countries not including confirmatory testing for infants in their guidelines.

• Cost is often cited as a key barrier; many low-resource countries struggle to implement EID programmes due to the high costs of virological tests.

• Our study was designed to estimate the clinical and economic value of confirmatory testing in EID programmes.

What did the researchers do and find?

• We used a computer simulation model of paediatric HIV infection, diagnosis, and treatment to examine the clinical and economic outcomes of EID programmes without and with confirmatory testing in South Africa.

• We found there was no clinical difference in the life expectancy or 1-year survival of HIV-infected infants between the 2 strategies, but without confirmatory testing, in settings with a mother-to-child transmission (MTCT) rate similar to that of South Africa, over 10% of infants initiating antiretroviral therapy (ART) would do so inappropriately as a result of a false-positive diagnosis.

• Confirmatory testing averted costly HIV care and ART in truly HIV-uninfected infants, leading the confirmatory testing strategy to be cost-saving compared to without confirmatory testing in all reasonable scenarios.

• ART should be initiated after the first positive test result; when ART was not initiated until the return of the confirmatory result, mortality during the delay to ART initiation substantially reduced survival for HIV-infected infants.

What do these findings mean?

• Use of confirmatory testing in EID programmes, with ART initiation after the first positive result, substantially reduces the proportion of infants incorrectly diagnosed as HIV-infected and initiated on ART.

• Confirmatory testing is cost-saving under a wide range of scenarios.

• Confirmatory testing should be implemented in settings using virological assays for EID.