Early HIV diagnosis in infants will save lives

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Early infant HIV diagnosis in South Africa will save lives, extend life expectancy and be cost-effective, according to a modelling study.

The study was led by corresponding author, Dr Andrea Ciaranello, division of general internal medicine, Massachusetts General Hospital. Compared to no early infant diagnosis (EID), testing at either birth or 6 weeks of life reduced one-year mortality rates, led to a longer life expectancy and was cost-effective. Testing at both birth and 6 weeks had further benefits.

Dr Lynne M Mofenson, of the Elizabeth Glaser Paediatric AIDS Foundation, and the author of an editorial comment on the study praised it as “an elegant analysis…of the expected clinical impact and cost-effectiveness of different strategies of early infant diagnosis in South Africa.”

Globally, there are approximately 150,000 infant HIV infections each year. Without antiretroviral therapy (ART), mortality in infants with HIV reaches between 50 and 65% by the age of 2 years. Three-quarters of these deaths could be prevented with prompt ART, but this requires early infant diagnosis. The World Health Organisation therefore recommends that all HIV-exposed infants should be screened for infection using a nucleic acid amplification test (NAT) at the age of 6 weeks.

However, changes to this strategy have been proposed as some infants contract the infection in the womb and have a significant mortality risk before screening at 6 weeks of age. Testing twice, at birth and 6 weeks of age, has therefore been suggested as an enhanced strategy.

Using data from South Africa, investigators modelled the clinical benefits and cost-effectiveness of four early infant diagnosis strategies: no early infant diagnosis; testing once – birth; testing once – 6 weeks of age; and testing twice – birth and 6 weeks of age.

Model outcomes included short- and long-term survival, life expectancy and HIV-related healthcare costs. Outcomes for HIV-infected and HIV-negative infants were modelled separately. The investigators also calculated the incremental cost-effectiveness ratio (ICER) for each strategy compared to the next least alternative. Interventions with ICERs below 50% of South Africa’s per capita gross domestic product (GDP) – $3,250 – were considered cost effective. Further analysis took into account the impact of different levels of engagement with the HIV testing and care cascade on the clinical benefits and cost effectiveness of each testing strategy.

The model was based on a mother-to-child HIV transmission rate of 5%, with 2% of infections occurring in the womb, 1% at birth and 2% postpartum.
No early infant diagnosis would lead to a 35% one-year mortality rate among HIV-infected infants, who had an overall life expectancy of 21 years.

Survival was increased substantially with any early infant diagnosis strategy – assuming 100% testing, result return and linkage to care.

Testing at birth alone was associated with a 28% one-year mortality rate and an overall life expectancy of 24 years. The six-week alone testing strategy had a 25% one-year mortality rate and a project life expectancy of 26 years. Testing twice increased survival, with a 24% one-year mortality rate and a life expectancy of 27 years.

There was only a modest impact on survival, regardless of testing strategy, for the HIV-uninfected infants, with one-year survival rates of approximately 93% and a life expectancy of approximately 61 years.

No early infant diagnosis had lifetime costs of $1,430 per HIV-exposed infant. Testing at birth alone had lifetime costs of $1,670 for each HIV-exposed infant, increasing to $1,770 with once-only testing at 6 weeks. Testing twice was associated with a lifetime cost per HIV-exposed infant of $1,840.

In the cost-effectiveness analysis testing at birth dominated. The ICER for 6 weeks alone was $1,250/year life saved, 19% of South Africa’s per capita GDP. The ICER for testing twice versus 6 weeks only was $2900/year life saved, (45% of per capita GDP).

In sensitivity analyses, all testing strategies remained cost effective (compared to no testing) when most scenarios were modelled, only equalling over 50% of per capita GDP with very low levels of testing, testing accuracy, test return, linkage to care and ART uptake and effectiveness. In a further analysis, increasing linkage to care and ART uptake with testing at 6 weeks alone improved survival more than adding a second test at birth.

“We find that current EID recommendations to test once at 6 weeks alone markedly improve infant outcomes and are good value in South Africa compared to no EID,” conclude the investigators. “Testing twice, at birth and 6 weeks, will further improve outcomes and be cost-effective when uptake is high. If scale-up costs are comparable, policymakers should add birth testing after optimising 6-week EID programmes, alongside careful attention to retaining infants with negative birth test results in care.”

The author of the editorial emphasises that early infant diagnosis just the first step in improving outcomes among HIV-infected infants, writing “it requires ensuring linkage to an effective longitudinal care system with age-appropriate antiretroviral drugs and rapid initiation of therapy for HIV-infected infants (and their parents).”

Background: Early infant HIV diagnosis (EID) and antiretroviral therapy dramatically reduce mortality. EID is recommended at six weeks of age, but many infant infections are missed.
Design/Methods: We simulated four EID strategies for HIV-exposed infants in South Africa: no EID (diagnosis only after illness), testing once (birth alone; 6 weeks alone) and twice (birth and 6 weeks). We calculated incremental cost-effectiveness ratios (ICERs) using discounted costs and life expectancies for all HIV-exposed (infected and uninfected) infants.
Results: In the base case (guideline-concordant care), no EID produced a life expectancy of 21.1y (HIV-infected) and 61.1y (HIV-exposed); lifetime cost averaged $1,430/HIV-exposed infant. The birth and 6 weeks strategy maximized life expectancy (HIV-infected: 26.5y; HIV-exposed: 61.4y), costing $1,840/infant tested. The ICER of 6 weeks alone vs. no EID was $1,250/year of life saved (YLS, 19% of South Africa’s per-capita GDP); birth and 6 weeks vs. 6 weeks alone was $2,900/YLS (45% of GDP). Increasing result-return and linkage to ART with 6 weeks alone improved survival more than adding a second test.
Conclusions: EID at birth and 6 weeks improves outcomes and is cost-effective, compared to 6 weeks alone. If scale-up costs are comparable, programs should add birth testing after strengthening 6-week testing programs

Jordan A Francke, Martina Penazzato, Taige Hou, Elaine J Abrams, Rachel L MacLean, Landon Myer, Rochelle P Walensky, Valériane Leroy, Milton C Weinstein, Robert A Parker, Kenneth A Freedberg, Andrea Ciaranello

Aidsmap material
Journal of Infectious Diseases abstract
Journal of Infectious Diseases editorial

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