Diagnostic performance, implementation fidelity, and costs of the World Health Organization three-test HIV testing strategy in Malawi: a national retrospective evaluation
- 1Directorate of HIV, STIs and Viral Hepatitis, Ministry of Health, Lilongwe, Malawi
Abstract
BackgroundIn 2019, WHO recommended three consecutive reactive serological test results for HIV diagnosis to reduce false-positive diagnoses. Malawi changed from a two-test to a three-test strategy in 2022 as HIV test positivity declined. We assessed diagnostic performance, implementation fidelity, and costs.
MethodsWe analysed national HIV testing data from Nov 1, 2022, to Oct 31, 2025. Using observed three-test classifications as the reference standard, we reconstructed classifications under the two-test strategy. We estimated positive predictive value (PPV), implementation fidelity, potential false-positive diagnoses prevented, incremental costs, and time to offset testing costs through avoided antiretroviral therapy expenditure.
ResultsAmong 9,885,599 encounters eligible for implementation-fidelity analysis, 99.98% followed a valid three-test pathway. The diagnostic-performance analysis included 9,862,908 encounters, of which 171,351 (1.7%) were classified HIV-positive and 9,138 (0.09%) were inconclusive. Under the two-test strategy, 1,209 inconclusive encounters with a T1+/T2+/T3- sequence would have been classified as HIV-positive. Retesting and reference-laboratory data indicated that 82.5% of these would subsequently be classified as HIV-negative, corresponding to 997 false-positive diagnoses prevented (10.3 per 100 000 three-test non-positive encounters; 95% CI 9.7-10.9). Retesting within 1-2 weeks was associated with the highest odds of potential false-positive classification (adjusted OR 39.37, 95% CrI 30.63-50.61). The incremental cost was US$471 per false-positive diagnosis averted and was offset within 7.30 years.
ConclusionsMalawis transition to a three-test HIV testing strategy prevented false-positive diagnoses and unnecessary antiretroviral therapy at modest cost, supporting broader adoption of WHO guidance in similar settings.
FundingGates Foundation.
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BibTeX
@misc{chimpandule2026diagnostic,
title = {{Diagnostic performance, implementation fidelity, and costs of the World Health Organization three-test HIV testing strategy in Malawi: a national retrospective evaluation}},
author = {T. Chimpandule and H. Tweya and L. Goeke and T. Masina and S. Macheso and N. Low and A. Jahn and J. W. W. Imai-Eaton},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.30.26361753},
url = {https://www.medrxiv.org/content/10.64898/2026.08.30.26361753v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Diagnostic performance, implementation fidelity, and costs of the World Health Organization three-test HIV testing strategy in Malawi: a national retrospective evaluation
AU - T. Chimpandule
AU - H. Tweya
AU - L. Goeke
AU - T. Masina
AU - S. Macheso
AU - N. Low
AU - A. Jahn
AU - J. W. W. Imai-Eaton
PY - 2026
DA - 2026/08/30
PB - medRxiv
DO - 10.64898/2026.08.30.26361753
UR - https://www.medrxiv.org/content/10.64898/2026.08.30.26361753v1
AB - BackgroundIn 2019, WHO recommended three consecutive reactive serological test results for HIV diagnosis to reduce false-positive diagnoses. Malawi changed from a two-test to a three-test strategy in 2022 as HIV test positivity declined. We assessed diagnostic performance, implementation fidelity, and costs. MethodsWe analysed national HIV testing data from Nov 1, 2022, to Oct 31, 2025. Using observed three-test classifications as the reference standard, we reconstructed classifications under the two-test strategy. We estimated positive predictive value (PPV), implementation fidelity, potential false-positive diagnoses prevented, incremental costs, and time to offset testing costs through avoided antiretroviral therapy expenditure. ResultsAmong 9,885,599 encounters eligible for implementation-fidelity analysis, 99.98% followed a valid three-test pathway. The diagnostic-performance analysis included 9,862,908 encounters, of which 171,351 (1.7%) were classified HIV-positive and 9,138 (0.09%) were inconclusive. Under the two-test strategy, 1,209 inconclusive encounters with a T1+/T2+/T3- sequence would have been classified as HIV-positive. Retesting and reference-laboratory data indicated that 82.5% of these would subsequently be classified as HIV-negative, corresponding to 997 false-positive diagnoses prevented (10.3 per 100 000 three-test non-positive encounters; 95% CI 9.7-10.9). Retesting within 1-2 weeks was associated with the highest odds of potential false-positive classification (adjusted OR 39.37, 95% CrI 30.63-50.61). The incremental cost was US$471 per false-positive diagnosis averted and was offset within 7.30 years. ConclusionsMalawis transition to a three-test HIV testing strategy prevented false-positive diagnoses and unnecessary antiretroviral therapy at modest cost, supporting broader adoption of WHO guidance in similar settings. FundingGates Foundation.
ER -