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A Mathematical Model Evaluating the Timing of Early Diagnostic Testing in HIV-Exposed Infants in South Africa

Lilian, Rivka R. MSc (Med)*; Johnson, Leigh F. PhD; Moolla, Haroon BBusSc; Sherman, Gayle G. MD, PhD*,‡,§

JAIDS Journal of Acquired Immune Deficiency Syndromes: November 1st, 2014 - Volume 67 - Issue 3 - p 341–348
doi: 10.1097/QAI.0000000000000307
Epidemiology and Prevention

Background: Antiretroviral therapy is often initiated too late to impact early HIV-related infant mortality. Earlier treatment requires an earlier diagnosis, and the currently recommended 6-week HIV polymerase chain reaction (PCR) test needs reconsideration. This study aims to identify (1) optimal testing intervals to maximize the number of perinatal HIV infections diagnosed and (2) programmatic issues that impact diagnosis.

Methods: A mathematical model was developed to simulate antiretroviral prophylaxis uptake and health outcomes in 240,000 HIV-exposed South African infants. The model considered routine early testing with 1 PCR (at birth, 6, 10, or 14 weeks of age) and with 2 PCR tests (at birth and at 6, 10, or 14 weeks of age).

Results: A single 6-week test would diagnose the same number of perinatal HIV infections as birth testing (P = 0.92) but fewer infections than a 10-week test (P < 0.01). Ten-week testing identifies the highest number of perinatally infected infants (P < 0.01 compared with a single test at all other ages) but does not save additional life years compared with birth testing (P = 0.27). Performing 2 PCR tests (at birth and 10 weeks) would identify the highest number of perinatal infections (P < 0.01 versus a second 6- or 14-week test). However, 25% of perinatal HIV infections would remain undiagnosed, largely because of failure to return PCR test results to caregivers.

Conclusions: Six weeks may no longer be the optimal age to diagnose perinatal HIV infections. Two early PCR tests (at birth and 10 weeks) would likely be the ideal diagnostic algorithm, but must be coupled with improved program coverage.

*Paediatric HIV Diagnostic Syndicate, Wits Health Consortium, Johannesburg, South Africa;

Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa;

Centre for HIV and STI, National Institute for Communicable Diseases, Johannesburg, South Africa; and

§Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Correspondence to: Gayle G. Sherman, MD, PhD, P.O. Box 79722, Senderwood, 2145 Johannesburg, South Africa (e-mail:

Supported by United Nations Children's Fund and the Hasso Plattner Foundation.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received February 21, 2014

Accepted July 21, 2014

© 2014 by Lippincott Williams & Wilkins