Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol

Carla J Chibwesha, Catherine E Ford, Katie R Mollan, Jeffrey S A Stringer, Carla J Chibwesha, Catherine E Ford, Katie R Mollan, Jeffrey S A Stringer

Abstract

Introduction: In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible.

Methods and design: The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4-12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw.

Discussion: Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa.

Trial registration: clinicaltrials.gov NCT02682810.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

References

    1. UNAIDS. 2015 Progress Report on the Global Plan. Available at: . Accessed February 1, 2016.
    1. Ladner J, Besson MH, Rodrigues M, et al. Performance of HIV prevention of mother-to-child transmission programs in sub-Saharan Africa: longitudinal assessment of 64 nevirapine-based programs implemented in 25 countries, 2000–2011. PLoS One. 2015;10:e0130103.
    1. Wettstein C, Mugglin C, Egger M, et al. Missed opportunities to prevent mother-to-child-transmission: systematic review and meta-analysis. AIDS. 2012;26:2361–2373.
    1. Stringer EM, Ekouevi DK, Coetzee D, et al. Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries. JAMA. 2010;304:293–302.
    1. Stringer JS, Sinkala M, Maclean CC, et al. Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia. AIDS. 2005;19:1309–1315.
    1. Violari A, Cotton MF, Gibb DM, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008;359:2233–2244.
    1. Penazzato M, Prendergast AJ, Muhe LM, et al. Optimization of antiretroviral therapy in HIV-infected children under 3 years of age: a systematic review. AIDS. 2014;28(suppl 2):S137–S146.
    1. Johnson LF, Davies MA, Moultrie H, et al. The effect of early initiation of antiretroviral treatment in infants on pediatric AIDS mortality in South Africa: a model-based analysis. Pediatr Infect Dis J. 2012;31:474–480.
    1. World Health Organization. Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access (2010 Revision). Available at: . Accessed February 1, 2016.
    1. Braun M, Kabue MM, McCollum ED, et al. Inadequate coordination of maternal and infant HIV services detrimentally affects early infant diagnosis outcomes in Lilongwe, Malawi. J Acquir Immune Defic Syndr. 2011;56:e122–128.
    1. Laursen L. Point-of-care tests poised to alter course of HIV treatment. Nat Med. 2012;18:1156.
    1. UNITAID. HIV/AIDS Diagnostic Technology Landscape: Technical Report. Geneva, Switzerland: WHO; 2012.
    1. Jani IV, Meggi B, Mabunda N, et al. Accurate early infant HIV diagnosis in primary health clinics using a point-of-care nucleic acid test. J Acquir Immune Defic Syndr. 2014;67:e1–4.
    1. Roland M, Torgerson DJ. What are pragmatic trials? BMJ. 1998;316:285.
    1. Yusuf S, Collins R, Peto R. Why do we need some large, simple randomized trials? Stat Med. 1984;3:409–422.
    1. Palumbo P, Lindsey JC, Hughes MD, et al. Antiretroviral treatment for children with peripartum nevirapine exposure. N Engl J Med. 2010;363:1510–1520.
    1. Bolton-Moore C, Mubiana-Mbewe M, Cantrell RA, et al. Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia. JAMA. 2007;298:1888–1899.
    1. Agresti A, Kateri M. “Categorical Data Analysis.” International Encyclopedia of Statistical Science. Ed. Miodrag Lovric. Berlin, Germany: Springer, 2011;206–208.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren