A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia
Carla J Chibwesha, Katie R Mollan, Catherine E Ford, Aaron Shibemba, Pooja T Saha, Mildred Lusaka, Felistas Mbewe, Andrew G Allmon, Rose Lungu, Hans M L Spiegel, Emmanuel Mweni, Humphrey Mwape, Chipepo Kankasa, Benjamin H Chi, Jeffrey S A Stringer, Carla J Chibwesha, Katie R Mollan, Catherine E Ford, Aaron Shibemba, Pooja T Saha, Mildred Lusaka, Felistas Mbewe, Andrew G Allmon, Rose Lungu, Hans M L Spiegel, Emmanuel Mweni, Humphrey Mwape, Chipepo Kankasa, Benjamin H Chi, Jeffrey S A Stringer
Abstract
Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART).
Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months.
Results: Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22-30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6-2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15-34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16-43%) infants in the POC group vs 7 (19%; 6-32%) in the SOC group (RR: 1.56; .7-3.50).
Conclusions: POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes.
Clinical trials registration: This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT02682810" title="See in ClinicalTrials.gov">NCT02682810).
Keywords: early infant diagnosis of HIV; pediatric HIV low- and middle income country; point of care diagnosis; prevention of mother to child HIV transmission.
Conflict of interest statement
Potential conflicts of interest. J. S. A. S. reports support from the Bill and Melinda Gates Foundation, outside the submitted work. All other authors report no potential conflicts. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
Figures
References
- Joint United Nations Programme on HIV/AIDS (UNAIDS). AIDSinfo data sheet: pregnant women needed ART for PMTCT. 2019. Available at: . Accessed 15 December 2019.
- UNAIDS. Start Free Stay Free AIDS Free: 2020 report. 2020. Available at: . Accessed 16 November 2020.
- UNAIDS. Start Free Stay Free AIDS Free: 2019 report. 2019. Available at: . Accessed 15 December 2019.
- Marston M, Becquet R, Zaba B, et al. . Net survival of perinatally and postnatally HIV-infected children: a pooled analysis of individual data from sub-Saharan Africa. Int J Epidemiol 2011; 40:385–96.
- Violari A, Cotton MF, Gibb DM, et al. ; CHER Study Team. . Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008; 359:2233–44.
- Ghadrshenas A, Ben Amor Y, Chang J, et al. ; Child Survival Working Group of the Interagency Task Team on the Prevention and Treatment of HIV Infection in Pregnant Women, Mothers and Children. . Improved access to early infant diagnosis is a critical part of a child-centric prevention of mother-to-child transmission agenda. AIDS 2013; 27(Suppl 2):S197–205.
- The Global Fund. HIV viral load and early infant diagnosis selection and procurement information tool 2017. Available at: . Accessed 15 December 2019.
- Chatterjee A, Tripathi S, Gass R, et al. . Implementing services for early infant diagnosis (EID) of HIV: a comparative descriptive analysis of national programs in four countries. BMC Public Health 2011; 11:553.
- Nuwagaba-Biribonwoha H, Werq-Semo B, Abdallah A, et al. . Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania. BMC Pediatr 2010; 10:44.
- Cantera JL, White H, Diaz MH, et al. . Assessment of eight nucleic acid amplification technologies for potential use to detect infectious agents in low-resource settings. PLoS One 2019; 14:e0215756.
- Agutu CA, Ngetsa CJ, Price MA, et al. . Systematic review of the performance and clinical utility of point of care HIV-1 RNA testing for diagnosis and care. PLoS One 2019; 14:e0218369.
- Frank SC, Cohn J, Dunning L, et al. . Clinical effect and cost-effectiveness of incorporation of point-of-care assays into early infant HIV diagnosis programmes in Zimbabwe: a modelling study. Lancet HIV 2019; 6:e182–90.
- Spooner E, Govender K, Reddy T, et al. . Point-of-care HIV testing best practice for early infant diagnosis: an implementation study. BMC Public Health 2019; 19:731.
- Meggi B, Vojnov L, Mabunda N, et al. . Performance of point-of-care birth HIV testing in primary health care clinics: an observational cohort study. PLoS One 2018; 13:e0198344.
- Dunning L, Kroon M, Hsiao NY, Myer L.. Field evaluation of HIV point-of-care testing for early infant diagnosis in Cape Town, South Africa. PLoS One 2017; 12:e0189226.
- Opollo VS, Nikuze A, Ben-Farhat J, et al. . Field evaluation of near point of care Cepheid GeneXpert HIV-1 Qual for early infant diagnosis. PLoS One 2018; 13:e0209778.
- Bianchi F, Cohn J, Sacks E, Bailey R, Lemaire JF, Machekano R; EGPAF POC EID Study Team. . Evaluation of a routine point-of-care intervention for early infant diagnosis of HIV: an observational study in eight African countries. Lancet HIV 2019; 6:e373–81.
- Jani IV, Meggi B, Loquiha O, et al. . Effect of point-of-care early infant diagnosis on antiretroviral therapy initiation and retention of patients. AIDS 2018; 32:1453–63.
- Sacks E, Cohn J, Ochuka B, et al. . Impact of routine point-of-care versus laboratory testing for early infant diagnosis of HIV: results from a multicountry stepped-wedge cluster-randomized controlled trial. J Acquir Immune Defic Syndr 2020; 84(Suppl 1):S5–S11.
- Chibwesha CJ, Ford CE, Mollan KR, Stringer JS.. Point-of-care virologic testing to improve outcomes of HIV-infected children in Zambia: a clinical trial protocol. J Acquir Immune Defic Syndr 2016; 72(Suppl 2):S197–201.
- World Health Organization. Prequalification of in vitro diagnostics public report—product: AlereTM q HIV-1/2 detect. 2016. Available at: . Accessed 15 December 2019.
- 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; 298:1888–99.
- Ford I, Norrie J.. Pragmatic trials. N Engl J Med 2016; 375:454–63.
- Zwarenstein M, Treweek S, Gagnier JJ, et al. ; CONSORT Group; Pragmatic Trials in Healthcare (Practihc) Group. . Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ 2008; 337:a2390.
- Lachin JM. Properties of simple randomization in clinical trials. Control Clin Trials 1988; 9:312–26.
- Doig GS, Simpson F.. Randomization and allocation concealment: a practical guide for researchers. J Crit Care 2005; 20:187–91; discussion 191–3.
- Schulz KF, Grimes DA.. Multiplicity in randomised trials II: subgroup and interim analyses. Lancet 2005; 365:1657–61.
- Schlatter AF, Deathe AR, Vreeman RC.. The need for pediatric formulations to treat children with HIV. AIDS Res Treat 2016; 2016:1654938.
- St Clair-Sullivan N, Mwamba C, Whetham J, Bolton Moore C, Darking M, Vera J.. Barriers to HIV care and adherence for young people living with HIV in Zambia and mHealth. mHealth 2019; 5:45.
- Girdwood SJ, Nichols BE, Moyo C, Crompton T, Chimhamhiwa D, Rosen S.. Optimizing viral load testing access for the last mile: Geospatial cost model for point of care instrument placement. PLoS One 2019; 14:e0221586.
Source: PubMed