Early infant diagnosis HIV-1 PCR cycle-threshold predicts infant viral load at birth

Ahmad Haeri Mazanderani; Tendesayi Kufa; Karl G Technau; Renate Strehlau; Faeezah Patel; Stephanie Shiau; Megan Burke; Louise Kuhn; Elaine J Abrams; Gayle G Sherman; LEOPARD Study Team

doi:10.1016/j.jcv.2019.03.009

Early infant diagnosis HIV-1 PCR cycle-threshold predicts infant viral load at birth

J Clin Virol. 2019 May:114:21-25. doi: 10.1016/j.jcv.2019.03.009. Epub 2019 Mar 18.

Affiliations

¹ Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa; Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. Electronic address: ahmadh@nicd.ac.za.
² Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
⁵ Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA; ICAP, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, USA.
⁶ Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa; Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Abstract

Background: HIV-1 viral load (VL) has been found to be an independent predictor for disease progression among untreated HIV-infected children. However, qualitative polymerase chain reaction (PCR) assays are routinely used for early infant diagnosis (EID).

Objectives: To predict HIV-1 VL at birth using qualitative EID real-time PCR cycle-threshold (Ct) values.

Study design: This study was a secondary analysis of results from a cohort of intrauterine HIV-1 infected neonates. Neonates were enrolled at Rahima Moosa Mother & Child Hospital in Johannesburg, South Africa between June 2014 and November 2017. Laboratory EID HIV-1 PCR testing was performed at birth using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test v2.0 (EID CAP/CTM). Some infants had simultaneous EID point-of-care (POC) testing using Xpert HIV-1 Qualitative assay (EID Xpert). Neonates with a confirmed HIV-1 detected EID result and plasma HIV-1 RNA VL test were included in this analysis. Bland-Altman analysis was used to determine extent of agreement between Ct values of both EID assays. Multivariable linear regression models adjusting for time between EID and VL testing were used to describe the association between EID Ct values and VL and to predict VL at given EID Ct values.

Results: Among 107 HIV-1 infected neonates included in the study, 59 had POC EID testing. Median VL was 28 400 copies per millilitre (cps/ml) (IQR: 1 918-218 358) - two neonates had VL < 100 cps/ml prior to antiretroviral therapy initiation. There was good correlation between Ct values of both EID assays (Spearman correlation coefficient 0.9, 95% CI: 0.8-1.0). The limits of agreement between EID CAP/CTM and Xpert Ct values were 4-11 cycles. For every one cycle increase in Ct value there was 0.3 log₁₀ RNA decrease (95% CI: -0.3 to -0.2) for both EID assays. An EID CAP/CTM Ct value ≤ 23 and an EID Xpert Ct value ≤ 31 predicted a VL of > 5.0 log₁₀ cps/ml in 82.2% (95% CI: 73.9-88.3) and 84.7% (95% CI: 73.7-91.8) of cases, respectively.

Conclusion: EID Ct values at birth predict VL and accurately identify infants with VL > 5.0 log₁₀ cps/ml.

Keywords: Early infant diagnosis; HIV; Point of care; Viral load.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Early Diagnosis*
Female
HIV Infections / blood
HIV Infections / diagnosis*
HIV-1
Humans
Infant, Newborn
Infectious Disease Transmission, Vertical
Limit of Detection
Point-of-Care Testing
Polymerase Chain Reaction
Pregnancy
RNA, Viral / blood
RNA, Viral / genetics
Sensitivity and Specificity
Specimen Handling
Viral Load / methods*

Substances

RNA, Viral

Grants and funding

U01 HD080441/HD/NICHD NIH HHS/United States