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Published on: September 6, 2019
Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding
Caroline C King1, Athena P Kourtis, Deborah Persaud
1aDivision of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia bDepartment of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA cDepartment of Microbiology and Immunology, School of Medicine dDepartment of Biostatistics, Gillings School of Global Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA eUNC Project-Malawi, Lilongwe, Malawi fDivision of Epidemiology and Biostatistics, University of Witwatersrand, Johannesburg, South Africa gDivision of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Insights
Antiretroviral prophylaxis for infants exposed to HIV during breastfeeding may delay diagnosis. Ultrasensitive testing revealed delayed HIV detection in infants on nevirapine or maternal antiretrovirals, suggesting repeat virologic testing is crucial.
Area of Science:
- Pediatric Infectious Diseases
- Virology
- Public Health
Background:
- Preventing mother-to-child HIV transmission (PMTCT) during breastfeeding is critical.
- Antiretroviral prophylaxis is used to reduce HIV transmission risk.
- The Breastfeeding, Antiretrovirals and Nutrition (BAN) study investigated PMTCT strategies.
Purpose of the Study:
- To determine if HIV detection was delayed in infants receiving antiretroviral prophylaxis.
- To assess the impact of different antiretroviral regimens on HIV diagnosis timing.
- To evaluate the effectiveness of ultrasensitive HIV testing in identifying early infections.
Main Methods:
- A randomized trial involving 2369 mother-infant pairs.
- Infants received different antiretroviral regimens during 28 weeks of breastfeeding.
- Ultrasensitive droplet digital PCR HIV testing was performed on stored infant samples at 24 weeks.
Main Results:
- HIV DNA was detectable at 24 weeks in 3/3 infants on infant nevirapine, 2/4 on maternal antiretrovirals, and 1/2 in the control arm.
- Median delay in detection by ultrasensitive vs. standard assays was 18.3 weeks (nevirapine), 15.4 weeks (maternal), and 9.4 weeks (control).
- Delayed detection suggests antiretrovirals may restrict HIV replication, masking early infection.
Conclusions:
- Early antiretroviral prophylaxis can lead to missed HIV diagnoses in infants.
- Standard HIV testing may be insufficient for detecting infections in infants on prophylaxis.
- Repeat virologic testing beyond current recommendations is warranted for infected infants.
Objective:
The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding.
Design:
The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was a randomized trial of 2369 mother-infant pairs conducted from 2004 to 2010. In addition to an intrapartum regimen, all mother-infant pairs were randomly assigned to three antiretroviral intervention arms during 28 weeks of breastfeeding: no further antiretroviral prophylaxis (control arm); infant-daily nevirapine (nevirapine arm); and maternal zidovudine, lamivudine and either nevirapine, nelfinavir or lopinavir-ritonavir (maternal arm). After breastfeeding cessation counselling and stopping the antiretroviral interventions by 28 weeks, 28 infant HIV infections occurred.
Methods:
To determine whether these infections occurred during the breastfeeding and antiretroviral intervention phase but had delayed detection on the antiretroviral arms, we performed ultrasensitive (droplet digital PCR) HIV testing on infants with stored peripheral blood mononuclear cell (PBMC) specimens at 24 weeks (n = 9).
Results:
Of the nine infants, all three on the infant nevirapine arm had detectable HIV DNA at 24 weeks, compared with two of four on the maternal antiretroviral arm and one of two on the control arm. For infants with detectable HIV at 24 weeks, the median delay in detection between the ultrasensitive and standard assays was 18.3 weeks for the nevirapine arm, 15.4 weeks for the maternal arm and 9.4 weeks for the control arm.
Conclusion:
The prolonged inability to detect HIV with standard assays in the context of postnatal antiretroviral prophylaxis suggests that early antiretrovirals may restrict HIV replication sufficiently to lead to missed diagnosis among infected infants. Therefore, repeat virologic testing is warranted beyond the WHO-recommended point of testing at 6 weeks after breastfeeding cessation.
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