Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding

Caroline C. King, Athena P. Kourtis, Deborah Persaud, Julie A E Nelson, Carrie Ziemniak, Michael G. Hudgens, Gerald Tegha, Charles S. Chasela, Denise J. Jamieson, Charles M. Van Der Horst

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1953-1961
Number of pages9
JournalAIDS
Volume29
Issue number15
DOIs
StatePublished - Sep 24 2015

Fingerprint

Breast Feeding
HIV
Nevirapine
Mothers
HIV Infections
Nelfinavir
Lopinavir
Ritonavir
Lamivudine
Zidovudine
Counseling
Blood Cells
Polymerase Chain Reaction
DNA
Infection

Keywords

  • antiretroviral
  • breastfeeding
  • detection
  • HIV
  • infant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

King, C. C., Kourtis, A. P., Persaud, D., Nelson, J. A. E., Ziemniak, C., Hudgens, M. G., ... Van Der Horst, C. M. (2015). Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding. AIDS, 29(15), 1953-1961. https://doi.org/10.1097/QAD.0000000000000794

Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding. / King, Caroline C.; Kourtis, Athena P.; Persaud, Deborah; Nelson, Julie A E; Ziemniak, Carrie; Hudgens, Michael G.; Tegha, Gerald; Chasela, Charles S.; Jamieson, Denise J.; Van Der Horst, Charles M.

In: AIDS, Vol. 29, No. 15, 24.09.2015, p. 1953-1961.

Research output: Contribution to journalArticle

King, CC, Kourtis, AP, Persaud, D, Nelson, JAE, Ziemniak, C, Hudgens, MG, Tegha, G, Chasela, CS, Jamieson, DJ & Van Der Horst, CM 2015, 'Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding', AIDS, vol. 29, no. 15, pp. 1953-1961. https://doi.org/10.1097/QAD.0000000000000794
King, Caroline C. ; Kourtis, Athena P. ; Persaud, Deborah ; Nelson, Julie A E ; Ziemniak, Carrie ; Hudgens, Michael G. ; Tegha, Gerald ; Chasela, Charles S. ; Jamieson, Denise J. ; Van Der Horst, Charles M. / Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding. In: AIDS. 2015 ; Vol. 29, No. 15. pp. 1953-1961.
@article{fdc4dcc87b1c47af971af89c8c2e10c6,
title = "Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding",
abstract = "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.",
keywords = "antiretroviral, breastfeeding, detection, HIV, infant",
author = "King, {Caroline C.} and Kourtis, {Athena P.} and Deborah Persaud and Nelson, {Julie A E} and Carrie Ziemniak and Hudgens, {Michael G.} and Gerald Tegha and Chasela, {Charles S.} and Jamieson, {Denise J.} and {Van Der Horst}, {Charles M.}",
year = "2015",
month = "9",
day = "24",
doi = "10.1097/QAD.0000000000000794",
language = "English (US)",
volume = "29",
pages = "1953--1961",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "15",

}

TY - JOUR

T1 - Delayed HIV detection among infants exposed to postnatal antiretroviral prophylaxis during breastfeeding

AU - King, Caroline C.

AU - Kourtis, Athena P.

AU - Persaud, Deborah

AU - Nelson, Julie A E

AU - Ziemniak, Carrie

AU - Hudgens, Michael G.

AU - Tegha, Gerald

AU - Chasela, Charles S.

AU - Jamieson, Denise J.

AU - Van Der Horst, Charles M.

PY - 2015/9/24

Y1 - 2015/9/24

N2 - 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.

AB - 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.

KW - antiretroviral

KW - breastfeeding

KW - detection

KW - HIV

KW - infant

UR - http://www.scopus.com/inward/record.url?scp=84965005745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84965005745&partnerID=8YFLogxK

U2 - 10.1097/QAD.0000000000000794

DO - 10.1097/QAD.0000000000000794

M3 - Article

VL - 29

SP - 1953

EP - 1961

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 15

ER -