TY - JOUR
T1 - Time to first positive HIV-1 DNA PCR may differ with antiretroviral regimen in infants infected with non-B subtype HIV-1
AU - Balasubramanian, Raji
AU - Fowler, Mary Glenn
AU - Dominguez, Kenneth
AU - Lockman, Shahin
AU - Tookey, Pat A.
AU - Huong, Nicole Ngo Giang
AU - Nesheim, Steven
AU - Hughes, Michael D.
AU - Lallemant, Marc
AU - Tosswill, Jennifer
AU - Shaffer, Nathan
AU - Sherman, Gayle
AU - Palumbo, Paul
AU - Shapiro, David E.
N1 - Funding Information:
aDepartment of Biostatistics and Epidemiology, University of Massachusetts-Amherst, Amherst, Massachusetts, bDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, cDivision of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, dDivision of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, eDepartment of Immunology and Infectious Diseases, Harvard University, T. H. Chan School of Public Health, Boston, Massachusetts, USA, fBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana, gUniversity College Institute of Child Health, London, UK, hInstitut de recherche pour le développement (IRD) UMI 174-PHPT, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand, iDepartment of Biostatistics, Harvard University T. H. Chan School of Public Health, Boston, Massachusetts, USA, jVirus Reference Department, National Infection Service, Public Health England, London, UK, kDepartment of HIV/AIDS, World Health Organization, Geneva, Switzerland, lDepartment of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand and National Institute for Communicable Diseases, Johannesburg, South Africa, mSection of Infectious Diseases and International Health, Geisel School of Medicine at Dartmouth, 1 Medical Center Dr, Lebanon, New Hampshire, and nCenter for Biostatistics in AIDS Research, Harvard University T. H. Chan School of Public Health. Boston, Massachusetts, USA. Correspondence to David E. Shapiro, Center for Biostatistics in AIDS Research, Harvard University T. H. Chan School of Public Health, 651 Huntington Avenue, Boston, MA 02115, USA. Tel: +1 617 432 2426; fax: +1 617 432 3163; e-mail: shapiro@sdac.harvard.edu *Present address: Nathan Shaffer, MD, Consultant, Decatur, GA 30030, USA. Received: 25 January 2017; revised: 4 August 2017; accepted: 3 September 2017.
Funding Information:
R.B., M.G.F., K.D., and Dr Shapiro were supported by a grant (R21 HD072792) from the National Institutes of Health, USA. S.L. was supported by funding by the National Institutes of Health R01 HD37793. P.A.T. received a grant (GHP/003/013/003) from the Health Protection Agency, UK and from the UK National Screening Programme; the NSHPC is managed within the Population, Policy & Practice Programme at the Institute of Child Health (ICH), University College London (UCL), which previously benefited from funding support from the Medical Research Council (MRC) in its capacity as the MRC Centre of Epidemiology for Child Health (grant number G0400546); the UCL ICH receives a proportion of funding from the UK Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. P.A.T. has also received grants from Public Health England, the UK National Screening Programme, the PENTA Foundation, AbbVie Inc, and IATEC/Kendle; she is a member of the Writing Group for the British HIV Association’s Guidelines for the Management of HIV Infection in Pregnant Women. N.G.G.H. and M.L. were supported by grants from The National Institutes of Health, USA (R01 HD 33326; R01 HD 39615). J.T. is a member of the Writing Group for the British HIVAssociation’s Guidelines for the Management of HIV Infection in Pregnant Women. P.P. has served as a consultant to Merck Pharmaceuticals and serves on DSMBs for Gilead and ApoPharma. All other authors report no conflicts of interest or sources of funding.
Publisher Copyright:
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/11/28
Y1 - 2017/11/28
N2 - Objective: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. Design: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N=405). Methods: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. Results: Maternal antiretroviral regimens included: no antiretrovirals (n=138), single-nucleoside analog reverse transcriptase inhibitor (n=165), single-dose nevirapine with zidovudine (n=66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n=36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P<0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P=0.04). Conclusion: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.
AB - Objective: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. Design: Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N=405). Methods: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. Results: Maternal antiretroviral regimens included: no antiretrovirals (n=138), single-nucleoside analog reverse transcriptase inhibitor (n=165), single-dose nevirapine with zidovudine (n=66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n=36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P<0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P=0.04). Conclusion: Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.
KW - DNA PCR assays
KW - early infant diagnosis of HIV
KW - mother-to-child transmission of HIV
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U2 - 10.1097/QAD.0000000000001640
DO - 10.1097/QAD.0000000000001640
M3 - Article
C2 - 28926397
AN - SCOPUS:85033791513
SN - 0269-9370
VL - 31
SP - 2465
EP - 2474
JO - AIDS
JF - AIDS
IS - 18
ER -