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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
African infants' CCL3 gene copies influence perinatal HIV transmission in the absence of maternal nevirapine
AIDS, Volume 21, No. 13, Year 2007
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Description
BACKGROUND: Individuals with more copies of CCL3L1 (CCR5 ligand) than their population median have been found to be less susceptible to HIV infection. We investigated whether maternal or infant CCL3L1 gene copy numbers are associated with perinatal HIV transmission when single-dose nevirapine is given for prevention. METHOD: A nested case-control study was undertaken combining data from four cohorts including 849 HIV-infected mothers and their infants followed prospectively in Johannesburg, South Africa. Access to antiretroviral drugs for the prevention of perinatal transmission differed across the cohorts. Maternal and infant CCL3L1 gene copy numbers per diploid genome (pdg) were determined by real-time polymerase chain reaction for 79 out of 83 transmitting pairs (∼10% transmission rate) and 235 randomly selected non-transmitting pairs. RESULTS: Higher numbers of infant, but not maternal, CCL3L1 gene copies were associated with reduced HIV transmission (P = 0.004) overall, but the association was attenuated if mothers took single-dose nevirapine or if the maternal viral load was low. Maternal nevirapine was also associated with reduced spontaneously released CCL3 (P = 0.007) and phytohemagglutinin- stimulated CCL3 (P = 0.005) production in cord blood mononuclear cells from uninfected infants. CONCLUSION: We observed a strong association between higher infant CCL3L1 gene copies and reduced susceptibility to HIV in the absence of maternal nevirapine. We also observed a reduction in newborn CCL3 production with nevirapine exposure. Taken together, we hypothesize that nevirapine may have direct or indirect effects that partly modify the role of the CCR5 ligand CCL3 in HIV transmission, obscuring the relationship between this genetic marker and perinatal HIV transmission. © 2007 Lippincott Williams & Wilkins, Inc.
Authors & Co-Authors
Kuhn, Louise
United States, New York
Vagelos College of Physicians and Surgeons
United States, New York
Mailman School of Public Health
United States, New York
Columbia University
Schramm, Diana B.
South Africa, Johannesburg
University of the Witwatersrand
Donninger, Samantha L.
South Africa, Johannesburg
University of the Witwatersrand
Meddows-Taylor, Stephen
South Africa, Johannesburg
University of the Witwatersrand
Coovadia, Ashraf Hassen
South Africa, Johannesburg
Rahima Moosa Mother and Child Hospital
Sherman, Gayle Gillian
South Africa, Johannesburg
University of the Witwatersrand
Gray, Glenda E.
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
Tiemessen, Caroline Tanya
South Africa, Johannesburg
University of the Witwatersrand
Statistics
Citations: 80
Authors: 8
Affiliations: 6
Identifiers
Doi:
10.1097/QAD.0b013e3282ba553a
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Study Locations
South Africa