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The molecular epidemiology of HIV-1 envelope diversity during HIV-1 subtype C vertical transmission in Malawian motherinfant pairs

Kwiek, Jesse Ja,1,*; Russell, Elizabeth Sb,*; Dang, Kristen Kc; Burch, Christina Ld; Mwapasa, Victore; Meshnick, Steven Ra,b; Swanstrom, Ronaldb,f

doi: 10.1097/QAD.0b013e3282f51ea0
Epidemiology and Social

Objectives: To study the relationship between HIV-1 subtype C genetic diversity and mother-to-child transmission and to determine if transmission of HIV-1 V1/V2 env variants occurs stochastically.

Design: Case–case–control study of Malawian mother–infant pairs consisting of 32 nontransmitting women, 25 intrauterine transmitters, and 23 intrapartum transmitters in Blantyre, Malawi.

Methods: A heteroduplex tracking assay against the highly variable HIV-1 env V1/V2 region was used to characterize the relationship between HIV-1 diversity and mother-to-child transmission. The relative abundance of the maternal env variants was quantified and categorized as transmitted or nontransmitted based on the env variants detected in the infant plasma. The V1/V2 region was sequenced from two mother–infant pairs and a phylogenetic tree was built.

Results: No relationship was found between transmission and overall maternal env diversity. Infants had less diverse HIV-1 populations than their mothers, and intrauterine-infected infants had fewer V1/V2 variants and were more likely to harbor a homogeneous V1/V2 population than infants infected intrapartum. V1/V2 sequences cloned from two mother–infant transmission pairs support multiple env variant transmission when multiple variants are detected, rather than single variant transmission followed by diversification. Almost 50% of the HIV-infected infants contained V1/V2 env variants that were not detected in maternal plasma samples. Finally transmission of env variants was not related to their abundance in maternal blood.

Conclusion: These data suggest that the predominant mechanism(s) of HIV-1 subtype C mother-to-child transmission differs by the timing of transmission and is unlikely to be explained by a simple stochastic model.

From the aDepartment of Epidemiology, Malawi

bDepartment of Microbiology and Immunology, Malawi

cDepartment of Biomedical Engineering, Malawi

dDepartment of Biology, Malawi

eDepartment of Community Health, Malawi College of Medicine, Blantyre, Malawi

fUNC Center for AIDS Research and Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

1Current address: Center for Microbial Interface Biology, Department of Internal Medicine, Division of Infectious Diseases, and the Department of Microbiology, The Ohio State University, 1008 BRT, 460 West 12th Avenue, Columbus, OH 43210, USA.

*Jesse J. Kwiek and Elizabeth S. Russell contributed equally to this work.

Correspondence to Ronald Swanstrom, CB# 7295, UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA. Tel: +1 919 966 5710; fax: +1 919 966 8212; e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.