Background. Human immunodeficiency virus type 1 (HIV-1) may utilize the CXCR4 coreceptor (X4 virus), the CCR5 coreceptor (R5 virus), or both (dual/mixed [DM] virus). We analyzed HIV-1 coreceptor tropism in Ugandan infants enrolled in the HIVNET (HIV Network for Prevention Trials) 012 trial. Methods. Plasma or serum was analyzed using a commercial coreceptor tropism assay. HIV env subtype was determined by phylogenetic methods. Results. Tropism results were obtained for 57 samples from infants collected 6-14 weeks after birth. Fifty-two infants had only R5 virus, and 5 had either X4 or DM virus. The mothers of those 5 infants also had X4 or DM virus. In infants, subtype D infection was associated with high-level infectivity in CCR5-bearing cells and also with the detection of X4 or DM strains. High-level infectivity in CCR5-bearing cells was associated with decreased infant survival, but infection with X4 or DM virus was not. HIV clones from infants with DM viral populations showed different patterns of coreceptor use. V3 loop sequence-based algorithms predicted the tropism of some, but not all, env clones. Conclusions. Complex patterns of HIV tropism were found in HIV-infected newborn infants. Subtype D infection was associated with X4 virus and with high-level replication in CCR5-bearing cells. High-level replication of R5 virus was associated with decreased infant survival.
Bibliographical noteFunding Information:
Financial support: Supported by the HIV Network for Prevention Trials and sponsored by (1) the US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through contract N01-AI-35173 with Family Health International, contract N01-AI-45200 with the Fred Hutchinson Cancer Research Center, and subcontract NOI-AI-35173-417 with Makerere University; (2) the HIV Prevention Trials Network, which is sponsored by the NIAID, the National Institute of Child Health and Human Development (NICHD), the National Institute on Drug Abuse, the National Institute of Mental Health, and the Office of AIDS Research of the NIH, DHHS (U01-AI-46745, U01-AI-48054, and U01-AI068613); (3) NICHD (R01-HD042965-01); and (4) Small Business Innovation Research program, NIH (grant 2 R44 A1048990-03).