Identification of a transmission chain of HIV type 1 containing drug resistance-associated mutations.
We have investigated a potential transmission chain of HIV-1 with drug resistance-associated mutations between three individuals over a period of 5 years by use of cloning and sequencing of viral genes, and phenotypic characterization. Viruses containing reverse transcriptase drug resistance-associated mutations were transmitted sequentially between three homosexual men (A, B, and C), and persisted in one individual for at least 4 years, despite intermittent therapy and reduced viral replicative capacity compared with wild-type strains. Clonal analysis of the envelope gene from semen and blood virus showed that the virus transmitted to patient C was more closely related to virus from the semen than the blood of patient B. Our data suggest that HIV variants with drug resistance-associated mutations can persist following primary infection, despite intervening antiretroviral therapy, and subsequently sexually transmitted. We provide "proof of principle" that such mutations can therefore become "fixed" within the circulating virus pool.
Taylor
Stephen
S
Public Health Laboratory Service Antiviral Susceptibility Reference Unit, Division of Immunity and Infection, University of Birmingham, Birmingham B9 5SS, UK.
Cane
Patricia
P
Hué
Stéphane
S
Xu
Li
L
Wrin
Terri
T
Lie
Yolanda
Y
Hellmann
Nicholas
N
Petropoulos
Christos
C
Workman
Judith
J
Ratcliffe
Daina
D
Choudhury
Bhudipa
B
Pillay
Deenan
D
D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D012661:Semen / Q000821:virology; D017422:Sequence Analysis, DNA; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase