title: Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection.
abstract: This study compared the incidence of HIV-1 variants harboring mutations conferring resistance to thymidine analogues, ie, thymidine analogue mutations (TAMs), nonnucleoside reverse transcriptase (RT) inhibitors (NNMs), lamivudine (3TC) (ie, M184V), and protease inhibitors (PIs) acquired in primary HIV infection (PHI) (n = 59) to their observed prevalence in a corresponding potential transmitter (PT) population of persons harboring resistant infections (n = 380). Both of these populations in the context of this cohort analysis possessed similar demographics. Whereas the frequencies of observed TAMs, NNMs, M184V, and protease-associated mutations (PRAMs) were similar in the PT groups, the prevalence of M184V and major PI mutations were significantly lower in the PHI group (PHI/PT ratios of 0.14 and 0.39, respectively). There was a decreased prevalence in the PHI population of resistant viruses co-expressing NNMs or TAMs with M184V compared with viruses that harbored NNMs or TAMs in the absence of M184V (P < 0.0001). It was also observed that individuals in the PT subgroups who harbored RT mutations or PRAMs with M184V had lower levels of plasma viremia than individuals who lacked M184V (P < 0.05). These findings suggest that both decreased viremia and viral fitness in the case of M184V-containing HIV-1 variants may impact on viral transmissibility.
authors.affiliation: McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
authors.forename: Bluma
authors.initials: B
authors.lastname: Brenner
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Daniela
authors.initials: D
authors.lastname: Moisi
authors.forename: Zeev
authors.initials: Z
authors.lastname: Rosberger
authors.forename: Michel
authors.initials: M
authors.lastname: Roger
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
mesh_terms: D000208:Acute Disease / Q000453:epidemiology; D002908:Chronic Disease / Q000188:drug therapy / Q000453:epidemiology; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D014766:Viremia / Q000821:virology; D014779:Virus Replication
chemical_list: D012367:RNA, Viral