title: Dynamics of proviral HIV-1 184M/V in circulating CD4+ T-cells: a 90 days follow-up study after initiation/switch of HAART.
abstract: HIV-1 viral load falls rapidly on initiation of HAART. This phase of decreasing yet substantial viral production in the presence of antiretroviral drugs could generate resistant HIV-1. Whether switching a drug from a failing regime changes the demography of the mutations associated with it in the CD4+ T-cell compartment is not well-defined. We investigated the presence/absence and quantity of 184M and 184V in the CD4+ T-cell compartment of naïve patients initiated to HAART (group I), and patients who shifted to a non-lamivudine therapy (group II). We initiated a prospective 90 d follow-up study of 11 patients to detect and quantity proviral HIV-1 184M and 184V in the CD4+ T-cell compartment with a sensitive real time PCR assay. Results showed that the 184V was not detected in the CD4+ T-cell compartment of any of the 7 naïve patients who started on HAART. Three out of the 4 patients in group II experienced a fall in the percentage of 184V, with reduction to below detection limits in 2 patients. It can be concluded that initiation of HAART does not allow the archiving of the lamivudine associated mutation, 184V, in the CD4+ T-cell compartment. Reduction in the quantity of 184V when therapy is switched to an effective non-lamivudine regime indicates that the mutation in this compartment is dynamic.
authors.affiliation: Department of Infectious Diseases, Skejby University Hospital, Aarhus, Denmark. mohey@dadlnet.dk
authors.forename: Rajesh
authors.initials: R
authors.lastname: Mohey
authors.forename: Terese L
authors.initials: TL
authors.lastname: Katzenstein
authors.forename: Finn T
authors.initials: FT
authors.lastname: Black
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015704:CD4 Antigens / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology*; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D009154:Mutation / Q000187:drug effects; D011446:Prospective Studies; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D019259:Lamivudine