title: Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.
abstract: In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.
authors.affiliation: Departmentsof Medicine and Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Dinoso
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: A M
authors.initials: AM
authors.lastname: Wiegand
authors.forename: S E
authors.initials: SE
authors.lastname: Palmer
authors.forename: S J
authors.initials: SJ
authors.lastname: Gange
authors.forename: L
authors.initials: L
authors.lastname: Cranmer
authors.forename: A
authors.initials: A
authors.lastname: O'Shea
authors.forename: M
authors.initials: M
authors.lastname: Callender
authors.forename: A
authors.initials: A
authors.lastname: Spivak
authors.forename: T
authors.initials: T
authors.lastname: Brennan
authors.forename: M F
authors.initials: MF
authors.lastname: Kearney
authors.forename: M A
authors.initials: MA
authors.lastname: Proschan
authors.forename: J M
authors.initials: JM
authors.lastname: Mican
authors.forename: C A
authors.initials: CA
authors.lastname: Rehm
authors.forename: J M
authors.initials: JM
authors.lastname: Coffin
authors.forename: J W
authors.initials: JW
authors.lastname: Mellors
authors.forename: R F
authors.initials: RF
authors.lastname: Siliciano
authors.forename: F
authors.initials: F
authors.lastname: Maldarelli
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents; D023241:Antiretroviral Therapy, Highly Active; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D011446:Prospective Studies; D014766:Viremia / Q000188:drug therapy*; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents