title: Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy.
abstract: Residual viremia can be detected in most HIV-1-infected patients on antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml, but the source and duration of this viremia is currently unknown. Therefore, we analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA assay with single-copy sensitivity. All patients were on therapy (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies per ml by week 96 of the study and thereafter. Single-copy assay results revealed that 77% of the patient samples had detectable low-level viremia (>/=1 copy per ml), and all patients had at least one sample with detectable viremia. A nonlinear mixed effects model revealed a biphasic decline in plasma RNA levels occurring over weeks 60 to 384: an initial phase of decay with a half-life of 39 weeks and a subsequent phase with no perceptible decay. The level of pretherapy viremia extrapolated for each phase of decay was significantly correlated with total baseline viremia for each patient (R(2) = 0.27, P = 0.001 and R(2) = 0.19, P < 0.005, respectively), supporting a biological link between the extent of overall baseline viral infection and the infection of long-lived reservoirs. These data suggest that low-level persistent viremia appears to arise from at least two cell compartments, one in which viral production decays over time and a second in which viral production remains stable for at least 7 years.
authors.affiliation: HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702-1201, USA. spalmer@ncifcrf.gov
authors.forename: Sarah
authors.initials: S
authors.lastname: Palmer
authors.forename: Frank
authors.initials: F
authors.lastname: Maldarelli
authors.forename: Ann
authors.initials: A
authors.lastname: Wiegand
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
authors.forename: George J
authors.initials: GJ
authors.lastname: Hanna
authors.forename: Scott C
authors.initials: SC
authors.lastname: Brun
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Kempf
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.forename: John M
authors.initials: JM
authors.lastname: Coffin
authors.forename: Martin S
authors.initials: MS
authors.lastname: King
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D002986:Clinical Trials as Topic; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1; D006801:Humans; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D014766:Viremia / Q000097:blood*
chemical_list: D012367:RNA, Viral