title: Residual activity of two HIV antiretroviral regimens prescribed without virological monitoring.
abstract: Virological residual activity (VRA) denotes the degree of HIV RNA suppression achieved by antiretroviral therapy in the presence of resistant virus. This concept is particularly important in resource-limited settings, where rapid switching after detection of virological failure may not be feasible. Using data from the NORA trial, we estimated VRA for two regimens-zidovudine-lamivudine-abacavir (ZDV-3TC-ABC) and zidovudine-lamivudine-nevirapine (ZDV-3TC-NVP)-and related this to the phenotypic drug sensitivity of the component drugs in the two regimens. Plasma samples at weeks 0, 48, and 96 were retrospectively assayed for HIV-1 RNA, and genotypic/phenotypic resistance testing was performed if HIV-1 RNA exceeded 1,000 copies/ml. Virological residual activity (VRA) was defined as the difference between log(10)(HIV RNA) at week 48 or 96 and week 0 and related to 50% inhibitory concentration (IC(50)) relative to wild-type virus for ZDV and ABC (fold change [FC]). Twenty-seven samples in the ZDV-3TC-NVP group and 56 in the ZDV-3TC-ABC group contributed to the analysis. Mean VRA was significantly higher in the ZDV-3TC-ABC group than in the ZDV-3TC-NVP at week 48 (1.62 versus 0.90) and week 96 (1.29 versus 0.78). There was a weak and nonsignificant relationship between VRA and ZDV FC, with VRA decreasing by 0.1 log(10) copies/ml per 2-fold increase in ZDV. The association with ABC FC was much stronger, with a marked reduction in VRA occurring at ABC FC values greater than approximately 2. This information should be considered in future treatment guidelines relevant to resource-poor settings.
authors.affiliation: MRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA, United Kingdom. d.dunn@ctu.mrc.ac.uk
authors.forename: D T
authors.initials: DT
authors.lastname: Dunn
authors.forename: R L
authors.initials: RL
authors.lastname: Goodall
authors.forename: P
authors.initials: P
authors.lastname: Munderi
authors.forename: C
authors.initials: C
authors.lastname: Kityo
authors.forename: M
authors.initials: M
authors.lastname: Ranopa
authors.forename: L
authors.initials: L
authors.lastname: Bacheler
authors.forename: M
authors.initials: M
authors.lastname: Van Houtte
authors.forename: C
authors.initials: C
authors.lastname: Gilks
authors.forename: P
authors.initials: P
authors.lastname: Kaleebu
authors.forename: D
authors.initials: D
authors.lastname: Pillay
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019829:Nevirapine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D019259:Lamivudine; D019829:Nevirapine; D012367:RNA, Viral; D015215:Zidovudine; D000099227:Abacavir