title: Predictors of loss of virologic response in subjects who simplified to lopinavir/ritonavir monotherapy from lopinavir/ritonavir plus zidovudine/lamivudine.
abstract: Previous studies have demonstrated that lopinavir/ritonavir monotherapy maintained plasma HIV-1 RNA suppression in a large proportion of antiretroviral naive subjects. However, more subjects receiving lopinavir/ritonavir monotherapy experienced confirmed virologic rebound >50 copies/ml compared to a standard three-drug HAART regimen. In this study, we sought to determine the factors associated with maintenance of virologic suppression in subjects receiving lopinavir/ritonavir monotherapy. Antiretroviral-naive HIV-1-infected volunteers were randomized 2:1 to initiate a lopinavir/ritonavir-based combination regimen followed by simplification to lopinavir/ritonavir monotherapy or an efavirenz-based triple combination therapy and followed for 96 weeks. Potential predictors of time to loss of virologic response included baseline demographics, baseline HIV-1 RNA levels, baseline CD4(+) T cell counts, adherence as determined by 4-day subject recall, duration of HIV-1 RNA <50 copies/ml prior to simplification, and lopinavir concentrations. By the Cox proportional hazards model, higher reported adherence levels and higher baseline CD4(+) T cell counts were associated with a greater likelihood of maintaining virologic suppression while receiving lopinavir/ritonavir monotherapy. Lopinavir concentrations, including trough concentrations, were not significantly associated with virologic outcomes. This analysis suggests that adherence and higher baseline CD4(+) T cell counts may help to predict who will sustain virologic suppression with lopinavir/ritonavir monotherapy. The data also suggest that measuring lopinavir concentrations is not useful in predicting virologic response in these patients.
authors.affiliation: University of Miami School of Medicine, Miami, Florida 33136, USA.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Campo
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Da Silva
authors.forename: Laurent
authors.initials: L
authors.lastname: Cotte
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Gathe
authors.forename: Brian
authors.initials: B
authors.lastname: Gazzard
authors.forename: Charles B
authors.initials: CB
authors.lastname: Hicks
authors.forename: Cheri E
authors.initials: CE
authors.lastname: Klein
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: Martin S
authors.initials: MS
authors.lastname: King
authors.forename: Barry M
authors.initials: BM
authors.lastname: Bernstein
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir; D010949:Plasma / Q000737:chemistry; D011744:Pyrimidinones / Q000097:blood / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir