title: Viral replication under combination antiretroviral therapy: a comparison of four different regimens.
abstract: A mathematical model of the interaction among CD4+ T-cells, HIV-1, and antiretroviral drugs was fitted to the viral load decline following initiation of combination therapy to estimate differences in the residual reproductive capacity of virus (R(0)) in the average patient in each group. Four regimens were studied: 12 patients on 5-drug nucleoside reverse transcriptase inhibitor (NRTIs), nonnucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitor (PI)-containing combination therapy, 11 patients on PI-containing triple therapy, 10 patients on double NRTI therapy, and 10 patients on NNRTI-containing triple therapy. Model fits were used to estimate R(0). The NNRTI-containing triple therapy and the 5-drug regimen blocked viral replication to the greatest extent (R(0) = 0.85; 95% confidence interval [CI], 0.79-0.91; and 0.90, 95% CI, 0.82-0.98, respectively), with the former being significantly better than the PI-containing triple regimen (R(0) = 0.98; 95% CI, 0.92-1.03; p =.007). Both the NNRTI-containing and the 5-drug regimen, as well as the PI-containing triple therapy, were significantly better at blocking viral replication than the double NRTI therapy (R(0) = 1.04; 95% CI, 1.0-1.07). Measurement of viral load after approximately 7 days provided the most accurate measure of the degree of viral suppression induced by a given drug regimen.
authors.affiliation: Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, UK. a.ghani@ic.ac.uk
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
authors.forename: Neil M
authors.initials: NM
authors.lastname: Ferguson
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraser
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.forename: Sven
authors.initials: S
authors.lastname: Danner
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Joep
authors.initials: J
authors.lastname: Lange
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Roy M
authors.initials: RM
authors.lastname: Anderson
authors.forename: Frank
authors.initials: F
authors.lastname: De Wolf
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008433:Mathematics; D008954:Models, Biological; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors