title: Twice-daily amprenavir 1200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-1-infected patients.
abstract: BACKGROUND
  Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200).
  
  
  METHODS
  ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with > or = 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was > or =-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period.
  
  
  RESULTS
  211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1-4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later.
  
  
  CONCLUSIONS
  APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.
authors.affiliation: University of South Florida, College of Medicine, Tampa, Florida, USA. jnadler@hsc.usf.edu
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Nadler
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Gathe
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Richmond
authors.forename: Qiming
authors.initials: Q
authors.lastname: Liao
authors.forename: Sandy
authors.initials: S
authors.lastname: Griffith
authors.forename: C Tracey
authors.initials: CT
authors.lastname: Lancaster
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Hernandez
authors.forename: Keith A
authors.initials: KA
authors.lastname: Pappa
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002219:Carbamates; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D012367:RNA, Viral; D013449:Sulfonamides; C095108:amprenavir; D019438:Ritonavir