Pharmacokinetics and 48-week safety and efficacy of generic ritonavir tablet-boosted atazanavir in HIV-1-infected Thai adults

Antivir Ther. 2018;23(8):699-703. doi: 10.3851/IMP3267.

Abstract

Background: Ritonavir (RTV) tablets were not available in Thailand until they were manufactured by the Government Pharmaceutical Organization of Thailand. We assessed pharmacokinetics (PK), safety and efficacy of generic RTV-boosted atazanavir (ATV) in virologically suppressed HIV-1-infected Thai adults.

Methods: Virologically suppressed HIV-1-infected Thai adults who currently use ATV (either 200 or 300 mg) with Norvir® soft gel capsule (SGC) 100-mg-based regimen were enrolled into this prospective, 48-week single-arm study. Participants switched from Norvir® SGC to generic RTV. Plasma trough concentration (Ctrough) was assessed at baseline before switching to generic RTV and week 24 in all participants, with the target ATV Ctrough of 0.15 mg/l. Plasma HIV-1 RNA and other laboratory safety parameters were assessed until week 48.

Results: Of 100 participants (51% male) enrolled, 50% was using ATV 200 mg and 50% was using 300 mg at the time RTV SGC were changed into generic tablets. All participants used two nucleoside reverse transcriptase inhibitors (NRTIs) as backbone. There were no significant changes in mean (sd) Ctrough of RTV (0.20 [0.33] versus 0.23 [0.39]; P=0.21) and ATV (0.83 [0.93] versus 0.88 [0.95]; P=0.62) between baseline and week 24. From entry to week 48, median alanine aminotransferase significantly increased from 25 to 30 IU/l (P=0.001) and total bilirubin significantly decreased from 1.7 to 1.3 (P=0.04). One study drug related grade 3 adverse event was reported. All but one participant maintained plasma HIV-1 RNA <50 copies/ml after 48 weeks.

Conclusions: Generic RTV-boosted ATV showed adequate levels, good tolerability and great efficacy after 48 weeks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics*
  • Atazanavir Sulfate / administration & dosage
  • Atazanavir Sulfate / adverse effects
  • Atazanavir Sulfate / pharmacokinetics*
  • Drug Monitoring
  • Drugs, Generic
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects
  • Ritonavir / pharmacokinetics*
  • Tablets
  • Time Factors
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Drugs, Generic
  • Tablets
  • Atazanavir Sulfate
  • Ritonavir