Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1-infected protease inhibitor-experienced patients.

نویسندگان

  • Constance A Benson
  • Steven G Deeks
  • Scott C Brun
  • Roy M Gulick
  • Joseph J Eron
  • Harold A Kessler
  • Robert L Murphy
  • Charles Hicks
  • Martin King
  • David Wheeler
  • Judith Feinberg
  • Richard Stryker
  • Paul E Sax
  • Sharon Riddler
  • Melanie Thompson
  • Kathryn Real
  • Ann Hsu
  • Dale Kempf
  • Anthony J Japour
  • Eugene Sun
چکیده

The safety and antiviral activity of lopinavir (Lpv), a protease inhibitor (PI) coformulated with ritonavir (Rtv) to enhance its pharmacokinetic properties, were evaluated in 70 patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL on a first PI-containing regimen. Patients were randomized to substitute only the PI with Lpv/Rtv, 400/100 mg or 400/200 mg twice daily. On day 15, nevirapine (200 mg 2x/day) was added, and nucleoside reverse-transcriptase inhibitors were changed. Despite a >4-fold reduction in phenotypic susceptibility to the preentry PI in 63% of patients, mean plasma HIV-1 RNA levels declined by 1.14 log(10) copies/mL after 2 weeks of Lpv/Rtv. At week 48, 86% of subjects receiving treatment had plasma HIV-1 RNA levels of <400 copies/mL; 76% had levels <50 HIV-1 RNA copies/mL (intent-to-treat: 70% and 60%, respectively). Mean CD4 cell counts increased by 125 cells/muL. Three patients discontinued therapy for drug-related adverse events.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Analysis of the virological response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1-infected patients receiving lopinavir/ritonavir therapy.

The virological response of multiple protease inhibitor-experienced, non-nucleoside reverse transcriptase inhibitor-naive, HIV-1-infected subjects was examined with respect to baseline viral phenotype and genotype through 72 weeks of therapy with lopinavir/ritonavir plus efavirenz and nucleoside reverse transcriptase inhibitors (Study M98-957). Using a 'dropouts as censored' analysis, plasma HI...

متن کامل

Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA).

BACKGROUND Nucleoside reverse-transcriptase inhibitor (NRTI)-related mitochondrial toxicity has been suggested as a key factor in the induction of antiretroviral-related lipoatrophy. This study aimed to evaluate in vivo the effects of NRTI withdrawal on mitochondrial parameters and body fat distribution. METHODS A multicenter, prospective, randomized trial assessed the efficacy and tolerabili...

متن کامل

Role of etravirine in the management of treatment-experienced patients with human immunodeficiency virus type 1

Etravirine is an oral diarylpyrimidine compound, a second-generation human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI) with expanded antiviral activity against NNRTI-resistant HIV-1, to be used in combination therapy for treatment-experienced patients. Compared with first-generation NNRTIs, etravirine has a high genetic barrier to resistance, and...

متن کامل

Novel four-drug salvage treatment regimens after failure of a human immunodeficiency virus type 1 protease inhibitor-containing regimen: antiviral activity and correlation of baseline phenotypic drug susceptibility with virologic outcome.

Twenty human immunodeficiency virus-infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n=10) or nevirapine (n=10). Patients treated with the nevirapine-containing regimen experienced significantly gr...

متن کامل

In vitro antiviral activity of the novel, tyrosyl-based human immunodeficiency virus (HIV) type 1 protease inhibitor brecanavir (GW640385) in combination with other antiretrovirals and against a panel of protease inhibitor-resistant HIV.

Brecanavir, a novel tyrosyl-based arylsulfonamide, high-affinity, human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI), has been evaluated for anti-HIV activity in several in vitro assays. Preclinical assessment of brecanavir indicated that this compound potently inhibited HIV-1 in cell culture assays with 50% effective concentrations (EC(50)s) of 0.2 to 0.53 nM and was equally a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of infectious diseases

دوره 185 5  شماره 

صفحات  -

تاریخ انتشار 2002