Antiretroviral-naive HIV-1-infected volunteers received zidovudine/lamivudine plus either lopinavir/ritonavir (n=104) or efavirenz (n=51). Lopinavir/ritonavir-treated subjects demonstrating 3 consecutive monthly HIV-1 RNA levels <50 copies/mL started lopinavir/ritonavir monotherapy. In previous-failure=failure analysis, 48% (lopinavir/ritonavir) and 61% (efavirenz) maintained HIV-1 RNA at <50 copies/mL through week 96, (P= .
View Article and Find Full Text PDFResidual viremia can be detected in most HIV-1-infected patients on antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml, but the source and duration of this viremia is currently unknown. Therefore, we analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA assay with single-copy sensitivity. All patients were on therapy (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies per ml by week 96 of the study and thereafter.
View Article and Find Full Text PDFObjective: Evaluate efficacy and tolerability of lopinavir/ritonavir (LPV/r) plus stavudine and lamivudine long term in antiretroviral-naïve patients.
Design: Open-label follow-up of prospective, randomized, multicenter trial.
Method: Antiretroviral-naïve HIV-infected subjects (N = 00) received of 3 doses of LPV/r plus stavudine and lamivudine for 48 weeks then received LPV/r soft-gel capsules 400/00 mg plus stavudine and lamivudine.
Objective: To investigate the efficacy and safety of high-dose lopinavir/ritonavir (LPV/r) therapy in multiple protease inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced subjects.
Method: Thirty-six HIV-1-infected subjects were randomized to LPV/r 400/300 mg or 667/167 mg bid in a 48-week, open-label study. Subjects also received investigator-selected nucleoside reverse transcriptase inhibitors (NRTIs).
Current antiretroviral therapy is effective in suppressing but not eliminating HIV-1 infection. Understanding the source of viral persistence is essential for developing strategies to eradicate HIV-1 infection. We therefore investigated the level of plasma HIV-1 RNA in patients with viremia suppressed to less than 50-75 copies/ml on standard protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy using a new, real-time PCR-based assay for HIV-1 RNA with a limit of detection of one copy of HIV-1 RNA.
View Article and Find Full Text PDFLopinavir, an HIV protease inhibitor, is coformulated with ritonavir to enhance the bioavailability and pharmacokinetics of lopinavir. The original solid oral formulation of lopinavir/ritonavir, a soft-gelatin capsule (SGC), requires refrigerated storage, is taken as 6 capsules daily at the recommended adult dose, and is administered with food to maximize the bioavailability of lopinavir. Melt extrusion technology was used to produce a tablet formulation reducing the number of dosage units administered per day and simplifying storage requirements.
View Article and Find Full Text PDFPurpose: Adverse effects are important determinants of quality of life (QOL) during highly active antiretroviral therapy (HAART). The PLATO study investigated the association between changes in patient-reported outcomes including QOL and substitution with lopinavir/ritonavir in patients experiencing side effects (SEs).
Method: HIV-1-infected participants (N = 849) with undetectable viral load experiencing Grade-2 SEs of the protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) component of their HAART regimen were randomized to immediate (baseline) or deferred (week 4) substitution with lopinavir/ritonavir soft-gel capsules 400/100 mg bid.
Objective: To evaluate the safety and noninferiority and to explore the efficacy of administration of once-daily versus twice-daily lopinavir/ritonavir (LPV/r) in antiretroviral-naive HIV-1-infected subjects.
Design: Randomized, open-label, multicenter, comparative study.
Methods: One hundred ninety antiretroviral-naive subjects with plasma HIV-1 RNA level >1000 copies/mL and any CD4 cell count were randomized to lopinavir/ritonavir at a dose of 800/200 mg administered once daily (n = 115) or lopinavir/ritonavir at a dose of 400/100 mg administered twice daily (n = 75).
The effect of hepatic impairment on lopinavir/ritonavir pharmacokinetics was investigated. Twenty-four HIV-1-infected subjects received lopinavir 400 mg/ritonavir 100 mg twice daily prior to and during the study: 6 each with mild or moderate hepatic impairment (and hepatitis C virus coinfected) and 12 with normal hepatic function. Mild and moderate hepatic impairment showed similar effects on lopinavir pharmacokinetics.
View Article and Find Full Text PDFBackground: Relationships between adherence to protease inhibitor (PI)-based therapy and resistance development have not been fully characterized.
Methods: We conducted a double-blind, randomized, controlled study of lopinavir/ritonavir versus nelfinavir, each administered with stavudine and lamivudine, in 653 antiretroviral-naive, human immunodeficiency virus (HIV)-1-infected patients. Relationships between adherence and probability of resistance development were evaluated by local linear regression or logistic regression.
Baseline CD4 cell counts and human immunodeficiency virus (HIV)-1 RNA levels have been shown to predict immunologic and virologic responses in HIV-infected patients receiving antiretroviral therapy. In our randomized, double-blind, comparative trial, 653 antiretroviral therapy-naive patients received lopinavir/ritonavir or nelfinavir, plus stavudine and lamivudine, for up to 96 weeks. The risk of loss of virologic response was significantly higher for nelfinavir-treated patients than for lopinavir/ritonavir-treated patients (Cox model hazard ratio, 2.
View Article and Find Full Text PDFObjective: Combination antiretroviral therapy with lopinavir/ritonavir (LPV/r) has been highly effective in clinical trials. Results of long-term therapy with LPV/r-based regimens have not been previously reported. This study describes the 4-year (204-week) safety and antiretroviral activity of LPV/r-based treatment in antiretroviral-naive individuals.
View Article and Find Full Text PDFThe 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 HIV RNA < or = 400 copies/ml was observed in 93% (25/27), 73% (11/15) and 25% (2/8) of subjects with <10-fold, 10- to 40-fold, and >40-fold reduced susceptibility to lopinavir at baseline, respectively. In addition, virological response was observed in 91% (21/23), 71% (15/21) and 33% (2/6) of subjects with baseline lopinavir mutation score of 0-5, 6-7 and > or = 8, respectively.
View Article and Find Full Text PDFThe 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.
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