Short Communication: Comparable Safety and Efficacy with Once-Daily Versus Twice-Daily Dosing of Lopinavir/Ritonavir Tablets with Emtricitabine + Tenofovir DF in Antiretroviral-Naïve, HIV Type 1-Infected Subjects: 96 Week Final Results of the Randomized Trial M05-730

Abstract

Sustained viral suppression with antiretroviral therapy improves clinical outcomes for HIV-infected individuals. Study M05-730 evaluated the long-term antiviral activity, safety, tolerability, emergence of resistance, and compliance with once-daily (QD) versus twice-daily (BID) lopinavir/ritonavir (LPV/r) combination therapy in treatment-naïve, HIV-1-infected subjects through 96 weeks. Antiretroviral-naïve subjects with HIV-1 RNA levels >1000 copies/ml were randomized to LPV/r QD (N = 333) or BID (N = 331) with tenofovir DF and emtricitabine. Through 96 weeks, 77 subjects from each group discontinued prematurely; adverse or HIV-related events contributed to discontinuation of 36 subjects overall, with no significant differences between treatment groups. At 96 weeks, 216 QD subjects (64.9%) and 229 BID subjects (69.2%) had HIV-1 RNA <50 copies/ml (p = 0.249) by intent-to-treat analysis. Evaluation of the time to virologic failure indicated that 85.0% and 80.7% of QD and BID subjects, respectively, maintained virologic suppression through 96 weeks (p = 0.638). QD subjects demonstrated greater adherence levels. There were no significant differences in virologic response when subjects were analyzed according to baseline disease state. Emergence of postbaseline resistance mutations occurred at similar low rates in each dosing group. Diarrhea was the most common moderate-to-severe drug-related adverse event reported; the most common Grade 3+ laboratory abnormalities were elevations of total cholesterol and triglycerides, occurring with similar incidence regardless of LPV/r dosing frequency. QD dosing of LPV/r was associated with similar durability of viral suppression and low rates of genotypic resistance and treatment-limiting adverse events as compared with BID dosing in treatment-naïve subjects through 96 weeks of treatment.

Lower Pill Burden and Once-Daily Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials

“…Of the 46 articles, 27 did not meet the inclusion criteria and were excluded. Nineteen studies [5, 17–19, 21, 22, 24, 41–49, 51–53 ] with useable outcome data involving 6312 individuals met the inclusion criteria and were included. Table 1 shows the characteristics of the included studies.…”

Impact of baseline HIV‐1 RNA levels on initial highly active antiretroviral therapy outcome: a meta‐analysis of 12,370 patients in 21 clinical trials*

“…The MEDLINE search produced 21 clinical trials with standardized efficacy data at week 48, analysed by baseline HIV‐1 RNA (Table ). Of the trials selected for the analysis, eight were comparisons of NNRTIs (Table a), eight were comparisons of boosted PIs (Table b) and five were comparisons of an NNRTI with a boosted PI ( n = 1), an integrase inhibitor ( n = 3) or a CCR5 antagonist ( n = 1) (Table c).…”

No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

“…Study 4 was an open-label, randomized phase 3 study comparing the pharmacokinetics and pharmacodynamics of LPV/r at 800/200 mg once daily (QD) and 400/100 mg BID in 664 treatment-naive HIV-infected male and nonpregnant female subjects receiving the LPV/r tablet and SGC formulations (22) Data from 316 subjects receiving the 400/100-mg BID regimen were included in this analysis.…”