Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

Abstract

There is significant intra-and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI 95 There is significant controversy regarding ritonavir-boosted protease inhibitor (PI) monotherapy as a maintenance therapeutic strategy (1-5). Notwithstanding, a considerable proportion of patients maintained an undetectable viremia on lopinavirritonavir maintenance monotherapy (mtLPVr) and could benefit from a simpler regimen without nucleoside analogues or other antiretroviral drugs. Moreover, lack of adherence has been indicated as the main reason for virological failure (VF) in different studies (6-13).Moreover, there is significant intra-and intersubject variability in LPV plasma concentrations after standard dosing, determined largely by variability in drug absorption, cytochrome P450 metabolism, plasma protein binding, and drug transporter activity, which may affect the disposition of the drug (14, 15). As LPV plasma concentrations and the genotype inhibitory quotient have been related to virological efficacy in experienced patients on LPVr-based regimens (16)(17)(18)(19), in this study, we tested whether low plasma LPV trough concentrations contribute to VF throughout the mtLPVr treatment period. The confirmation of this hypothesis would demonstrate that LPV therapeutic drug monitoring could be useful in improving the efficacy of LPV when prescribed as a monotherapy. MATERIALS AND METHODSStudy population and design. From April 2009 to April 2010, adult HIV-1-infected patients who started a regimen of mtLPVr at our outpatient clinic were consecutively included in this observational, prospective, open-label study. The LPVr dosing regimen (400 mg of LPV and 100 mg of ritonavir twice daily or 800 mg-200 mg once daily) was selected by the patients' physicians. All subjects had plasma HIV RNA levels of Ͻ50 copies/ml for at least 6 months. Patients with VF while on a PI-containing regimen were also included in the study when genotypic resistance tests showed no major or Յ3 minor resistance mutations associated with reduced...

Predictors of virological failure in HIV‐1‐infected patients switching to dolutegravir maintenance monotherapy

“…We were unable to analyse adherence as a predictor of VF because the inclusion and exclusion criteria of the study led to the selection of a very therapy-adherent study population: no history of VF on any previous cART regimen, self-reported adherence during DTG monotherapy > 95%, and therapeutic DTG plasma concentrations in all patients with and without VF. DTG plasma concentrations were adequate in both groups, and there was no significant difference in DTG plasma concentration between patients with and without VF, which is consistent with previous studies which did not identify lower PI plasma concentrations as a risk factor for VF in patients receiving PI monotherapy [16,17]. It must be noted that drug level measurement was only performed at single time-points, so the possibility of temporary nonadherence between study visits cannot be ruled out.…”

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

“…1B and Table 1). HIV-1 patients treated with 400 mg of lopinavir and 100 mg of ritonavir twice daily may reach the minimal lopinavir serum concentration at 9.4 μM (IQR 7.2-12.1 μM), which is below the EC 50 against SARS-CoV-2 virus in vitro (Lopez-Cortes et al, 2013). Currently, lopinavir/ritonavir at 400mg/100 mg twice daily with or without ribavirin are part of the recommended treatment for managing COVID-19 patients in China (China National Health Commission, 2020).…”

Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2’s main protease

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