Response of HIV positive patients to the long-term salvage therapy by lopinavir/ritonavir (original) (raw)
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Antiviral therapy, 2003
We evaluated the virological outcome of lopinavir/ritonavir (LPV/RTV) in 224 HIV-1-infected and protease inhibitor (PI)-experienced patients showing virological failure to a highly active antiretroviral therapy (HAART) regimen and followed up for at least 3 months. At baseline, the median level of plasma viraemia was 4.61 log10 copies/ml (range 3-6.48) and the median CD4 cell count was 219 cells/mm3 (range 1-836). During a median follow-up of 272 days (range 92-635), we observed an increase in the number of CD4 cells (P=0.02) and a dramatic decrease in plasma viraemia levels (P=0.0001), which became undetectable in 122 patients (54.5%). The closely related predictive factors were baseline plasma viraemia levels and the number of mutations known to reduce susceptibility to LPV/RTV. Thirty-one patients (13.8%) discontinued LPV/RTV during the follow-up, and one AIDS event and three deaths were recorded. Of the 134 patients (59.8%) who underwent a baseline genotype resistance test, 22 (...
Journal of the International Association of Providers of AIDS Care (JIAPAC), 2019
Background:Characterizing viral response to lopinavir/ritonavir (LPV/r) monotherapy as second-line treatment may guide recommendations for resource-limited settings (RLS).Methods:We conducted a 48-week prospective, single-arm study of LPV/r monotherapy in patients failing first-line therapy in Nigeria. The primary outcome was sustained HIV-1 viral load (VL) <400 copies/mL at 48 weeks.Results:Of 30 enrolled patients, 28 (93%) achieved viral suppression on LPV/r, while 29 (96%) experienced low-level viremia. At 48 weeks, 9 (30%) met the primary outcome of sustained viral suppression; 14 (47%) patients were suppressed on LPV/r in a snapshot analysis. Detectable VLs at 12 and 24 weeks were strongly associated with treatment failure at 48 weeks. New resistance mutations were not detected. The trial was stopped early due to treatment failure.Conclusion:In this study, the rate of virologic failure among patients on a second-line lopinavir monotherapy regimen was relatively high and predicted by early detectable viremia. However, no LPV/r-associated resistance mutations were detected despite fluctuating low-level viremia, demonstrating the high genetic barrier to resistance of the protease inhibitor class which could be useful in RLS.
Hiv Medicine, 2007
To describe outcomes in patients starting first-line antiretroviral regimens including lopinavir/ ritonavir (LPV/r) in a routine clinic setting. Methods Previously naïve patients starting LPV/r-containing antiretroviral therapy were included in the study. Virological failure was defined as the first of two viral loads 4500 HIV-1 RNA copies/mL more than 6 months after starting LPV/r. Cumulative percentages experiencing virological failure were calculated using Kaplan-Meier methods. Results A total of 195 individuals had a median follow-up time of 1.7 years. At 48 weeks, 87.9, 77.4 and 71.6% of patients with pretreatment CD4 counts of o50, 50-200 and 4200 cells/mL, respectively, remained on LPV/r. By 48, 72 and 96 weeks, 2.2, 3.0 and 5.0% of patients, respectively, had experienced virological failure, ignoring treatment changes but censoring follow-up at discontinuation of all antiretrovirals; these percentages became 24.0, 33.7 and 42.3% when LPV/r discontinuation was considered as virological failure. Censoring those who stopped LPV/r with a viral load o50 copies/mL and considering as virological failures those who stopped LPV/r with a viral load 450 copies/mL gave 12.1, 14.6 and 17.0% virological failure at 48, 72 and 96 weeks, respectively. Median CD4 count increases at 24, 48 and 72 weeks were 167, 230 and 253 cells/mL, respectively. Conclusions Few patients experienced virological failure whilst on a LPV/r-based regimen, although it was not uncommon for patients in our clinic with higher baseline CD4 counts to discontinue LPV/r.
Journal of Acquired Immune Deficiency Syndromes, 2002
To the Editor: Lopinavir, coformulated with a boosting dose of ritonavir, (LPV/r) has been recently licensed as a new protease inhibitor (PI) with excellent pharmacokinetic properties (1). Due to the achievement of high blood levels, there is a high genetic barrier to clinical resistance to LPV/r. Indeed, as many as 11 mutations at HIV-1 protease codons 10, 20, 24, 46, 53, 54, 63, 71, 82, 84 and 90 have been reported to contribute to LPV/r resistance, and at least 8 of these appear to be required for significant clinical resistance (2). Although preliminary LPV/r efficacy studies have yielded promising results, especially on drug-naive subjects (3-5), the role of LPV/r as a salvage therapy for heavily experienced patients in clinical practice has not yet been fully elucidated. We report an observational study of the first 41 patients shifted to an LPV/r-including regimen and reaching at least 16 weeks (mean ± SD, 23 ± 5 weeks) of LPV/r therapy in our area. The subjects were pretreated with a median of 5 (range 4-6) nucleoside reverse transcriptase inhibitors (NRTIs), 1 (range 1-2) nonnucleoside reverse transcriptase inhibitors (NNRTIs) and 4 (range 2-5) PIs. The median number of different treatment regimens used before commencing LPV/r therapy was 8 (range 4-13), including dual NRTI treatments, and the median HIV-1 RNA load and CD4 + counts at baseline were 5.29 (range 3.79-7.00) log 10 copies/mL and 138 (range 4-689) cells/L, respectively. A total of 26 (63.4%) and 30 (73.2%) subjects had >10 5 HIV-1 RNA copies/mL and <200 CD4 + cells/L, respectively. Genotypic antiretroviral resistance analysis (6) at baseline revealed a median number of 6 (range 0-10) NRTI resistance mutations, 1 (range 0-4) NNRTI resistance mutations, and 2 (range 0-4) and 5 (range 1-8) primary and accessory PI
Journal of Antimicrobial Chemotherapy, 2018
Background: Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection. Objectives: To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years. Methods: Adults on stable ART with plasma HIV-1 RNA viral load ,50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load ,50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death. Results: In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n " 98) and EFV/FTC/TDF arms (n " 97), yielding a difference of-6.8% (lower limit of the 95% two-sided CI:-19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n " 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n " 2). No unexpected serious clinical events occurred.
Journal of Antimicrobial Chemotherapy, 2010
We evaluated a monotherapy maintenance regimen with lopinavir/ritonavir versus continuing current combined antiretroviral treatment (cART) in HIV patients with suppressed plasma HIV-1 RNA. Patients and methods: This was an open-label, non-inferiority, multicentre trial in 23 sites in France. Adults were randomized if they had no history of virological failure while receiving a protease inhibitor, maintained HIV-1 RNA ,50 copies/mL for at least 6 months and did not change cART during the last 3 months. The primary endpoint was the proportion of patients with HIV-1 RNA ,50 copies/mL at Week 48 (non-inferiority margin set at 212%) with missing data and treatment modification considered as failure. The trial has been registered in ClinicalTrials.gov under the identifier NCT00140751. Results: At Week 48, 84% (73/87) of patients in the lopinavir/ritonavir monotherapy group met the primary endpoint compared with 88% (87/99) in the cART group [difference, 24.0%, lower limit of 90% two-sided confidence interval (CI) for difference, 212.4%]. In secondary analysis with success defined as plasma HIV-1 RNA ,400 copies/mL, 87% (76/87) of patients in the lopinavir/ritonavir monotherapy group were virologically suppressed compared with 88% (87/99) in the cART group (difference, 20.5%, lower limit of 90% two-sided CI for difference, 28.5%). If antiretroviral treatment intensification was taken into account, 91% (79/87) of patients in the lopinavir/ritonavir monotherapy group met the primary endpoint compared with 88% (87/99) in the cART group (difference, +2.9%, lower limit of 90% two-sided CI for difference, 24.5%). Failures of lopinavir/ritonavir monotherapy did not show acquired resistance mutations in the protease gene. Conclusions: Lopinavir/ritonavir monotherapy did not achieve non-inferiority versus cART for maintaining plasma HIV-1 RNA ,50 copies/mL. Nevertheless, the incidence of virological failure was low (mostly with HIV-1 RNA ,400 copies/mL) and easily managed by treatment intensification.
PloS one, 2017
The primary objective of this study was to estimate the incidence of treatment failure (TF) to protease inhibitor monotherapies (PI/r-MT) with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r). A multicenter cohort of HIV-infected patients with viral load (VL) ≤50 copies/mL, who underwent a switch from any triple combination therapy to PI/r-MT with either LPV/r or DRV/r. VL was assessed in each center according to local procedures. Residual viremia was defined by any HIV-RNA value detectable below 50 copies/mL by a Real-Time PCR method. Standard survival analysis was used to estimate the rate of TF (defined by virological failure or interruption of monotherapy or reintroduction of combination therapy). A multivariable Cox regression analysis with automatic stepwise procedures was used to identify factors independently associated with TF among nadir and baseline CD4+ counts, residual viremia, time spent with <50 HIV-RNA copies/mL before switch, history of virological fail...