ritonavir and Kidney-Calculi

There is no standard treatment of HIV-infected patients who fail protease inhibitor (PI)-containing antiretroviral therapy. This open-label, noncomparative 24-week study with a 24-week extension evaluated the efficacy, safety, and tolerability of twice-daily indinavir/ritonavir 800/200 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) in this population. Presented here are the results of the 24-week study. Patients were HIV-infected adults who had prior viral RNA (vRNA) suppression (<400 copies/mL), subsequent failure (> or =400 and < or =100,000 copies/mL) on antiretroviral therapy, and at least one new NRTI available for treatment. The proportions of patients achieving plasma vRNA <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat (ITT) models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F). Mean changes from baseline in vRNA and CD4 cell count were evaluated using DAO and an ITT mixed-model approach. Sixty-three patients (87% male) with a mean age of 42 years and mean baseline vRNA and CD4 cell counts of 3.8 log(10) copies/mL and 360 cells/mm(3), respectively, were enrolled. The proportion (95% confidence interval) of patients achieving vRNA <400 and <50 copies/mL at week 24 were 76% (61%, 87%) and 50% (35%, 65%) for DAO, 64% (50%, 75%) and 43% (30%, 56%) for GEE, and 56% (43%, 68%) and 37% (25%, 50%) for NC = F, respectively. At Week 24, baseline vRNA decreased by >1.0 log(10) copies/mL and CD4 cell counts increased by approximately 90 cells/mm(3). Three patients (5%) experienced serious drug-related adverse events. Seven patients (11%) discontinued treatment due to clinical or laboratory adverse events. In this study, the enhanced, twice-daily regimen of indinavir/ritonavir 800/200 mg plus 2 NRTIs provided suppression of HIV in many patients who had failed a PI-containing regimen and was generally well tolerated.

Topics: Acidosis; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Hyperbilirubinemia; Hypercholesterolemia; Hyperglycemia; Hypertriglyceridemia; Indinavir; Kidney Calculi; Male; Middle Aged; Ritonavir; RNA, Viral; Treatment Failure

Nephrolithiasis is a well-known side effect of many HIV protease inhibitors. However, there have not been reports of stones associated with ritonavir use. Here, we report the case of a 33-year-old woman with HIV on antiretroviral therapy who presented with sharp left flank pain and passed a stone that was later found to contain only ritonavir. Of note, the patient's treatment regimen had not included ritonavir for 2 years prior to this incidence. This case is notable both for the novel finding of a renal calculus composed entirely of ritonavir and the development of nephrolithiasis years after cessation of the aggravating drug. This finding suggests that patients on ritonavir should be more closely monitored and for longer periods of time for potential lithiasis formation.

Topics: Adult; Female; HIV Protease Inhibitors; Humans; Kidney Calculi; Ritonavir

New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin. Hyperbilirubinemia with or without jaundice is a well known side effect of atazanavir, because of its inhibition of uridine diphosphate-glucuronosyl transferase. We speculate that in this case hyperbilirubinemia worsening was due to atazanavir/ribavirin co-administration. However, pharmacokinetic data are lacking about atazanavir/daclatasvir concomitant administration in real life setting.

Topics: Adult; Anti-HIV Agents; Antiviral Agents; Atazanavir Sulfate; Biliary Tract Diseases; Carbamates; Coinfection; Dideoxynucleosides; Drug Combinations; Drug Interactions; Genotype; Hepacivirus; Hepatitis C; HIV Infections; Humans; Imidazoles; Kidney Calculi; Lamivudine; Lithiasis; Male; Pyrrolidines; Ribavirin; Ritonavir; Sofosbuvir; Valine

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; HIV Protease Inhibitors; Humans; Kidney Calculi; Male; Oligopeptides; Pyridines; Ritonavir

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Female; HIV Infections; HIV Protease Inhibitors; Humans; Kidney Calculi; Male; Oligopeptides; Pyridines; Ritonavir

Little information is available on the incidence of renal stones with ritonavir-boosted atazanavir (ATV/r) use.. In a single-center study, the incidence of renal stones was compared between human immunodeficiency virus (HIV)-infected patients who commenced ritonavir-boosted atazanavir (ATV/r)-containing antiretroviral (ARV) therapy (the ATV/r group) and those who were receiving other protease inhibitors (the other PIs group). The effects of ATV/r were estimated by univariate and multivariate Cox proportional hazards regression models. Other possible risk factors were evaluated by univariate analysis, and those found to be significant were entered into multivariate analysis.. Renal stones were diagnosed in 31 patients (23.7 cases per 1000 person-years) in the ATV/r group (n = 465) and 4 in patients (2.2 cases per 1000 person-years) in the other PIs group (n = 775). ATV/r use was significantly associated with renal stones, by univariate and multivariate analyses (adjusted hazard ratio, 10.44; 95% confidence interval [CI], 3.685-29.59; P < .001). ATV/r remained a significant risk factor for renal stones in all subgroups stratified by the median values of baseline variables. In the 31 patients receiving ATV/r who developed renal stones, the median time from commencement of ATV/r to diagnosis was 24.5 months (interquartile range, 14.7-34.6 months). Of the 18 patients who continued ATV/r despite the diagnosis of renal stones, 6 (33.3%) experienced recurrence. No patient who discontinued ATV/r experienced recurrence during the observation period (250.6 person-months).. The incidence of renal stones was substantially higher among patients in the ATV/r group, compared with patients in the other PIs group. Continuation of ATV/r after diagnosis of renal stones was associated with a high rate of recurrence. Switching ATV/r to other ARVs is warranted in patients who develop renal stones.

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Cohort Studies; Female; HIV Infections; HIV Protease Inhibitors; Humans; Incidence; Kidney Calculi; Male; Middle Aged; Oligopeptides; Pyridines; Retrospective Studies; Ritonavir

Topics: Adolescent; Anti-HIV Agents; Child Behavior Disorders; Drug Resistance, Multiple, Viral; Drug Therapy, Combination; Gastrointestinal Diseases; HIV Infections; HIV Protease Inhibitors; HIV Reverse Transcriptase; Humans; Kidney Calculi; Lopinavir; Male; Mutation, Missense; Pyrimidinones; Reverse Transcriptase Inhibitors; Ritonavir