ritonavir and Nervous-System-Diseases

Highly active antiretroviral therapy containing three nucleoside reverse transcriptase inhibitors has been somewhat successful, but the clinical efficacy is unclear.. Randomized, controlled, open-label trial of 180 antiretroviral drug-naive HIV-infected patients allocated to a regimen of abacavir, stavudine and didanosine (A/S/D, n = 60), ritonavir and saquinavir (R/S 400/400 mg twice daily; n = 60) or nelfinavir and nevirapine (N/N 1250/200 mg twice daily; n = 60); the latter two in combination with lamivudine and zidovudine. The primary endpoint was HIV plasma RNA < or = 20 copies/ml after 48 weeks.. At baseline, the median CD4 cell count was 161 x 106 cells/l (range, 0-920) and the HIV RNA was 5.0 log10 copies/ml (range, 2.7-6.7). At 48 weeks, 43% in the A/S/D arm had a HIV RNA < or = 20 copies/ml, compared with 69% in the N/N arm (P < 0.01) and 62% in the R/S arm (P < 0.05). In a multivariate analysis, the A/S/D arm had an odds ratio of obtaining a viral load of < or = 20 copies/ml at week 48 of 0.25 [95% confidence interval (CI) 0.10-0.59] versus N/N and 0.53 (95% CI, 0.33-0.83) versus R/S. The A/S/D arm had a particularly poor outcome in patients with higher viral load and AIDS at baseline: 63% had to discontinue A/S/D (any drug). Side effects were more frequent in the A/S/D arm and included neuropathy 27%, suspicion of hypersensitivity 12%, and increase in lactate accompanied by systemic symptoms 8%.. The A/S/D regimen had a low efficacy and a high frequency of adverse events and cannot be recommended.

Topics: Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Didanosine; Dideoxynucleosides; Drug Therapy, Combination; Female; HIV Infections; Humans; Lactates; Male; Middle Aged; Nelfinavir; Nervous System Diseases; Nevirapine; Ritonavir; RNA, Viral; Saquinavir; Stavudine; Treatment Outcome

Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.

Topics: Aged; Analgesics; Cardiovascular Diseases; Cohort Studies; COVID-19; COVID-19 Drug Treatment; Diuretics; Drug Interactions; Female; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Nervous System Diseases; Polypharmacy; Risk Factors; Ritonavir; SARS-CoV-2; Severity of Illness Index; Spain

Topics: Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Darunavir; Female; HIV Infections; Humans; Male; Mental Disorders; Middle Aged; Nervous System Diseases; Ritonavir; Sulfonamides

The incidence of Hodgkin lymphoma (HL) is rising among individuals infected with human immunodeficiency virus (HIV). Standard treatment regimens include vinblastine, which is known to cause neurotoxicity (NT) and is metabolized by cytochrome 3A4 (CYP3A4). This is inhibited by protease inhibitors (PIs), possibly increasing vinblastine exposure. There is little information on how interactions affect clinical outcome. A retrospective review of 32 patients with HIV-HL receiving chemotherapy with curative intent was performed to identify the frequency and risk factors for NT, hematologic toxicity (HT) and lung toxicity (LT). Treatment was: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in 90%, MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vinblastine) in 10% and HAART (highly active anti-retroviral therapy) in 63%. Seventeen potential risk factors and 18 individual anti-retroviral (ARV) agents were examined, and only ritonavir or lopinavir use was found to have a significant association with toxicity. Grade 3-4 NT occurred in five patients, grade 3-4 HT in 17, infectious complications in 10 and bleomycin LT in three. Ritonavir and lopinavir use was associated with grade 3-4 NT (p = 0.03 and p = 0.01, respectively), and ritonavir with any HT (p = 0.04). Patients with HIV-HL experienced an increased incidence of NT and possibly HT. The use of ritonavir or lopinavir was associated with NT, suggesting a clinically significant interaction with vinblastine. Prospective pharmacokinetic studies to devise a rational dosing strategy for vinblastine in patients receiving ritonavir/lopinavir are warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Dacarbazine; Doxorubicin; Female; Hematologic Diseases; HIV Infections; HIV Protease Inhibitors; Hodgkin Disease; Humans; Incidence; Kaplan-Meier Estimate; Lopinavir; Lung Diseases; Male; Mechlorethamine; Middle Aged; Nervous System Diseases; Prednisone; Procarbazine; Prognosis; Retrospective Studies; Ritonavir; Vinblastine; Vincristine