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BMC Infectious Diseases Apr 2017Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical... (Comparative Study)
Comparative Study
BACKGROUND
Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking.
METHODS
We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason). Additional endpoints included virologic failure, discontinuation due to virologic failure, discontinuation for other reasons, and virologic suppression.
RESULTS
We studied 222 patients treated with darunavir/ritonavir and 1791 patients treated with atazanavir/ritonavir. Following multivariable adjustment, there was no difference between darunavir/ritonavir and atazanavir-ritonavir in the risk of regimen failure (adjusted hazard ratio 0.76, 95% CI 0.56 to 1.03) Darunavir/ritonavir-treated patients were at lower risk of virologic failure relative to atazanavir/ritonavir treated patients (aHR 0.50, 95% CI 0.28 to 0.91), findings driven largely by high rates of virologic failure among atazanavir/ritonavir-treated patients in the province of British Columbia. Of 108 discontinuations due to virologic failure, all occurred in patients starting atazanavir/ritonavir. There was no difference between regimens in time to discontinuation for reasons other than virologic failure (aHR 0.93; 95% CI 0.65 to 1.33) or virologic suppression (aHR 0.99, 95% CI 0.82 to 1.21).
CONCLUSIONS
The risk of regimen failure was similar between patients treated with darunavir/ritonavir and atazanavir/ritonavir. Although darunavir/ritonavir was associated with a lower risk of virologic failure relative to atazanavir/ritonavir, this difference varied substantially by Canadian province and likely reflects regional variation in prescribing practices and patient characteristics.
Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; British Columbia; Canada; Cohort Studies; Darunavir; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Retrospective Studies; Ritonavir
PubMed: 28399819
DOI: 10.1186/s12879-017-2379-8 -
Enfermedades Infecciosas Y... Jan 2018To describe the experience using the combination abacavir, lamivudine plus non-boosted atazanavir (ABC/3TC+ATV) in a group of pretreated patients. (Observational Study)
Observational Study
OBJECTIVE
To describe the experience using the combination abacavir, lamivudine plus non-boosted atazanavir (ABC/3TC+ATV) in a group of pretreated patients.
PATIENTS AND METHODS
We performed a retrospective observational study to describe baseline characteristics and the evolution of patients who had received or were treating with ABC/3TC+ATV, from November 2004 and June 15th 2015, in the clinical setting.
RESULTS
Overall, 236 patients were included in the study. Median age (IQR) was 45 (42-50) years and 69% were male. The main reasons for using this combination were previous toxicity in 130 patients (56%), simplification in 60 (20%) and virologic failure in 29 (14%). Previous treatment was based in boosted protease inhibitor in 115 patients (48.7%), 3 analogs in 56 (28%) and non-analogous based in 19 (8.1%). Median treatment length was 2.2 years (IQR0.8-5.3). A total of 66 (28%) patients continue receiving ABC/3TC+ATV (median time 5.7, IQR2.2-8.3), treatment was changed in 170 patients (72%) (median time 1.6 years, IQR0.7-3.6), and 22 (9.3%) patients were lost. Virological failure was assessed in 30 patients.
CONCLUSION
In selected patients, ABC/3TC+ATV is a durable and attractive therapeutic alternative.
Topics: Adult; Atazanavir Sulfate; Dideoxynucleosides; Drug Combinations; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Male; Middle Aged; Retrospective Studies; Time Factors
PubMed: 27743681
DOI: 10.1016/j.eimc.2016.08.006 -
Expert Opinion on Pharmacotherapy Nov 2012Patients on antiretroviral combination therapy, experiencing drug toxicity or inconvenience, require alternative options maintaining virological suppression. The... (Review)
Review
INTRODUCTION
Patients on antiretroviral combination therapy, experiencing drug toxicity or inconvenience, require alternative options maintaining virological suppression. The protease inhibitor atazanavir is a promising candidate.
AREAS COVERED
Published studies exploring a switch to atazanavir-based regimens were systematically reviewed from medical databases and evaluated with regard to efficacy, safety, unboosted use, monotherapy, and hepatitis C coinfection. Randomized trials comparing a switch toward ritonavir-boosted atazanavir versus therapy continuation revealed for antiretroviral efficacy, lipid profiles, and glucose tolerance a similar outcome, if the comparator was lopinavir-ritonavir and better by trend for patients previously using nelfinavir/indinavir or subsequently switching to ritonavir-sparing atazanavir, whereas lipodystrophy was hardly improved. Most clinical chemistry markers improved, except for hyperbilirubinemia, but visible jaundice was rarely a discontinuation reason. ALT levels or glucose tolerance remained similar, or improved. Maintenance strategies including switch from boosted to unboosted atazanavir seemed to be very effective, especially if the regimen was tenofovir sparing; boosted PI monotherapy cannot be recommended to date. For HCV-genotype 1 coinfected individuals requiring treatment modification, atazanavir is the only protease inhibitor recommended for telaprevir coadministration.
EXPERT OPINION
Atazanavir-based antiretroviral triple therapy is a valuable and effective option for patients who need to switch from another stable protease inhibitor regimen for convenience or tolerability reasons.
Topics: Atazanavir Sulfate; HIV Infections; HIV Protease Inhibitors; Humans; Oligopeptides; Pyridines; Treatment Outcome
PubMed: 23050508
DOI: 10.1517/14656566.2012.734296 -
Antiviral Research Mar 2021While muscle fatigue, pain and weakness are common co-morbidities in HIV-1 infected people, their underlying cause remain poorly defined. To this end, we evaluated...
While muscle fatigue, pain and weakness are common co-morbidities in HIV-1 infected people, their underlying cause remain poorly defined. To this end, we evaluated whether the common antiretroviral drugs efavirenz (EFV), atazanavir (ATV) and ritonavir (RTV) could be a contributing factor by pertubating sarcoplasmic reticulum (SR) Ca cycling. In live-cell imaging, EFV (6.0 μM), ATV (6.0 μM), and RTV (3.0 μM) elicited Ca transients and blebbing of the plasma membranes of C2C12 skeletal muscle myotubes. Pretreating C2C12 skeletal muscle myotubes with the SR Ca release channel blocker ryanodine (50 μM), slowed the rate and amplitude of Ca release from and reuptake of Ca into the SR. EFV, ATV and RTV (1 nM - 20 μM) potentiated and then displaced [H] ryanodine binding to rabbit skeletal muscle ryanodine receptor Ca release channel (RyR1). These drugs at concentrations 0.25-31.2 μM also increased and or decreased the open probability of RyR1 by altering its gating and conductance. ATV (≤5 μM) potentiated and >5μM inhibited the ability of sarco (endo)plasmic reticulum Ca-ATPase (SERCA1) to hydrolyze ATP and transport Ca. RTV (2.5-31.5 μM) dose-dependently inhibited SERCA1-mediated, ATP-dependent Ca transport. EFV (0.25-31.5 μM) had no measurable effect on SERCA1's ability to hydrolyze ATP and transport Ca. These data support the notion that EFV, ATV and RTV could be contributing to skeletal muscle co-morbidities in PLWH by modulating SR Ca homeostasis.
Topics: Alkynes; Animals; Anti-HIV Agents; Atazanavir Sulfate; Benzoxazines; Calcium; Cell Line; Cyclopropanes; Homeostasis; Mice; Muscle, Skeletal; Myoblasts; Rabbits; Ritonavir; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Time-Lapse Imaging
PubMed: 33450312
DOI: 10.1016/j.antiviral.2020.104975 -
Project Inform Perspective Oct 2003Atazanavir (Reyataz) is a protease inhibitor that received FDA approval in June 2003. Other approved drugs in this class include amprenavir, indinavir, Kaletra...
Atazanavir (Reyataz) is a protease inhibitor that received FDA approval in June 2003. Other approved drugs in this class include amprenavir, indinavir, Kaletra (ritonavir + lopinavir), nelfinavir, ritonavir and saquinavir.
Topics: Atazanavir Sulfate; Drug Approval; Drug Resistance, Viral; Drug Therapy, Combination; Oligopeptides; Pyridines; United States; United States Food and Drug Administration
PubMed: 14696568
DOI: No ID Found -
AIDS (London, England) Sep 2017Patients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays...
OBJECTIVE
Patients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir (ATV) delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown.
DESIGN
Population-based, noninterventional, historical cohort study conducted from 1 July 2003 through 31 December 2015.
SETTING
Veterans Health Administration hospitals and clinics throughout the United States.
PARTICIPANTS
Treatment-naive patients with HIV infection (N = 9500).
ANTIRETROVIRAL EXPOSURES
Initiating antiretroviral regimens containing ATV, other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), or integrase strand transfer inhibitors (INSTIs).
MAIN OUTCOME/EFFECT SIZE MEASURES
Incidence rates of myocardial infarction (MI), stroke, and all-cause mortality within each regimen. ATV versus other protease inhibitor, NNRTI, or INSTI covariate-adjusted hazard ratios by using Cox proportional hazards models and inverse probability of treatment weighting.
RESULTS
Incidence rates for MI, stroke, and all-cause mortality with ATV-containing regimens (5.2, 10.4, and 16.0 per 1000 patient-years, respectively) were lower than with regimens containing other protease inhibitors (10.2, 21.9, and 23.3 per 1000 patient-years), NNRTIs (7.5, 15.9, and 17.5 per 1000 patient-years), or INSTIs (13.0, 33.1, and 21.5 per 1000 patient-years). After inverse probability of treatment weighting, adjusted hazard ratios (95% confidence intervals) for MI, stroke, and all-cause mortality with ATV-containing regimens versus all non-ATV-containing regimens were 0.59 (0.41-0.84), 0.64 (0.50-0.81), and 0.90 (0.73-1.11), respectively.
CONCLUSION
Among treatment-naive HIV-infected patients in the Veterans Health Administration initiating ATV-containing regimens, risk of both MI and stroke were significantly lower than in those initiating regimens containing other protease inhibitors, NNRTIs, or INSTIs.
Topics: Adult; Aged; Atazanavir Sulfate; Cohort Studies; Female; HIV Infections; HIV Protease Inhibitors; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Risk Assessment; Stroke; Treatment Outcome; United States; Veterans
PubMed: 28692532
DOI: 10.1097/QAD.0000000000001594 -
The Journal of Infectious Diseases Feb 2020
Topics: Atazanavir Sulfate; Cardiovascular Diseases; Case-Control Studies; Darunavir; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Myocardial Infarction; Risk Factors
PubMed: 31828327
DOI: 10.1093/infdis/jiz482 -
Journal of Medical Virology Dec 2021The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment... (Comparative Study)
Comparative Study Randomized Controlled Trial
The purpose of this study was to compare the effectiveness of Atazanavir/Ritonavir/Dolutegravir/Hydroxychloroquine and Lopinavir/Ritonavir/Hydroxychloroquine treatment regimens in COVID-19 patients based on clinical and laboratory parameters. We prospectively evaluated the clinical and laboratory outcomes of 62 moderate to severe COVID-19 patients during a 10-day treatment plan. Patients were randomly assigned to either KH (receiving Lopinavir/Ritonavir [Kaletra] plus Hydroxychloroquine) or ADH (receiving Atazanavir/Ritonavir, Dolutegravir, and Hydroxychloroquine) groups. During this period, clinical and laboratory parameters and outcomes such as intensive care unit (ICU) admission or mortality rate were recorded. Compared to the KH group, after the treatment period, patients in the ADH group had higher activated partial thromboplastin time (aPTT) (12, [95% confidence interval [CI]: 6.97, 17.06), p = <0.01), international normalized ratio (INR) (0.17, [95% CI: 0.07, 0.27), p = <0.01) and lower C-reactive protein (CRP) (-14.29, (95% CI: -26.87, -1.71), p = 0.03) and potassium (-0.53, (95% CI: -1.03, -0.03), p = 0.04) values. Moreover, a higher number of patients in the KH group needed invasive ventilation (6 (20%) vs. 1 (3.1%), p = 0.05) and antibiotic administration (27 (90%) vs. 21(65.6), p = 0.02) during hospitalization while patients in the ADH group needed more corticosteroid administration (9 (28.1%) vs. 2 (6.7%), p = 0.03). There was no difference in mortality rate, ICU admission rate, and hospitalization period between the study groups. Our results suggest that the Atazanavir/Dolutegravir treatment regimen may result in a less severe disease course compared to the Lopinavir/Ritonavir treatment regimen and can be considered as an alternative treatment option beside standard care. However, to confirm our results, larger-scale studies are recommended.
Topics: Antiviral Agents; Atazanavir Sulfate; COVID-19; Drug Combinations; Drug Therapy, Combination; Female; Heterocyclic Compounds, 3-Ring; Humans; Hydroxychloroquine; Lopinavir; Male; Middle Aged; Oxazines; Piperazines; Pyridones; Ritonavir; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34255369
DOI: 10.1002/jmv.27195 -
Current Medicinal Chemistry 2022For over 50 years of azapeptide synthetic techniques, developments have renewed the field of peptidomimetic therapeutics. Azapeptides are close surrogates of natural... (Review)
Review
For over 50 years of azapeptide synthetic techniques, developments have renewed the field of peptidomimetic therapeutics. Azapeptides are close surrogates of natural peptides: they contain a substitution of the amino acid α-carbon by a nitrogen atom. Goserelin (1989) and Atazanavir (2003) are two well-known, FDA-approved azapeptide-based drugs for the treatment of cancers and HIV infection, providing evidence for the successful clinical implementation of this class of therapeutic. This review highlights the azapeptides in recent medicinal chemistry applications and synthetic milestones. We describe the current techniques for azapeptide bond formation by introducing azapeptide coupling reagents and chain elongation methods both in solution and solid-phase strategies.
Topics: Humans; Peptidomimetics; Aza Compounds; Atazanavir Sulfate; Goserelin; HIV Infections; Peptides; Amino Acids; Carbon; Nitrogen
PubMed: 35538801
DOI: 10.2174/0929867329666220510214402 -
Revista Da Associacao Medica Brasileira... Jan 2020The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection... (Review)
Review
The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection and regarding the treatments available. As a result, the disease, which before was associated with high morbidity and mortality, is now seen as a chronic disease that can be controlled, regarding both transmission and symptoms. However, even when the virus replication is well controlled, the infected patient remains at high risk of developing renal involvement, either by acute kidney injury not associated with HIV, nephrotoxicity due to antiretroviral drugs, chronic diseases associated with increased survival, or glomerular disease associated to HIV. This review will cover the main aspects of kidney failure associated with HIV.
Topics: AIDS-Associated Nephropathy; Acute Kidney Injury; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Chronic Disease; HIV Infections; Humans; Kidney; Risk Factors; Tenofovir
PubMed: 31939539
DOI: 10.1590/1806-9282.66.S1.75