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Expert Review of Anti-infective Therapy Jun 2017During last two decades several drugs were developed to offer long-term benefits in terms of virologic efficacy, favourable tolerability and toxicity profiles in... (Review)
Review
During last two decades several drugs were developed to offer long-term benefits in terms of virologic efficacy, favourable tolerability and toxicity profiles in treatment of HIV infection. Pharmacokinetics boosting of protease inhibitor allows a higher genetic barrier, as few or no drug-resistant mutations are detected in patients with virologic failure. Areas covered: Atazanavir sulfate + cobicistat (ATV/c) was recently approved for the treatment of HIV-1 infection. Bioequivalence between cobicistat (COBI) and ritonavir (RTV) as a pharmacoenhancer of ATV was established. Additionally, randomized clinical trials demonstrated that ATV/c and ATV/ritonavir had comparable efficacy and safety profiles. Low rates of virologic failure and no ATV resistance mutations were observed in these clinical trials. Therefore, COBI shows increased advantages over RTV, such as no activity against HIV, fewer drug-drug interactions and better solubility, which promotes coformulation strategies with less pill burden, better tolerability, and, potentially, higher life-long treatment adherence. Expert commentary: ATV/c regimen supports its useas an effective treatment option for HIV-1 infected patients with increased cardiovascular disease and chronic kidney disease risk associated with aging. In addition, ATV/c is a new opportunity to expand the strategy of switch to a dual therapy to lower the risk of long-term toxicities as well as the advantage of its cost-benefit.
Topics: Atazanavir Sulfate; Clinical Trials as Topic; Cobicistat; Drug Synergism; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Patient Safety; Solubility; Treatment Outcome
PubMed: 28443391
DOI: 10.1080/14787210.2017.1323634 -
Drugs 2003Atazanavir is a novel azapeptide protease inhibitor with high specificity for, and activity against, HIV-1 protease. The resistance profile of atazanavir is distinct,... (Review)
Review
Atazanavir is a novel azapeptide protease inhibitor with high specificity for, and activity against, HIV-1 protease. The resistance profile of atazanavir is distinct, with an I50 L protease substitution appearing to be the signature mutation. Atazanavir was not associated with increases in total cholesterol, low density lipoprotein-cholesterol or triglyceride levels after 108 weeks. Atazanavir has a pharmacokinetic profile that allows for once-daily oral administration. It is a moderate inhibitor of hepatic cytochrome P450 enzymes and interacts with several drugs. In combination with stavudine plus didanosine, atazanavir 200, 400 or 500 mg once daily produced a rapid and sustained reduction from baseline in viral load of 2.57, 2.42 and 2.53 log(10) copies/mL, respectively, in treatment-naive patients after 48 weeks, compared with a decrease of 2.33 log(10) copies/mL with nelfinavir 750 mg three times daily. Nausea was the most clinically relevant adverse event reported in patients receiving atazanavir-based regimens.
Topics: Administration, Oral; Anti-HIV Agents; Atazanavir Sulfate; Capsules; Clinical Trials as Topic; Drug Administration Schedule; HIV Infections; HIV Protease; Oligopeptides; Pyridines
PubMed: 12904086
DOI: 10.2165/00003495-200363160-00003 -
Antimicrobial Agents and Chemotherapy May 2023Candida auris represents an urgent health threat. Here, we identified atazanavir as a potent drug capable of resensitizing C. auris clinical isolates to the activity of...
Candida auris represents an urgent health threat. Here, we identified atazanavir as a potent drug capable of resensitizing C. auris clinical isolates to the activity of azole antifungals. Atazanavir was able to significantly inhibit the efflux pumps, glucose transport, and ATP synthesis of all tested isolates of C. auris. In addition, the combination of itraconazole with atazanavir-ritonavir significantly reduced the burden of azole-resistant C. auris in murine kidneys by 1.3 log (95%), compared to itraconazole alone.
Topics: Animals; Mice; Azoles; Itraconazole; Candida auris; Candida; Atazanavir Sulfate; Microbial Sensitivity Tests; Antifungal Agents; Drug Resistance, Fungal; Fluconazole
PubMed: 37092991
DOI: 10.1128/aac.01631-22 -
American Journal of Kidney Diseases :... Oct 2017Crystalline nephropathy can occur following treatment with multiple therapeutic agents. We describe a human immunodeficiency virus (HIV)-infected patient treated for 2...
Crystalline nephropathy can occur following treatment with multiple therapeutic agents. We describe a human immunodeficiency virus (HIV)-infected patient treated for 2 years with combination antiretroviral therapy including atazanavir (ATV). Kidney biopsy revealed a crystalline nephropathy associated with diffuse chronic and granulomatous interstitial inflammation. Following the biopsy, treatment with ATV was discontinued and kidney function returned to pretreatment baseline levels. ATV, which has a well-established association with nephrolithiasis, is a rare but important cause of crystalline nephropathy. Recognition of this association and prompt withdrawal of the offending agent are critical to optimize outcomes.
Topics: Atazanavir Sulfate; Crystallization; HIV Protease Inhibitors; Humans; Kidney Diseases; Male; Middle Aged
PubMed: 28579422
DOI: 10.1053/j.ajkd.2017.02.376 -
The New England Journal of Medicine Nov 2006
Topics: Adult; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hydronephrosis; Male; Oligopeptides; Pyridines; Ureteral Calculi; Urolithiasis
PubMed: 17108352
DOI: 10.1056/NEJMc061892 -
Nature Reviews. Drug Discovery Nov 2003
Topics: Alkynes; Atazanavir Sulfate; Benzoxazines; Cyclopropanes; HIV Infections; HIV Protease Inhibitors; Humans; Oligopeptides; Oxazines; Pyridines; Randomized Controlled Trials as Topic; Structure-Activity Relationship
PubMed: 14702957
DOI: 10.1038/nrd1232 -
Drugs of Today (Barcelona, Spain : 1998) Nov 2004Atazanavir (formerly BMS-232632), an azapeptide protease inhibitor (PI), is a new human immunodeficiency virus (HIV) treatment that has recently received marketing... (Review)
Review
Atazanavir (formerly BMS-232632), an azapeptide protease inhibitor (PI), is a new human immunodeficiency virus (HIV) treatment that has recently received marketing approval from the FDA. It has a pharmacokinetic profile that supports once-daily dosing and has demonstrated a unique resistance profile and superior virologic potency compared with other antiretrovirals in vitro. In subjects with HIV, atazanavir (400 mg once daily) produced rapid and sustained improvements in viral load and CD4 counts in both antiretroviral-naive as well as previously treated patients when used in combination with dual nucleoside reverse transcriptase inhibitor (NRTI) treatment. In these studies atazanavir demonstrated comparable anti-HIV efficacy to nelfinavir (twice or three times daily), efavirenz and the combination of ritonavir and saquinavir. However, unlike these comparator agents, atazanavir did not adversely affect the plasma lipid profile, an advantage that sets it apart from other currently available PIs. Atazanavir was inferior to lopinavir/ritonavir in patients who previously failed an initial protease inhibitor containing regimen. Preliminary results in multiple PI-experienced patients indicate comparable efficacy to lopinavir/ritonavir in subjects receiving a boosted regimen of atazanavir plus ritonavir. In summary, atazanavir offers several therapeutic advantages, including a convenient once-daily dosing schedule, neutral lipid effects and a distinct resistance profile. These characteristics may ultimately help improve adherence, reduce the potential risk of long-term cardiovascular events associated with dyslipidemia, and increase the range of therapeutic options available for patients failing other antiretroviral regimens.
Topics: Area Under Curve; Atazanavir Sulfate; Biological Availability; Drug Therapy, Combination; HIV Infections; HIV Protease Inhibitors; Half-Life; Humans; Intestinal Absorption; Male; Oligopeptides; Pyridines; Randomized Controlled Trials as Topic
PubMed: 15645003
DOI: 10.1358/dot.2004.40.11.872579 -
Pharmacogenetics and Genomics May 2018
Topics: ATP Binding Cassette Transporter, Subfamily B; Atazanavir Sulfate; Drug Synergism; Glucuronosyltransferase; HIV Infections; HIV Protease Inhibitors; Humans; Liver-Specific Organic Anion Transporter 1; Pharmacogenetics; Pregnane X Receptor; Ritonavir
PubMed: 29517518
DOI: 10.1097/FPC.0000000000000331 -
Clinical Infectious Diseases : An... Jun 2004Atazanavir is a recently approved human immunodeficiency virus (HIV) protease inhibitor that has an important role in the treatment of both antiretroviral-naive and... (Review)
Review
Atazanavir is a recently approved human immunodeficiency virus (HIV) protease inhibitor that has an important role in the treatment of both antiretroviral-naive and antiretroviral-experienced individuals. Atazanavir (400 mg) can be administered once per day and requires only 2 capsules. Drug exposure can be safely increased with coadministration of a once-daily regimen of atazanavir (300 mg) and ritonavir (100 mg). Atazanavir is not associated with elevations in serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides, potentially reducing the need for lipid-lowering agents. Atazanavir is associated with elevations in unconjugated bilirubin levels, which are usually not dose limiting. For treatment-naive patients receiving atazanavir who experience virologic rebound, the I50L mutation in HIV protease arises, which does not confer cross-resistance to other protease inhibitors. In treatment-experienced patients with high-level resistance to other protease inhibitors, susceptibility to atazanavir is usually reduced, and optimal effects of atazanavir are seen when it is administered with ritonavir. Similar to other protease inhibitors, careful attention must be paid to drug interactions when administering atazanavir with concomitant medications.
Topics: Atazanavir Sulfate; Drug Resistance; HIV Infections; Humans; Oligopeptides; Pyridines
PubMed: 15156449
DOI: 10.1086/420932 -
Expert Review of Anti-infective Therapy Oct 2003Protease inhibitors are potent agents against HIV but their use is constrained by poor pharmacokinetics, cross-resistance and metabolic toxicities. Atazanavir [Reyataz]... (Review)
Review
Protease inhibitors are potent agents against HIV but their use is constrained by poor pharmacokinetics, cross-resistance and metabolic toxicities. Atazanavir [Reyataz] is a new protease inhibitors with once-daily dosing and minimal lipid and glycemic effects. Resistance studies of clinical isolates reveal a mutational pattern distinctive from that of other protease inhibitors. Atazanavir selects for the I50L mutation in HIV protease that confers increased susceptibility to other protease inhibitors in vitro. Clinical trials have shown comparable efficacy to nelfinavir (Viracept) and efavirenz (Sustiva) in treatment-naive patients, and in preliminary studies, ritonavir-boosted atazanavir is effective in patients failing previous protease inhibitor-containing regimens. Reversible elevations in bilirubin occur in some patients but are not associated with hepatic injury. Atazanavir improves upon aspects of currently-available protease inhibitors and appears useful for initial and possibly subsequent HIV therapy.
Topics: Animals; Atazanavir Sulfate; Clinical Trials as Topic; HIV Infections; HIV Protease Inhibitors; Humans; Oligopeptides; Pyridines
PubMed: 15482137
DOI: 10.1586/14787210.1.3.403