The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects.
Asian Continental Ancestry Group* ; Atazanavir Sulfate ; HIV* ; HIV-1* ; Humans ; Humans* ; Protease Inhibitors ; Reverse Transcriptase Inhibitors

BACKGROUND: Data regarding differences of intolerance between a ritonavir-unboosted and a ritonavir-boosted atazanavir regimen in HIV-infected Koreans is limited. MATERIALS AND METHODS: A review was conducted of the incidence of severe hyperbilirubinemia (serum total bilirubin >3.1 mg/dL) and discontinuation of atazanavir in HIV-infected patients who had received an atazanavir-containing regimen at Seoul National University Hospital from 2005 to 2009. Patients with active liver disease were excluded from the study. RESULTS: Of a total of 335 patients receiving an atazanavir-containing regimen, 145 (43.3%) received treatment with a ritonavir-boosted regimen. The cumulative incidence of severe hyperbilirubinemia at three months was 40.5% in patients receiving a ritonavir-boosted atazanavir regimen and 21.4% in patients receiving an un-boosted atazanavir regimen (P<0.001). The cumulative incidence of severe hyperbilirubinemia at 12 months was 58.5% in patients receiving a ritonavir-boosted regimen and 41.3% in those receiving an un-boosted regimen (P=0.008). The proportion of drug discontinuation due to jaundice during the 12-month period was 11.7% in patients receiving a ritonavir-boosted regimen and 5.3% in those receiving an un-boosted regimen (P=0.035). CONCLUSIONS: Occurrence of severe hyperbilirubinemia and discontinuation of atazanavir due to jaundice was significantly more common in HIV-infected Koreans who received a ritonavir-boosted atazanavir regimen than in those who received a ritonavir-un-boosted atazanavir regimen.
Atazanavir Sulfate ; Bilirubin ; HIV ; Humans ; Hyperbilirubinemia ; Incidence ; Jaundice ; Liver Diseases ; Oligopeptides ; Pyridines ; Ritonavir

Dyslipidemia, one of the major disadvantages of use of protease inhibitor (PI), is a risk factor for cardiovascular disease in HIV-infected patients receiving antiretroviral treatment. Little is known about the effect of a switch from another PI to unboosted atazanavir (ATV) on the lipid profile. The aim of this study was to evaluate changes in the lipid profile after switching from another PI to either unboosted or boosted ATV in HIV-infected Koreans. We retrospectively collected data on the serum lipid profile at the time of the switch (week 0), and weeks 12 and 24 after the switch, as well as clinical characteristics at week 0 in a total of 27 patients. Triglyceride (TG) showed a significant decrease at weeks 12 and 24 in all patients (196 vs. 174 mg/dL, P=0.048 and 196 vs. 150 mg/dL, P=0.021, respectively). However, these effects were only observed in the unboosted ATV group (N=14; 239 vs. 125 mg/dL, P=0.017 and 239 vs. 87 mg/dL, P=0.021, respectively). For total cholesterol, only the unboosted ATV group at 24 weeks showed a significant decrease (184 vs. 158 mg/dL, P=0.031). No significant changes were observed in LDL- and HDL-cholesterol at weeks 12 and 24 in both the unboosted and boosted ATV groups. These results suggest that changing to unboosted ATV from another PI may ameliorate high TG and total cholesterol in HIV-infected Koreans.
Antiretroviral Therapy, Highly Active ; Atazanavir Sulfate ; Cardiovascular Diseases ; Cholesterol ; Dyslipidemias ; HIV ; Humans ; Oligopeptides ; Protease Inhibitors ; Pyridines ; Retrospective Studies ; Risk Factors

Atazanavir is a protease inhibitor approved for use in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus infection. Atazanavir and other protease inhibitors can sometimes induce corrected QT prolongation and ventricular arrhythmia. A 40-year-old man with no comorbidities, except human immunodeficiency virus 1 infection, presented with palpitations 3 days after an overdose of 150 caps of atazanavir, with suicidal intent. His initial electrocardiogram showed monomorphic ventricular tachycardia, and hyperbilirubinemia was observed in his initial blood test. Immediately after magnesium sulfate infusion, his ventricular tachycardia was converted into junctional bradycardia with prolonged corrected QT. After 3 days of close observation in the intensive care unit, the corrected QT prolongation and hyperbilirubinemia were normalized.
Adult ; Arrhythmias, Cardiac ; Atazanavir Sulfate* ; Bradycardia ; Comorbidity ; Electrocardiography ; Hematologic Tests ; HIV ; HIV-1 ; Humans ; Hyperbilirubinemia ; Intensive Care Units ; Magnesium Sulfate ; Protease Inhibitors* ; Tachycardia, Ventricular*

BACKGROUND: The combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has been the first choice nucleoside reverse transcriptase inhibitor (NRTI) according to many reliable antiretroviral treatment (ART) guidelines because of its high efficacy. However, TDF-related renal toxicity reported in Western countries is a challenging issue regarding clinical use. We conducted this study to evaluate the incidence and characteristics of an acute increase in serum creatinine (Cr) level > 1.5 mg/dL among TDF/FTC-based highly active antiretroviral treatment (HAART)-treated patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 205 HIV-infected patients treated with TDF/FTC-containing regimens between 1 February 2010 and 30 April 2014. Three groups of TDF/FTC + ritonavir-boosted protease inhibitor (PI/r), TDF/FTC + non-nucleoside reverse transcriptase inhibitor (NNRTI), and TDF/FTC + integrase strand transfer inhibitor (INSTI), and three PI/r subgroups of TDF/FTC + lopinavir (LPV)/r, TDF/FTC + atazanavir (ATV)/r, TDF/FTC + darunavir (DRV)/r were evaluated. RESULTS: A total 136 patients (91 in the TDF/FTC + PI/r group, 20 in the TDF/FTC + NNRTI group and 25 in the TDF/FTC + INSTI group) were included in the statistical analysis. Four cases (4.9%; all in the TDF/FTC + PI/r group) among 136 patients showed an acute increase in serum Cr more than 1.5 mg/dL, so the overall incidence was 2.8 cases per 100 patient-years. One case was a patient treated with TDF/FTC + LPV/r, and the others were treated with TDF/FTC + ATV/r. No case of an acute increase in serum Cr was observed in the TDF/FTC + DRV/r group. The incidence of serum Cr increase more than 1.5 mg/dL in TDF/FTC + PI/r group was 4.0 cases per 100 patient-years. CONCLUSION: Although only a small number of patients were evaluated retrospectively from a single center, the TDF/FTC + PI/r regimen may have been related with relatively higher tendency of increment of serum Cr level. These findings reinforce the importance of close follow-ups of HIV-infected patients treated with the TDF/FTC + PI/r regimens.
Anti-Retroviral Agents ; Antiretroviral Therapy, Highly Active* ; Atazanavir Sulfate ; Creatinine* ; Darunavir ; Emtricitabine ; Follow-Up Studies ; HIV ; Humans ; Incidence* ; Integrases ; Lopinavir ; Medical Records ; Protease Inhibitors ; Retrospective Studies ; RNA-Directed DNA Polymerase ; Tenofovir

4-Hydroxycoumarins ; chemical synthesis ; chemistry ; pharmacology ; Anti-HIV Agents ; chemical synthesis ; chemistry ; pharmacology ; Atazanavir Sulfate ; HIV Protease Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Molecular Structure ; Oligopeptides ; chemical synthesis ; chemistry ; pharmacology ; Pyridines ; chemical synthesis ; chemistry ; pharmacology ; Saquinavir ; chemical synthesis ; chemistry ; pharmacology ; Urea ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology