Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudineresistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine-resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (>6 log 10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir-treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 10 5 copies/mL in contrast to 100% of the tenofovir-treated patients (P ‫؍‬ . T reatment of chronic hepatitis B virus (HBV) infection with the nucleoside analogue and reverse transcriptase inhibitor lamivudine has been shown to be very effective in suppressing HBV replication without major side effects. 1 In view of the long half-life of covalently closed circular HBV DNA and the variable turnover of infected hepatocytes, long-term treatment is required to achieve complete HBV elimination (i.e., hepatitis B surface antigen [HBsAg] loss). Unfortunately, the effect of this kind of treatment is often abolished by the selection of lamivudine-resistant mutants 2 followed by the reappearance of HBV DNA to baseline levels and reactivation of chronic hepatitis B.The efficacy of the acyclic nucleotide analogue adefovir dipivoxil (adefovir) in the treatment of wild-type and lamivudine-resistant HBV infection has been described, and a daily adefovir dose of 10 mg was recently approved for the treatment of chronic HBV infection. [3][4][5][6] Tenofovir disoproxil fumarate, another acyclic nucleotide analogue that is the pro-drug of tenofovir, has been approved as a novel oral agent for the treatment of human immunodeficiency virus (HIV) infection. Its effect in lamivudine drug resistance has been recently described by us as well as by other authors. [7][8][9][10][11][12][13][14] In view of the close structural relationship between these two drugs, we conducted a study in patients suffering from lamivudine drug resistance to compare their ef-

The efficacy, safety, and tolerability of voriconazole and fluconazole were compared in 391 immunocompromised patients with mycology- and biopsy-proven esophageal candidiasis. Primary efficacy analysis (256 patients) of esophageal treatment as assessed by esophagoscopy revealed success rates of 98.3% with voriconazole and 95.1% with fluconazole. The 95% confidence interval for the difference in success rates ranged from -1.0% to 7.5%. The overall safety and tolerability of both antifungals were acceptable. Fewer patients discontinued voriconazole treatment because of insufficient clinical response (4 patients [2.0%] vs. 5 patients [2.6%]). More patients discontinued voriconazole than fluconazole treatment because of laboratory test abnormalities (7 patients [3.5%] vs. 2 patients [1.0%]) or treatment-related adverse events (5 patients [2.5%] vs. 1 patient [0.5%]). The most frequent adverse events (23%) with voriconazole were mild, transient visual disturbances. Voriconazole (200 mg, b.i.d.) was shown to be at least as effective as fluconazole in the treatment of biopsy-proven esophageal candidiasis in immunocompromised patients.

Background. Human immunodeficiency virus (HIV)–infected individuals are at increased risk of herpes zoster (HZ), even in the antiretroviral therapy (ART) era. Because concerns exist about the use of live-attenuated vaccines in immunocompromised individuals, a subunit vaccine may be an appropriate alternative.Methods. This phase 1/2, randomized, placebo-controlled study evaluated the immunogenicity and safety of an investigational HZ subunit vaccine (HZ/su). Three cohorts of HIV-infected adults aged ≥18 years were enrolled: 94 ART recipients with a CD4+ T-cell count of ≥200 cells/mm3, 14 ART recipients with a CD4+ T-cell count of 50–199 cells/mm3, and 15 ART-naive adults with a CD4+ T-cell count of ≥500 cells/mm3. Subjects received 3 doses of HZ/su (50 µg varicella-zoster virus glycoprotein E [gE] combined with AS01B adjuvant) or 3 doses of saline at months 0, 2, and 6.Results. One month after dose 3, serum anti-gE antibody concentrations and frequencies of gE-specific CD4+ T cells were higher following HZ/su vaccination than after receipt of saline (P < .0001). Median cell-mediated immune responses peaked after dose 2. Humoral and cell-mediated immune responses persisted until the end of the study (month 18). No vaccination-related serious adverse events were reported. No sustained impact on HIV load or CD4+ T-cell count was noted following vaccinations.Conclusions. HZ/su was immunogenic and had a clinically acceptable safety profile in HIV-infected adults.Clinical Trials Registration. NCT01165203.

The objective of the present trial was to compare the efficacy, safety, and tolerability of moxifloxacin (400 mg) given intravenously (i.v.) once daily followed by oral moxifloxacin (400 mg) for 7 to 14 days with the efficacy, safety, and tolerability of co-amoxiclav (1.2 g) administered by i.v. infusion three times a day followed by oral co-amoxiclav (625 mg) three times a day, with or without clarithromycin (500 mg) twice daily (i.v. or orally), for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy. The rates of drug-related adverse events were comparable in both groups (38.9% in each treatment group). The overall incidence of laboratory abnormalities was similar in both groups. Thus, it is concluded that monotherapy with moxifloxacin is superior to that with a standard combination regimen of a ␤-lactam and a ␤-lactamase inhibitor, co-amoxiclav, with or without a macrolide, clarithromycin, in the treatment of patients with community-acquired pneumonia admitted to a hospital.