Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment-naïve, noncirrhotic HCV genotype 3-infected patients.

Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed-dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR+GZR was assessed in HCV GT3-infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment-naïve, noncirrhotic HCV GT3-infected patients. Randomized patients received open-label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV. The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy (SVR12). SVR12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR+GZR+RBV for 12 weeks or 18 weeks, respectively. On-treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance-associated substitutions (RASs) with a >five-fold shift in potency occurred in the NS3 region in six (35%) patients and in the NS5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR+GZR+RBV was suboptimal in HCV GT3-infected patients due to a high rate of on-treatment virologic failure and treatment-emergent RASs which demonstrates an inadequate barrier to the development of GT3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR+GZR+RBV in GT3-infected patients.clinicaltrials.gov: NCT01717326.

HIV-1 reverse transcriptase mutations found in a drug-experienced patient confer reduced susceptibility to multiple nucleoside reverse transcriptase inhibitors.

HIV-1 reverse transcriptase (RT) genotypes were obtained from 13 patients treated with stavudine. No previously-reported mutations indicative of stavudine resistance were found in these patients and no novel mutations occurred in more than two patients. One patient, treated with stavudine for 1 month and treated previously with zidovudine, zalcitabine and lamivudine, carried a mutation at codon 75 of the RT (V75M). A chimeric virus, including the patient's RT sequence from codon 25 to codon 220, which carried the resistance mutations M41 L, D67N, T69D, K70R, L210W and T215Y in addition to V75M, displayed reduced susceptibility to multiple nucleoside RT inhibitors (NRTIs). Removal of V75M from this RT background resulted in a return of susceptibility to didanosine and lamivudine. Our data are in agreement with previous studies demonstrating the rarity of stavudine resistance mutations in stavudine-treated patients. However, we describe a new set of mutations, found in the RT of a heavily-treated patient, that can confer reduced susceptibility to multiple NRTIs. These results underscore the importance of increased vigilance for possible multiple-drug resistance in patients who have been heavily treated with NRTIs.

Safety of oral versus intravenous hydration during induction therapy with intravenous foscarnet in AIDS patients with cytomegalovirus infections.

We undertook a study to compare the safety of intravenous (i.v.) versus oral hydration to prevent nephrotoxicity associated with the use of foscarnet for induction therapy of cytomegalovirus (CMV) infection in HIV-infected persons. Patients, given foscarnet at a dose of 90 mg/kg every 12 h, were randomized to receive either i.v. or oral hydration. Thirty-seven patients were given i.v. hydration and 44 were given oral hydration. Median duration of therapy for both groups was 17 days. There was no difference between the 2 groups in either serious adverse events or rise of creatinine to > or = 2.0 mg/dl. However, serum creatinine, while generally remained within normal limits, increased more in patients who received oral hydration after 10 days of therapy (significant only by slope analysis, P < 0.05). Although i.v. hydration provided better protection against nephrotoxicity, oral hydration was relatively safe and convenient provided that creatinine clearance (CrCl) is monitored closely.

Vertebral osteomyelitis due to Roseomonas species: case report and review of the evaluation of vertebral osteomyelitis.

We report what we believe is the first case of vertebral osteomyelitis caused by Roseomonas species. The diagnosis of vertebral osteomyelitis can be difficult. The case illustrates the importance of the establishment of an etiologic diagnosis in vertebral osteomyelitis. The features of Roseomonas species and the evaluation of cases of vertebral osteomyelitis are reviewed.

AIDS-associated cryptosporidiosis with gastric stricture and a therapeutic response to paromomycin.

AIDS-associated cryptosporidiosis has been associated with severe, watery diarrhea and with multifocal biliary stricture. Gastric involvement has not been reported prominently. We report here the case of a 28-yr-old AIDS patient who developed typical watery diarrhea, followed by subtotal gastric obstruction secondary to antral stricturing. Biopsy of the stricture revealed severe inflammation and marked cryptosporidial infestation. Extensive workup excluded causes of stricture. He was empirically treated with paromomycin, with a surprisingly positive therapeutic response and clinical resolution of obstruction. Antral stricture may be another manifestation of cryptosporidial infection in AIDS. Paromomycin deserves further evaluation as an agent for treatment of this infection.

Infective endocarditis in intravenous drug users: a comparison of human immunodeficiency virus type 1-negative and -positive patients.

In a study of 34 human immunodeficiency virus (HIV)-seropositive and 12 HIV-seronegative intravenous drug users with 40 and 14 episodes, respectively, of infective endocarditis (IE), there were no differences between groups in the presentation of IE. Staphylococcus aureus was the infecting microorganism in 75% of the HIV-positive patients and 86% of the HIV-negative patients. Overall survival for the HIV-positive patients was 85% compared with 93% for the HIV-negative patients. Ninety percent of patients with asymptomatic HIV infection survived, whereas 60% of patients in CDC group IV survived (P = .052). In contrast to New Jersey seroprevalence surveys showing HIV antibody in 10%-50% of intravenous drug users, HIV antibody seroprevalence rate in this selected population was 75%. IE in the HIV-seropositive intravenous drug user is essentially the same as in the seronegative user. However, patients with symptomatic HIV infection may be more likely to die from their IE. Intravenous drug users with IE have a greater-than-expected seroprevalence of HIV; the reason remains to be determined.

Radiologic distinction of pyogenic pulmonary infection from Pneumocystis carinii pneumonia in AIDS patients.

Thirty-four episodes of pyogenic pulmonary infection in 30 patients infected with human immunodeficiency virus (HIV) and 30 episodes of Pneumocystis carinii pneumonia (PCP) in 30 AIDS patients were reviewed to determine if the radiologic features were more helpful than clinical and laboratory findings in the differential diagnosis. The radiologic features of pyogenic pulmonary infection included lobar consolidation, nodules, infiltrates with pleural effusions, round infiltrates, and pleural effusions alone. These features are uncommon in PCP. The chest radiograph may be highly suggestive of a pyogenic process, especially when it shows local consolidation or nodules. Since bacterial pneumonias have a more favorable outcome, it is concluded that the radiologic features should be the primary guide to prompt diagnosis and treatment.

Qualitative intravascular catheter tip cultures do not predict catheter-related bacteremia.

During a 5-month period, we evaluated the sensitivity, specificity, and predictive value of qualitative cultures of intravenous catheters submitted to a university hospital microbiology laboratory. Of 36 catheters submitted for culture from nonseptic patients, 10 (28%) grew one or more microorganisms on qualitative culture. Of 44 catheters cultured from septic patients, 20 (45%) grew one or more microorganisms, but only 5 grew microorganisms that also were isolated from blood cultures. The sensitivity, specificity, and positive predictive values for catheter-related bacteremia were 71%, 96%, and 17%, values similar to those reported for quantitative methods. Although acceptable in terms of sensitivity and specificity, the very low positive predictive value suggests that catheter-related bacteremia cannot be predicted reliably by this test. We conclude, therefore, that nonstandardized qualitative IV catheter cultures have minimal value as predictors of bacteremia and recommend that they not be performed in clinical microbiology laboratories.

Chronic constrictive pericarditis. A case report and review of the literature.

Actinomycosis is typically a chronic infection of the cervicofascial, thoracic, or abdominal region. Involvement of the heart occurs but is unusual. We present a case of chronic constrictive pericarditis caused by actinomycetes. The actinomycosis infection was present for 20 years, thereby representing the longest duration reported in the literature, to our knowledge.

Toxic shock syndrome associated with use of a nasal tampon.

Toxic shock syndrome has been noted to occur with nasal surgery, both with and without packing. A new synthetic sponge, described as a nasal tampon, has become available for use as packing after surgery. Herein is reported the first case of toxic shock syndrome associated with the use of this nasal tampon.