ABSTRACT
HIV-HCV-HBV-coinfected patients were assessed to characterize the viral interactions in the setting of HIV coinfection and in the HAART era. All positive anti-HCV antibody and HBs antigen-positive HIV-infected patients were identified at five HIV clinics. Antihepatitis delta (HDV) antibody, serum HIV RNA, HCV RNA, and HBV DNA quantification and genotype determinations were performed. Out of 67 patients identified 47 (70%) were receiving anti-HBV therapy. HCV RNA and HBV DNA were detectable in 52.5% and 37% of patients, respectively. All possible patterns were found, regardless of anti-HBV therapy. HDV coinfection was associated with undetectable HCV RNA [RR 9.52 (95% CI 1.85-49.01); p = 0.007]. Independent factors predicting undetectable HBV DNA lacked HBeAg [RR 13.94 (95% CI 3.05-63.72); p = 0.001] and use of anti-HBV therapy [RR 11.42 (95% CI 2.43-53.54); p = 0.002]. Replication and genotypes of HCV or HBV had no impact on the replication of the other virus. In conclusion, in this cohort of triple infection (HBV/HCV/HIV) various viral patterns were identified. Spontaneous HCV clearance was frequent, and it was independently associated with HDV coinfection. In the absence of HBV therapy, HBV most often actively replicates. HBV/HCV replication or genotypes were not related to the replication of the other virus.
Subject(s)
HIV Infections/drug therapy , HIV Infections/epidemiology , HIV/physiology , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Adult , Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Antiviral Agents/therapeutic use , Comorbidity , Cross-Sectional Studies , DNA, Viral/analysis , DNA, Viral/genetics , Female , HIV Infections/virology , Hepacivirus/classification , Hepacivirus/isolation & purification , Hepacivirus/physiology , Hepatitis B/blood , Hepatitis B/drug therapy , Hepatitis B/virology , Hepatitis B Surface Antigens/blood , Hepatitis B virus/classification , Hepatitis B virus/isolation & purification , Hepatitis B virus/physiology , Hepatitis C/blood , Hepatitis C Antibodies/blood , Hepatitis D/epidemiology , Hepatitis Delta Virus/genetics , Hepatitis Delta Virus/isolation & purification , Humans , Italy/epidemiology , Male , Mexico/epidemiology , Middle Aged , North Carolina/epidemiology , RNA, Viral/analysis , Retrospective Studies , Risk Factors , Spain/epidemiology , Virus ReplicationABSTRACT
Fozivudine tidoxil (FZD) is a thioether lipid-zidovudine (ZDV) conjugate with anti-HIV activity demonstrated in vitro and in pilot phase I studies. To assess its safety, efficacy and pharmacokinetics, we conducted a multicenter, randomized, double-blind, placebo-controlled trial of FZD monotherapy in 72 HIV-infected patients who had not previously received antiretroviral therapy. In each dosage group (200 mg daily, 400 mg daily, 200 mg twice daily, 800 mg daily, 400 mg twice daily, and 600 mg twice daily), 12 patients were randomized to receive in a 10:2 ratio either FZD or a placebo for 4 weeks. Overall, FZD was well tolerated in all dosage groups; only 1 patient discontinued the drug, because of a moderate rise in aminotransaminase activity. HIV viral load fell in all the patients who were receiving FZD, except in the 200 mg daily group. The largest decrease (-0.67 log10) was observed in the 600 mg twice daily group. The plasma half-life was significantly longer (approximately 3.8 hours) than that of the parent drug ZDV. Exposure to ZDV, as reflected by the area under the time-concentration curve, was much lower after FZD than after ZDV administration. FZD thus appears to be as effective as and potentially better tolerated than ZDV during short-term administration and has the advantage of once daily intake.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1/genetics , Lipids/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Zidovudine/analogs & derivatives , Adult , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , Area Under Curve , Dose-Response Relationship, Drug , Double-Blind Method , Female , HIV Infections/metabolism , Humans , Lipids/adverse effects , Lipids/pharmacokinetics , Male , RNA, Viral/blood , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/pharmacokinetics , Viral Load , Zidovudine/adverse effects , Zidovudine/pharmacokinetics , Zidovudine/therapeutic useSubject(s)
Antiviral Agents/adverse effects , Neuraminidase/antagonists & inhibitors , Respiratory Insufficiency/chemically induced , Sialic Acids/adverse effects , Bronchial Spasm/chemically induced , Guanidines , Humans , Influenza, Human/complications , Influenza, Human/drug therapy , Lung Diseases, Obstructive/complications , Male , Middle Aged , Pyrans , ZanamivirABSTRACT
The records of 206 patients with advanced infection due to human immunodeficiency virus type 1 who were receiving prophylaxis with clindamycin/primaquine (C/P), trimethoprim-sulfamethoxazole (TMP-SMZ), or dapsone to prevent Pneumocystis carinii pneumonia (PCP) were retrospectively examined. Two hundred sixty-two patient-years of prophylaxis were accrued (176.2 of TMP-SMZ, 63.4 of dapsone, and 22.8 of C/P). The rates of PCP in the TMP-SMZ, dapsone, and C/P groups were 3.4, 11.0, and 30.7 per 100 patient-years, respectively. Pairwise comparisons showed C/P to be less effective than TMP-SMZ (relative risk [RR], 9.02; 95% confidence interval [CI], 3.03-26.83). A similar trend was apparent for C/P vs. dapsone (RR, 2.78; 95% CI, 0.98-7.93). When only those receiving primary prophylaxis were analyzed, C/P recipients remained at greater risk than TMP-SMZ recipients (RR, 13.19; 95% CI, 3.54-49.12) and dapsone recipients (RR, 3.85; 95% CI, 1.12-13.31). Failure of C/P prophylaxis could be due, at least in part, to underdosing (clindamycin, 300 mg/d; primaquine, 15 mg/d). C/P recipients had more nonspecific diarrhea than did TMP-SMZ recipients (RR, 2.99; 95% CI, 1.61-5.55).
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimalarials/therapeutic use , Clindamycin/therapeutic use , HIV Infections/complications , HIV-1 , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/prevention & control , Primaquine/therapeutic use , Adult , Anti-Bacterial Agents/adverse effects , Anti-Infective Agents/adverse effects , Anti-Infective Agents/therapeutic use , Antimalarials/adverse effects , CD4 Lymphocyte Count , Clindamycin/adverse effects , Dapsone/adverse effects , Dapsone/therapeutic use , Diarrhea/complications , Diarrhea/diagnosis , Diarrhea/microbiology , Drug Hypersensitivity , Drug Therapy, Combination , Female , Gastrointestinal Diseases/complications , Hematologic Diseases/complications , Humans , Male , Primaquine/adverse effects , Retrospective Studies , Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useSubject(s)
AIDS-Related Opportunistic Infections/etiology , Acquired Immunodeficiency Syndrome/complications , Candidiasis/drug therapy , Esophageal Diseases/drug therapy , Triazoles/therapeutic use , AIDS-Related Opportunistic Infections/drug therapy , Adult , Amphotericin B/therapeutic use , Candidiasis/etiology , Candidiasis, Oral/drug therapy , Candidiasis, Oral/etiology , Child, Preschool , Drug Resistance, Microbial , Esophageal Diseases/etiology , Female , Humans , Male , Middle AgedSubject(s)
AIDS-Related Opportunistic Infections/drug therapy , Doxycycline/therapeutic use , Encephalitis/drug therapy , Toxoplasmosis, Cerebral/drug therapy , AIDS-Related Opportunistic Infections/diagnosis , Adult , Encephalitis/complications , Encephalitis/diagnosis , Humans , Magnetic Resonance Imaging , Male , Toxoplasmosis, Cerebral/complications , Toxoplasmosis, Cerebral/diagnosisABSTRACT
Bronchopulmonary Kaposi's sarcoma (KS) occurs in 20 percent of AIDS patients with cutaneous involvement; however, complete endobronchial occlusion is uncommon. Moreover, bronchopulmonary KS is infrequent in the absence of cutaneous manifestations. We report a case of documented complete endobronchial obstruction by KS without cutaneous involvement.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , Bronchial Neoplasms/pathology , Sarcoma, Kaposi/pathology , Adult , Airway Obstruction/etiology , Bronchial Neoplasms/diagnostic imaging , Bronchial Neoplasms/etiology , Humans , Male , Radiography , Sarcoma, Kaposi/diagnostic imaging , Sarcoma, Kaposi/etiology , Skin Neoplasms/pathologyABSTRACT
Hypersensitivity pneumonitis is an important but underdiagnosed form of interstitial lung disease. Its clinical hallmark is recurrent or chronic pulmonary symptoms of variable severity associated with an array of systemic symptoms but without extrapulmonary structural abnormalities. Clinical suspicion is the key to diagnosis, which is supported by establishing an environmental or occupational exposure to a causative inhaled antigen; by excluding infectious and other causes of recurrent, migratory, or progressive radiologic lung abnormalities; and by demonstrating antigen-specific antibodies in the serum. Two cases of hypersensitivity pneumonitis are described that illustrate the widely variable clinical, laboratory, and radiologic presentations and emphasize the importance of diagnosing this treatable condition.
Subject(s)
Alveolitis, Extrinsic Allergic/diagnosis , Aged , Alveolitis, Extrinsic Allergic/diagnostic imaging , Alveolitis, Extrinsic Allergic/etiology , Diagnosis, Differential , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , RadiographySubject(s)
Esophageal Diseases/chemically induced , Zalcitabine/adverse effects , Adult , Esophageal Diseases/diagnostic imaging , Esophageal Diseases/pathology , Esophagoscopy , HIV Infections/drug therapy , Humans , Male , Radiography , Recurrence , Ulcer/chemically induced , Ulcer/diagnostic imaging , Ulcer/pathologyABSTRACT
In a prospective, comparative trial, 47 hospitalized patients with serious infections that required parenteral antibiotic therapy were randomly assigned to receive either ciprofloxacin (200 mg every 12 hours intravenously followed by 500 mg every 12 hours orally at a time dependent on the patients' clinical and bacteriologic responses) or ceftazidime (2 g every eight to 12 hours intravenously). All evaluable subjects (39 patients) had documented infections, 23 percent of which were associated with bacteremia. The mean/median duration of intravenous antibiotic use for ciprofloxacin was 7.37/five days and for ceftazidime 9.95/seven days; 63 percent of the ciprofloxacin patients received an additional 17 days of oral therapy with ciprofloxacin, whereas intravenous therapy with ceftazidime was followed by an average of 12 days of an oral regimen in 55 percent of patients. Overall response rates for patients receiving ciprofloxacin and ceftazidime were 76 percent (16 of 21) and 82 percent (18 of 22), respectively. Four out of five bacteremias in each group were successfully treated. Overall, 69 percent of the pathogens were gram-negative aerobes, and 47 percent of the infections involved the urinary tract. Failure of therapy was most often associated with pneumonia (two of five failures with ciprofloxacin and three of four failures with ceftazidime). Adverse effects occurred in approximately 20 percent of patients in each group and were mild and reversible. Superinfections occurred in five of 19 (26 percent) ciprofloxacin recipients and seven of 20 (35 percent) ceftazidime recipients. All fungal superinfections involved the genitourinary tract and occurred most often in association with chronic indwelling catheters. Enterococcal superinfections occurred in both groups (a bacteremic urinary tract infection in a ceftazidime patient and osteomyelitis in a ciprofloxacin patient). Clostridium difficile-associated diarrhea was documented in a ceftazidime recipient. The mean duration of hospitalization following the onset of antibiotic treatment was 10.45 days in the ciprofloxacin group and 12.95 days in the ceftazidime group. Sequential intravenous/oral ciprofloxacin was as safe and effective as intravenous ceftazidime in the treatment of infections due to susceptible gram-positive and gram-negative organisms.
Subject(s)
Bacterial Infections/drug therapy , Ceftazidime/administration & dosage , Ciprofloxacin/administration & dosage , Administration, Oral , Adult , Aged , Aged, 80 and over , Ceftazidime/therapeutic use , Ciprofloxacin/adverse effects , Ciprofloxacin/therapeutic use , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Prospective StudiesABSTRACT
In a prospective, randomized trial of 195 febrile episodes in granulocytopenic patients short course aminoglycoside treatment (initial tobramycin and cefoperazone followed by tobramycin discontinuation at day four of therapy) was compared with two regimens (tobramycin plus cefoperazone and tobramycin plus mezlocillin) in which both drugs were continued for up to 26 days. All regimens were successful as empirical therapy with comparable response rates of just over seventy per cent. Fifty-three per cent of the initial episodes of fever were related to documented infections which responded less well (P = 0.007) than unexplained fever. Patients with bacteraemia, pneumonia or Gram-positive aerobic or Pseudomonas aeruginosa infections responded poorly to all regimens. The recovery from granulocytopenia was the most important determinant of successful response. Aminoglycoside discontinuation followed by cefoperazone monotherapy after day four was statistically as effective as the combination regimens. Short course tobramycin therapy eliminated the nephrotoxicity seen in the combination limbs. The use of cefoperazone was not associated with an increased incidence of hypoprothrombinemia; however, the only three bleeding episodes occurred in patients given cefoperazone but not vitamin K. Short course aminoglycoside therapy will reduce cost and nephrotoxicity when compared with prolonged combination therapy and should be further explored in this setting, with use of different agents and comparison with monotherapy.
Subject(s)
Agranulocytosis/complications , Bacterial Infections/drug therapy , Cefoperazone/therapeutic use , Fever/complications , Mezlocillin/therapeutic use , Tobramycin/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Infections/complications , Bacterial Infections/microbiology , Cefoperazone/adverse effects , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/therapeutic use , Female , Humans , Leukocyte Count , Male , Mezlocillin/adverse effects , Middle Aged , Prospective Studies , Randomized Controlled Trials as Topic , Tobramycin/adverse effectsABSTRACT
An arthropathy has been recently described in association with human parvovirus infection (HPV-B19). Human parvovirus B19 has also been implicated as the etiologic agent in erythema infectiosum, a childhood exanthem that may occur in adults in association with joint manifestations. In this study, two adults are described, in whom an acute arthropathy and rash developed after contact with children with erythema infectiosum.
Subject(s)
Arthritis, Infectious/etiology , Erythema/etiology , Parvoviridae Infections/etiology , Skin Diseases, Infectious/etiology , Adult , Arthritis, Infectious/diagnosis , Female , Humans , Parvoviridae Infections/diagnosis , Synovial Fluid/analysisABSTRACT
We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin.
Subject(s)
Infections/drug therapy , Neoplasms/complications , Netilmicin/therapeutic use , Tobramycin/therapeutic use , Adult , Chemical and Drug Induced Liver Injury , Clinical Trials as Topic , Drug Therapy, Combination , Hearing Loss/chemically induced , Humans , Immune Tolerance , Middle Aged , Neoplasms/immunology , Netilmicin/adverse effects , Piperacillin/therapeutic use , Prospective Studies , Random Allocation , Tobramycin/adverse effectsABSTRACT
We conducted a two-center dose ranging study to evaluate the efficacy, tolerance, and toxicity of cefpimizole, a new cephalosporin, in the treatment of uncomplicated gonorrhea in 96 males. Twelve patients at each center were treated intramuscularly with single doses of 1.0, 0.5, 0.25, and 0.125 g of cefpimizole. All urethral infections were cured at the highest dose, but lower doses produced progressively decreasing cure rates of 90% (0.5 g), 83% (0.25 g), and 71% (0.125 g). Treatment failures of rectal and pharyngeal infections occurred at the highest dose level. Geometric mean MICs for cefpimizole for successfully and unsuccessfully treated volunteers were 0.088 and 0.282 micrograms/ml, respectively. A prominent adverse effect was clinically significant pain at the injection site, which occurred in 57 (59%) of 96 patients. Results of the study demonstrate that cefpimizole offers no advantage over currently available antibiotics in the treatment of uncomplicated gonorrhea in men.
Subject(s)
Cephalosporins/therapeutic use , Gonorrhea/drug therapy , Adolescent , Adult , Cephalosporins/administration & dosage , Cephalosporins/adverse effects , Gonorrhea/microbiology , Humans , Male , Microbial Sensitivity Tests , Neisseria gonorrhoeae/drug effectsABSTRACT
A 46-year-old woman had a chronic, unresponsive wrist infection that was proved to be due to the algaelike organism Prototheca wickerhamii. Treatment with ketoconazole resulted in prompt improvement and ultimate healing. Therapy was complicated by hepatitis that was ketoconazole-related. Ketoconazole may be effective and easily administered therapy for this generally unresponsive infection.
Subject(s)
Imidazoles/therapeutic use , Infections/drug therapy , Piperazines/therapeutic use , Prototheca , Wrist , Chemical and Drug Induced Liver Injury , Female , Humans , Imidazoles/adverse effects , Ketoconazole , Middle Aged , Piperazines/adverse effectsABSTRACT
We report two cases of Lyme disease in North Carolina, further expanding the distribution of known sporadic cases of this predominantly northeastern problem in southern states. Physicians in areas where Lyme disease has traditionally not been recognized should be alerted to its characteristic rash (erythema chronicum migrans), tick vector (Ixodes species), possible severe manifestations (neurologic, arthritic, and cardiac), and response to appropriate antibiotic therapy (penicillin or tetracycline).