Irving E. Salit

A Comparison of Two Regimens for the Treatment of Mycobacterium avium Complex Bacteremia in AIDS: Rifabutin, Ethambutol, and Clarithromycin versus Rifampin, Ethambutol, Clofazimine, and Ciprofloxacin

BACKGROUND Bacteremia with the Mycobacterium avium complex is common in patients with the acquired immunodeficiency syndrome (AIDS), but the most effective treatment for this infection remains unclear. METHODS We randomly assigned 229 patients with AIDS and M. avium complex bacteremia to receive either rifampin (600 mg daily), ethambutol (approximately 15 mg per kilogram of body weight daily), clofazimine (100 mg daily), and ciprofloxacin (750 mg twice daily) (the four-drug group) or rifabutin (600 mg daily), ethambutol (as above), and clarithromycin (1000 mg twice daily) (the three-drug group). In the three-drug group the dose of rifabutin was reduced by half after 125 patients were randomized, because 24 of 63 patients had uveitis. RESULTS Among 187 patients who could be evaluated, blood cultures became negative more often in the three-drug group than in the four-drug group (69 percent vs. 29 percent, P<0.001). Among patients treated for at least four weeks, the bacteremia resolved more frequently in the three-drug group (78 percent vs. 40 percent, P<0.001). In the three-drug group, bacteremia resolved more often with the 600-mg dose of rifabutin than with the 300-mg dose (P=0.025), but the latter regimen was more effective than the four-drug regimen (P<0.05). The median survival was 8.6 months in the three-drug group and 5.2 months in the four-drug group (P = 0.001). The median Karnofsky performance score was higher in the three-drug group than in the four-drug group from week 2 to week 16 (P<0.05). Mild uveitis developed in 3 of the 53 patients receiving the 300-mg dose of rifabutin, an incidence about one quarter that observed with the 600-mg dose (P<0.001). CONCLUSIONS In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects.

Objectives:The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. Design:A randomized placebo-controlled, double-blind study. Methods:Forty-nine HIV-positive patients were randomized to receive supplements of both DL-α-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded. Results:The vitamin group (n = 26) had an increase in plasma concentrations of α-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean ± SD changes over 3 months, −0.45 ± 0.39 versus +0.50 ± 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, −0.21 to −2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group. Conclusion:Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.

Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients

A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1∶:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due toCandida glabrata orCandida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p=0.39; one-sided 95% Cl, −8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p=0.66: one-sided 95% Cl, −12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p=0.52; chi-square test) and remained similar throughout the course of follow-up. Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.

Depression in Patients with Neuromyasthenia (Benign Myalgic Encephalomyelitis)

Neuromyasthenia (benign myalgic encephalomyelitis) is a term used to describe a protracted and incomplete recovery phase following viral-like illnesses. There are few significant physical findings or abnormal laboratory determinations. Although depressive symptoms have been observed in individuals with neuromyasthenia, systematic psychological investigations based on a standardized interview technique have not been reported. This study was designed to investigate the prevalence of psychiatric disorders and psychiatric symptoms in a group of patients presenting with neuromyasthenia. The study consisted of three parts: a structured psychiatric interview (The National Institute of Mental Health Diagnostic Interview Schedule), a self-report measure (The Beck Depression Inventory) and Dexamethasone Suppression Test. Results indicated that relative to a matched comparison group of non-clinical volunteers, a significant percentage (67%) of neuromyasthenic patients met criteria for major depression. Even more striking was the observation that 50 percent of the sample had a major depressive episode prior to the development of neuromyasthenia. These findings suggest that sporadic neuromyasthenia may be the result of an organic illness in psychologically susceptible individuals.

The role of cytology (Pap tests) and human papillomavirus testing in anal cancer screening.

Objective:To assess anal oncogenic human papillomavirus (HPV) and anal cytology as screening tests for detecting high-grade anal intraepithelial neoplasia (AIN 2+), as this is an immediate anal cancer precursor. Design:Cross-sectional study of 401 HIV-positive men who have sex with men (MSM). The endpoint was histologically confirmed AIN 2+ obtained by high-resolution anoscopy. Cytology and biopsy specimens were assigned random numbers and independently assessed by two pathologists. Methods:We did concomitant anal cytology, anal HPV testing and HRA with directed biopsies without knowing the results of each intervention. The main outcome measures were the sensitivity, specificity, negative predictive value and positive predictive value of anal cytology and oncogenic HPV for the detection of AIN 2+. Results:Cytology was abnormal in 67% of patients: high-grade squamous intraepithelial lesion, 12%; low-grade squamous intraepithelial lesion, 43% and atypical squamous cells of undetermined significance, 12%. Biopsies were abnormal in 68% of patients: AIN 2+, 25% and AIN 1, 43%. HPV was detected in 93% with multiple HPV types in 92% and oncogenic HPV types in 88%. Test performance characteristics for the detection of AIN 2+ using any abnormality on anal cytology were: sensitivity 84%, specificity 39%, negative predictive value 88% and positive predictive value 31%; using oncogenic HPV: sensitivity 100%, specificity 16%, negative predictive value 100% and positive predictive value 28%. Conclusion:Anal cytology and HPV detection have high sensitivity but low specificity for detecting AIN 2+. HIV-positive men who have sex with men have a high prevalence of AIN 2+ and require high-resolution anoscopy for optimal detection of high-grade anal dysplasia.

Travel patterns and risk behaviour of HIV-positive people travelling internationally

Background: International travel is associated with an increased risk of enteric, vector-borne, sexually transmitted and blood-borne infections. These risks are even higher among immunocompromised people, such as those with HIV infection. We conducted a study to determine HIV-positive peoples travel patterns and risk behaviours while abroad. Methods: We conducted an anonymous survey of HIV-positive people attending an HIV clinic in a tertiary care hospital in Toronto about their travel activities and pretravel precautions as well as their burden of illness and risk exposure during travel. We compared the characteristics of respondents who had travelled outside Canada and the United States (international travellers) with those of respondents who had not travelled internationally. Results: Of 290 HIV-positive people who participated in the study, 133 (45.9%) indicated that they had travelled internationally in the 5 years before the survey. These people were predominantly men (93.2%) and well educated (60.0% had a university level education), and they had travelled mostly for personal reasons (89.5%) on trips that lasted 3.6 weeks on average. Only 58 (43.6%) sought health advice before travelling, and only 17 (12.8%) sought advice from a travel clinic. Five (3.8%) had received live vaccines before travel, and 9 (6.8%) had taken malaria chemoprophylaxis. Of the 119 international travellers who were taking antiretroviral therapy; 35 (29.4%) reported either discontinuing their medications or being poorly compliant with the therapy while travelling. Thirty-one (23.3%) of the 133 international travellers reported having had casual sexual activity with new partners while travelling, and only 18 (58.1%) of them reported always using a condom. Twenty-one (15.8%) of the 133 reported having had risky exposure to sharps. Twenty-four (18.0%) said they had become ill enough while travelling to require medical attention. Interpretation: Only one-fifth of HIV-positive people surveyed who travelled internationally sought advice from a health professional before their trip. Their travel was associated with poor adherence to antiretroviral therapy, risky sexual practices and risky exposure to sharps.

Travel Patterns and Risk Behavior in Solid Organ Transplant Recipients

BACKGROUND International travel is associated with an increased risk of enteric, vector-borne and bloodborne infections. The risk of acquiring travel-related illness is higher in those who are immunocompromised. However, little is known about travel practices and risk behaviors in transplant recipients who travel. We herein profile transplant recipients who travel, and characterize their pre-travel precautions, travel activities, burden of illness, and exposure history. METHODS With the use of a standardized and validated questionnaire, patients attending a transplant clinic were surveyed regarding recent travel and risk behaviors. RESULTS Of 267 transplant recipients who participated, 95 (36%) indicated that they had recently traveled outside Canada and the USA. Their mean age was 49.9 years, 54% were male, and 54% were born outside Canada. Eighty-six percent of travelers were receiving at least two immunosuppressive drugs at the time of their trip. Sixty-six percent of travelers sought pre-travel advice, primarily from their transplant physician. Sixty-three percent traveled to areas where hepatitis A is endemic, but only 5% had received hepatitis A immunization. Fifty percent traveled to dengue- and malaria-endemic areas, but,25% adhered to mosquito prevention measures. Ten percent reported behaviors that exposed them to blood or body fluids, including injections, body piercing, and casual sexual activity. CONCLUSIONS Solid organ transplant recipients represent a unique group of compromised travelers; however, few were adequately protected against travel-associated enteric, vector-borne and bloodborne pathogens.

Cost-effectiveness of screening for anal precancers in HIV-positive men.

Objective:To assess the cost-effectiveness of high-resolution anoscopy (HRA), anal cytology, and anal human papillomavirus (HPV) detection in screening for histologic high-grade anal intraepithelial neoplasia (AIN 2/3) in HIV-positive MSM. Design:Participants were 401 HIV-positive MSM who were screened for anal cancer in a tertiary care HIV clinic. Methods:A decision analytical model was used to determine the cost-effectiveness of three anal cancer screening strategies: the direct use of HRA; HRA only if anal cytology was abnormal; and HRA only if oncogenic HPV was present. The model included the use of different thresholds for abnormal cytology and also combined cytology and HPV testing. The outcome was the number of AIN 2/3 cases detected. Costs were estimated from institutional data and sensitivity/specificity of cytology and HPV tests were obtained from the screening study. Results:The costs (

Long-Term Quality-of-Life Outcomes Among Adults Living with HIV in the HAART Era: The Interplay of Changes in Clinical Factors and Symptom Profile

US) per procedure for HRA, cytology, and HPV testing were

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

193,