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Biomedical subjects

F Gordin

Publications and source records attributed to F Gordin.

15 recordsLinked to original sources

CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS: A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

AIDS-Related Opportunistic Infections↗

Discontinuation of prophylaxis against Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy. METHODS: We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia. RESULTS: A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of confirmed M. avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years). Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002). CONCLUSIONS: Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group.

CONTEXT: Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed. OBJECTIVE: To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection. DESIGN: Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997. SETTING: Outpatient clinics in the United States, Mexico, Haiti, and Brazil. PARTICIPANTS: A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result. INTERVENTIONS: Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791). MAIN OUTCOME MEASURES: The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group. RESULTS: Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis. CONCLUSIONS: Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.

AIDS-Related Opportunistic Infections↗

Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

AIDS Vaccines↗

Delayed diagnosis of pulmonary tuberculosis in city hospitals.

BACKGROUND: Delays in the diagnosis of tuberculosis may result in increased patient morbidity and in further spread of the disease. We examined the clinical acumen of the medical staff in the diagnosis of tuberculosis and investigated the reasons for delay in the identification and treatment of patients with pulmonary tuberculosis. METHODS: A retrospective chart review was undertaken between July 1985 and June 1988 on all patients with culture-proven pulmonary tuberculosis at two inner city hospitals. Time intervals between admission and the clinical suspicion, diagnosis, and treatment of tuberculosis were determined. Clinical features were evaluated for their effect on these time intervals. RESULTS: Eighty-five patients with culture-proven pulmonary tuberculosis were identified. Tuberculosis was suspected in 36 patients on admission. By the end of 1 week, tuberculosis was confirmed in 50 patients and suspected in 23 others. Twenty percent of patients either died or were discharged before the diagnosis of tuberculosis was made. Older patients (> 65 years) were misdiagnosed more commonly than younger patients (82% vs 48%). Patients without respiratory symptoms were misdiagnosed more frequently (78% vs 49%) than were those with symptoms. Other reasons for delayed diagnosis and treatment included low use of tuberculin skin tests, misinterpretation of unusual chest roentgenograms, and waiting for culture results in patients with negative acid-fast smears. CONCLUSIONS: The diagnosis and treatment of patients with pulmonary tuberculosis is often delayed owing to atypical presentations and slow confirmation by culture. Improved clinical acumen, development of rapid diagnostic tests, and the institution of early empiric therapy are desirable to control this disease.

Adult↗

Prophylaxis of Mycobacterium avium complex bacteremia in patients with AIDS.

Prevention of opportunistic infections is an integral part of caring for patients infected with human immunodeficiency virus. Mycobacterium avium complex (MAC) bacteremia can cause severe morbidity and excess mortality among these patients. Controlled trials of rifabutin for the prophylaxis of MAC bacteremia have been completed. Rifabutin reduced the incidence of MAC bacteremia by approximately one-half and, when disseminated disease due to MAC (DMAC) did develop, reduced the frequency of associated clinical symptoms. Moreover, prophylaxis with rifabutin was well tolerated. Prophylaxis of MAC bacteremia with macrolide antibiotics is currently being investigated, but no data from large-scale prospective trials are yet available. On the basis of trials completed thus far, the U.S. Public Health Service has recently recommended the use of rifabutin (300 mg/d) as prophylaxis for MAC bacteremia in patients with fewer than 100 CD4+ lymphocytes/mm3. The widespread use of this prophylactic regimen could reduce the rates of morbidity and mortality caused by DMAC. However, rifabutin must be administered only after careful consideration of the circumstances of individual patients. Potential drug interactions, cost, and compliance are important factors in the decision about which patients should receive prophylaxis.

AIDS-Related Opportunistic Infections↗

The validity of acid-fast smears in the diagnosis of pulmonary tuberculosis.

The acid-fast smear remains an important tool in the diagnosis of tuberculosis. Some reports have questioned the validity of this stain in situations of low prevalence. We examined the relationship between prevalence and predictive value of sputum smears in one laboratory during periods of both low and high laboratory prevalence of Mycobacterium tuberculosis. Smears were examined by fluorescence and confirmed by Kinyoun stain. The number of samples positive for mycobacteria increased from 128 (4.3%) of 2956 during the 1975 through 1978 study period to 197 (8.4%) of 2347 during the 1979 through 1982 study period. Of 47 positive smears during the first study period, only one was a false-positive. None of 96 positive smears during the second period was a false-positive. The positive predictive value of acid-fast microscopy was 97.9% and 100% for the two periods examined. We have demonstrated in practice the small effect of a shift in prevalence on the positive predictive value of an acid-fast smear when specificity is maintained.

Humans↗

Spontaneous pneumothorax with Pneumocystis carinii infection. Occurrence in patients with acquired immunodeficiency syndrome.

Two patients with acquired immunodeficiency syndrome developed spontaneous pneumothorax during the course of Pneumocystis carinii pneumonia. The pneumothorax in each of these patients was a primary event, unrelated to biopsy or mechanical ventilation. To our knowledge, this complication of P carinii infection has not been noted in adults before and is an important consideration for those caring for persons with this illness.

Acquired Immunodeficiency Syndrome↗

Surface antigens on cat leukemic cells induced by feline leukemia virus: area density and antibody-binding affinity.

The binding of autologous bovine antibody to feline leukemia virus-induced cell surface antigens (FeCSA) on cat leukemia cells was studied by performing certain titration procedures with a mixture of immune and normal sera labeled with different iodine radioisotopes (paired-label technique). By using plots of titration data which conformed to linear equations derived from the mass action law, we determined the following constants. (i) The density of FeCSA was 2.03 x 10(6) sites per cell, or 5,230 sites per mum(2). (ii) The equilibrium constant of the FeCSA-antibody reaction was 2.67 x 10(7), from which the antibody binding affinity or standard free energy of the FeCSA-antibody bond was determined to be - 10.48 kcal (-43,869.28 J) per mol. The use of the techniques described to measure the concentration of antibody in antiserum, in micrograms per milliliter, is discussed.

Animals↗

Pyogenic psoas abscesses: noninvasive diagnostic techniques and review of the literature.

Psoas muscle abscesses are a diagnostic and therapeutic challenge. Until recently, surgery was mandated for diagnosis and drainage of these deep posterior lesions. Scanning techniques such as computerized tomography, radionuclide imaging, and ultrasonography now enable noninvasive visualization of abnormalities of the psoas muscle. Patients with abscesses in the greater psoas muscle fall into two distinct groups. Six of 12 patients reviewed had no apparent predisposing conditions. These patients presented with subacute symptoms of fever, pain, and disability. Staphylococcus aureus was the predominant organism isolated. Psoas infections developed in six other patients secondarily to infection or trauma elsewhere in the abdomen. Gram-negative and enteric organisms were the predominant bacteria isolated from this group. Surgical drainage in selected patients and appropriate antimicrobial therapy is necessary for treatment of these infections. Late complications such as osteomyelitis are not unusual.

Abscess↗