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Biomedical subjects

R E Chaisson

Publications and source records attributed to R E Chaisson.

At least 145 records · Page 8Linked to original sources

Efficacy of engineering controls in reducing occupational exposure to aerosolized pentamidine.

Aerosolized pentamidine administration may pose potential risks to health care workers exposed to fugitive drug and to infectious respiratory pathogens (eg, tuberculosis) generated by pentamidine-induced cough. Classic infection control methods may be applied to this problem, although the effectiveness of these measures in mitigating environmental pentamidine exposure is unknown. Lack of data fully characterizing pentamidine's mechanism of action or potential mutagenicity, carcinogenicity, or teratogenicity raises concern and suggests worker exposed and environmental contamination be minimized. We report herein on the efficacy of an aerosol containment hood in containing fugitive pentamidine aerosol during administration.

Aerosols↗

Immune serum markers and CD4 cell counts in HIV-infected intravenous drug users.

We examined the association of three serum immune markers with CD4 cell counts in a large cohort of i.v. drug users with and without human immunodeficiency virus (HIV) infection. Levels of beta 2-microglobulin and neopterin were significantly elevated in HIV-infected subjects and increased in association with decline in CD4 cell counts (all p less than 0.001). Serum IgA levels in HIV-seropositive individuals were significantly elevated only when the CD4 cell count was less than 200/microliters (p less than 0.001). After controlling for HIV status and CD4 count, recent history of hepatitis was associated with significantly higher beta 2-microglobulin (p = 0.028) and marginally higher neopterin (p = 0.052) levels. There was no association of race, gender, or drug use patterns with levels of serum immune markers after controlling for HIV status and CD4 count. These data indicate that immune activation is coupled with immunosuppression in HIV-infected i.v. drug users. In addition, beta 2-microglobulin and neopterin levels are elevated in persons with a recent history of hepatitis but not in those with recent non-AIDS-defining bacterial infections. Markers of immune activation do not vary by race, gender, or drug use patterns among i.v. drug users.

Biomarkers↗

Pneumocystis prophylaxis and survival in patients with advanced human immunodeficiency virus infection treated with zidovudine. The Zidovudine Epidemiology Group.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and mortality in persons with advanced human immunodeficiency virus (HIV) infection. We assessed the impact of prophylaxis for PCP on survival in patients with advanced HIV disease who were treated with zidovudine. METHODS: A cohort of 1048 patients with prior PCP (N = 437), another acquired immunodeficiency syndrome-defining diagnosis (N = 168) or acquired immunodeficiency syndrome-related complex (N = 443) and with less than 0.250 x 10(9)/L CD4 cells initiated zidovudine treatment between April 1987 and April 1988. They were then followed up for 24 months. Morbidity and mortality outcomes were assessed every 2 months. A time-dependent, Cox proportional hazards model was used to identify factors associated with new episodes of PCP and with survival. RESULTS: Three hundred thirty-six patients (32%) developed PCP after beginning treatment with zidovudine, with a 24-month actuarial rate of 41%. Patients with prior PCP were more likely to develop PCP during follow up (40%) than those without a history of PCP at entry (27% with PCP at follow-up). Other factors associated with developing PCP were baseline acquired immunodeficiency syndrome vs acquired immunodeficiency syndrome-related complex, and dose interruptions of zidovudine. Thirty-six (17%) of 210 patients who received trimethoprim-sulfamethoxazole prophylaxis developed PCP vs 299 (36%) of 838 who never received trimethoprim-sulfamethoxazole (odds ratio, 0.48). One hundred seven (22%) of 483 patients who ever received aerosol pentamidine prophylaxis developed PCP vs 228 (40%) of 565 who did not receive aerosol pentamidine (odds ratio, 0.55). In a time-dependent Cox proportional hazards analysis, trimethoprim-sulfamethoxazole (relative hazard, 0.21; 95% confidence interval [CI], 0.11 to 0.4) and aerosol pentamidine prophylaxis (relative hazard, 0.25; 95% CI, 0.16 to 0.39) were associated with decreased risk of PCP. Pneumocystis carinii pneumonia during follow-up was strongly associated with death when controlling for other factors (odds ratio, 1.8). For all patients, aerosol pentamidine prophylaxis was associated with a reduced risk of death during follow-up (relative hazard, 0.59; 95% CI, 0.44 to 0.78), while trimethoprim-sulfamethoxazole showed a weaker association (relative hazard, 0.74; 95% CI, 0.54 to 1.1). However, there was a significantly reduced risk of death overall for patients who consistently used trimethoprim-sulfamethoxazole (relative hazard, 0.55; 95% CI, 0.35 to 0.88) or aerosol pentamidine (relative hazard, 0.57; 95% CI, 0.42 to 0.77) and this was most pronounced in patients with a baseline history of PCP. DISCUSSION AND CONCLUSIONS: Pneumocystis carinii pneumonia was common in advanced HIV infection treated with zidovudine. Prophylaxis with trimethoprim-sulfamethoxazole and aerosol pentamidine both were associated with a decreased likelihood of PCP, and consistent use of each was associated with improved survival. Prophylaxis for PCP is associated with prolonged survival for patients with advanced HIV disease.

AIDS-Related Opportunistic Infections↗

Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group.

OBJECTIVE: To describe the natural history of advanced HIV disease in patients treated with zidovudine. DESIGN: Longitudinal, observational study. SETTING: Twelve academic and community-based sites. PATIENTS, PARTICIPANTS: Eight hundred and sixty-three patients with AIDS or AIDS-related complex (ARC) with a CD4+ lymphocyte count less than 250 x 10(6)/l, who first received zidovudine between 15 April 1987 and 14 April 1988. MAIN OUTCOME MEASURES: Survival, progression to AIDS and first development of specific opportunistic illness. RESULTS: Median survival after initiation of zidovudine therapy ranged from greater than 900 days in patients with a baseline CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 560 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/1. Other factors associated significantly with poorer survival were diagnosis of AIDS (versus ARC), baseline age greater than or equal to 40 years, hematocrit less than 35%, and diminished functional status. In patients with ARC at enrollment, median time of progression to AIDS ranged from 810 days in patients with a CD4+ lymphocyte count greater than or equal to 150 x 10(6)/l to 310 days in patients with a CD4+ lymphocyte count less than 50 x 10(6)/l. Rates of development of specific opportunistic infections or neoplasms and HIV encephalopathy were determined for different baseline CD4+ lymphocyte count ranges. Myelosuppression was significantly more common in patients with CD4+ lymphocyte counts greater than or equal to 100 x 10(6)/l. Sixty-five per cent of patients with a CD4+ lymphocyte count greater than or equal to 100 x 10(6)/l and 51% with a CD4+ lymphocyte count less than 100 x 10(6)/l continued to receive zidovudine 2 years after starting therapy. CONCLUSIONS: We describe the natural history of a cohort of patients treated with zidovudine for advanced HIV disease. These CD4+ lymphocyte count-stratified estimates of disease progression should provide prognostic information useful in the clinical management of advanced disease and the design of future studies.

AIDS-Related Complex↗

Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at increased risk for serious infections caused by Haemophilus influenzae, yet there are few data on their antibody responses to the H. influenzae type b vaccines. METHODS: We evaluated antibody responses in 248 men who were randomly assigned to receive a single dose of either the H. influenzae type b polysaccharide (PRP) vaccine or the polysaccharide-mutant diphtheria toxoid conjugate vaccine (PRP-CRM). The subjects were stratified into four groups: seronegative men (67 subjects), men with asymptomatic HIV infection (79), men with symptomatic HIV infection (47), and men with the acquired immunodeficiency syndrome (AIDS) (55). RESULTS: Before immunization, the subjects with AIDS had the lowest PRP-antibody titers; 40 percent had titers below the putative protective level (less than 0.15 micrograms per milliliter). In the seronegative subjects, those with asymptomatic HIV infection, and those with symptomatic HIV infection, the PRP-CRM vaccine led to a threefold greater increase in geometric mean antibody titers than did the PRP vaccine (P less than 0.01). However, the subjects with AIDS had a greater antibody response to the PRP vaccine. The antibody response of HIV-seropositive men to the PRP-CRM vaccine correlated significantly with the number of CD4 lymphocytes (r = 0.47, P less than 0.0001, as compared with r = -0.01 for the PRP vaccine). In these HIV-infected men, both vaccines elicited the dominant anti-PRP idiotype described previously in populations not infected with HIV. CONCLUSIONS: Immunization with the PRP-CRM conjugate vaccine early in the course of HIV infection is likely to confer protection against disease caused by H. influenzae type b.

AIDS Vaccines↗

Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease. Zidovudine Epidemiology Study Group.

UNLABELLED: OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study. SETTING: -Hospital and private clinics in 12 metropolitan centers. PATIENTS: -The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis.

Acquired Immunodeficiency Syndrome↗

Zidovudine and the natural history of the acquired immunodeficiency syndrome.

BACKGROUND AND METHODS: We sought to describe the trends in survival from 1983 to 1989 among persons with the acquired immunodeficiency syndrome (AIDS) and to examine the relative effects on the natural history of AIDS of zidovudine use and demographic and clinical characteristics. This longitudinal, observational, population-based study used data from the Maryland Human Immunodeficiency Virus Information System, a data base that links information from the Maryland AIDS Registry with data on public and private health care claims, vital statistics, and hospital, long-term care, and ambulatory care records. RESULTS: The median survival after diagnosis among persons with AIDS (n = 1028) was 140 days longer for those given their diagnoses between 1987 and 1989 than for those given their diagnoses between 1983 and 1985 (450 vs 310 days). Among the 714 persons in whom AIDS was diagnosed after April 1987 (when zidovudine became available), two-year survival was greater among men than women (P less than 0.03), among persons less than 45 years old than among older persons (P less than 0.001), among non-Hispanic whites than among minorities (P less than 0.001), and among persons whose category of human immunodeficiency virus transmission was homosexual contact than among those with heterosexual, transfusion-related, or less common modes of transmission (P less than 0.02). In all the analyses the groups with the longer survival were more likely to have received zidovudine. The median survival among those who received zidovudine was 770 days, as compared with 190 days among those who never received the drug (P less than 0.001). By proportional-hazards analysis, zidovudine therapy was the factor most strongly associated with improved survival. CONCLUSIONS: For Maryland residents with AIDS there has been an improvement in survival since 1987. Zidovudine therapy and perhaps other aspects of care associated with it have contributed substantially to the improved survival.

Acquired Immunodeficiency Syndrome↗

Mycobacterium kansasii: a cause of treatable pulmonary disease associated with advanced human immunodeficiency virus (HIV) infection.

OBJECTIVE: To assess the clinical features and response to therapy of Mycobacterium kansasii infection in patients with human immunodeficiency virus (HIV) infection. DESIGN: We reviewed the records of all patients with M. kansasii and HIV infection treated between January 1985 and June 1990. SETTING: The Johns Hopkins Hospital, Baltimore, Maryland. RESULTS: Nineteen patients with M. kansasii and HIV infection were identified; 14 patients had exclusive pulmonary infection, 3 patients had pulmonary and extrapulmonary infection, and 2 patients had exclusive extrapulmonary infection. At the time of diagnosis of M. kansasii infection, the median CD4+ lymphocyte count was 49 cells/microL (range, 0 to 198 cells/microL), and 16 of 19 patients had a previous diagnosis of the acquired immunodeficiency syndrome (AIDS). All 17 patients with pulmonary infection presented with fever and cough of at least 2 weeks duration. Chest radiographs showed either focal upper lobe infiltrates (n = 8) or diffuse interstitial infiltrates (n = 9); 9 patients also had thin-walled cavitary lesions. Nine patients with pulmonary M. kansasii infection were treated with antituberculosis chemotherapy, with resolution of fever and respiratory symptoms, improvement of radiographic infiltrates, and sputum conversion; 1 patient with M. kansasii osteomyelitis also responded to antituberculosis therapy. Autopsies done on 3 treated patients did not reveal any evidence of M. kansasii infection. Nine patients did not receive any antituberculosis chemotherapy; 2 untreated patients developed progressive cavitary pulmonary disease and died from M. kansasii pneumonia. CONCLUSIONS: Mycobacterium kansasii causes serious and potentially life-threatening pulmonary disease in patients with advanced HIV-related immunosuppression. In contrast to previous reports, our findings indicate that disease produced by M. kansasii in patients with HIV infection is responsive to antituberculosis chemotherapy.

Adult↗

Non-Hodgkin's lymphoma in patients with advanced HIV infection treated with zidovudine.

We wished to determine the incidence of human immunodeficiency virus-related high-grade non-Hodgkin's lymphoma (NHL) and identify factors associated with the development of NHL in patients receiving zidovudine. Data are from a 2-year prospective, observational, multisite study of 1030 patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex who received zidovudine. Non-Hodgkin's lymphoma developed in 24 (2.3%) of 1030 patients who received zidovudine during 1463 person-years of follow-up (rate, 1.6 per 100 person-years of therapy). The relative hazard for development of NHL was stable throughout 2 years of therapy, with the risk of developing NHL 0.8% for each additional 6 months of therapy. Factors associated with development of NHL were a prior diagnosis of Kaposi's sarcoma, herpes simplex virus infection, or lower mean neutrophil count. Less strongly associated was a prior diagnosis of oral hairy leukoplakia or homosexual transmission of HIV. By Cox proportional hazards analysis, a prior diagnosis of Kaposi's sarcoma, cytomegalovirus disease, or oral hairy leukoplakia was most strongly associated with development of NHL. Our study demonstrates a relatively high incidence of NHL in patients with advanced human immunodeficiency virus disease who are undergoing antiretroviral therapy and suggests possible risk factors for development of NHL.

AIDS-Related Complex↗

Routine prenatal screening for HIV infection.

Guidelines in most developed countries for testing pregnant women for HIV infection recommend that screening should be directed to groups with acknowledged risk factors for infection. Our prospective study of HIV seroprevalence among 2724 pregnant women in an inner-city area of Baltimore, USA, showed that if these guidelines had been applied only 57% of HIV-seropositive women would have been detected. By offering counselling and HIV testing to all pregnant women, the detection rate was raised to 87%. We conclude that screening directed at women who admit risk factors is not effective in identifying HIV-infected women and that routine HIV screening should be offered to all pregnant women.

Adult↗

Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection.

BACKGROUND AND METHODS: Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS: At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS: Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Acquired Immunodeficiency Syndrome↗

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine.

OBJECTIVE: To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. DESIGN: Retrospective study of changes in laboratory markers and survival. SETTING: Multicentre trial at university hospital clinics. SUBJECTS: 90 Patients with AIDS or AIDS related complex. INTERVENTION: Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. MAIN OUTCOME MEASURES: Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, beta 2 microglobulin, and neopterin; survival of the patient. RESULTS: The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (v AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum beta 2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. CONCLUSION: These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

AIDS-Related Complex↗

Racial heterogeneity of HIV antigenemia in people with HIV infection.

We compared the prevalence of HIV p24 antigenemia in black and white US patients with HIV infection. The prevalence of HIV antigenemia increased with severity of HIV disease (P less than 0.001). In all clinical categories, whites were more likely to be HIV-antigenemic than blacks (overall prevalence 38 versus 18%; P less than 0.01). Anti-p24 antibodies were detected in a higher proportion of blacks (84%) than whites (65%; P = 0.02). Blacks had significantly higher total serum immunoglobulin levels than whites (median 3.8 versus 3.2 mg/dl; P less than 0.00001). Racial differences in HIV antigen expression may result from differences in humoral response to HIV infection. These differences should be considered when HIV antigen is used as a surrogate marker in clinical trials.

Adult↗

Pharmacokinetics, toxicity, and activity of intravenous dextran sulfate in human immunodeficiency virus infection.

Polysulfated polysaccharides are attractive candidates for antiviral drug development because of their potent in vitro activities against human immunodeficiency virus (HIV), herpesviruses, and other enveloped viruses. To determine the potential anti-HIV activity of a prototypical polysulfated polysaccharide, we administered the maximally tolerated dose of dextran sulfate by continuous intravenous infusion to 10 subjects with symptomatic HIV infection for up to 14 days. Since parenteral dextran sulfate is an anticoagulant, the infusion was adjusted to produce the greatest acceptable increase in activated partial thromboplastin time. Drug concentrations in plasma achieved with this protocol were up to 200-fold greater than the 50% inhibitory concentration for free HIV infectivity in vitro. Despite this, circulating HIV antigen (p24) levels increased in all eight subjects who received the drug for more than 3 days (median proportional increase, 73.5%; range, 32 to 130%); this increase was highly significant when it was compared with that in a large cohort of untreated historical controls (Fisher's exact test, P less than 0.001). Frequent decreases in infusion rate were required in all subjects to maintain a constant activated partial thromboplastin time; plasma dextran sulfate levels did not fall as the infusion rate decreased, suggesting a decline in estimated drug clearance over time. Continuous intravenous dextran sulfate was toxic, producing profound but reversible thrombocytopenia in all eight subjects who received drug for more than 3 days and extensive but reversible alopecia in five of these subjects. Because of its toxicity and lack of beneficial effect on surrogate markers, dextran sulfate is unlikely to have a practical role in the treatment of symptomatic HIV infection.

Acquired Immunodeficiency Syndrome↗

Control of tuberculosis during aerosol therapy administration.

In summary, despite the major benefits conferred by aerosol therapy, the risk of transmission of M tuberculosis remains a concern. The most effective approach to preventing nosocomial transmission of respiratory infections such as tuberculosis is to prevent disease in patients at risk, particularly those receiving aerosol therapy. Tuberculin skin tests should be applied to all HIV-infected persons and chemoprophylaxis administered to those with greater than or equal to 5mm reaction. Early detection and treatment of tuberculosis are essential to prevent transmission both inside and outside of health-care settings. Cough-reduction measures should be taken when giving pentamidine aerosol, and patients who do cough should cover their mouths. Proper ventilation of treatment areas with negative air pressure and at least 10 air changes per hour, and more if feasible, is essential. HEPA filters should be installed to cleanse exhaust air from treatment rooms, and air should not be recirculated. The use of UV light to disinfect air is recommended only for special situations. Finally, personal protective devices should be worn by health-care workers who are exposed to patients receiving aerosol therapy when other measures do not offer adequate protection.

Aerosols↗