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Biomedical subjects

R E Chaisson

Publications and source records attributed to R E Chaisson.

At least 109 records · Page 6Linked to original sources

Neutropenia and bacterial infection in acquired immunodeficiency syndrome.

BACKGROUND: In human immunodeficiency virus (HIV) disease, neutropenia occurs most commonly in patients who are also severely immunosuppressed. It is not currently known whether neutropenia is an independent risk factor for the development of bacterial infection, which is a potentially serious complication of advanced HIV disease. METHODS: We compared the incidence of bacterial infection between 118 neutropenic patients (absolute neutrophil count [ANC], < 1 x 10(9)/L) and 118 nonneutropenic patients matched for CD4+ lymphocyte count, use of injecting drugs, and follow-up time from a demographically heterogeneous urban cohort of HIV-infected patients followed up longitudinally at the Johns Hopkins Hospital. The incidence of serious infection was analyzed separately for patients with an ANC of less than 1, less than 0.75, or less than 0.5 x 10(9)/L. RESULTS: There were no statistically significant associations found between neutropenia and several individual bacterial infections, including bacteremia, pneumonia, endocarditis, bacterial enterocolitis, and infection of normally sterile sites for any level of neutropenia. However, for all these infections combined, the adjusted relative risk for the occurrence of bacterial infection was 2.33 (95% confidence interval, 1.00 to 5.40; P = .05) for patients with an ANC of less than 1 x 10(9)/L and 7.92 (95% confidence interval, 1.18 to 53.2; P = .03) for those with an ANC of less than 0.5 x 10(9)/L. The incidence of serious bacterial infection ranged from two to three infections per 100 person-months of neutropenia for patients with an ANC of less than 1 x 10(9)/L and three to five infections per 100 person-months of neutropenia for patients with an ANC of less than 0.5 x 10(9)/L for all bacterial infections combined. CONCLUSIONS: Our matched cohort analysis indicates that neutropenia is an independent risk factor for bacterial infection in patients with advanced HIV disease. Given the incidence of infection, the cost-effectiveness of interventions to prevent neutropenia in advanced HIV disease should be assessed.

AIDS-Related Opportunistic Infections↗

Eleven years of community-based directly observed therapy for tuberculosis.

OBJECTIVE: To evaluate community-based directly observed therapy (DOT) for tuberculosis (TB) control. DESIGN: Ecological study. METHODS: Three comparisons were made in this descriptive study. (1) An 11-year retrospective comparison of TB case rates, sputum conversion rates (SCRs), rates of therapy completion, and confounding factors (acquired immunodeficiency syndrome [AIDS], immigration, unemployment, and poverty) in Baltimore, Md, with those of the five major US cities having the highest TB incidence in 1981 but which did not have comprehensive DOT programs. (2) An 11-year trend of TB in Baltimore and the 19 major US cities with the highest TB incidence in 1981. (3) A 7-year trend in TB in both city groups between 1985 and 1992. SETTING: Twenty US metropolitan cities with more than 250,000 residents. RESULTS: Since 1981, Baltimore experienced the greatest decline in TB incidence (35.6 cases per 100,000 population, 1981; 17.2 cases per 100,000 population, 1992 [-51.7%]), and city rank for TB (sixth in 1981, 28th in 1992). Conversely, the average incidence of TB increased 2.1% in the five-city cohort and increased 1.8% in the 19-city cohort. Since 1985, TB incidence increased 35.3% in the five-city cohort and 28.5% in the 19-city cohort, but declined 29.5% in Baltimore. From 1986 through 1992, Baltimore's DOT-managed cases had the highest annual SCRs at 3 months (mean, 90.7%), and the highest completion rates for standard anti-TB therapy (mean, 90.1%) when compared with the five cities. These trends could not be attributed to differentials in AIDS, immigration, poverty, or unemployment. Increasingly, more Baltimore cases were treated under DOT (86.5%, 1993) over time. Disease relapse rates remained low, even among HIV-infected patients. Within Baltimore, the documented SCR was significantly higher among DOT-managed cases compared with non-DOT-managed cases (P < .05); multidrug resistance remains rare (0.57%). Within Maryland, Baltimore accounted for 44.4% of all TB cases in 1981, compared with 28.7% in 1992 (P < .001). CONCLUSIONS: In contrast to the national TB upswing during the 1980s, Baltimore experienced a substantial decline in TB following implementation of community-based DOT, despite highly prevalent medicosocial risk factors. Directly observed therapy facilitated high treatment completion rates and bacteriologic evidence of cure. Directly observed therapy could help reduce TB incidence in the United States, particularly in cities with high case rates.

Baltimore↗

Race, sex, drug use, and progression of human immunodeficiency virus disease.

BACKGROUND: The rates of progression of human immunodeficiency virus (HIV) infection and survival have been reported to differ among sociodemographic groups. It is unclear whether these differences reflect biologic differences or differences in access to medical care. METHODS: We measured disease progression and survival in a cohort of 1372 patients seropositive for HIV who were treated at a single urban center (median follow-up, 1.6 years). We calculated the rates of survival for the entire cohort and the rates of progression to the acquired immunodeficiency syndrome (AIDS) or death among the 740 patients who presented without AIDS. We used Cox proportional-hazards analysis to examine factors associated with progression to AIDS and death. RESULTS: Progression to AIDS or death was associated with a CD4 cell count of 201 to 350 per cubic millimeter (relative risk, 2.0; P < 0.001), the presence of symptoms at base line (relative risk, 2.0; P < 0.001), prior antiretroviral therapy (relative risk, 1.7; P = 0.003), and older age (relative risk per year of age, 1.02; P = 0.03). However, there was no relation between disease progression and sex, race, injection-drug use, income, level of education, or insurance status. In the entire cohort, a lower CD4 cell count, a diagnosis of AIDS, older age, and the receipt of antiretroviral therapy before enrollment were associated with an increased risk of death, whereas the use of prophylaxis against pneumocystis pneumonia, zidovudine use after enrollment, and having a job at base line were associated with lower risks of death. There was no significant difference in survival between men and women, blacks and whites, injection-drug users and those who did not use drugs, or patients whose median annual incomes were $5,000 or less and those whose incomes were more than $5,000. CONCLUSIONS: Among patients with HIV infection who received medical care from a single urban center, there were no differences in disease progression or survival associated with sex, race, injection-drug use, or socioeconomic status. Differences found in other studies may reflect differences in the use of medical care.

Acquired Immunodeficiency Syndrome↗

Clinical spectrum of herpes zoster in adults infected with human immunodeficiency virus.

To determine the incidence and clinical manifestations of herpes zoster in a hospital-based clinic for adults infected with human immunodeficiency virus (HIV), we reviewed the records of all patients for whom zoster was diagnosed at or after their first clinic visit. Fifty-two episodes of zoster occurred in 45 patients during 1,614 person-years of follow-up (incidence, 3.2 episodes per 100 person-years). The following major complications of zoster occurred in 12 patients (27%): ocular complications (5), neurological complications (4), and chronic atypical skin lesions (5). Six patients each had postherpetic neuralgia and bacterial superinfection, which were the common minor complications of zoster. Multivariate analysis revealed that only a low CD4 cell count (< or = 200/mm3) was predictive of a major complication of zoster (OR, 13.2; 95% CI, 1.52-114; P = .019). Thus, complications of herpes zoster are common in patients with HIV infection, especially those with advanced immunosuppression.

Adult↗

Lack of association between acyclovir use and survival in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group.

To evaluate the association between acyclovir use and survival in patients with advanced human immunodeficiency virus infection, observational data from 1044 persons with AIDS or AIDS-related complex (ARC) and < or = 250 CD4 cells/mm3 following initiation of zidovudine were analyzed. Of these patients, 336 (32%) received regular acyclovir (> or = 6 weeks in 2 months). There were no differences in mortality data between acyclovir users and nonusers overall or when analyzed from 1 year after first use of zidovudine, from time of AIDS in those with ARC at enrollment, from patients with AIDS or < 100 CD4 cells/mm3 at enrollment, or from patients taking acyclovir for up to 10 months. Acyclovir use was associated with increased mortality (relative hazard, 1.28; P = .057) independent of herpesvirus infections and of other characteristics associated with mortality. In this study, the use of acyclovir at doses for treatment of herpes simplex virus infection in combination with zidovudine was not associated with prolonged survival.

AIDS-Related Complex↗

Survival analysis of two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex in AIDS.

OBJECTIVES: Rifabutin prophylaxis has been shown to significantly decrease the incidence of Mycobacterium avium complex (MAC) bacteremia in two randomized controlled clinical trials, but a survival benefit has not been observed. An analysis of complete follow-up of these patients through August 1992 was performed to assess subsequent survival, because although follow-up in the previous trials was limited at the time of initial analysis, the analysis did suggest that a survival benefit might be emerging. METHODS: Data from 1146 AIDS patients with CD4+ counts < or = 200 x 10(6)/l enrolled at 73 US and Canadian sites in two clinical trials of MAC prophylaxis were analyzed using Cox proportional hazards analysis with rifabutin use modeled as a time-dependent covariate, taking into account the initial randomized double-blind phase of the trials and the subsequent open-label phase of follow-up of those patients. Survival from date of enrollment was analyzed. Other covariates adjusted for in the analysis were CD4+ lymphocytes count, Karnofsky performance score and hospitalization for opportunistic complications of AIDS. RESULTS: Patients who received open-label rifabutin may have had a better prognosis than those who did not, based on Karnofsky score and occurrence of opportunistic disease. Adjusting for these variables and for use of rifabutin as time-dependent covariates, the relative hazard (RH) of dying while receiving rifabutin prophylaxis was 0.74 for the entire cohort [95% confidence interval (CI), 0.60-0.91; P < 0.004]. For patients with an enrollment CD4+ count < or = 50 x 10(6)/l (n = 655), the RH was 0.75 (95% CI, 0.58-0.98), and for patients with an enrollment CD4+ count of > 50 x 10(6)/l (n = 491), the RH was 0.69 (95% CI, 0.49-0.99). CONCLUSIONS: An analysis of the combined double-blind and open-label follow-up of two clinical trials of rifabutin prophylaxis for MAC supports the suggestion of the double-blind study that rifabutin improves survival of AIDS patients.

AIDS-Related Opportunistic Infections↗

The impact of prophylaxis on outcome and resource utilization in Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: Pneumocystis carinii pneumonia (PCP) is a major late complication of HIV infection associated with morbidity and mortality. Because chemoprophylaxis is highly effective, cases of PCP can be viewed as failures in the management of HIV disease. METHODS: We reviewed demographic, clinical, and cost data for all cases of confirmed HIV-related PCP at The Johns Hopkins Hospital in 1991 to determine consequences of missed prophylaxis. We also analyzed hospital discharge data for Maryland in 1991 to assess hospital charges, length of stay, and outcome for all patients with a principal diagnosis of HIV-related PCP. RESULTS: Pneumocystis carinii pneumonia was diagnosed in 79 patients. Of the 79 patients, 61 (77%) did not receive prophylaxis, including 26 who were not previously known to have HIV infection, 17 who did not have prophylaxis prescribed, and 18 who had prophylaxis prescribed, but were not compliant with the regimen. Patients not taking prophylaxis accounted for all 12 deaths ascribed to PCP. This group also accounted for 85% of the hospital days, 100% of the ICU days, and 89% of the inpatient charges. The total hospital charges were $849,540. Extrapolation of these figures for the state of Maryland suggest that the failure to receive prophylaxis in 1991 resulted in 62 patient deaths and a cost of approximately $4.7 million. CONCLUSION: Patients who developed PCP despite prophylaxis had a better outcome and used fewer resources than patients not receiving preventive therapy. This study emphasizes the impact of PCP prophylaxis on the morbidity, mortality, and economics of HIV health care.

AIDS-Related Opportunistic Infections↗

Hepatomegaly and steatosis in HIV-infected patients receiving nucleoside analog antiretroviral therapy.

BACKGROUND: A syndrome of hepatomegaly with severe steatosis has been described in case reports and case series in HIV-infected patients receiving nucleoside analog antiretroviral therapy. We wished to quantitate the incidence of this syndrome in a well characterized, demographically heterogeneous cohort of HIV-infected patients followed longitudinally. METHODS: All patients enrolled into a comprehensive primary care HIV Clinic from July 1989 through July 1994 (N = 1836) were screened for evidence of steatosis and liver disease by assessment of hospital discharge diagnoses, pathology reports, out- and in-patient laboratory data, and clinic records. RESULTS: A total of 322 (18%) patients had evidence of a liver abnormality. In these patients, viral hepatitis and alcohol-induced liver disease were the most common diagnoses. Only two patients had hepatomegaly with moderate to severe steatosis and acidosis. Both cases occurred in white men with very advanced HIV disease who were receiving nucleoside analog antiretroviral therapy. The incidence of the syndrome was 1.3 per 1000 person-yr of follow-up in antiretroviral users in our cohort (95% confidence interval: 0.2, 4.5 per 1000 person-yr). CONCLUSION: The hepatic steatosis syndrome manifesting as a severe, potentially fatal complication of antiretroviral therapy in HIV disease is rare. Both men and women and patients in early and late stages of HIV infection appear to be susceptible. It is not currently known whether a milder form of this syndrome is occurring in a larger population.

Acidosis, Lactic↗

Adverse reactions to therapy for HIV infection.

Although chronic drug therapy with antiretroviral agents and chemoprophylaxis has led to longer survival without disease, high rates of adverse reactions to agents used to treat HIV infection have been reported. The incidence of adverse drug reactions in patients with HIV infection varies with the type of drug therapy, dosage, drug-to-drug interactions, and the stage of HIV infection. This article discusses recognition, treatment, and prevention of adverse reactions to specific drugs and classifications of drugs.

AIDS-Related Opportunistic Infections↗

Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team.

OBJECTIVE: To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A randomized, double-blind, dose-ranging study. SETTING: Outpatient clinics. PATIENTS: 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M. avium complex who had symptomatic disease. INTERVENTIONS: Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks. MAIN OUTCOME MEASURE: Median number of colony-forming units of M. avium complex per milliliter of blood. RESULTS: Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P < 0.0001). After 2 weeks, patients receiving 500 mg twice daily were less likely to be culture negative than were patients receiving 1000 or 2000 mg twice daily (11% compared with 33% or 29%; P = 0.08). At 6 weeks, the median number of CFUs of M. avium complex/mL of blood was 0 or 1 for all three groups. Clarithromycin-resistant isolates of M. avium complex developed in 46% of patients at a median of 16 weeks. Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg. Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007). CONCLUSIONS: Clarithromycin therapy acutely decreased M. avium complex bacteremia in patients with HIV infection by more than 99%. Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival. Emergence of clarithromycin-resistant organisms was an important problem.

AIDS-Related Opportunistic Infections↗

Prophylaxis for opportunistic infections in patients with HIV infection.

OBJECTIVE: To review the efficacy of chemoprophylaxis for opportunistic infections in persons infected with human immunodeficiency virus (HIV). DATA SOURCES: English-language articles on the prevention of HIV-related opportunistic infections were identified through MEDLINE (1985 to 1993) and through review of abstracts presented at the International Conferences on AIDS, the Interscience Conferences on Antimicrobial Agents and Chemotherapy, and the National Conference on Human Retroviruses and Related Diseases. STUDY SELECTION: Importance was assigned in descending order to controlled clinical trials, uncontrolled trials and retrospective studies, and prospective observational studies. DATA SYNTHESIS: Persons infected with HIV who are at risk for Pneumocystis carinii pneumonia should receive prophylaxis, preferably with trimethoprim-sulfamethoxazole. Alternative agents are aerosolized pentamidine, dapsone, and dapsone-pyrimethamine. Patients who are seropositive for Toxoplasma gondii may benefit from primary prophylaxis against toxoplasmosis using trimethoprim-sulfamethoxazole or dapsone-pyrimethamine. Life-long secondary prophylaxis is indicated for all patients previously treated for toxoplasmic encephalitis. Long-term suppressive therapy is required for all patients with cryptococcal meningitis and histoplasmosis, and many patients with recurrent mucosal candidiasis also benefit from long-term suppression. The role of primary prophylaxis of fungal infections, however, is uncertain. Rifabutin has been approved to prevent disseminated infection with Mycobacterium avium complex and is indicated for all patients with CD4 counts less than 100/mm3. Chemoprophylaxis with isoniazid for 12 months is indicated in all patients infected with HIV who have or are at high risk for M. tuberculosis infection. No effective primary prophylactic agent is available for cytomegalovirus disease, although several investigational drugs are being studied. Acyclovir is effective in decreasing recurrences of herpes simplex virus infection. The incidence of common bacterial infections is decreased by trimethoprim-sulfamethoxazole. Pneumococcal polysaccharide vaccine is recommended for adult patients infected with HIV, and Haemophilus influenzae type b conjugate vaccine is recommended for children infected with HIV. CONCLUSIONS: A growing number of infections related to the acquired immunodeficiency syndrome are preventable with currently available agents. Issues of drug interactions, toxicity, and cost-effectiveness will become increasingly important in the management of patients with advanced HIV disease.

AIDS-Related Opportunistic Infections↗

Racial differences in the use of drug therapy for HIV disease in an urban community.

BACKGROUND: Guidelines for drug therapy in human immunodeficiency virus (HIV) disease are based primarily on the stage of the disease. To determine whether sociodemographic characteristics of patients influence drug therapy in practice, we analyzed the use of antiretroviral therapy and prophylactic therapy for Pneumocystis carinii pneumonia (PCP) in an urban population infected with HIV. METHODS: All patients presenting for the first time to our HIV clinic from March 1990 through December 1992 were enrolled. Data on sociodemographic and clinical variables and on drug use were collected at the time of presentation and after six months. We asked whether patients with CD4+ cell counts of 500 or less per cubic millimeter were receiving antiretroviral therapy at the time of presentation, and whether patients with CD4+ cell counts of 200 or less per cubic millimeter were receiving PCP prophylaxis. RESULTS: Among the 838 patients enrolled, 656 (79 percent) were blacks, 167 (20 percent) were non-Hispanic whites, and 15 (2 percent) were Asian or Hispanic descent or were not racially classified. There were no racial differences in the stage of HIV disease at the time of presentation. However, there were racial disparities in the receipt of antiretroviral therapy: 63 percent of eligible whites but only 48 percent of eligible blacks received such therapy (P = 0.003). PCP prophylaxis was received by 82 percent of eligible whites but only 58 percent of eligible blacks (P < 0.001). There were no significant differences in the receipt of drug therapy with respect to age, sex, mode of HIV transmission, type of insurance, income, education, or place of residence. In a logistic-regression analysis, race was the feature most strongly associated with the receipt of drug therapy. When blacks were compared with whites, the adjusted relative odds were 0.59 (95 percent confidence interval, 0.38 to 0.93) for the receipt of an antiretroviral agent and 0.27 (95 percent confidence interval, 0.13 to 0.56) for the receipt of PCP prophylaxis. CONCLUSIONS: Among patients infected with HIV, blacks were significantly less likely than whites to have received antiretroviral therapy or PCP prophylaxis when they were first referred to an HIV clinic. This disparity suggests a need for culturally specific interventions to ensure uniform access to care, including drug therapy, and uniform standards of care.

AIDS-Related Opportunistic Infections↗

Risk factors for Kaposi's sarcoma in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group.

BACKGROUND: Although the cause of Kaposi's sarcoma (KS) is unknown, its unique epidemiology suggests that an infectious, sexually transmitted agent or agents may contribute to its pathogenesis. METHODS: To assess the natural history of KS associated with the acquired immunodeficiency syndrome and to identify factors associated with its development, data were analyzed from a multicenter, observational cohort study of 1044 persons with the acquired immunodeficiency syndrome or the acquired immunodeficiency syndrome-related complex and a total CD4 cell count of less than 0.25 x 10(9)/L who were treated with zidovudine between April 1987 and April 1988. Records were reviewed bi-monthly. Follow-up continued for 2 years or until death. RESULTS: One hundred thirty-one patients (13%) had KS a study enrollment, and 143 developed KS (14%) during follow-up, with a 2-year actuarial risk of 21%. The probability of KS at 2 years for patients with initial CD4 cell counts of less than 0.1 x 10(9)/L was 25%, compared with 15% for those with counts of 0.1 x 10(9)/L or more. By logistic regression, a baseline CD4 cell count of less than 0.1 x 10(9)/L (relative odds, 1.43; 95% confidence interval, 1.04 to 1.95), homosexuality (relative odds, 3.71; 95% confidence interval, 1.82 to 7.56), cytomegalovirus disease (relative odds, 1.56; 95% confidence interval, 1.01 to 2.41), and white race (relative odds, 1.64; 95% confidence interval, 1.11 to 2.43) were independently associated with KS. Median survival after KS was 408 days, and KS was an independent predictor of death (relative hazard, 1.78; 95% confidence interval, 1.26 to 2.52). CONCLUSIONS: Kaposi's sarcoma contributes to human immunodeficiency virus-related morbidity and mortality, especially among male homosexuals. This large cohort study provides further evidence for an association between risk for cytomegalovirus infection and KS.

AIDS-Related Complex↗