Opportunistic infections: down but not out.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R E Chaisson.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
CONTEXT: Recent studies suggest that one third of tuberculosis cases in urban areas result from recent transmission. Improved tuberculosis control measures such as uniform implementation of directly observed therapy might reduce the proportion of cases resulting from recent transmission. OBJECTIVE: To determine patterns of tuberculosis transmission in Baltimore, Md, after 15 years of community-based directly observed therapy. DESIGN: A 30-month (January 1994-June 1996), prospective, city-wide study of all cases of tuberculosis using traditional contact investigations, geographic information systems data, and molecular epidemiologic comparison of Mycobacterium tuberculosis isolates with 2 DNA probes. PATIENTS: One hundred eighty-two patients with culture-positive tuberculosis. MAIN OUTCOME MEASURES: Proportion of disease defined as recently transmitted based on epidemiologic linkage by traditional contact tracing and molecular linkage by DNA fingerprint analysis of isolates; geographic foci of transmission based on linkage of residences by geographic information systems data. RESULTS: Of the 182 patients who had isolates of M tuberculosis available, 84 (46%) showed molecular clustering with 58 (32%) defined as being recently transmitted. Only 20 (24%) of 84 cases with clustered DNA fingerprints had epidemiologic evidence of recent contact. Geographic analysis showed significant spatial aggregation of the 20 clustered cases with epidemiologic links (P<.001), occurring in areas of low socioeconomic status and high drug use. The 64 cases with clustered DNA fingerprints but without epidemiologic links shared common risk factors and demographic features with the 20 clustered patients who did have epidemiologic links. CONCLUSIONS: Recently transmitted tuberculosis accounts for a high proportion of tuberculosis cases in Baltimore. Recently transmitted cases occur in geographically distinct areas of Baltimore, and location-based control efforts may be more effective than contact tracing for the early identification of cases.
Several clinical studies have suggested that anemia is an independent risk factor for dying in patients with HIV disease. We analyzed data from a large urban HIV clinical practice in Baltimore to assess the annual incidence of anemia, the risk of dying in patients who develop anemia, and the association between recombinant human erythropoietin use to treat anemia and subsequent survival. In 2348 patients observed between 1989 and 1996, 498 (21%) developed at least grade 1 anemia (hemoglobin <9.4 g/dl); 95 (4%) developed grade 4 anemia (hemoglobin <6.9 g/dl). Development of anemia was associated with decreased survival, independent of other prognostic factors. Use of erythropoietin was more likely in patients of nonminority race, those who did not inject drugs, those with a lower CD4 count or AIDS, and those being treated for cytomegalovirus disease (p < .05). Adjusting for these factors as well as severity of anemia, age, diagnosis of opportunistic disease, blood transfusion, and antiretroviral therapy in a time-dependent Cox proportional hazards analysis, erythropoietin use (n=91) was associated with a decreased hazard of dying (relative hazard [RH]=0.57; 95% confidence interval [CII, 0.40-0.81; p=.002). Although we cannot rule out a treatment selection bias, adjusting for available prognostic factors and factors potentially associated with a decision to use erythropoietin suggests that erythropoietin for treatment of anemia is associated with improved survival in HIV disease.
OBJECTIVE: To determine the relationship between Mycobacterium tuberculosis infection and disease and subsequent disseminated M. avium complex (MAC) disease in HIV-infected persons. DESIGN: A prospective observational cohort study. SETTING: The AIDS Linked to the Intravenous Experience (ALIVE) cohort of injecting drug users and the Johns Hopkins Hospital Adult HIV Clinic (JHHAHC). PARTICIPANTS: HIV-infected persons aged > 18 years with CD4 lymphocytes < 100 x 10(6)/l were followed between July 1989 and 31 October 1996. There were 182 persons in the ALIVE cohort and 1129 persons in JHHAHC who met these criteria. MAIN OUTCOME MEASURE: The relative risk of disseminated MAC was determined according to a history of prior opportunistic infection, MAC prophylaxis, antiretroviral therapy, M. tuberculosis infection or disease, race, sex, and injecting drug use. RESULTS: Amongst the 30 patients with active tuberculosis, eight developed disseminated MAC, compared with 208 cases of disseminated MAC amongst 1148 patients without prior M. tuberculosis infection or disease [relative risk (RR), 1.5; 95% confidence interval (CI), 0.8-2.7; P=0.2]. Amongst the 10 patients with extrapulmonary tuberculosis, five developed disseminated MAC (RR, 2.8; 95% CI, 1.5-5.2; P=0.02). Injecting drug use was associated with a decreased risk of disseminated MAC (RR, 0.7; 95% CI, 0.6-0.9; P=0.007). In a logistic regression analysis, disseminated MAC was significantly associated with extrapulmonary tuberculosis and other opportunistic disease, whereas antibiotic prophylaxis and injecting drug use were protective. CONCLUSIONS: A history of M. tuberculosis infection or disease was not associated with protection against subsequent disseminated MAC disease in HIV-infected persons. However, persons with extrapulmonary tuberculosis were at increased risk for disseminated MAC, particularly at low CD4 cell levels.
BACKGROUND: Medication nonadherence in the treatment of chronic diseases compromises the effectiveness of therapy. Little information is available about the extent of medication adherence or determinants of medication adherence in HIV disease, an issue of increasing importance in this new therapeutic era of combination antiretroviral therapy. METHODS: We studied 244 HIV-infected Medicaid-insured patients attending an HIV hospital-based clinic regarding the extent of and predictors of adherence to antiretroviral therapy and Pneumocystis carinii pneumonia (PCP) prophylaxis. Patients were asked to report medications being taken, patterns of use, and knowledge and attitudes about HIV therapies. Medical record report of type, dose, and frequency of medication was compared with self-report using the kappa statistic. Urine sulfamethoxazole assay was obtained from patients prescribed sulfamethoxazole-trimethoprim. RESULTS: Among patients prescribed antiretroviral therapy, 60% reported > or = 80% adherence in the previous 7 days; 49% reported > or = 80% adherence with PCP prophylaxis in the previous seven days. Seventy-nine percent of patients who reported taking daily sulfamethoxazole-trimethoprim had detectable urinary sulfamethoxazole. In multivariate analysis, > or = 80% adherence to antiretroviral therapy was associated with taking medication < or = twice a day (odds ratio [OR]=1.44; 95% confidence interval [CI], 1.01, 1.96), being likely to take medication when not at home, (OR=1.41; 95% CI, 1.04, 2.00) and patients' belief in their ability to adhere to therapy (OR=1.57; 95% CI, 1.13, 2.17). For PCP prophylaxis, > or = 80% adherence was associated with presence of family (OR=2.39; 95% CI, 1.01, 5.63) and patients' belief in their ability to adhere to therapy (OR=2.87; 95% CI, 1.44-1.78). Sociodemographic characteristics and belief in the efficacy of medications were not associated with adherence. CONCLUSIONS: A relatively low level of adherence to antiretroviral therapy and PCP prophylactic regimens was found. Although our results are principally from patients receiving antiretroviral monotherapy, these findings may have important implications for patients receiving highly active antiretroviral therapy (HAART). Decreasing the complexity of antiretroviral regimens, and working with patients to modify identified barriers to adherence may improve effectiveness of medications and prolong survival.
BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. INTERPRETATION: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.
OBJECTIVE: To assess the impact of opportunistic diseases on survival in patients with HIV disease. METHODS: A cohort of 2081 patients followed for a mean of 30 months was studied. Time-dependent Cox proportional hazards analyses were performed using incident opportunistic diseases and CD4 cell counts as independent variables. RESULTS: During follow-up, 730 (35%) patients died. The occurrence of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV) disease, Mycobacterium avium complex (MAC) disease, Candida esophagitis, Kaposi's sarcoma, lymphoma, progressive multifocal leukoencephalopathy (PML), dementia, wasting, toxoplasmosis, and cryptosporidiosis were all significantly associated with death, independently of CD4 cell count (all P<0.001 for opportunistic diseases controlling for CD4 cell count). The magnitude of increased risk was greatest for lymphoma [relative hazard (RH), 7.2], PML (RH, 3.9), MAC (RH, 3.0) and CMV (RH, 2.2). Cryptococcosis (RH, 0.94) and herpes zoster (RH, 0.85) were not associated with death. In a multivariate Cox proportional hazards analysis, MAC [RH, 2.56; 95% confidence interval (CI), 2.1-3.1], CMV (RH, 1.63; 95% CI, 1.3-2.1), toxoplasmosis (RH, 1.85; 95% CI, 1.3-2.6), PCP (RH, 1.29; 95% CI, 1.1-1.5), and CD4 cell count were significantly associated with death. Patients who had opportunistic diseases had significantly greatly monthly declines in CD4 counts (-11 x 10(6)/l per month) than those who did not (-6 x 10(6)/l per month; P <0.001). CONCLUSION: Most opportunistic diseases increase the risk of death independently of CD4 cell count. These data support the hypothesis that opportunistic diseases enhance HIV pathogenesis and further underscore the importance of prophylaxis.
Explore the source record for details and available documents.
The effect of acute coinfections on plasma human immunodeficiency virus (HIV) load and immune activation markers was evaluated. Thirty-two HIV-infected persons were prospectively enrolled; 18 had pre-illness, acute, and follow-up specimens. Plasma HIV RNA levels were determined by reverse transcriptase-polymerase chain reaction, and serum levels of activation markers, including tumor necrosis factor (TNF)-alpha, soluble (s) TNF receptors (R)-I and -II, interleukin (IL)-2, IL-6, IL-10, sIL-2R, sCD4, and sCD8, were assessed by commercial ELISAs. Median plasma HIV load increased 7. 8-fold during illness (P=.001) and decreased 1.5-fold (P=.01) during convalescence (median, 15 days). Significant virus load reductions were limited to subjects with clinical recovery. By regression analysis, changes in plasma HIV RNA were significantly associated with changes in sTNFR-I, sTNFR-II, and sIL-2R. Increased HIV replication during acute coinfections is associated with in vivo immune activation, which underscores the need to prevent and promptly treat intercurrent illnesses.
Although 10%-15% of patients with AIDS in the United States may acquire cryptosporidium infection, little data exist on clinical or histological characteristics that differentiate clinical outcomes. A case-control study of 83 HIV-positive adult patients with cryptosporidiosis was conducted, as was a histopathologic review of data on gastrointestinal biopsy specimens from 30 patients. Four clinical syndromes were identified: chronic diarrhea (36% of patients), choleralike disease (33%), transient diarrhea (15%), and relapsing illness (15%). A multivariate analysis of data for cases and controls revealed that acquiring cryptosporidiosis was associated with the presence of candidal esophagitis (odds ratio [OR], 2.53; P < .002) and Caucasian race (OR, 6.71; P = .0001) but not with sexual orientation. Cases had a significantly shorter duration of survival from the time of diagnosis than did controls (240 vs. 666 days, respectively; P = .0004), which was independent of sex, race, or or injection drug use. Antiretroviral use was protective against disease (OR, 0.072; P = .0001). All four clinical syndromes were represented among the histological data. There was no statistically significant correlation between histological intensity of infection and clinical severity of illness.
OBJECTIVE: To assess the long-term safety of adjunctive corticosteroids in the treatment of Pneumocystis carinii pneumonia (PCP). DESIGN: Analysis of data from a large prospective observational database. SETTING: HIV clinic at a large urban teaching hospital. PATIENTS: One hundred seventy-four patients who developed PCP after being enrolled in the database. RESULTS: Fifty-three patients (30%) received adjunctive corticosteroids and 121 (70%) did not. Survival did not differ between groups after adjusting for CD4 count (relative risk for adjunctive corticosteroids = 0.74, p = 0.13). There were no differences in the incidence of cytomegalovirus disease (adjunctive corticosteroids: 18.5 cases per 100 person-years vs no adjunctive corticosteroids: 15.7, p = 0.22), Mycobacterium avium complex (23.4 vs 27.0, p = 0.73), cryptococcal meningitis (1.8 vs 4.1, p = 0.58), toxoplasmosis (3.6 vs 11.0, p = 0.28), Kaposi's sarcoma (1.8 vs 2.2, p = 0.92), herpes simplex (27.1 vs 42.7, p = 0.66), herpes zoster (3.8 vs 6.9, p = 0.71), oropharyngeal candidiasis (18.9 vs 10.9, p = 0.09), or non-Hodgkin's lymphoma (3.5 vs 4.2, p = 0.92). Esophageal candidiasis was more common among adjunctive corticosteroid recipients (45.1 vs 26.6, p = 0.01). Results were similar for time to development of opportunistic conditions. CONCLUSIONS: Adjunctive corticosteroids do not increase mortality or the risk of most common HIV-associated complications.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The hypothesis that quiescent CD4+ T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus-type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes. The frequency of resting CD4+ T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10(6) cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4+ T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.
CONTEXT: An ongoing restriction fragment length polymorphism (RFLP) study of Mycobacterium tuberculosis isolates from tuberculosis (TB) cases revealed an identical 10-banded IS6110 RFLP pattern unique to 2 patients diagnosed as having TB 6 months apart. Their only identifiable link was care at the same hospital. OBJECTIVE: To determine if nosocomial transmission had occurred. DESIGN: Traditional and molecular epidemiologic investigation. MEASUREMENTS: We reviewed medical charts and bronchoscopic records, examined hospital locations visited by both patients, evaluated hospital ventilation systems, and observed cleaning and disinfection of bronchoscopes. RESULTS: A patient with cough, hoarseness, and fever underwent bronchoscopy and was diagnosed as having TB. A second patient with a mediastinal mass underwent bronchoscopy 2 days later and was diagnosed as having small cell carcinoma. Following 6 months of chemotherapy and radiation therapy, the second patient developed fever and an infiltrate of the right upper lobe of the lung. Bronchoscopic washings revealed acid-fast bacilli and were culture positive for M tuberculosis. Both patients had undergone bronchoscopy with the same instrument in the same operating room with no intervening bronchoscopies. Bronchoscope cleaning and disinfection procedures were inconsistent with national guidelines. CONCLUSIONS: A contaminated bronchoscope was the most likely source of M tuberculosis transmission between these 2 patients. The RFLP analysis of M tuberculosis isolates was responsible for detecting this nosocomial source of transmission and led to the implementation of public health measures to prevent further spread of infection and disease. This study emphasizes the need for continued vigilance in endoscope cleaning techniques.
OBJECTIVE: Cytomegalovirus (CMV) retinitis is a relatively common opportunistic infection in late-stage HIV disease, causing significant morbidity and mortality. Prophylactic use of oral ganciclovir has recently been shown to decrease the incidence of CMV retinitis but is relatively expensive and may not be very well tolerated by many patients. We performed a decision analysis to assess the cost-effectiveness of prophylactic oral ganciclovir therapy. METHODS: A decision analysis using a Markov approach compared absence of prophylaxis and prophylaxis with oral ganciclovir. Estimates of effectiveness of prophylaxis and costs of illness were obtained from published literature. Drug costs were based on national average wholesale prices. All health care costs were based on 1996 U.S. dollars. Sensitivity analyses were done over ranges of estimates of cost and effectiveness. RESULTS: Using our baseline estimates of cost and effectiveness, use of oral ganciclovir prophylaxis in patients with CD4 counts <50 cells/mm3 would be associated with average lifetime health care costs of $104,746, compared with $90,985 for no prophylaxis. Using oral ganciclovir, the average quality-adjusted life-years (QALYs) would be 2.05, and the CMV retinitis-free life-years would be 1.64, compared with 1.87 and 1.27, respectively, for no prophylaxis. The incremental cost-utility of oral ganciclovir is $76,676 per year of life saved and $37,542 per year of additional CMV retinitis-free life. Oral ganciclovir would become more cost-effective relative to no prophylaxis if the probability of CMV retinitis while taking oral ganciclovir declined. Oral ganciclovir would be less cost-effective if the cost of treating CMV retinitis declines, if our estimates of quality of life are low, or if the overall incidence of CMV retinitis declines. CONCLUSIONS: Oral ganciclovir is a less cost-effective approach than several other interventions used for HIV-disease prophylaxis. It would potentially become cost-effective if it is possible to target oral ganciclovir prophylaxis to patients who are most likely to benefit.