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Biomedical subjects

R E Chaisson

Publications and source records attributed to R E Chaisson.

At least 55 records · Page 3Linked to original sources
PubMed1999

Relapse rates after short-course (6-month) treatment of tuberculosis in HIV-infected and uninfected persons.

OBJECTIVE: To determine the rate of tuberculosis relapse among HIV-seropositive and -seronegative persons treated for active tuberculosis with short-course (6-month) therapy. DESIGN: Consecutive cohort study. SETTING: City of Baltimore tuberculosis clinic. PATIENTS: Tuberculosis patients treated between 1 January 1993 and 31 December 1996. INTERVENTION: Patients received 2 months of isoniazid, rifampin, pyrazinamide and ethambutol followed by 4 months of isoniazid and rifampin. MAIN OUTCOME MEASURE: Passive follow-up for tuberculosis relapse was performed through September 30, 1998. RESULTS: There were 423 cases of tuberculosis during the study period; 280 patients completed a 6-month course of therapy. Therapy was directly-observed for 94% of patients. Of those who completed therapy, 47 (17%) were HIV-seropositive, 127 (45%) were HIV-seronegative, and 106 (38%) had unknown HIV status. HIV-infected patients required more time to complete therapy (median 225 versus 205 days; P = 0.04) but converted sputum culture to negative within the same time period (median 77 versus 72 days; P = 0.43) as HIV-seronegative or unknown patients. Relapse occurred in three out of 47 (6.4%) HIV-infected patients compared to seven out of 127 (5.5%) HIV-seronegative patients (P = 1.0). Relapse rates also did not differ when HIV-seropositive patients were compared with HIV-seronegative and patients with unknown HIV status (6.4% versus 3.0%; P = 0.38). Of the 10 patients with tuberculosis relapse, restriction fragment length polymorphism data were available for five; all five relapse isolates matched the initial isolate. CONCLUSIONS: These results support current recommendations to treat tuberculosis in HIV-infected patients with short-course (6-month) therapy.

AIDS-Related Opportunistic Infections↗
PubMed1999

Natural history of HIV infection in the era of combination antiretroviral therapy.

BACKGROUND: The use of protease inhibitor-containing (PI) combination antiretroviral therapy has led to a reduction in the incidence of opportunistic illness and mortality (events) in HIV infection. We wished to quantify the changing incidence of these events in our clinical practice and delineate the relationship between CD4, HIV-1 RNA, and development of events in patients receiving PI combination therapy. METHODS: We assessed HIV-infected patients with CD4 counts < or =500 cells x10(6)/l. We calculated the incidence of events from 1994 through 1998 and analyzed the association of temporal changes in event incidence and use of antiretroviral therapy. In patients on PI combination therapy, we determined the probability of achieving and maintaining an undetectable HIV-1 RNA response and determined the association of CD4, HIV-1 RNA, and developing an event. RESULTS: The incidence of opportunistic illness declined from 23.7 events/100 person-years in 1994 to 14.0 events/100 person-years in 1998 (P<0.001). Mortality declined from 20.2 deaths/100 person-years in 1994 to 8.4 deaths/ 100 person-years in 1998 (P<0.001). Use of PI combination therapy was associated with a relative rate of opportunistic illness or death of 0.66 [95% confidence interval (CI), 0.51-0.85; P<0.001]. The relative incidence of each of 16 opportunistic illnesses was approximately the same in 1998 as in 1994 except for lymphoma, cervical cancer and wasting syndrome which do not appeared to have declined in incidence. Approximately 60% of patients who received PI therapy achieved an undetectable HIV-1 RNA, and 65% of these patients maintained durable suppression of HIV-1 RNA. Achieving an undetectable HIV-1 RNA was associated with a decreased risk of an event, and was the variable most strongly associated with an increase in CD4 level. By multivariate analysis, the concurrent CD4 level was most strongly associated with developing an event. CONCLUSIONS: We observed a significant decline in the incidence of opportunistic illness and death from 1994 through 1998 associated with combination antiretroviral therapy. Patients who develop events while being treated with PI combination therapy were not likely to have achieved an undetectable HIV-1 RNA and are likely to have a low concurrent CD4 level.

AIDS-Related Opportunistic Infections↗
PubMed1999

Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions.

BACKGROUND: In clinical trials, highly active antiretroviral therapy (HAART) reduces plasma HIV-1 RNA levels to less than 500 copies/mL in 60% to 90% of patients with HIV-1 infection. The performance of such therapy outside of the clinical trial setting is unclear. OBJECTIVE: To determine factors associated with failure to suppress HIV-1 RNA levels and adverse drug reactions in a cohort of patients in whom protease inhibitor-containing therapy was begun in a large urban clinic. DESIGN: Retrospective cohort study. SETTING: Johns Hopkins HIV Clinic in Baltimore, Maryland. PATIENTS: 273 protease inhibitor-naive patients began taking a protease inhibitor regimen containing at least one other antiretroviral drug to which the patients had not previously been exposed. MEASUREMENTS: Demographic variables, plasma HIV-1 RNA levels, CD4+ lymphocyte counts, and adverse drug reactions. RESULTS: Levels of HIV-1 RNA were undetectable in 42% of the cohort at 1 to 90 days, in 44% at 3 to 7 months, and in 37% at 7 to 14 months. Factors associated with failure to suppress viral load at two or more time points included higher rates of missed clinic appointments, nonwhite ethnicity, age 40 years or younger, injection drug use, lower baseline CD4+ lymphocyte count, and higher baseline viral load. In a multivariate model, only higher rates of missed clinic appointments were independently associated with viral suppression at 1 year. Ritonavir was associated with adverse drug reactions about twice as frequently as indinavir or nelfinavir, and women experienced significantly more adverse effects than men. CONCLUSIONS: Unselected patients in whom HAART is started in a clinic setting achieve viral suppression substantially less frequently than do patients in controlled clinical trials. Missed clinic visits were the most important risk factor for failure to suppress HIV-1 RNA levels. Studies are needed to identify interventions that maximize the performance of HAART in inner-city clinics.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Costs of HIV medical care in the era of highly active antiretroviral therapy.

OBJECTIVES: In the USA, Medicaid is the principal payer of the health care costs of patients with HIV infection. We wished to determine how the costs to Medicaid of patients in Maryland infected with HIV have changed in the setting of highly active antiretroviral treatment. DESIGN: Observational cohort study. METHODS: Analysis of combined economic and clinical data of patients from the Johns Hopkins HIV Service, the provider of primary and sub-specialty care for a majority of HIV-infected patients in the Baltimore metropolitan region. All patients were enrolled in Medicaid and received care longitudinally in Maryland from 1 January 1995 through 31 December 1997. Monthly Medicaid payments were calculated for all inpatient and outpatient services by fiscal year, CD4 cell count, and use of protease inhibitors. RESULTS: For inpatients with a CD4 cell count < or = 50 x 10(6) cells/l, the total health care average monthly payments remained unchanged ($2629 in 1995, $2585 in 1997). Total mean monthly payments increased for those with a CD4 cell count > 50 x 10(6) cells/l (CD4 cell count 50-200 x 10(6) cells/l, $1172 in 1995 and $1615 in 1997, P < 0.05; CD4 cell count 201-500 x 10(6) cells/l, $1078 in 1995 and $1305 in 1997, P < 0.05). However, when data were stratified according to use of a protease inhibitor-containing regimen (used during approximately 50% of follow-up time in 1996-1997) it was found that hospital inpatient payments decreased significantly in all CD4 strata for patients on a protease inhibitor-containing regimen whereas pharmacy payments increased significantly. Inpatient payments associated with treating opportunistic illness were lower in 1996-1997 for patients receiving protease inhibitor therapy compared with those not receiving protease inhibitors. On balance, total health care payments tended to be slightly lower for patients receiving a protease inhibitor regimen. CONCLUSION: Although protease inhibitor-containing antiretroviral regimens are being used by only about half of our Medicaid-insured patients, when they are used, there are significantly lower hospital inpatient and community care costs, as well as lower costs associated with the treatment of opportunistic illness. Even with the concurrent increase in their pharmacy costs, total health care costs were stable or slightly lower for these patients. We believe this is a favorable result suggesting a good clinical value being achieved without an increase in costs.

AIDS-Related Opportunistic Infections↗
PubMed1999

Risk factors for cryptococcal meningitis in HIV-infected patients.

To identify the risk factors for cryptococcal meningitis in patients with HIV disease we conducted a nested case-control study of 37 incident cases of cryptococcal meningitis and 74 controls, identified from a cohort of more than 2000 HIV-infected patients. Conditional logistic regression was used to study demographic and AIDS-related variables in addition to fluconazole and steroid use. No difference in demographic variables, HIV risk factors, or stage of AIDS was detected between cases and controls. Exposure to fluconazole for more than 90 days reduced the risk of cryptococcal meningitis by 82% (OR=0.18; 95% CI=0.04-0.85; p=0.03). We did not find a difference in steroid use between cases and controls for either the length or amount of steroid exposure (p=0.41). No difference in survival during follow-up in the clinic was observed by the log-rank test (p=0.74). Among the cases, a cryptococcal antigen was positive in more than 97% of the CSF or blood samples. CSF and blood cultures were positive in 81 and 44% of the samples, respectively. We conclude that demographic factors did not affect the risk of cryptococcal meningitis in an inner city United States population. While fluconazole use has a protective effect, steroid use was not associated with an increased risk of cryptococcal meningitis in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Stavudine in zidovudine (ZDV)-experienced compared with ZDV-naive patients.

OBJECTIVE: To assess the effect of prior zidovudine (ZDV) use on subsequent response to stavudine (D4T)-containing regimens. DESIGN: Analysis of data from prospective observational database. METHODS: Patients were ZDV-experienced if they had previously received more than 90 days of ZDV and ZDV-naive if they had never received ZDV. HIV-1 RNA and CD4 cell counts were compared at 3, 6, and 12 months after initiation of D4T. Univariate and multivariate analyses were performed, adjusting for baseline HIV-1 RNA and CD4 cell count, age, sex, race, HIV transmission category, time since enrollment, and protease inhibitor use. RESULTS: No difference was found between ZDV-experienced (n = 130) and naive (n = 98) patients in age, sex, race, transmission category, use of a concurrent protease inhibitor, or baseline CD4 cell count and HIV-1 RNA. There was no difference in the median decline in HIV-1 RNA (-1.29 log10 copies/ml for experienced patients versus -1.19 log10 copies/ml for naive patients; P = 0.39), in achieving HIV-1 RNA < 400 copies/ml at 3 months (51% versus 49%; P = 0.79) or 6 months (48% versus 56%; P = 0.33). There was no difference in CD4 cell response (+73 x 10(6)/l versus + 87 x 10(6)/l; P = 0.51). By multivariate adjustment in a repeated measures analysis, there was no significant difference in achieving undetectable HIV-1 RNA or in CD4 cell response between experienced and naive patients. CONCLUSION: No difference in response to a D4T-containing regimen between ZDV-experienced and naive patients was found over a 1-year period. In contrast to previous trials, most patients in this study also received a protease inhibitor. These findings may be more relevant in the current era of highly active antiretroviral therapy.

Adult↗
PubMed1999

Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy.

Combination therapy for HIV-1 infection can reduce plasma virus to undetectable levels, indicating that prolonged treatment might eradicate the infection. However, HIV-1 can persist in a latent form in resting CD4+ T cells. We measured the decay rate of this latent reservoir in 34 treated adults whose plasma virus levels were undetectable. The mean half-life of the latent reservoir was very long (43.9 months). If the latent reservoir consists of only 1 x 10(5) cells, eradication could take as long as 60 years. Thus, latent infection of resting CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective anti-retroviral therapy.

Adult↗
PubMed1999

Comparison between a whole blood interferon-gamma release assay and tuberculin skin testing for the detection of tuberculosis infection among patients at risk for tuberculosis exposure.

A new test that measures interferon-gamma (IFN-gamma) release in whole blood following stimulation with tuberculin has the potential to detect tuberculosis infection using a single blood draw. The IFN-gamma release assay was compared with the standard tuberculin skin test (TST) among 467 intravenous drug users at risk for tuberculosis in urban Baltimore. Among 300 human immunodeficiency virus (HIV)-seronegative patients, the IFN-gamma release assay was positive in 177 (59%), whereas the TST was positive in 71 (24%), for a percent agreement of 59% (kappa=26%). Among 167 HIV-seropositive subjects, the IFN-gamma release assay identified 32 reactors (19%); the TST identified 16 reactors (9.6%), for a percent agreement of 82% (kappa=28%). The IFN-gamma release assay detected more reactors than did the TST, but its agreement with TST was weak. As the TST is an imperfect standard, further evaluation of the IFN-gamma release assay among uninfected persons and persons with culture-confirmed tuberculosis will be useful.

Evaluation Studies as Topic↗
PubMed1999

Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis.

Moxifloxacin (BAY12-8039) is a new 8-methoxyquinolone shown to be active against Mycobacterium tuberculosis in vitro. We tested moxifloxacin for activity in mice against M. tuberculosis CSU93, a highly virulent, recently isolated clinical strain. The MIC of moxifloxacin for the CSU93 strain was 0.25 microg/ml. The serum moxifloxacin concentration after oral administration in mice peaked within 0.25 h, reaching 7.8 microg/ml with doses of 100 mg/kg of body weight; the maximum concentration and the analysis of the area under the concentration-time curve revealed dose dependency. When mice were infected with a sublethal inoculum of mycobacteria and then treated with moxifloxacin at 100 mg/kg per day for 8 weeks, the log10 CFU counts in the organs of treated mice were significantly lower than those for the control group (0.6 +/- 0.2 versus 5.6 +/- 0. 3 in the lungs and 1.5 +/- 0.7 versus 4.9 +/- 0.5 in the spleens, respectively; P < 0.001 in both organs). The effectiveness of moxifloxacin monotherapy was comparable to that seen in mice receiving isoniazid alone. Combination therapy with moxifloxacin plus isoniazid was superior to that with moxifloxacin or with isoniazid alone in reducing bacillary counts in the organs studied. Using a sensitive broth-passage subculture method, we demonstrated that 8 weeks of treatment with moxifloxacin (100 mg/kg per day) or with moxifloxacin plus isoniazid (100 mg/kg and 25 mg/kg, respectively, per day) sterilized the lungs in seven of eight and in eight of eight mice, respectively. Among surviving bacilli isolated from animals infected with a high-titer inoculum and treated for 7 weeks with low-dose moxifloxacin (20 mg/kg per day), breakthrough resistance to moxifloxacin was not observed. These results indicate that moxifloxacin is highly effective in reducing M. tuberculosis infection in mice and has activity comparable to that of isoniazid. Combination therapy with moxifloxacin and isoniazid was highly effective, suggesting that moxifloxacin may be useful in multiple-drug regimens for human tuberculosis.

Animals↗
PubMed1999

Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis.

Rifapentine is a long-acting rifamycin which may be useful for intermittent drug therapy against tuberculosis. In this study we measured the efficacies of rifapentine-containing intermittent drug regimens for preventive therapy using the Cornell mouse model of latent tuberculosis. We infected groups of mice intravenously with Mycobacterium tuberculosis and then treated them with isoniazid and pyrazinamide for 12 weeks according to the Cornell latency development protocol. After a 4-week interval of no treatment, experimental preventive therapy was administered by esophageal gavage for 12 or 18 weeks. After equilibration and dexamethasone amplification treatment, mouse organs were analyzed by quantitative colony counts to measure the effectiveness of therapy. Our results showed that once-weekly isoniazid plus rifapentine combination therapy for 18 weeks was an effective preventive regimen with sterilizing potency and bacillary load reduction comparable to those of daily isoniazid therapy for 18 weeks. Monotherapy with rifapentine weekly or fortnightly or with rifampin twice weekly for up to 18 weeks did not offer advantages in reducing bacillary load or in sterilizing organs compared to the effects of a placebo. These results with the Cornell mouse model indicate that once-weekly, short-course preventive therapy with isoniazid plus rifapentine is effective and may warrant investigation in humans with latent tuberculosis infection.

Animals↗
PubMed1999

Nontuberculous mycobacteria: defining disease in a prospective cohort of South African miners.

A gold mining work force was followed prospectively over 1 yr for sputum nontuberculous mycobacterial (NTM) isolates. NTM were isolated from 118 men, of whom 32 (27%) met the American Thoracic Society (ATS) case-definitions for pulmonary NTM disease (23 M. kansasii, seven M. scrofulaceum, one M. avium, and one M. abscessus). Determining isolate significance was difficult because most men had been started on presumptive TB treatment before isolate identification (70%). Histologic criteria were considered inappropriate for this high M. tuberculosis incidence population, particularly for patients who had stabilized on presumptive TB treatment. Among men not meeting case-definitions, indicators of disease were significantly more prevalent for M. kansasii than for M. fortuitum, the local laboratory contaminant (ORs: 6.5 for cough, 7. 2 for smear-positivity, 36.0 for radiologic changes, and 14.3 for presumptive TB treatment), suggesting underdiagnosis of M. kansasii disease. Of 53 men with definite or possible M. kansasii disease, 18 (34%) were HIV-positive. HIV-associated M. kansasii disease occurred at an early stage of immunosuppression (median CD4 count, 381 x 10(6)/L) with a good outcome (83% cured after 12 mo of treatment). ATS case-definitions for NTM disease are difficult to apply in this population, and treatment decisions should be guided by the pathogenic potential of the isolate.

Adult↗
PubMed1999

Tuberculosis vaccination versus isoniazid preventive therapy: a decision analysis to determine the preferred strategy of tuberculosis prevention in HIV-infected adults in the developing world.

SETTING: The developing world. OBJECTIVE: To compare the strategy of TB vaccination with that of tuberculin skin-testing in conjunction with isoniazid (INH) in preventing tuberculosis in HIV-infected persons. For any clinical scenarios in which immunization would be more effective than INH preventive therapy, to determine the minimum necessary vaccine safety and effectiveness required. DESIGN: Decision analysis. A hypothetical cohort of 10000 HIV-infected persons, 65% of whom were tuberculin positive, living in the developing world, was studied. Probability estimates were based on BCG vaccine for the baseline analysis, and it was assumed that the vaccine cannot protect if given after infection. RESULTS: Under the probability estimates and assumptions of the analysis, tuberculin skin testing/INH preventive therapy would prevent 458 more cases of TB and 45 more deaths due to TB than TB vaccination. One- and two-way sensitivity analyses revealed no thresholds at which TB vaccination would be the preferred strategy. Vaccine safety did not impact the outcome of the analysis. Three-way sensitivity analysis revealed that if the prevalence of anergy were 35% and the risk of progression to active TB among anergic persons 12.2 cases per 100 person-years, a vaccine would have to be at least 87% effective to be preferred over INH preventive therapy. CONCLUSIONS: Under the conditions of the analysis, which did not account for cost or logistics, tuberculin skin testing/INH preventive therapy would be more effective than TB vaccination in preventing TB among HIV-infected persons. The hypothesized TB vaccine would prevent more TB than INH preventive therapy only in areas where the prevalence of anergy and risk of active TB if anergic were high, and vaccine effectiveness exceeded 87%.

Adult↗
PubMed1999

Will DOTS do it? A reappraisal of tuberculosis control in countries with high rates of HIV infection.

In 1993 the WHO declared tuberculosis a global emergency, and subsequently introduced the DOTS strategy, a technical and management package based on earlier work of the IUATLD and international experience with directly observed therapy. Despite successful implementation of most of the elements of this strategy in several African countries and settings, tuberculosis case rates continue to escalate where the prevalence of HIV infection is high. We explore possible reasons for the failure to control tuberculosis even in the context of tuberculosis programmes that have been considered models for others to emulate. In many African countries half or more of tuberculosis patients are now HIV-infected; in such settings, the overall epidemiology of tuberculosis is disproportionately affected by what happens in the HIV-infected subpopulation of the community. Persons with HIV infection are at increased risk of rapid progression following primary infection or re-infection, and also from reactivation of latent infection with Mycobacterium tuberculosis. More intensive strategies need to be targeted to the HIV-infected to interrupt on-going transmission (active and passive case detection; prevention of nosocomial transmission) and reactivation (preventive therapy). The high burden of other HIV-related disease in patients with tuberculosis, such as other bacterial infections, toxoplasmosis and other manifestations of AIDS, require that tuberculosis programmes integrate their activities better with those of HIV/AIDS programmes, including those for provision of HIV/AIDS care. Enhanced epidemiological surveillance is required to follow tuberculosis trends in the HIV-positive and negative sub-populations of communities, which may respond differently to control efforts. Strategies for tuberculosis control programmes in countries of high and low HIV prevalence cannot be the same, but must take into account the epidemiology of HIV infection. HIV/AIDS in Africa poses severe challenges of purpose and identity to tuberculosis control programmes, which have not adapted to the altered realities of the HIV/AIDS era. DOTS alone is unlikely to control tuberculosis in sub-Saharan Africa; one major achievement of DOTS when implemented, however, has been its apparent ability to limit the development and spread of drug resistance.

AIDS-Related Opportunistic Infections↗