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Biomedical subjects

R E Chaisson

Publications and source records attributed to R E Chaisson.

At least 37 records · Page 2Linked to original sources

Detrimental effects of continued illicit drug use on the treatment of HIV-1 infection.

OBJECTIVE: To identify the effects of substance abuse status (active, former, and never) on utilization of highly active antiretroviral therapy (HAART), medication adherence, and virologic and immunologic responses to therapy. DESIGN: Prospective cohort study of 764 HIV-1-infected patients who attended an urban HIV clinic and participated in a standardized interview. MAIN OUTCOME MEASURES: Past utilization of HAART, self-reported nonadherence with antiretroviral therapy, and changes in HIV-1 RNA level and CD4+ lymphocyte count relative to prior peak and nadir, respectively. RESULTS: Forty-four percent of active drug users failed to utilize HAART compared with 22% of former drug users and 18% of non-drug users (p <.001 for both comparisons). Among participants who were taking antiretroviral therapy when interviewed, active drug users were more likely to report medication nonadherence (34% vs. 24% of nonusers and 17% of former users), had a smaller median reduction in HIV-1 RNA from baseline (0.8 log10 copies/ml vs. 1.7 in nonusers and 1.6 in former users), and had smaller median increases in CD4+ lymphocyte count from baseline (65 cells/mm3 vs. 116 in nonusers and 122 in former users) (p <.05 for all comparisons with active users). CONCLUSIONS: Active drug use was strongly associated with underutilization of HAART, nonadherence, and inferior virologic and immunologic responses to therapy, whereas former drug users and non-drug users were similar in all outcomes. Effective strategies are needed that integrate HIV-1 and substance abuse treatments.

Adult↗

Use of audio computer-assisted self-interviews to assess tuberculosis-related risk behaviors.

UNLABELLED: The objective of this study was to compare self-reported tuberculosis and human immunodeficiency virus (HIV) risk factors obtained from computer-assisted questionnaires and interviewer-assisted questionnaires among participants of a needle exchange program. Between June 1998 and May 1999, needle exchange program participants requesting tuberculosis screening underwent interviews regarding demographics and risk factors for tuberculosis and HIV infection. The first 190 participants underwent traditional interviewer-assisted questionnaires, whereas the remaining 92 underwent computer-assisted questionnaires. Data were analyzed by interview technique using odds ratios (OR) and multiple logistic regression. Among 282 participants, demographic characteristics, health status, HIV serostatus, visits to homeless shelters, alcohol intake, and cigarette smoking were all similar by interview technique. However, respondents receiving computer-assisted questionnaires were more likely than those receiving interviewer-assisted questionnaires to report smoking marijuana (OR = 5.56), crack (OR = 1.88), and heroin (OR = 2.60); as well as sharing cocaine smoking equipment (OR = 4.49), sharing heroin smoking equipment (OR = 2.85), "shotgunning" (OR = 4.48), and visiting crack houses (OR = 4.39). In the final multivariate model, respondents receiving computer-assisted questionnaires were more likely to report "shotgunning" and visiting a crack house relative to respondents receiving interviewer-assisted questionnaires. In conclusion, increased odds of high-risk behaviors for tuberculosis and HIV infection among computer-assisted questionnaire respondents support the use of computer-assisted questionnaires to ascertain risk behavior data for both tuberculosis and HIV. KEYWORDS: tuberculosis; HIV; self-report; drug use; computer-assisted

Baltimore↗

Differences in HIV disease progression by injection drug use and by sex in the era of highly active antiretroviral therapy.

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has reduced the incidence of most AIDS-related opportunistic illnesses (OI) and death in HIV-infected individuals. We investigated whether there are demographic disparities in HIV disease progression in the HAART era compared with before. METHODS: HIV-infected patients in an urban HIV clinical practice in the USA were compared using survival methods for time to a new AIDS-defining OI or death in therapeutic era 1 (monotherapy and combination therapy; 1990--1995; n = 2016) versus era 2 (HAART; 1996--1999; n = 2165). RESULTS: A total of 1037 (51.4%) events occurred in era 1; 666 (30.8%) events occurred in era 2. In women, the median disease-free survival time increased by 14% (CD4 cell counts > 200 cells/mm(3) at baseline) and 34% (CD4 cell counts < or = 200) in era 2 compared with era 1, whereas for men it increased by 43 and 100%. The relative hazard (RH) of progression for women compared with men in era 2 compared with era 1 was 1.34. For injecting drug use (IDU), disease-free survival time increased by 16% and 34% in era 2 compared with era 1, whereas non-IDU improved by 65 and 135%. The RH of progression for IDU compared with non-IDU in era 2 compared with era 1 was 1.39. No significant differences were detected by race or other HIV transmission risk group. CONCLUSION: Disease-free survival time was extended with the use of HAART, but these gains were not equally distributed by sex and IDU in our cohort.

Adult↗

A randomized, controlled trial of interventions to improve adherence to isoniazid therapy to prevent tuberculosis in injection drug users.

PURPOSE: To determine the effect of several interventions on adherence to tuberculosis preventive therapy. METHODS: We conducted a randomized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis. Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly (Supervised group, n = 99), daily self-administered isoniazid with peer counseling and education (Peer group, n = 101), or routine care (Routine group, n = 100). Patients within each arm were also randomly assigned to receive an immediate or deferred monthly $10 stipend for maintaining adherence. The endpoints of the trial were completing 6 months of treatment, pill-taking as measured by self-report or observation, isoniazid metabolites present in urine, and bottle opening as determined by electronic monitors in a subset of patients. RESULTS: Completion of therapy was 80% for patients in the Supervised group, 78% in the Peer group, and 79% in the Routine group (P = 0.70). Completion was 83% (125 of 150) among patients receiving immediate incentives versus 75% (112 of 150) among patients with deferred incentives (P = 0.09). The proportion of patients who were observed or reported taking at least 80% of their doses was 82% for the Supervised arm of the study, compared with 71% for the Peer arm and 90% for the Routine arm. The proportion of patients who took 100% of doses was 77% for the Supervised arm (by observation), 6% for the Peer arm (by report), and 10% for the Routine arm (by report; P <0.001). Direct observation showed the median proportion of doses taken by the Supervised group was 100%, while electronic monitoring in a subset of patients showed the Peer group (n = 27) took 57% of prescribed doses and the Routine group (n = 32) took 49% (P <0.001). Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold standard. There were no significant differences in electronically monitored adherence by type of incentive. CONCLUSION: Adherence to isoniazid preventive therapy by injection drug users is best with supervised care. Peer counseling improves adherence over routine care, as measured by electronic monitoring of pill caps, and patients receiving peer counseling more accurately reported their adherence. More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups.

Adult↗

Incidence of pancreatitis in HIV-infected patients receiving nucleoside reverse transcriptase inhibitor drugs.

BACKGROUND: Pancreatitis is a known adverse effect of the nucleoside reverse transcriptase inhibitors, particularly didanosine. Hydroxyurea has been used to potentiate the antiviral efficacy of didanosine, but recently there has been concern that severe and even fatal pancreatitis may be more likely to occur when hydroxyurea is used in combination with didanosine. We investigated the incidence of pancreatitis in patients using nucleoside analogues with or without hydroxyurea. METHODS: Data were obtained from patients followed longitudinally on the Johns Hopkins HIV Clinic. Incidence rates of pancreatitis were calculated for each antiretroviral regimen that included zidovudine, stavudine, didanosine (+ hydroxyurea), and didanosine + stavudine (+ hydroxyurea). Poisson regression was used to compare the relative rate of pancreatitis for each regimen adjusting for other covariates. RESULTS: A total of 2613 patients received at least one of the nucleoside reverse transcriptase inhibitor-containing regimens. There were 33 cases of pancreatitis. The crude incidence rate of pancreatitis ranged from 0.18 cases per 100 person-years on therapy for zidovudine to 6.25 cases per 100 person-years for didanosine + hydroxyurea. Compared to didanosine alone, and adjusting for CD4 cell count and other variables, the relative risk (RR) of pancreatitis was 8.56 [95% confidence interval) CI, 1.85-35.59] for didanosine + hydroxyurea, and 2.35 (95% CI, 0.46-11.89) for didanosine + stavudine + hydroxyurea. For any use of hydroxyurea, the RR = 4.01 (95% CI, 1.02-15.89). Other risk factors for pancreatitis included a CD4 cell count < 200 x 106 cells/l, female sex, and a history of pancreatitis. CONCLUSIONS: Our data show that the risk of pancreatitis is four-fold higher when hydroxyurea is used. The use of hydroxyurea with didanosine should probably be discouraged if other treatment options are available.

Adult↗

An outbreak of scabies in a teaching hospital: lessons learned.

OBJECTIVE: To investigate an outbreak of scabies in an inner-city teaching hospital, identify pathways of transmission, institute effective control measures to end the outbreak, and prevent future occurrences. DESIGN: Outbreak investigation, case-control study, and chart review. SETTING: Large tertiary acute-care hospital. RESULTS: A patient with unrecognized Norwegian (crusted) scabies was admitted to the acquired immunodeficiency syndrome (AIDS) service of a 940-bed acute-care hospital. Over 4 months, 773 healthcare workers (HCWs) and 204 patients were exposed to scabies. Of the exposed HCWs, 147 (19%) worked on the AIDS service. Risk factors for being infested with scabies among HCWs included working on the AIDS service (odds ratio [OR], 5.3; 95% confidence interval [CI95], 2.17-13.15) and being a nurse, physical therapist, or HCW with extensive physical contact with infected patients (OR, 4.5; CI95, 1.26-17.45). Aggressive infection control precautions beyond Centers for Disease Control and Prevention barrier and isolation recommendations were instituted, including the following: (1) early identification of infected patients; (2) prophylactic treatment with topical applications for all exposed HCWs; (3) use of two treatments 1 week apart for all cases of Norwegian scabies; (4) maintaining isolation for 8 days and barrier precautions for 24 hours after completing second treatment for a diagnosis of Norwegian scabies; and (5) oral ivermectin for treatment of patients who failed conventional therapy. CONCLUSIONS: HCWs with the most patient contact are at highest risk of acquiring scabies. Because HCWs who used traditionally accepted barriers while caring for patients with Norwegian scabies continued to develop scabies, we found additional measures were required in the acute-care hospital. HCWs with skin exposure to patients with scabies should receive prophylactic treatment. We recommend (1) using heightened barrier precautions for care of patients with scabies and (2) extending the isolation period for 8 days or 24 hours after the second treatment with a scabicide for those patients with Norwegian scabies. Oral ivermectin was well tolerated for treating patients and HCWs who failed conventional treatment. Finally, we developed a surveillance system that provides a "barometric measure" of the infection rate in the community. If scabies increases in the community, a tiered triage system is activated to protect against transmission among HCWs or hospital patients.

Adult↗

Paradoxical worsening of tuberculosis in HIV-infected persons.

OBJECTIVE: To determine the incidence of paradoxical worsening of tuberculosis (TB) in HIV-infected persons. DESIGN: Observational cohort study. SETTING: Public, urban TB clinic. PATIENTS: HIV-infected persons treated for TB between January 1, 1996, and December 31, 1999, and followed through June 30, 2000. INTERVENTION: Patients received standard anti-TB therapy. Antiretroviral therapy was provided by primary medical providers. Patients receiving antiretroviral therapy were given nucleoside reverse transcriptase inhibitors alone or highly active antiretroviral therapy (HAART; nucleoside reverse transcriptase inhibitors in combination with a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor). MAIN OUTCOME MEASURE: Paradoxical worsening of TB. RESULTS: There were 82 TB cases in 76 patients. Paradoxical worsening was identified in 6 of 82 cases (7%; 95% confidence interval, 3 to 15%). Paradoxical worsening occurred in 3 of 28 cases (11%) in patients receiving HAART and in 3 of 44 cases (7%) in patients not receiving antiretroviral therapy (p = 0.67). Cases complicated by paradoxical worsening were more likely to have both pulmonary and extrapulmonary disease at initial diagnosis than cases without paradoxical worsening (83% vs 24%; p = 0.006). TB relapse occurred in 2 of 6 cases (33%) in patients with paradoxical worsening and in 4 of 76 cases (5%) in patients without paradoxical worsening (p = 0.06). CONCLUSIONS: Paradoxical worsening of TB occurred less frequently than in previous reports and was not associated with HAART. Paradoxical worsening also appeared to be associated with an increased risk of TB relapse. Further studies are warranted to better characterize the risk factors for paradoxical worsening and the appropriate duration of anti-TB therapy in patients in whom it occurs.

AIDS-Related Opportunistic Infections↗

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

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

AIDS-Related Opportunistic Infections↗

Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection.

CONTEXT: Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus. OBJECTIVES: To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development. DESIGN: Prospective cohort study. SETTING: University-based urban HIV clinic. PATIENTS: A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively. MAIN OUTCOME MEASURE: Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy. RESULTS: Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9% -44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %). Although chronicviral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 x 10(9)/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity. CONCLUSIONS: Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus.

Adult↗

Effect of antiretroviral therapy on the incidence of bacterial pneumonia in patients with advanced HIV infection.

To determine the relationship of combination antiretroviral therapy and bacterial pneumonia, we assessed incidence of and risk factors for bacterial pneumonia in 1,898 human immunodeficiency virus (HIV)-infected patients with CD4 cell counts < 200/mm(3) followed in the Johns Hopkins HIV clinic between 1993 and 1998. A total of 352 episodes of bacterial pneumonia occurred during 2,310 patient-years of follow-up. Incidence of bacterial pneumonia decreased from 22.7 episodes/100 person-years (py) in the first half of 1993 to 12.3 episodes/100 py in the first half of 1996, reaching a nadir of 9.1 episodes/100 py in the second half of 1997 (p < 0.05). The use of protease inhibitor-containing regimens was associated with a decreased risk of bacterial pneumonia (risk ratio [RR] 0.55, 95% CI 0.31 to 0.94). Lower CD4 cell counts (RR 2.22, 95% CI 1.54 to 3.18), injection drug use as HIV transmission category (RR2.0, 95% CI 1.43 to 2.76), and prior Pneumocystis carinii pneumonia (RR 3.88, 95% CI 1.65 to 9.16) were also significantly associated with bacterial pneumonia. Trimethoprim-sulfamethoxazole and macrolide use were not significantly associated with risk of bacterial pneumonia. There has been a dramatic decline in the incidence of bacterial pneumonia resulting from the use of combination antiretroviral therapy containing protease inhibitors.

Adolescent↗

Errors in the treatment of tuberculosis in Baltimore.

BACKGROUND: Incomplete or incorrect antibiotic therapy, especially in the initial phase of antituberculosis (anti-TB) treatment, is a major cause of acquired drug resistance and treatment failure. We determined the extent of errors in anti-TB treatment regimens by way of nonadherence to recommended treatment protocols among patients with TB in Baltimore, MD, a city with declining rates of disease. An error was defined as using too few drugs or the wrong drugs, giving inadequate doses of drugs, or prescribing an inadequate duration of treatment. METHODS: We reviewed the records of all patients with culture-positive, pulmonary TB reported in the city of Baltimore from January 1, 1994, to December 31, 1995. We determined demographic information, initial anti-TB regimen, doses and duration of therapy, history or presence of resistance to anti-TB drugs, injecting-drug or alcohol abuse, HIV status, and whether treatment was given by a private physician or by the Tuberculosis Clinic of the Baltimore City Health Department (BCHD). RESULTS: Of the 110 cases of active pulmonary TB, 17 cases (15.4%) had errors in treatment for control of their current disease. Thirteen of 34 privately treated patients (38%) had some error in their initial anti-TB regimen, compared with 4 of 76 patients (5.2%) treated by the Tuberculosis Clinic of the BCHD (p < 0.0001). Patients were otherwise similar as determined by age, sex, HIV status, drug-resistance characteristics, and injecting-drug use, regardless of whether they had erroneous anti-TB regimens. CONCLUSION: In a low-prevalence area, private physicians make frequent errors in prescribing anti-TB therapy. Additional educational resources for physicians and increased use of expert consultation may contribute to improved TB control.

AIDS-Related Opportunistic Infections↗

A multi-state outbreak of tuberculosis among members of a highly mobile social network: implications for tuberculosis elimination.

SETTING: Baltimore, Maryland. OBJECTIVE: To describe a tuberculosis (TB) outbreak among a highly mobile population and the efforts required to control it. DESIGN: Epidemiologic outbreak investigation. RESULTS: Between June 1998 and January 2000, 20 TB outbreak cases were identified, of which 18 were culture-confirmed. Seventeen isolates of Mycobacterium tuberculosis had an identical 11-band DNA fingerprint; another isolate had one additional band and was considered a match. Two cases were diagnosed in New York City; another patient lived primarily in Atlanta, but was diagnosed in Baltimore. Persons in the outbreak were predominantly young (median age 24 years), black, male, infected with the human immunodeficiency virus (HIV), and gay, transvestite or transsexual. Activities common among many TB cases included attending two nightclubs, membership in one of three social 'Houses', attending balls or pageants in East Coast cities, marijuana use, and prostitution. Community outreach, extended contact tracing, DNA fingerprinting, directly-observed therapy, and expanded use of preventive therapy were utilized to assess and control the outbreak. During the outbreak period the Baltimore City TB rate declined by 10%. However, additional public health personnel were required to control the outbreak, resulting in a 17% increase in TB clinic staff. CONCLUSION: As TB rates decline, remaining cases are likely to occur in difficult-to-reach populations. Increased resources per case of TB treated will be required to eliminate TB.

AIDS-Related Opportunistic Infections↗

New developments in the treatment of latent tuberculosis.

Tuberculosis control strategies include the treatment of cases, treatment of latent tuberculosis infection and vaccination. Recent evidence underscores the importance of treating latent infection to reduce disease incidence. Diagnosis of latent infection relies on the tuberculin skin test, although newer methods are under development. Targeting screening to high risk groups will identify true positives who will benefit from preventive therapy. Isoniazid (INH) has been the mainstay of preventive therapy for 40 years, but its use is limited by concerns about toxicity and poor adherence. Careful monitoring of patients allows for the safe use of INH, even in those older than 35 years. Supervised preventive therapy can improve adherence. New short-course regimens for the treatment of latent tuberculosis have been evaluated in the past decade, and are efficacious and associated with better adherence. Guidelines for the treatment of latent tuberculosis infection have recently been published by the American Thoracic Society and the Centers for Disease Control and Prevention. These guidelines should contribute to improved tuberculosis control globally, and to tuberculosis elimination in the United States.

Antitubercular Agents↗

Guidelines for the management of community-acquired pneumonia.

Guidelines for the treatment of community-acquired pneumonia (CAP) have been issued by various institutions. These therapeutic recommendations, culled from available medical literature, can be conflicting and confusing. The following factors further complicate clinical management: Accurate diagnosis is sometimes challenging therapeutic options are abundant and aggressively marketed, and drug resistance is an increasing concern. Moreover, costs of care and clinical outcomes can vary significantly with therapeutic approaches. All of these factors point to a critical need for more consistent medical guidelines for treating CAP.

Anti-Bacterial Agents↗