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Richard E Chaisson

Publications and source records attributed to Richard E Chaisson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis.

Tuberculosis continues to be a major cause of morbidity and mortality in the world. The expansion of tuberculosis control programs has been limited by the lengthy and cumbersome nature of current chemotherapeutic regimens. A new drug that improves the sterilizing activity of current regimens would reduce the duration of therapy without sacrificing efficacy, thereby enhancing treatment completion rates and preserving precious public health resources. The new 8-methoxyfluoroquinolone moxifloxacin has potent activity against both actively multiplying and nonactively multiplying tubercle bacilli. Using a murine model that is representative of chemotherapy for human tuberculosis, we show that the combination of moxifloxacin, rifampin, and pyrazinamide reduced the time needed to eradicate Mycobacterium tuberculosis from the lungs of infected mice by up to 2 months when compared with the standard regimen of isoniazid, rifampin, and pyrazinamide. The findings suggest that this regimen has the potential to substantially shorten the duration of therapy needed to cure human tuberculosis.

Analysis of Variance↗
PubMed2003

Efficacy of secondary isoniazid preventive therapy among HIV-infected Southern Africans: time to change policy?

OBJECTIVE: To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among gold miners working in South Africa. DESIGN: An observational study. SETTING: Health service providing comprehensive care for gold miners. METHODS: The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort (n = 338) had received secondary preventive therapy with isoniazid (IPT) and the other had not (n = 221). RESULTS: The overall incidence of recurrent TB was reduced by 55% among men who received IPT compared with those who did not (incidence rates 8.6 and 19.1 per 100 person-years, respectively; incidence rate ratio, 0.45; 95% confidence interval 0.26-0.78). The efficacy of isoniazid preventive therapy was unchanged after controlling for CD4 cell count and age. The number of person-years of IPT required to prevent one case of recurrent TB among individuals with a CD4 cell count < 200 x 106 cells/l, and > or = 200 x 106 cells/l was 5 and 19, respectively. CONCLUSION: Secondary preventive therapy reduces TB recurrence: the absolute impact appears to be greatest among individuals with low CD4 cell counts. International TB preventive therapy guidelines for HIV-infected individuals need to be expanded to include recommendations for secondary preventive therapy in settings where TB prevalence is high.

Adult↗
PubMed2003

The effect of HAART and HCV infection on the development of hyperglycemia among HIV-infected persons.

OBJECTIVE: To examine the prevalence and incidence of hyperglycemia among HIV-infected patients by hepatitis C virus (HCV) infection and type of highly active antiretroviral therapy (HAART). DESIGN Retrospective cohort analysis of 1230 persons on their first HAART regimen who had at least 1 random glucose measurement before and during antiretroviral therapy. METHODS: The prevalence of hyperglycemia and the incidence of hyperglycemia were compared among persons with and without HCV infection while on a protease inhibitor (PI)-containing HAART regimen, a nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen, or a regimen that contained both a PI and an NNRTI. Hyperglycemia was defined as either 2 random glucose levels > 11.1 mM (200 mg/dL) or documentation of the diagnosis of diabetes in the medical record. RESULTS: The prevalence of hyperglycemia was significantly higher in HCV-coinfected (5.9%) than HCV-uninfected persons (3.3%, P = 0.02). Among persons receiving HAART, both HCV coinfection (adjusted relative hazard [ARH], 2.28; 95% CI, 1.23-4.22) and PI use (ARH, 5.02; 95% CI, 1.39-18.16) were independent risk factors of developing hyperglycemia. The incidence of hyperglycemia was highest among HCV-coinfected persons receiving a PI (5.6 cases per 100-person years) and only 1 person who was neither HCV-infected nor receiving a PI developed hyperglycemia. CONCLUSION: In this urban HIV cohort, the risk of hyperglycemia was increased in HCV-coinfected patients and those prescribed a PI.

Adult↗
PubMed2003

Survival in an urban HIV-1 clinic in the era of highly active antiretroviral therapy: a 5-year cohort study.

OBJECTIVE: To examine the implications of early virologic response to highly active antiretroviral therapy (HAART) on long-term HAART utilization patterns, development of diabetes or hyperlipidemia, and mortality in an urban HIV-1 clinic. DESIGN: A cohort of 444 patients in an urban HIV-1 clinic, who started HAART prior to January 1, 1999, were categorized by virologic response in the first 18 months of therapy: durable viral suppression, initial suppression followed by rebound, and failure to achieve suppression. Antiretroviral exposure, HIV-1 RNA levels, CD4 cell counts, development of diabetes or hyperlipidemia, and survival were compared in the three groups. RESULTS: Over 4 years of follow-up, patients in the durable suppression group used HAART 82% of the time compared with 60% in the rebound group (p <.001) and 23% in the failure to suppress group (p <.001). Through 4 years of follow-up, patients in the rebound group had a cumulative exposure to a median of seven antiretroviral drugs (interquartile range [IQR]: 6-9) compared with five drugs in the durable suppression group (IQR: 4-6) and five drugs in the failure to suppress group (IQR: 3-7) (p <.001 for both comparisons with the rebound group). At 5 years, the estimated proportions surviving were 89% in the durable suppression group, 76% in the rebound group (p =.04), and 56% in the failure to suppress group (p <.001). During follow-up, 35% in the durable suppression group developed diabetes or hyperlipidemia compared with 24% in the rebound group (p =.15) and 8% in the failure to suppress group (p <.001). CONCLUSIONS: This study highlights the long-term implications of early virologic response to HAART for survival, accumulation of triple-class antiretroviral exposure, and development of HAART-associated toxicities.

Adult↗
PubMed2003

Human immunodeficiency virus-1 RNA levels and CD4 lymphocyte counts, during treatment for active tuberculosis, in South African patients.

During 6 months of treatment, we measured human immunodeficiency virus (HIV)-1 virus loads, CD4 T cell counts, and immune activation markers, in 111 HIV-1-infected patients with active tuberculosis (TB). The median virus load (baseline, 5.58 log(10) copies/mL) significantly increased at 1 month (5.71 log(10) copies/mL), then returned to near-baseline levels at 3 months (5.40 log(10) copies/mL) and at 6 months (5.36 log(10) copies/mL). In contrast, the median CD4 counts increased at 1 month (186/mm(3)), at 3 months (238/mm(3)), and at 6 months (239/mm(3)). CD4 counts and virus loads did not change during therapy. Expression of CD38 and HLA-DR remained high throughout treatment, whereas plasma levels of interleukin-6 decreased over time.

AIDS-Related Opportunistic Infections↗
PubMed2003

Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection.

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Administration, Oral↗
PubMed2003

Initiation of highly active antiretroviral therapy at CD4+ T lymphocyte counts of >350 cells/mm3: disease progression, treatment durability, and drug toxicity.

We compared clinical disease progression in 159 human immunodeficiency virus (HIV)-infected persons for whom highly active antiretroviral therapy (HAART) was initiated when they had CD4(+) T lymphocyte counts of 350-499 cells/mm(3) with progression in 174 HIV-infected patients for whom it was not. Disease progression did not differ between the 2 groups (P=.21, log-rank test). Fifty-three percent of the 159 treated patients had HIV type 1 RNA levels of >400 copies/mL at the most recent evaluation, and 41% had experienced adverse drug reactions necessitating a change in regimen. These findings support the recommendation that HAART not be initiated for patients with CD4(+) cell counts of >350 cells/mm(3).

Adult↗
PubMed2003

Tuberculosis drug resistance: a global threat.

Resistance to antituberculosis drugs has been a problem since the era of chemotherapy began. After dramatic outbreaks of multidrug-resistant tuberculosis (MDR-TB) in the early 1990s, resistance became recognized as a global problem. MDR-TB now threatens the inhabitants of countries in Europe, Asia, Africa, and the Americas. An understanding of the molecular basis of drug resistance may contribute to the development of new drugs. Management of MDR-TB relies on prompt recognition and treatment with at least 3 drugs to which an isolate is susceptible.

Antitubercular Agents↗
PubMed2002

Hepatitis C and progression of HIV disease.

CONTEXT: Conflicting reports exist regarding the effect of hepatitis C virus (HCV) on the progression of human immunodeficiency virus (HIV) disease. OBJECTIVE: To assess the effect of HCV infection on clinical and immunologic progression of HIV disease and immunologic response to highly active antiretroviral therapy (HAART). DESIGN: Prospective cohort study. SETTING: University-based, urban HIV clinic in the United States. PATIENTS: There were 1955 patients enrolled between January 1995 and January 2001 who were eligible for analysis because of having at least 1 return visit to the clinic and being free of acquired immunodeficiency syndrome (AIDS) at enrollment. Median (interquartile range) length of follow-up was 2.19 (1.00-3.50) years for HCV-infected and 2.00 (1.00-3.00) years for HCV-uninfected patients. MAIN OUTCOME MEASURES: Progression to an AIDS-defining illness, survival, and progression to a CD4 cell count below 200/microL; CD4 cell count change following initiation of effective HAART (resulting in a viral load of <400 copies/mL recorded at > or = 75% of measurements). RESULTS: No difference was detected in the risk of acquiring an AIDS-defining illness (HCV-infected patients, 231 events [26.4%] and HCV-uninfected patients, 264 events [24.4%]; relative hazard [RH], 1.03; 95% confidence interval [CI], 0.86-1.23) or in the risk of death (HCV-infected patients, 153 deaths [17.5%] and HCV-uninfected patients, 168 deaths [15.5%]; RH, 1.05; 95% CI, 0.85 -1.30). Although an increased risk of death was detected in the subgroup of 429 HCV-infected patients with a baseline CD4 cell count of 50/microL through 200/microL (RH, 1.51; 95% CI, 1.01-2.27), after adjustment for exposure to HAART and its effectiveness in a multivariate Cox regression analysis, death was not independently associated with HCV infection in this subgroup (RH, 1.01; 95% CI, 0.65-1.56). Similarly, in those receiving effective HAART (n = 208), there was no difference in the increase in CD4 cell count or CD4 percentage during HAART in HCV-infected compared with HCV-uninfected patients. CONCLUSIONS: Among patients in this urban US cohort, we did not detect evidence that HCV infection substantially alters the risk of dying, developing AIDS, or responding immunologically to HAART, especially after accounting for differences in its administration and effectiveness.

Adult↗
PubMed2002

Evaluation of a whole-blood interferon-gamma release assay for the detection of Mycobacterium tuberculosis infection in 2 study populations.

A whole-blood interferon-gamma release assay (IGRA) is being evaluated for its potential to replace the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. To test the assay in a population in which tuberculosis is highly endemic and in another population that is representative of an urban United States population, 253 volunteers from Ethiopia and 175 volunteers from Baltimore were studied for responsiveness on IGRA compared with a simultaneously performed TST. The agreement between the 2 tests, beyond that due to chance, was 68% among subjects from Baltimore and only 35% among those from Ethiopia. IGRA had a sensitivity of 71%, compared with 95% sensitivity for the TST, among 21 subjects who had undergone treatment for culture-confirmed tuberculosis. The specificity was 85% for IGRA and 96% for TST among 52 subjects with no known history of exposure to tuberculosis. In its current form, with purified protein derivative used as the stimulation antigen, the IGRA was found to perform poorly in comparison to the TST in diagnosing M. tuberculosis infection.

Ethiopia↗
PubMed2002

Longitudinal assessment of the effects of drug and alcohol abuse on HIV-1 treatment outcomes in an urban clinic.

OBJECTIVE: To assess the temporal association of changes in substance abuse with antiretroviral therapy use and adherence, HIV-1 RNA suppression, and CD4 cell count changes in patients attending an urban clinic. DESIGN: Prospective cohort study. METHODS: Six-hundred and ninety-five HIV-1-infected individuals, who completed two or more semi-annual standardized surveys and in whom antiretroviral therapy was indicated, were included in the analysis. Surveys addressed antiretroviral therapy use and adherence, and use of illicit drugs and alcohol. Substance abuse was defined as active heroin, cocaine, or heavy alcohol use in the 6 months preceding survey. The units of analysis were consecutive pairs of surveys (couplets) in individual participants. Couplets in which participants denied substance abuse in both surveys were compared to couplets in which participants switched from non-use to substance abuse, and couplets in which participants reported substance abuse in both surveys were compared to couplets where participants switched from substance abuse to non-use. RESULTS: Switching from non-use to substance abuse was strongly associated with worsening antiretroviral therapy use and adherence, less frequent HIV-1 RNA suppression, and blunted CD4 cell increases, compared to remaining free of substance abuse. Alternatively, switching from substance abuse to non-use was strongly associated with improvements in antiretroviral therapy use and adherence, and HIV-1 treatment outcomes, compared to persisting with substance abuse. CONCLUSIONS: This longitudinal study highlights the dynamic nature of substance abuse and its temporal association with the effectiveness of HIV-1 treatment in patients attending an inner-city clinic.

Adult↗
PubMed2002

Survival of patients with pulmonary tuberculosis: clinical and molecular epidemiologic factors.

Using restriction fragment-length polymorphism data, we conducted a retrospective cohort study of 139 adult patients with pulmonary tuberculosis to investigate the clinical impact of Mycobacterium tuberculosis infection with a clustered isolate. The cumulative all-cause mortality rate during treatment was 21%. Patients with clustered DNA fingerprint patterns had a reduced risk of death, compared with patients with unique patterns (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.2-1.1), but this finding was confounded by age (adjusted HR, 0.8; 95% CI, 0.4-1.8). After adjustment for age, the strongest predictors of death were such underlying illnesses as diabetes mellitus, renal failure, chronic obstructive pulmonary disease, and human immunodeficiency virus infection. We conclude that comorbidity and immunosuppression are important predictors of survival for patients with pulmonary tuberculosis in an inner-city cohort. Recently transmitted infection, as determined by use of DNA fingerprinting to classify patients' isolates as being either clustered or unique, was not independently associated with death.

Adolescent↗