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Timothy R Sterling

Publications and source records attributed to Timothy R Sterling.

17 recordsLinked to original sources
PubMed2003

Improved outcomes with earlier initiation of highly active antiretroviral therapy among human immunodeficiency virus-infected patients who achieve durable virologic suppression: longer follow-up of an observational cohort study.

On the basis of studies with relatively short follow-up, treatment guidelines currently recommend that highly active antiretroviral therapy (HAART) be initiated in asymptomatic human immunodeficiency virus-infected patients when the CD4+ lymphocyte count is < or =200 cells/mm3. We assessed the development of a new opportunistic infection or death among 1173 patients initiating HAART. Durable virologic suppression was defined as having more undetectable (<400 copies/mL) than detectable virus loads after the initiation of therapy. The median durations of therapy and follow-up were 29 and 36 months, respectively. Among patients who achieved durable virologic suppression, those with baseline CD4+ lymphocyte counts of <200 cells/mm3 tended to progress faster than those with baseline CD4+ lymphocyte counts of 201-350 cells/mm3 (P=.09) and progressed faster than those with baseline CD4+ lymphocyte counts of >350 cells/mm3 (P=.01). Among those with durable virologic suppression, there was no difference in disease progression between those with baseline CD4+ lymphocyte counts of 201-350 cells/mm3 and those with durable virologic suppression with baseline CD4+ lymphocyte counts of >350 cells/mm3 (P=.40). Initiating HAART with a CD4+ lymphocyte count of <200 cells/mm3 was associated with a higher risk of disease progression, even with durable virologic suppression. HAART should be initiated at CD4+ lymphocyte counts of >200 cells/mm3.

Adult↗
PubMed2003

Fluoroquinolone resistance in patients with newly diagnosed tuberculosis.

Fluoroquinolones are widely used for the treatment of bacterial infections and are also second-line therapy for tuberculosis. However, fluoroquinolone resistance in patients with newly diagnosed cases of tuberculosis is not routinely assessed. We performed in vitro susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones for all culture-confirmed tuberculosis cases in adults that were diagnosed at Johns Hopkins Hospital (Baltimore) between January 1998 and March 2002. Fifty-five patients were included in the study; 19 received fluoroquinolone monotherapy before the initiation of antituberculosis therapy. Two of 55 M. tuberculosis isolates (4%; 95% CI, 1%-13%) had decreased susceptibility to fluoroquinolones, including 2 of 19 of those from patients who had received fluoroquinolones (11%; 95% CI, 1%-33%) and 0 of 36 isolates from those who had not (95% CI, 0%-10%). The 2 fluoroquinolone-resistant M. tuberculosis strains were both from patients with acquired immunodeficiency syndrome and a CD4+ lymphocyte count of <50 cells/mm3. The incidence of M. tuberculosis fluoroquinolone resistance in this small sample of patients with newly diagnosed tuberculosis was high, particularly among patients with prior fluoroquinolone exposure.

Adult↗
PubMed2003

Tuberculosis.

Among communicable diseases, tuberculosis is the second leading cause of death worldwide, killing nearly 2 million people each year. Most cases are in less-developed countries; over the past decade, tuberculosis incidence has increased in Africa, mainly as a result of the burden of HIV infection, and in the former Soviet Union, owing to socioeconomic change and decline of the health-care system. Definitive diagnosis of tuberculosis remains based on culture for Mycobacterium tuberculosis, but rapid diagnosis of infectious tuberculosis by simple sputum smear for acid-fast bacilli remains an important tool, and more rapid molecular techniques hold promise. Treatment with several drugs for 6 months or more can cure more than 95% of patients; direct observation of treatment, a component of the recommended five-element DOTS strategy, is judged to be the standard of care by most authorities, but currently only a third of cases worldwide are treated under this approach. Systematic monitoring of case detection and treatment outcomes is essential to effective service delivery. The proportion of patients diagnosed and treated effectively has increased greatly over the past decade but is still far short of global targets. Efforts to develop more effective tuberculosis vaccines are under way, but even if one is identified, more effective treatment systems are likely to be required for decades. Other modes of tuberculosis control, such as treatment of latent infection, have a potentially important role in some contexts. Until tuberculosis is controlled worldwide, it will continue to be a major killer in less-developed countries and a constant threat in most of the more-developed countries.

Adolescent↗
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

Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis.

OBJECTIVE: This study sought to determine the impact of the World Health Organization's directly observed treatment strategy (DOTS) compared with that of DOTS-plus on tuberculosis deaths, mainly in the developing world. DESIGN: Decision analysis with Monte Carlo simulation of a Markov decision tree. DATA SOURCES: People with smear positive pulmonary tuberculosis. DATA ANALYSIS: Analyses modelled different levels of programme effectiveness of DOTS and DOTS-plus, and high (10%) and intermediate (3%) proportions of primary multidrug resistant tuberculosis, while accounting for exogenous reinfection. MAIN OUTCOME MEASURE: The cumulative number of tuberculosis deaths per 100 000 population over 10 years. RESULTS: The model predicted that under DOTS, 276 people would die from tuberculosis (24 multidrug resistant and 252 not multidrug resistant) over 10 years under optimal implementation in an area with 3% primary multidrug resistant tuberculosis. Optimal implementation of DOTS-plus would result in four (1.5%) fewer deaths. If implementation of DOTS-plus were to result in a decrease of just 5% in the effectiveness of DOTS, 16% more people would die with tuberculosis than under DOTS alone. In an area with 10% primary multidrug resistant tuberculosis, 10% fewer deaths would occur under optimal DOTS-plus than under optimal DOTS, but 16% more deaths would occur if implementation of DOTS-plus were to result in a 5% decrease in the effectiveness of DOTS CONCLUSIONS: Under optimal implementation, fewer tuberculosis deaths would occur under DOTS-plus than under DOTS. If, however, implementation of DOTS-plus were associated with even minimal decreases in the effectiveness of treatment, substantially more patients would die than under DOTS.

Cost-Benefit Analysis↗
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↗
PubMed2002

Heat-denatured human immunodeficiency virus type 1 protein 24 antigen: prognostic value in adults with early-stage disease.

CD4(+) lymphocyte count and human immunodeficiency virus (HIV) type 1 RNA level are useful for determining when to initiate antiretroviral therapy but are not used widely in developing countries due to the high cost. Heat-denatured protein 24 (p24) antigen is an inexpensive assay that predicts disease progression among persons with advanced disease but has not been assessed among persons with early-stage disease. Plasma levels of heat-denatured p24 antigen were quantified in baseline study-visit specimens obtained from injection drug users enrolled in a longitudinal cohort study of HIV-1 infection. Of the 494 study participants (median initial CD4(+) lymphocyte count, 518 lymphocytes/mm(3)), 90 (18%) progressed to acquired immunodeficiency syndrome within 5 years. p24 antigen level correlated with both CD4(+) lymphocyte count (r=-0.34; P<.0001) and HIV-1 RNA level (r=0.55; P<.0001). p24 antigen level >5 pg/mL predicted disease progression, comparable with that of cutoff CD4(+) lymphocyte count <350 lymphocytes/mm(3) and HIV-1 RNA level >30,000 copies/mL. Heat-denatured p24 antigen level predicted subsequent clinical disease progression in early-stage HIV-1 infection and correlated with both CD4(+) lymphocyte count and HIV-1 RNA level.

Acquired Immunodeficiency Syndrome↗
PubMed2002

A prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1,200 mg plus isoniazid in the continuation phase of tuberculosis treatment.

Once-weekly rifapentine 600 mg plus isoniazid (INH) during the continuation phase treatment of tuberculosis is associated with a relapse rate higher than that of twice-weekly rifampin plus INH. The safety and tolerability of higher rifapentine doses need to be determined. We conducted a prospective, randomized, double-blind trial of rifapentine at three doses (600, 900, and 1,200 mg) plus INH 15 mg/kg once weekly in the continuation phase treatment of culture-positive tuberculosis in 150 human immunodeficiency virus-seronegative adults. Outcome measures were discontinuation of therapy for any reason and adverse events on therapy. Treatment was discontinued in 3 of 52 (6%), 2 of 51 (4%), and 3 of 47 (6%) in the rifapentine 600-, 900-, and 1,200-mg treatment arms, respectively. Only one discontinuation, in the rifapentine 1,200-mg arm, was due to an adverse event possibly associated with study therapy. There was a trend toward more adverse events, possibly associated with study therapy, in the highest-dose arms (p = 0.051). Rifapentine 900-mg, once-weekly dosing appears to be safe and well tolerated and is being evaluated in Phase III efficacy trials of treatment of latent tuberculosis. Further evaluation of the safety and tolerability of rifapentine 1,200 mg is warranted.

Adult↗
PubMed2002

Empiric treatment of community-acquired pneumonia with fluoroquinolones, and delays in the treatment of tuberculosis.

Fluoroquinolones, which are widely used to treat community-acquired pneumonia, also have excellent in vitro activity against Mycobacterium tuberculosis. A retrospective cohort study was conducted among adults with culture-confirmed tuberculosis to assess the effect of empiric fluoroquinolone therapy on delays in the treatment of tuberculosis. Sixteen (48%) of 33 patients received fluoroquinolones for presumed bacterial pneumonia before tuberculosis was diagnosed and treated. There were no differences between the group who did and the group who did not receive fluoroquinolones, except that patients who received fluoroquinolones were more likely to present with shortness of breath. Among patients treated empirically with fluoroquinolones, the median time between presentation to the hospital and initiation of antituberculosis treatment was 21 days (interquartile range, 5-32 days); among those who were not, it was 5 days (interquartile range, 1-16 days; P=.04). Initial empiric therapy with a fluoroquinolone was associated with a delay in the initiation of appropriate antituberculosis treatment.

Anti-Infective Agents↗
PubMed2002

Use of DNA fingerprinting to investigate a multiyear, multistate tuberculosis outbreak.

In 1998-1999, the Baltimore TB control program detected a cluster of 21 tuberculosis (TB) cases. Patients reported frequent travel to various East Coast cities. An investigation was conducted to determine whether transmission of the same Mycobacterium tuberculosis strain was occurring in these other localities. A collaborative investigation among federal, state, and local TB controllers included TB record reviews, interviews of patients, and restriction fragment length polymorphism (RFLP) analysis of selected M. tuberculosis isolates from diagnosed TB patients in several cities in 1996-2001. A national TB genotyping database was searched for RFLP patterns that matched the outbreak pattern. Eighteen additional outbreak-related cases were detected outside of Baltimore-the earliest diagnosed in New Jersey in 1996, and the most recent in New York City in late 2001. The outbreak demonstrates the need for strategies to detect links among patients diagnosed with TB across multiple TB control jurisdictions.

Adolescent↗
PubMed2002

Tuberculosis and HIV.

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AIDS-Related Opportunistic Infections↗