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Biomedical subjects

Timothy R Sterling

Publications and source records attributed to Timothy R Sterling.

At least 19 recordsLinked to original sources
PubMed2005

CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3.

BACKGROUND: The optimal timing of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients with > or = 200 absolute CD4 lymphocytes/mm3 is unknown. CD4 lymphocyte percentage could add prognostic information. METHODS: Persons who initiated HAART between 1 January 1998 and 1 January 2003, received > or = 30 days of therapy, and had baseline CD4 lymphocyte data available were included in the study. The log-rank test for time to event and Cox proportional hazards models were used to determine predictors of a new acquired immunodeficiency syndrome-defining illness or death. RESULTS: A total of 788 patients met the inclusion criteria. At baseline, subjects had a median of 225 CD4 lymphocytes/mm3 and 17% CD4 lymphocytes. Subjects with < 17% CD4 lymphocytes had earlier disease progression, compared with subjects with > or = 17%, both in the entire cohort (P<.0001) and of those subjects with > 350 absolute CD4 lymphocytes/mm3 at baseline (P=.03). CD4 lymphocyte percentage < 17% was the strongest predictor of disease progression among subjects in this latter group (hazard ratio, 3.57; P=.045). CONCLUSIONS: In this cohort, CD4 lymphocyte percentage predicted disease progression in HIV-infected subjects who initiated therapy with > 350 CD4 lymphocytes/mm3. This information may help identify persons who will derive the greatest benefit from initiation of HAART.

Adolescent↗
PubMed2005

Effectiveness of highly active antiretroviral therapy among injection drug users with late-stage human immunodeficiency virus infection.

Highly active antiretroviral therapy (HAART) has been shown to be effective in different populations, but data among injection drug users are limited. Human immunodeficiency virus-infected injection drug users recruited into the Acquired Immunodeficiency Syndrome Link to Intravenous Experiences (ALIVE) Study as early as 1988 were tested semiannually to identify their first CD4-positive T-lymphocyte cell count below 200/microl; they were followed for mortality through 2002. Visits were categorized into the pre-HAART (before mid-1996) and the HAART eras and further categorized by HAART use. Survival analysis with staggered entry was used to evaluate the effect of HAART on acquired immunodeficiency syndrome-related mortality, adjusting for other medications and demographic, clinical, and behavioral factors. Among 665 participants, 258 died during 2,402 person-years of follow-up. Compared with survival in the pre-HAART era, survival in the HAART era was shown by multivariate analysis to be improved for both those who did and did not receive HAART (relative hazards = 0.06 and 0.33, respectively; p < 0.001). Inferences were unchanged after restricting analyses to data starting with 1993 and considerations of lead-time bias and human immunodeficiency viral load. The annual CD4-positive T-lymphocyte cell decline was less in untreated HAART-era participants than in pre-HAART-era participants (-10/microl vs. -37/microl, respectively), suggesting that changing indications for treatment may have contributed to improved survival and that analyses restricted to the HAART era probably underestimate HAART effectiveness.

Adult↗
PubMed2005

Prescribing of contraindicated protease inhibitor and statin combinations among HIV-infected persons.

HIV-1 protease inhibitors (PIs) contribute to hyperlipidemia in persons treated for HIV infection. There are potential drug-drug interactions between PIs and some statins, which are drugs frequently used to treat hyperlipidemia. We performed a retrospective cohort study using the TennCare program to determine prescribing rates of contraindicated combinations of PIs and statins in HIV-infected persons in Tennessee and to assess changes in prescribing after publication of treatment guidelines. Computerized files identified adult patients with antiretroviral prescriptions and overlapping prescriptions for PIs and statins from January 1, 1996 through June 30, 2002. A subset of these combinations was defined as contraindicated based on published guidelines. Changes in patterns of prescribing after publication of preliminary treatment guidelines were examined using a mixed-effects logistic regression model. There were 3448 persons who received PIs during the study period. The proportion of PI users receiving statins increased from 3.5% during January 1996 through December 2000 to 7.9% during January 2001 through June 2002 (P < 0.001). Contraindicated PI-statin use decreased from 42.0% of combinations to 20.8% during the same periods (P < 0.001). Use of PIs and statins has increased in the adult TennCare population. Contraindicated combinations have decreased but remain unacceptably high.

Adolescent↗
PubMed2005

Sex-based differences in T lymphocyte responses in HIV-1-seropositive individuals.

Sex-based differences in the levels of human immunodeficiency virus 1 (HIV-1) RNA in plasma could be associated with differences in the strength of HIV-1-specific CD8(+) T cell responses. CD8(+) effector responses in 18 men and 15 women were measured 0-2 years (time A) and 5-7 years (time B) after seroconversion. CD8(+) effector responses were seen in 7 (39%) of 18 men and 2 (13%) of 15 women at time A (P=.13) and in 12 (67%) of 18 men and 10 (67%) of 15 women at time B (P=.99). At time B, the strength of CD8(+) effector responses correlated with the number of CD4(+) lymphocytes in women ( rho =-0.68; P=.005) but not in men ( rho =-0.14; P=.58). The level of HIV-1 RNA was not associated with the strength of CD8(+) effector responses according to sex, but there was a sex-based difference in the correlation between the strength of CD8(+) effector response and the number of CD4(+) lymphocytes.

Adult↗
PubMed2005

Prognostic factors for survival differ according to CD4+ cell count among HIV-infected injection drug users: pre-HAART and HAART eras.

To identify prognostic indicators of survival at different CD4 cell levels, independent of highly active antiretroviral therapy (HAART), among injection drug users (IDUs). A community-recruited cohort of injection drug users followed semiannually from 1988 through 2000. Five partially overlapping subcohorts were defined by when participants first reached a CD4 cell level of 351 to 500, 201 to 350, 101 to 200, 51 to 100, or </=50 cells/microL. Prognostic factors were measured at entry into each category. Kaplan-Meier survival estimates for HIV-related death and Cox regression models were constructed by CD4 category. Among the 1030 HIV-infected IDUs, survival improved in the HAART-era with hazard ratios 0.42, 0.36, 0.24, 0.21, and 0.25, respectively, for CD4 cell groups of 500 to 351, 350 to 201, 200 to 101, 100 to 51, and </=50 cells/microL. Shorter survival was associated with prior hospitalization, AIDS, and sexually transmitted disease, with similar effects in the pre-HAART and HAART eras. For the lowest CD4 cell level, prior sepsis or endocarditis, outpatient/emergency room visits, and alcohol use provide additional prognostic value. Survival among HIV-infected IDUs improved since the introduction of HAART, even though utilization of HAART was incomplete. Clinical and behavioral variables provided prognostic information about survival, including substance use indicators.

Adult↗
PubMed2004

Mortality in HIV-seropositive versus -seronegative persons in the era of highly active antiretroviral therapy: implications for when to initiate therapy.

BACKGROUND: The optimal time to initiate highly active antiretroviral therapy (HAART) remains unclear. METHODS: Five hundred eighty-three human immunodeficiency virus (HIV)-seropositive and 920 HIV-seronegative injection drug users (IDUs) were followed from 1997 to 2000. HIV-seropositive participants were categorized according to receipt of HAART (either initiated or switched to HAART) and initial CD4 cell count. Survival analysis that included delayed-entry and Cox proportional-hazards models was used to evaluate the effect of HAART, with adjustments for factors associated with access to HAART. RESULTS: Compared with HIV-seronegative participants, overall survival was similar in HIV-seropositive participants who received HAART at >350 CD4 cells/microL, but mortality was higher both in participants with >350 CD4 cells/microL who did not receive HAART and in participants who received HAART at 200-350 CD4 cells/microL (mortality rates, 19.9, 24.0, 43.0, and 50.5/1000 person-years, respectively). In proportional-hazards models in which HIV-seronegative participants were the reference group and in which age, sex, race, frequency of drug use, substance-abuse treatment, and health-care utilization were adjusted for, hazard ratios were 1.01 (95% confidence interval [CI], 0.41-2.45), 2.28 (95% CI, 1.38-3.78), and 2.09 (95% CI, 1.07-4.10) for the latter 3 groups. In HIV-seropositive participants, HAART significantly improved survival when initiated at CD4 cell counts < 200 cells/microL. CONCLUSIONS: Survival of HIV-seropositive participants receiving HAART approximated that of HIV-seronegative participants only when therapy was given at CD4 cell counts > 350 cells/microL. These data, restricted to IDUs, suggest initiating or switching to HAART at higher CD4 cell levels than are currently recommended.

Adult↗
PubMed2004

Risk factors for relapse and acquired rifamycin resistance after directly observed tuberculosis treatment: a comparison by HIV serostatus and rifamycin use.

We sought to determine the risk of acquired rifamycin resistant (ARR) tuberculosis associated with rifampin- versus rifabutin-based directly observed therapy and to assess the risk factors for relapse of tuberculosis. This observational cohort study included patients with culture-confirmed rifamycin-susceptible tuberculosis reported to the Baltimore City Health Department (Baltimore, MD) during the period of January 1993 through December 2001. Of the 407 patients, 108 (27%) were human immunodeficiency virus (HIV) seropositive, 161 (40%) were HIV seronegative, and 138 (34%) had an unknown serostatus. Three (2.8%) of 108 HIV-seropositive persons had ARR tuberculosis, compared with 0 of 299 persons with negative or unknown HIV serostatus (P=.02). Among HIV-seropositive patients, 3 (3.7%) of 81 who were treated with rifampin and 0 of 27 who were treated with rifabutin had ARR tuberculosis (P=.57). Among HIV-seropositive patients, the only risk factor for recurrent tuberculosis was a low median initial CD4+ T lymphocyte count (51 vs. 138 cells/mm3; P=.02). The median CD4+ T lymphocyte count among patients with ARR tuberculosis was 51 cells/mm3. ARR tuberculosis can occur with rifampin-based regimens, but in this study, the risk was not significantly higher than that for a rifabutin-based regimen.

Adult↗
PubMed2004

Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy.

The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean area under the plasma concentration-time curve (AUC(0-infinity)) increased significantly with dose (rifapentine AUC(0- infinity): 296, 410, and 477 microg.hour/ml at 600, 900, and 1,200 mg, respectively; p = 0.02 by linear regression). In multivariate stepwise regression analyses, AUC(0-infinity) values for rifapentine and the active 25-desacetyl metabolite were associated with drug dose and plasma albumin concentration, and were lower among men and among white individuals. Fifty-four percent of patients had total (free and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after clearance of concurrently administered isoniazid. Serious adverse effects of therapy in these study patients were infrequent (1 of 35 cases; 3%) and not linked with higher rifapentine AUC(0-infinity) or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis.

Adult↗
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↗