Biomedical subjects

Florin Vaida

Publications and source records attributed to Florin Vaida.

10 recordsLinked to original sources

PubMed2025

A randomized controlled trial to unveil the influence of an exercise intervention on brain integrity and gut microbiome structure in individuals with HIV.

OBJECTIVE: Exercise intervention programs enhance physical fitness, cognition, neuroimaging measures, and alter the structure of the gut microbiome in individuals without HIV. However, interventional studies exploring the effects of exercise in persons with HIV (PWH) have not included neuroimaging or gut microbiome analyses. DESIGN: A randomized controlled trial conducted at Washington University in St. Louis, MO, USA. METHODS: 65 PWH (aged ≥40 years, self-reported sedentary lifestyle) were randomly assigned to a 6-month cardiorespiratory and resistance training (EXS) or stretching control (SIS) intervention in a 2 : 1 ratio. Longitudinal change in cognition, cerebral blood flow (CBF), physical and cardiorespiratory fitness, and gut microbiome diversity and composition were examined among participants ( n  = 62) who completed any portion of the intervention (ClinicalTrials.gov: NCT02663934). RESULTS: Better fitness and better cognitive performance were associated with greater phylogenetic diversity in gut microbiome composition at baseline. Longitudinal findings indicated slight but significant improvements in psychomotor speed and executive function, reductions in body mass index, improvements in physical fitness, and increased gut microbiome diversity. These changes were observed regardless of assigned intervention group. There were no observed changes in CBF for either group. CONCLUSIONS: These findings highlight physical fitness as a modifiable factor in PWH that may improve cognitive performance and change gut microbiome composition. Both interventions were beneficial, suggesting light stretching exercise or study participation alone could have been sufficient to introduce positive cognitive shifts in previously sedentary PWH. Longer interventions with more participants are needed to identify changes in neuroimaging metrics related to brain integrity.

Humans↗

PubMed2007

Random changepoint modelling of HIV immunologic responses.

We propose a changepoint model for the analysis of longitudinal CD4 T-cell counts for HIV infected subjects following highly active antiretroviral treatment. The profile of CD4 counts for each subject follows a simple, 'broken stick' changepoint model, with random subject-specific parameters, including the changepoint. The model accounts for baseline covariates. The longitudinal CD4 records are censored at the time of the subject going off-study-treatment. This is a potentially informative drop-out mechanism, which we address by modelling it jointly with the CD4 count outcome. The drop-out model incorporates terms from the CD4 model, including the changepoint. The estimation is done in a Bayesian framework, with implementation via Markov chain Monte Carlo methods in the WinBUGS software. Model selection using DIC indicates that the data support the complex random changepoint and informative censoring model.

Antiretroviral Therapy, Highly Active↗

PubMed2006

Synergy of small molecular inhibitors of hepatitis C virus replication directed at multiple viral targets.

Chronic hepatitis C virus (HCV) infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.

Antiviral Agents↗

PubMed2006

Changes in the slope of the CD4 cell count increase after initiation of potent antiretroviral treatment.

SUMMARY: Two phases of CD4+ T-cell increases are seen soon after potent antiretroviral therapy (ART) is initiated. In this 72-week analysis of 101 subjects with sustained viral suppression, we estimate the inflection point between the 2 phases to be 10 weeks after treatment initiation. Higher pretreatment HIV-1 RNA levels were associated with steeper initial CD4+ T-cell increases, likely reflecting greater redistribution of cells from lymphoid tissue to the peripheral blood compartment.

Anti-HIV Agents↗

PubMed2006

A randomized trial of treatment interruption before optimized antiretroviral therapy for persons with drug-resistant HIV: 48-week virologic results of ACTG A5086.

BACKGROUND: The role of structured treatment interruption (STI) before optimized antiretroviral therapy (ART) in patients with drug-resistant human immunodeficiency virus type 1 (HIV-1) is uncertain. METHODS: AIDS Clinical Trial Group protocol A5086 was a prospective trial of 41 patients with multiple drug class-resistant HIV who were randomized to undergo a 16-week STI followed by optimized ART (STI) or immediate optimized ART (no STI). The primary end point was the proportion of subjects with HIV-1 RNA loads <400 copies/mL 48 weeks after randomization. RESULTS: Of 39 evaluable patients, 4 (19%) in the STI arm and 6 (33%) in the no STI arm had HIV-1 RNA loads <400 copies/mL at 48 weeks (P=.44). Median changes from baseline in CD4+ cell counts and HIV-1 RNA loads were similar for both arms. Standard genotypes at the end of STI showed nearly complete reversion to wild-type virus in a minority of patients (n=5; 28%). Virus with 3-drug class resistance reemerged even when ART included only 1 or 2 drug classes. Single-genome sequencing showed that each genome encoded resistance mutations for 3 drug classes. CONCLUSIONS: A 16-week STI before optimized ART did not improve virologic response. Genetic analyses strongly suggest that virologic failure resulted from the reemergence of virus present before STI that encoded 3-drug class resistance on the same genome.

Adult↗

PubMed2006

Robust analysis of biomarker data with informative missingness using a two-stage hypothesis test in an HIV treatment interruption trial: AIEDRP AIN503/ACTG A5217.

Clinical trial AIN503/A5217 investigates whether a period of early treatment with antiretroviral therapy might lower the viral setpoint in subjects recently infected with HIV-1. We consider two statistical issues. First, even under the null hypothesis control arm subjects are more likely than treatment arm subjects to be missing final outcome data because of disease progression. The analysis must adjust for this missing data, or it may be unacceptably biased. Second, comparing outcomes between treatment and control arms at identical times post-randomization gives different information than comparing outcomes at the same amount of time off-therapy, as measured post-randomization. This may make interpretation of results problematic. We formulate the null hypothesis of the study as exchangeability under a time-shift between arms, which we call "time delay" between the study arms. This captures clinically relevant information, and allows us to formalize a two-stage hypothesis test in which stage one is a comparison between arms at identical times post-randomization, and stage two is a comparison between arms at identical times off-therapy, as measured post-randomization. Importantly, within this framework we can show that the two-stage test can be adjusted for the missing data using a simple worst-rank substitution.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Cross-sectional study to evaluate factors associated with adherence to antiretroviral therapy by Brazilian HIV-infected patients.

Antiretroviral therapy success is highly dependent on the ability of the patient to fully adhere to the prescribed treatment regimen. We present the results of a cross-sectional study that evaluates the predictive value of a self-administered questionnaire of adherence to antiretroviral (ARV) therapy. Study participants were interviewed using a 36-item Patient Medication Adherence Questionnaire (PMAQ) designed to assess knowledge about ARV therapy, motivation to adhere to treatment, and behavioral skills. Plasma HIV-1 RNA levels were correlated with the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were receiving their initial ARV regimen. Of the remaining patients, 39 (21%) and 61 (34%) were on a second or additional ARV regimen, respectively. An undetectable viral load was documented in 47/62 (76%) patients on their first regimen who reported missing medication on less than 4 days in the last 3 months. The PMAQ had a higher predictive value of plasma viral suppression for patients in the initial regimen than for patients in salvage therapy. The overall predictive value of the PMAQ to identify adherence was 74%, and 59% for nonadherence, with an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the concept of antiretroviral therapy, 80% were failing or had previously failed the ARV treatment. Of 35 patients with doubts about their HIV status or skeptical of the benefits of ARV therapy, 29 (84%) were nonadherent. Despite the positive predictive value of PMAQ in identifying adherence, self-reported adherence is not a sufficiently precise predictor of treatment success to substitute for viral load monitoring. On the other hand, the use of such an instrument to identify factors associated with nonadherence provides an excellent opportunity to apply early intervention designed to specifically address factors that might be contributing to the lack of adherence prior to regimen failure.

Adolescent↗

PubMed2003

Age and temporal trends of total physical activity in Swedish men.

INTRODUCTION/PURPOSE: Despite a large public health interest in physical activity and its role in obesity and other chronic diseases, only few reports to date have addressed total levels and trends of physical activity. We have studied in a cross-sectional setting with a retrospective recall of physical activity an association of levels of total physical activity and different types of activities with age and with calendar-time. METHODS: In a population-based study of 33,466 men aged 45-79 yr in central Sweden, information on physical activity and other lifestyle factors was collected through a self-administered questionnaire. Level of total activity at ages 15, 30, and 50 yr was assessed quantitatively, based on six questions on different activities: work/occupation, housework, walking/bicycling, exercise, inactive leisure time, and sleeping. The physical activity levels were measured as metabolic equivalents, MET-hours per days. RESULTS: Total daily physical activity decreased at age 30 yr (-1.6%, 95% CI: -1.7, -1.4) and at age 50 yr (-3.9%, 95% CI: -4.0, -3.7) compared with age 15 yr. Total physical activity decreased over a period of 60 yr in all three separate age groups (-9.1% among 15-yr-olds, 95% CI: -9.8, -8.5; -2.3% among 30-yr-olds 95% CI: -3.0, -1.6; and -2.9% among 50-yr-olds, 95% CI: -3.4, -2.5). CONCLUSION: These negative trends in physical activity observed by age and with time might explain the trends in increasing prevalence of obesity.

Age Factors↗

PubMed2002

Modelling HIV viral rebound using non-linear mixed effects models.

Individuals infected with the human immunodeficiency virus type 1 (HIV-1) who initiate antiretroviral therapy typically experience a marked decline in concentrations of HIV-1 RNA in plasma. Often, however, viral rebound occurs within the first year of treatment and this rebound may be associated with resistance to antiretroviral therapy. For this reason, it is important to study the patterns of virological response of HIV-1 RNA to treatment. In particular, there is interest in the relationship between the lowest level of plasma HIV-1 RNA attained after initiation of therapy (nadir value) and the time until rebound. To investigate this question, we implement a simple and flexible non-linear mixed effects model for the trajectory of the HIV-1 RNA until rebound. This model is also consistent with biological insights into the effects of treatment. We also show how the problem of censoring of HIV-1 RNA values at the lower limit of assay quantification can be addressed using a multiple imputation scheme. The algorithm is simple to implement and is based on accessible software. Our application makes use of data from clinical trial 315 conducted by the AIDS Clinical Trials Group (ACTG 315). We find a strong relationship between HIV-1 RNA nadir and time to rebound, with potentially important consequences for the management of HIV-infected individuals.

Adolescent↗

PubMed2002

Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.

CONTEXT: Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge. OBJECTIVE: To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen. DESIGN: Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks. SETTING: Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States. PARTICIPANTS: A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL. INTERVENTION: Selectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n = 69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil. MAIN OUTCOME MEASURES: Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility. RESULTS: Of 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P =.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270] vs 16% [33/211], respectively; P<.001). Baseline HIV-1 hypersusceptibility to efavirenz (< or = 0.4-fold difference in susceptibility compared with reference virus) was associated with suppression of viral load at 24 weeks to below 200 copies/mL (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.62-7.33; P =.001), and more than 10-fold reduction in efavirenz susceptibility, with less likelihood of suppression at 24 weeks (OR, 0.28; 95% CI, 0.09-0.87; P =.03). CONCLUSIONS: In this study of antiretroviral-experienced patients with advanced immunodeficiency, viral load suppression to below 200 copies/mL was achieved in 31% of patients with regimens containing 4 or 5 new drugs. Use of 2 PIs, being naive to NNRTIs, and baseline hypersusceptibility to efavirenz were associated with a favorable outcome.

Adenine↗