Biomedical subjects

Abdel G Babiker

Publications and source records attributed to Abdel G Babiker.

6 recordsLinked to original sources

PubMed2004

Differences in HIV RNA levels before the initiation of antiretroviral therapy among 1864 individuals with known HIV-1 seroconversion dates.

OBJECTIVE: To assess the effects of sex, risk group, age at and year of seroconversion (SC), and presentation during acute infection on HIV RNA trends before antiretroviral therapy (ART) initiation. METHODS: Multiple HIV RNA measurements from 1864 individuals with reliably estimated dates of SC, aged >/= 15 years at SC were studied using random effects models. Models were adjusted for selective HIV RNA data truncation due to ART initiation or AIDS development and for HIV RNA quantification assay. RESULTS: HIV RNA levels declined precipitously during the first 10 months after SC followed by a slow increase. Women infected heterosexually and through injecting drug use, had an average 34% [95% confidence interval (CI), 2.3-56%] and 46% (95% CI, 17-66%) lower HIV RNA load respectively, compared to men in the same risk group. Among men, those infected heterosexually and by injecting drug use had on average 56% (95% CI, 36-69%) lower HIV RNA levels than homosexual men. Older subjects tended to have higher viral levels. There was no evidence that differences by sex, risk or age group diminished over time, but follow-up was mostly before CD4 cell count had fallen below 200 x 10 cells/l. CONCLUSIONS: HIV RNA levels at the same stage of HIV-1 infection differ significantly by sex, risk group and age at SC. Given the lack of evidence of a survival difference by sex or risk group prior to initiation of effective therapy, further research on differential effects of virus load on treatment-free disease progression is needed, before a conclusion about considering these factors for ART initiation is drawn.

Adolescent↗

PubMed2004

Interval-censored survival time data: confidence intervals for the non-parametric survivor function.

Survival data are described as interval censored when the failure time is not measured exactly but is known only to have occurred within a defined interval. In this paper, we describe and assess three methods for calculating pointwise confidence intervals for the non-parametric survivor function estimated from interval-censored data: the first based on the full information matrix, the second a modification of this approach involving deletion of rows and columns of the information matrix corresponding to zero estimates prior to inversion and the third based on likelihood ratio inference. In a simulation study the likelihood ratio method gave the most accurate confidence intervals with coverage consistently close to the nominal level of 95 per cent.

Antiviral Agents↗

PubMed2004

Parametric randomization-based methods for correcting for treatment changes in the assessment of the causal effect of treatment.

We develop parametric maximum likelihood methods to adjust for treatment changes during follow-up in order to assess the causal effect of treatment in clinical trials with time-to-event outcomes. The accelerated failure time model of Robins and Tsiatis relates each observed event time to the underlying event time that would have been observed if the control treatment had been given throughout the trial. We introduce a bivariate parametric frailty model for time to treatment change and time to trial endpoint. Estimating equations which respect the randomization are constructed and compared to maximum likelihood methods in a simulation study. The Concorde trial of immediate versus deferred zidovudine in HIV infection is used as a motivating example and illustration of the methods.

Anti-HIV Agents↗

PubMed2004

HIV drug resistance testing: is the evidence really there?

OBJECTIVES: To assess the strength of evidence supporting the routine use of HIV drug resistance testing. DESIGN: A critical review of all studies relating to the clinical utility of HIV resistance testing, with a focus on randomized trials. RESULTS: Two cohort studies found no evidence of a difference in virological response in patients who had resistance testing compared with matched controls. We identified nine published randomized trials that were specifically designed to assess the clinical utility of drug resistance testing. In a meta-analysis of these trials, resistance testing increased the proportion of patients who achieved undetectable viral load by an average of 7% (95% confidence interval: 3-11%). However, this may be an over-estimate of the impact of resistance testing in clinical practice because of the idealized design and analytical approaches used in most of the studies. CONCLUSIONS: The available evidence does not clearly demonstrate that HIV drug resistance testing is clinically effective. To optimize their value for health decision-making, future trials of HIV resistance testing should be carefully designed to mimic the circumstances of routine clinical practice.

Anti-HIV Agents↗

PubMed2002

Impact of missing data due to selective dropouts in cohort studies and clinical trials.

BACKGROUND: Many cohort studies and clinical trials use repeated measurements of laboratory markers to track disease progression and to evaluate new therapies. A major problem in the analysis of such studies is that marker data are censored in some patients owing to withdrawal, loss to follow-up, or death. The objective of this paper is to evaluate the impact of selective dropouts attributable to death or disease progression on the estimates of marker change among different groups. METHODS: Data on CD4 cell count in human immunodeficiency virus 1-infected individuals from a clinical trial and a cohort study are used to illustrate this problem and a possible solution. Simulation studies are also presented. RESULTS: When the rate of dropout is greater in subjects whose marker status is declining rapidly, commonly used methods, like random effects models, that ignore informative dropouts lead to overoptimistic statements about the marker trends in all compared groups, because subjects with steeper marker drops tend to have shorter follow-up times and hence are weighted less in the estimation of the group rate of the average marker decline. CONCLUSIONS: The potential biases attributable to incomplete data require greater recognition in longitudinal studies. Sensitivity analyses to assess the effect of dropouts are important.

Adolescent↗

PubMed2002

Evolution of antiretroviral phenotypic and genotypic drug resistance in antiretroviral-naive HIV-1-infected children treated with abacavir/lamivudine, zidovudine/lamivudine or abacavir/zidovudine, with or without nelfinavir (the PENTA 5 trial).

PURPOSE AND METHODS: To describe the evolution of resistance to zidovudine (ZDV), lamivudine (3TC), abacavir (ABC) and nelfinavir (NFV), 113 previously untreated children in the PENTA 5 trial had resistance assayed at baseline, rebound and/or 24, 48, 72 weeks (VIRCO: phenotyping and genotyping with 'Virtual Phenotype' interpretation). RESULTS: At baseline, few reverse transcriptase mutations and no primary protease inhibitor mutations were observed. Time to detectable HIV-1 RNA with reduced phenotypic susceptibility to any drug was shortest in the ZDV+3TC arm (overall logrank P=0.02). Through a median follow-up of 55 weeks, at their last assessment 11 (28%), 16 (40%) and 13 (32%) children with detectable HIV-1 RNA and a resistance test available had mutations conferring resistance to none, one, or two or more trial drugs, respectively, according to the virtual phenotype. Reduced phenotypic susceptibility to ABC only occurred in the 3TC+ABC arm and required K65R and/or L74V in addition to M184V. NFV-resistant virus was selected slowly through D30N or L90M pathways, and selection of ZDV-resistant virus was rare. CONCLUSIONS: Selection of 3TC-resistant virus was most frequent, followed by NFV and/or ABC; selection of ZDV-resistant virus was rare. Importantly, although in vitro, ABC selects for M184V as the first mutation, ABC did not select for M184V when combined with ZDV without 3TC. The most sustained HIV-1 RNA response was in the 3TC+ABC arm, but mutations conferring reduced susceptibility to 3TC and/or ABC evolved more frequently if virological failure occurred with 3TC+ABC than with ZDV+ABC.

Acquired Immunodeficiency Syndrome↗