The CHARTER Data Query Tool is a web-based utility that allows researchers to browse the clinical research data generated for the cross-sectional cohort enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study. The data for the CHARTER Data Query tool were collected during the CHARTER Study, and currently includes only data associated with each participants’ baseline, cross-sectional CHARTER visit; no longitudinal visit data is presented. The Query Tool allows researchers to browse the cross-sectional CHARTER cohort by selected variables to identify subpopulations of interest. There are 1,610 cases in the CHARTER cross-sectional cohort.
Please note the following key features of query tool:
There were three major data collections periods for the CHARTER study. During the initial study period, from 2004 - 2007 the CHARTER study’s aims were to determine how central and peripheral nervous system complications of HIV are affected by different histories and regimens of antiretroviral therapy.
To address these aims, the CHARTER study divided the study population into several substudies with common and differing assessments administered to participants within each substudy. Participants received comprehensive neuromedical, neurocognitive, and laboratory examinations, with a subset undergoing neuroimaging assessments. The specific study aims for this study period are outlined below:
CHARTER 2004 – 2007 Period Research aims:
CHARTER 2004 – 2007 Supplementary Aims:
While the above aims were seen as central in guiding CHARTER, the original protocol also envisioned a number of additional questions which might be addressed through examinations of selected subsets of participants.
The second phase of the CHARTER study began in 2007 and ended in 2010. This period focused on host genetics via SNP genotyping, viral genetics, peripheral neuropathy, and neuroimaging. Two exploratory aims were investigated during this period. Firstly, a subset of the original CHARTER participant population was identified for follow up in this period in the CHARTER Acute and Early Infection Substudy. These participants were well-characterized to understand the risk factors associated with the development of neurocognitive impairment. Secondly, the period from 2007 – 2010 sought to explore the relationship between new antiretroviral regimens and the development of HIV associated neurological complications. The specific aims of each element of this study are outlined below:
CHARTER 2007 – 2010 Period Research aims:
Host genetics research aims:
Viral genetics research aims:
Peripheral neuropathy research aims:
Neuroimaging research aims:
Additional research aims:
The final phase of CHARTER data collection ran from September, 2010 – 2015. This period further refined the goals of the CHARTER study by focusing on extended follow-up of a select subset of participants. The goal of this period was to examine the effects of low-level viral replication in the CNS, predictors of neurocognitive and neuroimaging worsening, and the reversibility of nerve injury in the context of antiretroviral therapy. The specific aims and hypotheses are outlined below:
CHARTER 2010 – 2015 Period Research aims:
In order to have a broad representation of participant characteristics, CHARTER was conducted at six performance sites nationally whose activities were coordinated by the University of California San Diego (UCSD), the principal grantee institution. The central data was curated by several technical, scientific, and administrative cores working cooperatively at UCSD. The six sites for clinical data collection were located at UCSD, University of Washington, Washington University in St. Louis, Icahn School of Medicine, Johns Hopkins University, and University of Texas Medical Branch.
Subject recruitment began in September, 2003 at the six clinical data collection sites, and concluded in August, 2007. The study population was recruited with minimal exclusion criteria. Of the 2,016 potential participants who were screened for the study, 1,610 (79.9%) elected to participate in at least the cross-sectional portion of the study, with 723 recruiting from the cross-sectional sample into the longitudinal study. The subjects were recruited from the screening interview into the cross-sectional sample with few exclusion criteria. The main mechanism driving failure to recruit into the cross-sectional sample was self-selection out by screened participants who elected not to continue. In around 2% of cases, screened participants were not asked to continue into the cross-sectional sample because their screening interviewer doubted their ability to participate (e.g. when the screener felt they had the potential to be dangerous).
The use of minimal exclusion criteria was in an effort to broadly represent the population of HIV-positive patients being followed in the site’s university based clinics, and thus care should be taken when generalizing the results outside of this setting. The CHARTER population may not be reflective of the HIV-positive population being served in other clinical settings or of the population who elect not to volunteer for research studies.
Participants were recruited into the CHARTER Cross-Sectional study from the screening interview. These participants completed a standardized set of Cross-Sectional study assessments at their baseline visit. This section outlines participant recruitment into the Cross-Sectional study and the Cross-Sectional neuromedical and neurobehavioral assessments performed.
Approximately 1,608 HIV-infected participants were enrolled into the CHARTER Cross-Sectional study during the period from 2003 – 2007. Participants were recruited from six participating university centers whose activities were coordinated by the University of California San Diego (UCSD), the principal grantee institution. The central data was curated by several technical, scientific, and administrative cores working cooperatively at UCSD. The number of participants recruited from each of the six participating clinical sites is summarized below:
Of the 2,016 potential participants who were screened for the study, 1,608 (~80%) elected to participate in at least the Cross-Sectional portion of the study. The participants recruited into CHARTER were at varying stages of disease and reported differing histories of antiretroviral treatment. CHARTER Cross-Sectional participants were recruited with relatively few exclusion criteria in an effort to broadly represent the population of HIV-positive patients being followed in the site’s university based clinics.
The subjects were recruited from the screening interview into the Cross-Sectional sample with relatively few exclusion criteria. The main mechanism driving failure to recruit into the cross-sectional sample was self-selection out by screened participants who elected not to continue. In around 2% of cases, screened participants were not asked to continue into the cross-sectional sample because their screening interviewer doubted their ability to participate (e.g. when the screener felt they had the potential to be dangerous).
The use of minimal exclusion criteria was in an effort to broadly represent the population of HIV-positive patients being followed in the site’s university based clinics, and thus care should be taken when generalizing results derived from CHARTER to populations outside the scope of this study. The CHARTER population may not be reflective of the HIV-positive population being served in other clinical settings or of the population who elect not to volunteer for research studies.
The likelihood of new neurocognitive complications, remission of such complications, or fluctuating patterns of complications were hypothesized to be related to several key variables. These variables include whether or not virus is suppressed in the CSF compartment, whether or not the individual is currently on treatment, the history of past treatment, and whether or not a particular neurological complication has already occurred. To determine the importance of these influences on changes in neurocognitive and neurological complications, CHARTER enrolled a subset of participants from the Cross-Sectional cohort in the Longitudinal ARV Substudy.
The CHARTER Longitudinal ARV substudy cohort consists of individuals characterized by the following variables:
It was anticipated that careful six monthly observation of this cohort would reveal the degree to which HAART history and viral suppression predict near future onset of neurological complications; and secondly, would shed light on some of the intermediate steps in this link, for example, evolution of resistant virus in the CSF compartment.
Metabolic disorders such as lipoatrophy and centripetal fat re-distribution, elevated blood cholesterol and triglyceride levels (dyslipidemias), and insulin resistance (diabetes and impaired glucose tolerance) are commonly induced by HAART, but their impact on the CNS not been assessed systematically. Patients in the HAART era appear to have reduced rates of more severe cognitive deterioration. However, epidemiologic data showing the continuing incidence and prevalence of cognitive problems in HAART-treated patients raises concern about the possibility that HAART has protective effects through its antiviral effects, but is also toxic for the CNS in some patients. The primary aim was to relate lipoatrophy indicators to manifestations of HIV-associated neurocognitive dysfunction HAND and peripheral neuropathy.
Exposure to ARV regimens containing d-drugs ddC (zalcitabine, Hivid), ddI (didanosine, Videx EC) and d4T (stavudine, Zerit) is known to cause or contribute to peripheral neuropathy in some cases; however it is unclear how specific drugs, duration of exposure, and recency of exposure interact with individual characteristics as risk factors for developing distal sensory-predominant polyneuropathy (DSPN).
During the initial study period from 2004 – 2007, the CHARTER Longitudinal Peripheral Neuropathy Substudy was focused on understanding the short-term neurotoxic impact of ARV regimens containing d-drugs on distal sensory polyneuropathy. To this end, the Longitudinal Peripheral Neuropathy Substudy enrolled participants into three subgroups:
Severity of neuropathy was characterized according to the Total Neuropathy Score, including nerve conduction studies and quantitative sensory testing. Serum lactate levels were measured as a marker of mitochondrial dysfunction to investigate whether changes in lactate levels correlate with stabilization or improvement in neuropathy as measured by the Total Neuropathy Score.
During the study period from 2007 – 2015, the goals of the Longitudinal Peripheral Neuropathy Substudy were revised to emphasize the influence of long term antiretroviral drug exposure and genetic risk factors on the pathogenesis of neuropathy. To improve earlier ascertainment and longitudinal monitoring of nerve injury, intraepidermal nerve fiber (IENF) layer assessments (skin biopsies) were added to the CHARTER Longitudinal Peripheral Neuropathy substudy battery and performed from 2007 – 2010. The IENF technique, developed and validated over the past 5 to 10 years, provides a more direct measure of cutaneous innervation than clinical examinations or electrophysiological testing.
HIV penetrates the central nervous system shortly after infection, which may result in neurocognitive impairment in individuals who are otherwise in a physically “asymptomatic” phase of illness. The timing, characteristics, features and factors affecting the risk of neurocognitive impairment, and these factors’ relationship to antiretroviral therapy remain unclear. The goal of the Acute and Early Infection Substudy enrolled participants who were identified as either Acute or Early in their HIV infection, defined as those whose duration of infection was less than or equal to one year. These participants were enrolled into the Acute and Early Infection Substudy starting in 2007 and underwent the neuromedical and neurobehavioral protocols outlined below.