Option Period Aims
In September 2007, the Option Period of CHARTER began. The Option Period was an opportunity to take findings from the initial study period and refine the study to focus on current areas of interest in neuroAIDS. To this end the Option Period will focus on these four major areas: host genetics, viral genetics, peripheral neuropathy, and white matter disease . In addition, we will take advantage of the CHARTER infrastructure and population to begin characterizing the effects of newly emerging ARV treatments on HAND, and to characterize the neurologic profiles of the subset of early/acute infection cases that have become available to us.
Host Genetics
- Specific Aim 1: Validation of the genetic signature associated with HAND derived during the initial period
- Specific Aim 2: To determine the association of genetic variability with longer term neurocognitive and peripheral neurological outcomes
- Specific Aim 3: To determine the pharmacogenetic associations for newer antiretrovirals
Viral Genetics
- Specific Aim 1: To determine the prevalence of HIV env mutations in CSF and plasma among participants with and without HAND at enrollment
- Specific Aim 2: To determine the impact of viral genetics on the evolution of HAND in treated and untreated HIV infected participants over 7 years of follow-up
- Service Aim: To provide an initial database of HIV env sequences that can be used as a reference for future studies aimed at defining the evolution of drug resistance in CSF virus to antiretroviral drugs that target viral binding and fusion
Peripheral Neuropathy
- Specific Aim 1: To evaluate genetic susceptibility factors that may influence the expression of DSPN and d-drug neurotoxicity in patients with HIV infection
- Specific Aim 2: To determine the potential impact on peripheral neuropathy of long term exposure to HAART and its component antiretroviral agents
Supplementary Aims
- To detect potential increases in epidermal nerve fiber densities during a lengthy period of virological control in HAART-treated subjects
- To evaluate whether lower epidermal nerve fiber densities predict the appearance of symptomatic neuropathy (SN) in those previously neuropathy-free, and worsening of SN in those with extant SN
- To determine the potential neurotoxicity of protease inhibitor (PI)-containing HAART regimens[1]
- To better define the relationship between DSPN in HIV and the metabolic syndrome, a recognized complication of HAART and perhaps of HIV infection itself
Neuroimaging
- Specific Aim 1: To assess the longitudinal relationship between volume of white matter abnormality and markers of neuroinflammation
- Specific Aim 2: To investigate the relationship over time between volumes of AbWM and WM metabolites and executive functioning performance
- Specific Aim 3: To characterize the association between cortical damage and cumulative effects of neuroinflammation in the presence of high viral load
- Specific Aim 4: To investigate the performance impact of cortical tissue loss on learning and speed of information processing
Scientific Exploratory Aims
Acute and Early Infection
- Specific Aim: To further our understanding of acute and early HIV infection, particularly the risk factors associated with the development of neurocognitive impairment
New Antiretroviral Agents
- Specific Aim 1: To determine the distribution of selected new antiretrovirals in cerebrospinal fluid (CSF)
- Specific Aim 2: To determine the effectiveness of new antiretrovirals and regimen types in reducing HIV ribonucleic acid (RNA) levels (viral load) in CSF
- Specific Aim 3: To determine the relationships between new antiretrovirals and regimen types on the neurological and neurocognitive complications of HIV
