Christina M Marra

University of Washington Seattle, Seattle, Washington, United States

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Publications (141)918.15 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We reviewed 68 cases of possible neurosyphilis among 573 syphilis cases in King County, WA, from 3rd January 2012 to 30th September 2013; 7.9% (95% confidence interval, 5.8%-10.5%) had vision or hearing changes, and 3.5% (95% confidence interval, 2.2%-5.4%) had both symptoms and objective confirmation of complicated syphilis with either abnormal cerebrospinal fluid or an abnormal ophthalmologic examination.
    Sexually transmitted diseases 11/2015; 42(12):702-704. DOI:10.1097/OLQ.0000000000000368 · 2.84 Impact Factor
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    ABSTRACT: Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n = 272, mean duration 17.9 months) or LPV/r (n = 173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be taking their first ART regimen (p < 0.001), were less likely to have AIDS (p < 0.001) or hepatitis C virus (HCV) coinfection (p < 0.05), had higher CD4+ T cell nadirs (p < 0.001), had lower peak (p < 0.001) and current (p < 0.001) plasma HIV RNA levels, and were less likely to have detectable HIV RNA in cerebrospinal fluid (CSF) (p < 0.001). Overall, EFV users had worse speed of information processing (p = 0.04), verbal fluency (p = 0.03), and working memory (p = 0.03). An interaction with HCV serostatus was present: Overall among HCV seronegatives (n = 329), EFV users performed poorly, whereas among HCV seropositives (n = 116), LPV/r users had overall worse performance. In the subgroup with undetectable plasma HIV RNA (n = 269), EFV users had worse speed of information processing (p = 0.02) and executive functioning (p = 0.03). Substantial differences exist between EFV and LPV/r users in this observational cohort, possibly because of channeling by clinicians who may have prescribed LPV/r to more severely ill patients or as second-line therapy. Despite these differences, EFV users had worse functioning in several cognitive abilities. A potentially important interaction was identified that could indicate that the NC consequences of specific antiretroviral drugs may differ based on HCV coinfection. The complexity of these data is substantial, and findings would best be confirmed in a randomized clinical trial.
    Journal of NeuroVirology 09/2015; DOI:10.1007/s13365-015-0382-7 · 2.60 Impact Factor
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    ABSTRACT: Background: Neurocognitive impairment (NCI) remains an important complication in persons infected with human immunodeficiency virus (HIV). Ancestry-related mitochondrial DNA (mtDNA) haplogroups have been associated with outcomes of HIV infection and combination antiretroviral therapy (CART), and with neurodegenerative diseases. We hypothesize that mtDNA haplogroups are associated with NCI in HIV-infected adults and performed a genetic association study in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Methods: CHARTER is an observational study of ambulatory HIV-infected adults. Haplogroups were assigned using mtDNA sequence, and principal components were derived from ancestry-informative nuclear DNA variants. Outcomes were cross-sectional global deficit score (GDS) as a continuous measure, GDS impairment (GDS ≥ 0.50), and HIV-associated neurocognitive disorder (HAND) using international criteria. Multivariable models were adjusted for comorbidity status (incidental vs contributing), current CART, plasma HIV RNA, reading ability, and CD4 cell nadir. Results: Haplogroups were available from 1027 persons; median age 43 years, median CD4 nadir 178 cells/mm(3), 72% on CART, and 46% with HAND. The 102 (9.9%) persons of genetically determined admixed Hispanic ancestry had more impairment by GDS or HAND than persons of European or African ancestry (P < .001 for all). In multivariate models including persons of admixed Hispanic ancestry, those with haplogroup B had lower GDS (β = -0.34; P = .008) and less GDS impairment (odds ratio = 0.16; 95% confidence interval, .04, .63; P = .009) than other haplogroups. There were no significant haplogroup associations among persons of European or African ancestry. Conclusions: In these mostly CART-treated persons, mtDNA haplogroup B was associated with less NCI among persons of genetically determined Hispanic ancestry. mtDNA variation may represent an ancestry-specific factor influencing NCI in HIV-infected persons.
    Clinical Infectious Diseases 06/2015; DOI:10.1093/cid/civ527 · 8.89 Impact Factor
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    ABSTRACT: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R 2 0.179, p
    Journal of NeuroVirology 06/2015; 21(5). DOI:10.1007/s13365-015-0359-6 · 2.60 Impact Factor
  • Christina M Marra ·
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    ABSTRACT: The current prevalence of cognitive impairment in HIV-infected individuals is surprisingly high, even in those with undetectable plasma HIV RNA. The etiology is unknown, but one possibility is inadequate control of persistent central nervous system (CNS) HIV infection. The CNS Penetration Effectiveness (CPE) rank has been proposed to predict how well an ARV regimen treats CNS infection. Fabbiani and colleagues report that "correcting" the CPE rank of each drug in an individual's regimen for the results of genotypic susceptibility (the CPE-GSS score) results in better ability to predict whether the regimen will improve cognition. The CPE-GSS score may help us better understand the etiology of HIV-associated cognitive impairment. Whether it will be useful in the management of individual patients requires further study.
    Antiviral therapy 03/2015; 20(4). DOI:10.3851/IMP2951 · 3.02 Impact Factor
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    ABSTRACT: Despite modern combination antiretroviral therapy (CART), distal neuropathic pain (DNP) continues to affect many individuals with HIV infection. We evaluated risk factors for new onset DNP in the CNS Antiretroviral Therapy Effects Research (CHARTER) study, an observational cohort. Standardized, semi-annual clinical evaluations were administered at six U.S. sites. DNP was defined by using a clinician-administered instrument standardized across sites. All participants analyzed were free of DNP at study entry. New onset DNP was recorded at the first follow-up visit at which it was reported. Mixed effects logistic regression was used to evaluate potential predictors including HIV disease and treatment factors, demographics, medical comorbidities and neuropsychiatric factors. Among 493 participants, 131 (27%) reported new DNP over 2,306 visits during a median follow-up of 24 months [interquartile range (IQR) 12-42]. In multivariable regression, after adjusting for other covariates, significant entry predictors of new DNP were older age, female sex, current and past antiretroviral treatment, lack of virologic suppression, and lifetime history of opioid use disorder. During follow-up, more severe depression symptoms conferred a significantly elevated risk. The associations with opioid use disorders and depression reinforce the view that the clinical expression of neuropathic pain with peripheral nerve disease is strongly influenced by neuropsychiatric factors. Delineating such risk factors might help target emerging preventive strategies, for example, to individuals with a prior history of opioid use disorder, or might lead to new treatment approaches such as the use of tools to ameliorate depressed mood.
    Pain 02/2015; 156(4). DOI:10.1097/ · 5.21 Impact Factor

  • Clinical Infectious Diseases 02/2015; 60(9). DOI:10.1093/cid/civ045 · 8.89 Impact Factor
  • Emily L Ho · Lauren C Tantalo · Trudy Jones · Sharon K Sahi · Christina M Marra ·
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    ABSTRACT: The laboratory diagnosis of neurosyphilis rests upon identifying cerebrospinal fluid (CSF) abnormalities, including CSF-Venereal Disease Research Laboratory (VDRL) reactivity. The CSF-VDRL may not be available in the parts of the world where neurosyphilis is most common. Treponemal immunochromatographic strip tests (ICSTs) have been developed as point-of-care tests on blood for syphilis diagnosis in resource-limited settings. We optimized 3 commercial ICSTs for performance on CSF and tested CSF samples from 217 patients with syphilis. The Syphicheck-WB test (Qualpro Diagnostics, Goa, India; "Syphicheck") was chosen for further study based on agreement with CSF-VDRL test results. We determined CSF-Syphicheck titers for 152 samples. We modified the CSF-Syphicheck for point-of-care testing in a US sexually transmitted diseases clinic and compared results on 102 paired centrifuged and uncentrifuged CSF samples obtained in the laboratory to the results obtained at point of care; results of samples diluted 1:4 were compared in a subset. The diagnostic sensitivity of a reactive CSF-Syphicheck (62%-64%) and the diagnostic specificity of a CSF-Syphicheck titer at or above 1:4 (79%-81%) were equivalent to the CSF-VDRL (54%-69% sensitivity, 73%-75% specificity) for laboratory and clinical neurosyphilis diagnoses. The CSF-Syphicheck normalized after neurosyphilis therapy similarly to the CSF-VDRL. The modified CSF-Syphicheck performed well at the point of care, albeit with better performance on cell-free compared with uncentrifuged CSF. Cerebrospinal fluid treponemal ICSTs hold promise for point-of-care neurosyphilis diagnosis in regions where the CSF-VDRL is not available. Further study should address the performance of CSF ICSTs in resource-limited settings.
    Sex Transm Dis 01/2015; 42(1):48-52. DOI:10.1097/OLQ.0000000000000222 · 2.84 Impact Factor
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    ABSTRACT: To investigate the effect of hepatitis C virus (HCV) on neurocognitive performance in chronically HIV-infected patients enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study. A total of 1,582 participants in CHARTER who were tested for HCV antibody underwent neurocognitive testing; serum HCV RNA was available for 346 seropositive patients. Neurocognitive performance was compared in 408 HCV-seropositive and 1,174 HCV-seronegative participants and in a subset of 160 seropositive and 707 seronegative participants without serious comorbid neurologic conditions that might impair neurocognitive performance, using linear regression and taking into account HIV-associated and demographic factors (including IV drug use) and liver function. Neurocognitive performance characterized by global deficit scores and the proportion of individuals who were impaired were the same in the HCV-seropositive and HCV-seronegative groups. In univariable analyses in the entire sample, only verbal domain scores showed small statistically different superior performance in the HCV+ group that was not evident in multivariable analysis. In the subgroup without significant comorbidities, scores in all 7 domains of neurocognitive functioning did not differ by HCV serostatus. Among the HCV-seropositive participants, there was no association between neurocognitive performance and serum HCV RNA concentration. In HIV-infected patients, HCV coinfection does not contribute to neurocognitive impairment, at least in the absence of substantial HCV-associated liver damage, which was not evident in our cohort. © 2014 American Academy of Neurology.
    Neurology 12/2014; 84(3). DOI:10.1212/WNL.0000000000001156 · 8.29 Impact Factor
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    ABSTRACT: We tested our hypothesis that abdominal obesity when associated with increased levels of systemic and CNS immuno-inflammatory mediators contributes to neurocognitive impairment (NCI). Cross-sectional SETTING:: Six Academic Centers PARTICIPANTS:: 152 patients with plasma HIV RNA <1,000copies/ml had clinical evaluations and cognitive function quantified by global deficit scores (GDS). GDS, waist circumference (WC) and plasma IL-6, sCD163, and sCD14 and CSF sCD40L, sTNFrII, MCP-1, sICAM, and MMP-9. WC and plasma IL-6 levels positively correlated with GDS; the WC correlation was strongest in the high tertile of IL-6 (rho=0.39, p=0.005). IL-6 correlated with GDS only if WC was ≥99cm. In the high tertile of CSF sCD40L, a biomarker of macrophage and microglial activation, the correlation of IL-6 to GDS was strongest (rho=0.60, p<0.0001). Across 3-5 visits within ±1year of the index visit, GDS remained worse in patients with IL-6 levels in the high-versus-low tertile (p=0.02). Path analysis to explore potential mediators of NCI produced a strong, integrated model for patients in the high CSF sCD40L tertile. In this model, WC affected GDS both directly and via a second path that was mediated by IL-6. Inclusion of plasma sCD14 levels strengthened the model. NCI was more common in men and for individuals with components of the metabolic syndrome. NC function was significantly linked to abdominal obesity, systemic inflammation (high IL-6), and immune activation in plasma (high sCD14) and CSF (high sCD40L). Abdominal obesity, inflammation, and CNS immune activation are potential therapeutic targets for NCI in HIV+ patients.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2014; 68(3). DOI:10.1097/QAI.0000000000000458 · 4.56 Impact Factor
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    ABSTRACT: Rates of depression are high among individuals living with HIV. Accurate assessment of depressive symptoms among this population is important for ensuring proper diagnosis and treatment. The Beck Depression Inventory-II (BDI-II) is a widely used measure for assessing depression, however its psychometric properties have not yet been investigated for use with HIV-positive populations in the United States. The current study was the first to assess the psychometric properties of the BDI-II among a large cohort of HIV-positive participants sampled at multiple sites across the United States as part of the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study. The BDI-II test scores showed good internal consistency (α = .93) and adequate test-retest reliability (internal consistency coefficient = 0.83) over a 6-mo period. Using a "gold standard" of major depressive disorder determined by the Composite International Diagnostic Interview, sensitivity and specificity were maximized at a total cut-off score of 17 and a receiver operating characteristic analysis confirmed that the BDI-II is an adequate diagnostic measure for the sample (area under the curve = 0.83). The sensitivity and specificity of each score are provided graphically. Confirmatory factor analyses confirmed the best fit for a three-factor model over one-factor and two-factor models and models with a higher-order factor included. The results suggest that the BDI-II is an adequate measure for assessing depressive symptoms among U.S. HIV-positive patients. Cut-off scores should be adjusted to enhance sensitivity or specificity as needed and the measure can be differentiated into cognitive, affective, and somatic depressive symptoms. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Psychological Assessment 11/2014; 27(2). DOI:10.1037/pas0000040 · 2.99 Impact Factor
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    ABSTRACT: Background: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods: We investigated the incidence and predictors of NC change over 16-72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results: Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions: NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.
    Clinical Infectious Diseases 10/2014; 60(3). DOI:10.1093/cid/ciu862 · 8.89 Impact Factor
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    ABSTRACT: Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multisite CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort, cross-sectional study of 222 HIV-infected individuals. Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Greater BMI was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction.
    Journal of NeuroVirology 09/2014; 20(6). DOI:10.1007/s13365-014-0284-0 · 2.60 Impact Factor
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    ABSTRACT: HIV sensory neuropathy and distal neuropathic pain (DNP) are common, disabling complications associated with combination antiretroviral therapy (cART). We previously associated iron-regulatory genetic polymorphisms with a reduced risk of HIV sensory neuropathy during more neurotoxic types of cART. We here evaluated the impact of polymorphisms in 19 iron-regulatory genes on DNP in 560 HIV-infected subjects from a prospective, observational study, who underwent neurological examinations to ascertain peripheral neuropathy and structured interviews to ascertain DNP. Genotype-DNP associations were explored by logistic regression and permutation-based analytical methods. Among 559 evaluable subjects, 331 (59%) developed HIV-SN, and 168 (30%) reported DNP. Fifteen polymorphisms in 8 genes (p<0.05) and 5 variants in 4 genes (p<0.01) were nominally associated with DNP: polymorphisms in TF, TFRC, BMP6, ACO1, SLC11A2, and FXN conferred reduced risk (adjusted odds ratios [ORs] ranging from 0.2 to 0.7, all p<0.05); other variants in TF, CP, ACO1, BMP6, and B2M conferred increased risk (ORs ranging from 1.3 to 3.1, all p<0.05). Risks associated with some variants were statistically significant either in black or white subgroups but were consistent in direction. ACO1 rs2026739 remained significantly associated with DNP in whites (permutation p<0.0001) after correction for multiple tests. Several of the same iron-regulatory-gene polymorphisms, including ACO1 rs2026739, were also associated with severity of DNP (all p<0.05). Common polymorphisms in iron-management genes are associated with DNP and with DNP severity in HIV-infected persons receiving cART. Consistent risk estimates across population subgroups and persistence of the ACO1 rs2026739 association after adjustment for multiple testing suggest that genetic variation in iron-regulation and transport modulates susceptibility to DNP.
    PLoS ONE 08/2014; 9(8):e103123. DOI:10.1371/journal.pone.0103123 · 3.23 Impact Factor
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    ABSTRACT: Background: Single-nucleotide polymorphisms (SNPs) in toll-like receptors (TLR) 1, 2, and 6 impair cell signaling in response to spirochetal lipoproteins. We investigated whether common SNPs in TLR1, TLR2, or TLR6 were associated with laboratory- or clinically-defined neurosyphilis. Methods: Polymorphisms in the genes for TLR1 (a T→G mutation at position 1805), TLR2 (a G→A mutation at position 2258), and TLR6 (a C→T mutation at position 745) were sought in 456 white patients with syphilis. Laboratory-defined neurosyphilis included a reactive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) test. Clinically-defined neurosyphilis included new vision or hearing loss. Controls had CSF white blood cells of 5/μL or less, nonreactive CSF-Venereal Disease Research Laboratory, and no vision or hearing loss. Results: Overall, 26.2% of patients had laboratory-defined and 36.2% had clinically-defined neurosyphilis. Compared with controls, patients with any of the 3 SNPs were more likely to have laboratory-defined neurosyphilis. Those with TLR2 or TLR6 SNPs were more likely to have clinically-defined neurosyphilis. These associations were independent of serum rapid plasma reagin titer. Conclusions: A common TLR1 polymorphism is associated with an increased risk of laboratory-defined neurosyphilis, and common TLR2 and TLR6 polymorphisms are associated with an increased risk of both laboratory- and clinically-defined neurosyphilis. These data suggest that host factors impact the natural history of syphilis.
    Sex Transm Dis 07/2014; 41(7):440-446. DOI:10.1097/OLQ.0000000000000149 · 2.84 Impact Factor
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    ABSTRACT: Detectable human immunodeficiency virus (HIV) RNA in the cerebrospinal fluid (CSF) is associated with central nervous system (CNS) complications. We developed the CSF HIV risk score through prediction modeling to estimate the risk of detectable CSF HIV RNA (threshold >50 copies/mL) to help identify persons who might benefit most from CSF monitoring. We used baseline data from 1,053 participants receiving combination antiretroviral therapy who were enrolled in the 6-center, US-based CNS HIV Antiretroviral Therapy Effects Research (CHARTER) prospective cohort in 2004-2007. Plasma HIV RNA, CNS penetration effectiveness, duration of combination antiretroviral therapy, medication adherence, race, and depression status were retained correlates of CSF HIV RNA, displaying good discrimination (C statistic = 0.90, 95% confidence interval (CI): 0.87, 0.93) and calibration (Hosmer-Lemeshow P = 0.85). The CSF HIV risk score ranges from 0 to 42 points, with a mean of 15.4 (standard deviation, 7.3) points. At risk scores greater than 25, the probability of detecting CSF HIV RNA was at least 42.9% (95% CI: 36.6, 49.6). For each 1-point increase, the odds of detecting CSF HIV RNA increased by 26% (odds ratio = 1.26, 95% CI: 1.21, 1.31; P < 0.01). The risk score correlates with detection of CSF HIV RNA. It represents an advance in HIV management and monitoring of CNS effects, providing a potentially useful tool for clinicians.
    American Journal of Epidemiology 06/2014; 180(3). DOI:10.1093/aje/kwu098 · 5.23 Impact Factor
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    ABSTRACT: Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50 % of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling, and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Anti-Retroviral Treatment Effects Research Study, CHARTER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (r = -0.24; p = 0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance.
    Journal of NeuroVirology 06/2014; 20(3). DOI:10.1007/s13365-014-0236-8 · 2.60 Impact Factor
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    ABSTRACT: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline). A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n = 226) or had ANI (n = 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD4+ T-lymphocyte count (CD4), virologic suppression, CART, and mood. The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p = 0.02) for SR, 5.8 (CI 3.2-10.7; p < 0.0001) for PB, and 3.2 (CI 2.0-5.0; p < 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not. This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.
    Neurology 05/2014; 82(23). DOI:10.1212/WNL.0000000000000492 · 8.29 Impact Factor
  • Christina M. Marra ·

    Headache The Journal of Head and Face Pain 05/2014; 54(5). DOI:10.1111/head.12355 · 2.71 Impact Factor
  • Emily L Ho · Christina M Marra ·
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    ABSTRACT: With the widespread use of combination antiretroviral therapy (cART), the incidence of central nervous system (CNS) opportunistic infections and coinfections has significantly decreased. This review focuses on the clinical presentation, diagnostic laboratory and radiologic findings, as well as the treatment of neurosyphilis, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and toxoplasmosis, which are CNS opportunistic infections and coinfections that are most relevant to clinicians in North America.
    Seminars in Neurology 02/2014; 34(1):61-9. DOI:10.1055/s-0034-1372343 · 1.79 Impact Factor

Publication Stats

7k Citations
918.15 Total Impact Points


  • 1991-2015
    • University of Washington Seattle
      • • Department of Neurology
      • • Department of Medicine
      Seattle, Washington, United States
  • 2014
    • Swedish Medical Center Seattle
      Seattle, Washington, United States
  • 1992-2014
    • Johns Hopkins University
      • Department of Neurology
      Baltimore, Maryland, United States
  • 2011
    • Mount Sinai School of Medicine
      • Department of Neurology
      Manhattan, New York, United States
  • 2010
    • University of California, San Diego
      • Department of Neurosciences
      San Diego, California, United States
  • 2002-2009
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2002-2008
    • Washington University in St. Louis
      • Department of Neurology
      San Luis, Missouri, United States
  • 1999
    • University of Texas Medical Branch at Galveston
      Galveston, Texas, United States