Papers by Christopher Ferraris
Aids Research and Therapy, Sep 13, 2023
Background Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequen... more Background Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA. Methods Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome. Of 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227-661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150-247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch;%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H). Conclusion TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.
Journal of acquired immune deficiency syndromes, Jun 21, 2024
Journal of the International Neuropsychological Society, Oct 31, 2023
Discriminability (z=-0.44). SRT (z=-0.70), CRT Accuracy (z=-1.37), TMT-B (z=-0.79), HVLT-R Total ... more Discriminability (z=-0.44). SRT (z=-0.70), CRT Accuracy (z=-1.37), TMT-B (z=-0.79), HVLT-R Total Recall and Percent Retained (z's=-0.88), and Delayed Recall and True Positives (z's=-1.27) were low average. Conclusions: In this sample of pre-surgical bariatric candidates with average intelligence, baseline evaluations revealed mild deficits in reaction time accuracy, visual motoric setshifting, and verbal learning/memory. These deficits may be the result of microvascular changes in the brain secondary to physical compromise. Results provide additional insight into potential early-onset executive dysfunction, psychomotor slowing, and verbal learning/memory difficulties. In addition to these relative areas of neuropsychological weakness, candidates demonstrated relative strengths in attention, working memory, and visuospatial functioning. These insights provide pre-surgical evaluators with additional information to tailor recommendations and treatment approaches that foster surgical success. With a remote, concise, easy-to-administer battery of tests, routine neuropsychological assessment for bariatric surgery candidates is both a feasible and a useful tool for identifying areas of cognitive strengths and weaknesses. Documenting a patients' cognitive baseline can assist with monitoring long-term vascular riskfactors and potential cognitive impairment.
Journal of the International Neuropsychological Society, Oct 31, 2023
lower scores would be associated with a higher likelihood of a feigned ADHD presentation. Other M... more lower scores would be associated with a higher likelihood of a feigned ADHD presentation. Other MMPI-2-RF validity scales of interest included F-r, Fs, Fp-r, FBS-r, and RBS. The established MMPI-2-RF validity scales were significantly correlated with PVT group membership, but correlations were weak to moderately strong (rS ranged from -.43 to -.18; ps < .05). A series of stepwise regression models were completed with the Ds-ADHD scale and one of the MMPI-2-RF validity scales as independent variables, with group membership as the dependent variable. Ds-ADHD contributed uniquely to each model ( ranged from .03 to .04, ps < .05). The established MMPI-2-RF validity scales effectively classified group membership (AUC values ranged from .57 to .68), and the Ds-ADHD scale had a marginally higher AUC (.69); however, it was not statistically significantly stronger than any of the established scales (ps > .05). Conclusions: Clinicians interested in identifying potentially simulated ADHD presentations with the MMPI-2-RF may desire to calculate the Ds-ADHD scale, which previously only had support from a simulator-based study. The Ds-ADHD scale significantly contributed to each model, suggesting that it helped explain groups over and above each of the traditional MMPI-2-RF validity scales. However, it only had a marginally stronger ability to classify participants, indicating that there may be diminishing returns for clinicians. Among the traditional validity scales, RBS and F-r best classified groups, and FBS-r was the least effective. This study employed a cross-sectional design in a mixed sample of Veterans undergoing a neuropsychological evaluation. Future research should focus on replicating the findings using a credible sample that was limited to an independently verified diagnosis of ADHD.
Journal of the International Neuropsychological Society, Oct 31, 2023
The autocorrelation between t-scores for task scores within each participant was computed and the... more The autocorrelation between t-scores for task scores within each participant was computed and then compared between control and outpatient participants to determine if there are differences between groups. Group mean t-scores for each task were also compared between groups. Results: We found no significant difference in autocorrelations across MCCB tasks between healthy comparison participants and outpatients. However, mean performance in all tasks was lower for the outpatient group than for the healthy comparison group. None of the tasks used stood out as having significantly lower mean scores than other tasks for either group. Conclusions: Our findings suggest that performance on individual MCCB tasks do not affect performance throughout the battery differently between the healthy comparison group and outpatients. This suggests that participants with schizophrenia are not particularly reactive to past performance on MCCB tasks. Additionally, this finding further supports use of the MCCB in this population. Further research is needed to determine whether subgroups of patients and/or different batteries of measures show different patterns of reactivity.
TMS Proceedings 2021, May 12, 2022
Open Forum Infectious Diseases, Nov 1, 2021
COVID-19, but negatively correlated with viral loads (Fig 1). MIS-C showed stronger inflammatory ... more COVID-19, but negatively correlated with viral loads (Fig 1). MIS-C showed stronger inflammatory response than acute COVID-19 (Fig 2). Correlation of Age-adjusted cytokine expression values with viral load, disease severity, CRP and D-dimer. Pearson correlation coefficient is shown for each pair. Red: positive correlation; blue: negative correlation Cytokines that differentiate MIS-C from acute COVID-19 Heatmap shows the differential expressed cytokines between MIS-C and acute severe COVID-19 (padj<0.05, FC>2). The age-adjusted expression values are normalized the median of healthy controls. Red: up-regulation, blue: down-regulation. Conclusion. We identified three cytokine clusters in children with COVID-19 according to clinical presentations. Correlations of serum cytokines with clinical/laboratory parameters could be used to identify potential biomarkers associated with disease severity in COVID-19 Disclosures.
medRxiv (Cold Spring Harbor Laboratory), Apr 26, 2022
Acknowledgments and declarations are included on the page immediately preceding references. This ... more Acknowledgments and declarations are included on the page immediately preceding references. This is the original version of the following article and has not undergone peer-review. This preprint may differ from the authoritative version published subsequently. .
medRxiv (Cold Spring Harbor Laboratory), Apr 28, 2022
Acknowledgments and declarations are included on the page immediately preceding references. This ... more Acknowledgments and declarations are included on the page immediately preceding references. This is the original version of the following article and has not undergone peer-review. This preprint may differ from the authoritative version published subsequently. .
Aids and Behavior, Apr 12, 2023
JAIDS Journal of Acquired Immune Deficiency Syndromes
Background: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DB... more Background: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART. Setting: Four primary health clinics in Cape Town, South Africa. Methods: We enrolled 250 virally suppressed PWH receiving tenofovir-based ART. We collected EA data, monthly viral load, and TFV-DP in DBS for 12 months. We used logistic regression to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CIs) for future viral breakthrough (VB) (>400 copies/mL) for each adherence measure. Receiver operating characteristics (ROCs) provided the predictive power of these measures. Results: Participants had a median (IQR) age of 34 (27–42); 78% were women. Twenty-one (8%) developed VB. Logistic regression showed that when percent EA and TFV-DP concentrations increased, the odds of VB decreased. Th...
Schizophrenia Research: Cognition
Host genetic factors may modify the risk of developing HIV-associated neurocognitive impairment (... more Host genetic factors may modify the risk of developing HIV-associated neurocognitive impairment (HIV-NCI), and genetic research has the potential to inform novel treatments for HIV-NCI. However, there is a need to better understand the acceptability of genetic testing among distinct populations of people living with HIV at increased risk for HIV-NCI, such as young people living with perinatally-acquired HIV (PHIV) in low- and middle-income countries (LMICs), to gauge the feasibility of genetic research within these populations. This pilot study evaluated the acceptability and feasibility of genetic testing to assess risk of future neurocognitive problems in fifty Thai adolescents and young adults (12-24 years; Mage=19.16; 52% female) with PHIV and demographically similar HIV-negative controls. Participants completed a survey assessing acceptability of and concerns about genetic testing and were asked to provide blood samples for genetic testing. Descriptive statistics and blood draw...
BackgroundHeme oxygenase-1 (HO-1) gene promoter (GT)n dinucleotide repeat length variations may m... more BackgroundHeme oxygenase-1 (HO-1) gene promoter (GT)n dinucleotide repeat length variations may modify HIV-associated neurocognitive impairment (HIV-NCI) risk. Among adults, short HO-1 (GT)n alleles associate with greater HO-1 antioxidant enzyme inducibility and lower rates of HIV-NCI. This pilot study examined associations between HO-1 (GT)n alleles and neurocognitive outcomes in a sample of Thai youth (13-23 years) with perinatally-acquired HIV (PHIV) and demographically-matched HIV-negative controls.MethodsParticipants completed neurocognitive testing and provided blood samples for DNA extraction and sequencing of HO-1 promoter (GT)n dinucleotide repeat lengths. Allele lengths were assigned based on number of (GT)n repeats: <27 Short (S); 27-34 Medium (M); >34 Long (L). Relationships between HO-1 (GT)n repeat lengths and neurocognitive measures were examined, and differences by HO-1 (GT)n allele genotypes were explored.ResultsNearly half (48%) of all HO-1 (GT)n promoter all...
Open Forum Infectious Diseases, 2021
Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with potent anti-inflammatory, and anti-oxidan... more Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with potent anti-inflammatory, and anti-oxidant effects. The HO-1 response is modulated by functional polymorphisms (a dinucleotide (GT)n repeat length variation) in the HO-1 gene promoter region which have been associated with cardiovascular disease (CVD) susceptibility in adults. HO-1 polymorphisms and their associations with markers of inflammation and CVD in Ugandan adolescents with (HIV+) and without HIV (HIV-) have not been investigated. We included 177 children (92 HIV+, 85 HIV-) enrolled in an ongoing observational cohort study at the Joint Clinical Research Center, Kampala, Uganda. All HIV+ participants were on ART. HO-1 (GT)n allele genotypes were determined by PCR of the (GT)n repeat region followed by fragment size determination on a capillary sequencer in DNA extracted from blood samples. Allele designations were assigned by number of (GT)n repeats: S < 27, M 27-34, or L > 34 repeats. We measured mean common carot...
AIDS, 2022
OBJECTIVES Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of AR... more OBJECTIVES Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of ART adherence. Recent treatment studies have shown that TFV-DP predicts future viremia in persons with HIV (PWH) but there are few data from high-burden settings. We investigated whether TFV-DP in DBS predicts future viral breakthrough in South African PWH. DESIGN Prospective observational cohort. METHODS We enrolled 250 adults receiving tenofovir-containing regimens, currently virally suppressed (<50 copies/mL), but at risk of future viral breakthrough, from four primary health clinics in Cape Town. Paired viral load (VL) and DBS for TFV-DP were collected monthly for 12 months. Viral breakthrough was the first confirmed VL >400 copies/mL. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals for future viral breakthrough at the next visit. RESULTS Participants provided 2,944 paired DBS and VL samples. Median (IQR) age was 34 (27 - 42) years; median duration on ART at study entry was 11 (4-12) months; 78% were women. Twenty-one (8%) participants developed viral breakthrough. Participants with TFV-DP ≤400 fmol/punch had an adjusted OR of 16.1 (95% CI: 3.9-67.4; p < 0.001) for developing viral breakthrough one month later compared to participants with TFV-DP >800 fmol/punch. CONCLUSIONS TFV-DP in DBS strongly predicted future viral breakthrough in a clinical cohort of South African PWH. A biomarker able to identify PWH at risk for future viral breakthrough has the potential to improve health outcomes through timely intervention. Future studies exploring the clinical use of TFV-DP in DBS in conjunction with viral load in ART monitoring are warranted.
AIDS Care, 2021
Despite the prominence of self-efficacy as a predictor of antiretroviral therapy (ART) adherence,... more Despite the prominence of self-efficacy as a predictor of antiretroviral therapy (ART) adherence, relatively little work has examined domain-specific associations with steps in the care continuum or the possibility that substance use may have domain-specific associations with self-efficacy. This study analyzed data from a sample of 174 people living with HIV recruited through three clinics in the New York City metro area. Consistent with hypotheses, path analysis showed that appointments kept and viral load were each predicted only by their respective domain-specific self-efficacy components (i.e., self-efficacy for keeping appointments, B = 0.01, p = .04; and self-efficacy for taking ART medications, B = -0.02, p < .01). Path models also indicated domain-specific associations with substance use. Self-efficacy for keeping appointments was negatively associated with severity of drug use (B = -1.81, p < .01); meanwhile, self-efficacy for taking ART medications was negatively associated with severity of alcohol use (B = -0.52, p < .01). Accordingly, studies assessing barriers to retention in the HIV care continuum should conduct multi-domain assessments of self-efficacy for differential associations with specific behaviors. Furthermore, HIV care providers might consider screening for domain-specific self-efficacy to identify patients at risk of drop-out and tailoring interventions to various care continuum domains.
Uploads
Papers by Christopher Ferraris