Frederick M Hecht

University of California, San Francisco, San Francisco, California, United States

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Publications (197)1246.15 Total impact

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    ABSTRACT: We used a stress and coping model to examine the association of dispositional mindfulness, defined as the tendency to intentionally bring non-judgmental attention and awareness to one's experience in the present moment, with psychological and physical health in adults with HIV. Data were collected at baseline of a randomized controlled trial of Mindfulness-Based Stress Reduction (MBSR). Four facets of mindfulness (acting with attention/awareness, non-judging of inner experience, observing, and describing) were examined as correlates of appraisal, positive and negative affect, coping, and indicators of psychological well-being and physical health. We found that mindfulness was inversely related to depression, stress appraisal, and negative affect, and positively related to positive affect. Mindfulness was also inversely related to escape/avoidance and self-blame forms of coping. Mediational analyses indicate that perceived stress and negative affect were the most consistent mediators of the association of mindfulness and psychological well-being. The findings from this paper contribute to a growing understanding of the potential adaptive role of mindfulness in people living with the stress of serious illness.
    Personality and Individual Differences 11/2015; 86. DOI:10.1016/j.paid.2015.05.039 · 1.86 Impact Factor
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    ABSTRACT: T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and T-cell activation-induced DNA methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an evolutionarily conserved CpG (CpG -41), CCR5 cis-regions manifest lower vs. higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naïve T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and in vitro induced T-cell activation is associated with demethylation of these cis-regions. CCR5 haplotypes associated with increased vs. decreased gene/surface expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell activation-associated demethylation. Methylation status of CCR5 intron 2 explains a larger proportion of the variation in CCR5 levels than genotype or T-cell activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at CpG -41 that is (i) specific to southern Africa, (ii) abrogates binding of the transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for overrepresentation in persons with reduced susceptibility to HIV and disease progression. Genotypes lacking the CCR5-Δ32 mutation but with hypermethylated cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-Δ32. In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite restoration of CD4+ counts (≥800 cells per mm(3)) with antiretroviral therapy. Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant of T-cell CCR5 levels, and possibly HIV-related outcomes.
    Proceedings of the National Academy of Sciences 08/2015; 112(34):E4762-71. DOI:10.1073/pnas.1423228112 · 9.81 Impact Factor
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    ABSTRACT: Obese individuals vary in their experience of food cravings and tendency to engage in reward-driven eating, both of which can be modulated by the neural reward system rather than physiological hunger. We examined two predictions in a sample of obese women: (1) whether opioidergic blockade reduced food-craving intensity, and (2) whether opioidergic blockade reduced an association between food-craving intensity and reward-driven eating, which is a trait-like index of three factors (lack of control over eating, lack of satiation, preoccupation with food). Forty-four obese, pre-menopausal women completed the Reward-Based Eating Drive (RED) scale at study start and daily food-craving intensity on 5days on which they ingested either a pill-placebo (2days), a 25mg naltrexone dose (1day), or a standard 50mg naltrexone dose (2days). Craving intensity was similar under naltrexone and placebo doses. The association between food-craving intensity and reward-driven eating significantly differed between placebo and 50mg naltrexone doses. Reward-driven eating and craving intensity were significantly positively associated under both placebo doses. As predicted, opioidergic blockade (for both doses 25mg and 50mg naltrexone) reduced the positive association between reward-driven eating and craving intensity to non-significance. Opioidergic blockade did not reduce craving intensity; however, blockade reduced an association between trait-like reward-driven eating and daily food-craving intensity, and may help identify an important endophenotype within obesity. Published by Elsevier Ltd.
    Eating behaviors 07/2015; DOI:10.1016/j.eatbeh.2015.06.008
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    ABSTRACT: Quantifying latently infected cells is critical to evaluate the efficacy of therapeutic strategies aimed at reducing the size of the long-lived viral reservoir, but the low frequency of these cells makes this very challenging.
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    ABSTRACT: Introdução: As estratégias de prevenção da transmissão da infecção pelo vírus da imunodeficiência humana (HIV) em casais sorodiscordantes geralmente são voltadas para as pessoas HIV positivas, não havendo consenso sobre a abordagem das parcerias soronegativas. Objetivo: Identificar e quantificar a ocorrência de comportamentos de risco em pessoas HIV negativas com parceria HIV positiva fixa. Métodos: Examinamos a frequência com que os participantes de um estudo transversal relataram ter parceria HIV positiva no formulário padrão do serviço e/ou no questionário do estudo. Avaliamos comportamentos de risco e novos diagnósticos de infecção pelo HIV em pacientes “potencialmente sorodiscordantes” em comparação com os outros pacientes na população em geral. O diagnóstico de HIV foi realizado seguindo o algoritmo de testagem padrão. O teste BED EIA HIV-1 (Calypte Biomedical, Portland, OR; ODn cutoff=0,8) foi utilizado para classificar pessoas recentemente infectadas pelo HIV. Resultados: Entre os 3.100 pacientes com nenhum teste reagente para HIV anterior, 490 (15,8%) relataram estar em um relacionamento fixo com uma pessoa HIV positiva. Esta proporção foi semelhante tanto para homens que fazem sexo com homens (HSH) como em heterossexuais. Menos da metade dos participantes reportou ter usado o preservativo durante o último ato sexual com o parceiro HIV positivo. Apenas um quarto dos homens heterossexuais e um terço dos HSH e mulheres reportaram o uso consistente de preservativos com seu parceiro no último ano. Os principais motivos para não usar preservativo com o parceiro fixo foram: “confia no parceiro” (31,7%), seguido de “não gosta” (15,1%) e “parceiro não aceita” (8,9%). Foram diagnosticadas novas infecções pelo HIV em 23% do grupo de pacientes potencialmente discordantes (versus 13% na população geral; p=0,01). Participantes com uso inconsistente de preservativos com parceiro fixo apresentaram uma chance 4 vezes maior de ter resultado positivo para HIV, quando comparados com aqueles que reportaram sempre usar preservativos com o parceiro fixo (OR=4,2; IC95% 2,3–7,5). Houve uma maior adesão à utilização de preservativos com parcerias casuais no último ato sexual, variando de 58,5% (homens heterossexuais) a 75% (HSH e mulheres). Conclusão: Parcerias sorodiscordantes fixas, com elevado risco de transmissão do HIV, podem ser identificadas no momento da testagem e do aconselhamento. O acesso a essa população é fundamental para a implantação de estratégias de prevenção em localidades com alta incidência de HIV.
    X Congresso da Sociedade Brasileira de DST - VI Congresso Brasileiro de AIDS, São Paulo, SP, Brazil; 05/2015
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    PLoS ONE 04/2015; 10(4):e0120787. DOI:10.1371/journal.pone.0120787 · 3.23 Impact Factor
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    ABSTRACT: There are currently no commonly used or easily accessible 'biomarkers' of hedonic eating. Physiologic responses to acute opioidergic blockade, indexed by cortisol changes and nausea, may represent indirect functional measures of opioid-mediated hedonic eating drive and predict weight loss following a mindfulness-based intervention for stress eating. In the current study, we tested whether cortisol and nausea responses induced by oral ingestion of an opioidergic antagonist (naltrexone) correlated with weight and self-report measures of hedonic eating and predicted changes in these measures following a mindfulness-based weight loss intervention. Obese women (N=88; age=46.7±13.2 years; BMI=35.8±3.8) elected to complete an optional sub-study prior to a 5.5-month weight loss intervention with or without mindfulness training. On two separate days, participants ingested naltrexone and placebo pills, collected saliva samples, and reported nausea levels. Supporting previous findings, naltrexone-induced cortisol increases were associated with greater hedonic eating (greater food addiction symptoms and reward-driven eating) and less mindful eating. Among participants with larger cortisol increases (+1 SD above mean), mindfulness participants (relative to control participants) reported greater reductions in food addiction symptoms, b=-0.95, SE(b)=0.40, 95% CI [-1.74, -0.15], p=.021. Naltrexone-induced nausea was marginally associated with reward-based eating. Among participants who endorsed naltrexone-induced nausea (n=38), mindfulness participants (relative to control participants) reported greater reductions in food addiction symptoms, b=-1.00, 95% CI [-1.85, -0.77], p=.024, and trended toward reduced reward-based eating, binge eating, and weight, post-intervention. Single assessments of naltrexone-induced cortisol increases and nausea responses may be useful time- and cost-effective biological markers to identify obese individuals with greater opioid-mediated hedonic eating drive who may benefit from weight loss interventions with adjuvant mindfulness training that targets hedonic eating. Copyright © 2015. Published by Elsevier Ltd.
    Appetite 04/2015; 91. DOI:10.1016/j.appet.2015.04.062 · 2.69 Impact Factor
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    Wolf E Mehling · Mark H Ebell · Andrew L Avins · Frederick M Hecht
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    ABSTRACT: Primary care clinicians need to identify candidates for early interventions to prevent patients with acute pain from developing chronic pain. We conducted a 2-year prospective cohort study of risk factors for the progression to chronic pain and developed and internally validated a clinical decision rule (CDR) that stratifies patients into low, medium and high-risk groups for chronic pain. Prospective cohort study in primary care. Patients with acute low back pain (LBP; ≤30 days duration) OUTCOME MEASURES: Self-reported perceived non-recovery and chronic pain. Patients were surveyed at baseline, 6 months and 2 years. We conducted bivariate and multivariate regression analyses of demographic, clinical and psychosocial variables for chronic pain outcomes, developed a CDR and assessed its performance by calculating the bootstrapped areas under the receiver operating characteristic curve (AUC) and likelihood ratios. This study was supported by NIH/NCCAM grants K23 AT002298, R21 AT004467, NIH/NCCAM K24 AT007827, the Research Evaluation and Allocation Committee (REAC) of the University of California San Francisco, and the Mount Zion Health Fund, San Francisco. The funding agencies played no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The authors report no conflict of interests. 605 patients enrolled. 13% had chronic pain at 6 months, 19% at 2 years. An eight-item CDR was most parsimonious for classifying patients into three risk levels. Bootstrapped AUC was 0.76 (0.70-0.82) for the 6-month CDR. Each 10-point score increase (60-point range) was associated with an odds ratio of 11.1 (10.8-11.4) for developing chronic pain. Using a <5% probability of chronic pain as the cutoff for low risk and a >40% probability for high risk, likelihood ratios were 0.26 (0.14-0.48) and 4.4 (3.0-6.3) for these groups, respectively. A CDR was developed that may help primary care clinicians classify patients with strictly defined acute LBP into low, moderate and high-risk groups for developing chronic pain and performed acceptably in 1,000 bootstrapped replications. Validation in a separate sample is needed. Copyright © 2015 Elsevier Inc. All rights reserved.
    The spine journal: official journal of the North American Spine Society 03/2015; 15(7). DOI:10.1016/j.spinee.2015.03.003 · 2.80 Impact Factor
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    ABSTRACT: BACKGROUND: The stability of the HIV-1 reservoir and the contribution of cellular proliferation to the maintenance of the reservoir during treatment are uncertain. Therefore, we conducted a longitudinal analysis of HIV-1 in T-cell subsets in different tissue compartments from subjects on effective antiretroviral therapy (ART). METHODS: Using single-proviral sequencing, we isolated intracellular HIV-1 genomes derived from defined subsets of CD4+ T-cells from peripheral blood, gut-associated lymphoid tissue and lymph node tissue, from eight virally suppressed subjects on long-term ART at two time points, separated by 7-9 months. RESULTS: DNA integrant frequencies were stable over time (<4-fold difference) and were highest in memory T-cells. Phylogenetic analyses showed that subjects treated during chronic infection contained viral populations with up to 73% identical sequence expansions, only three of which were observed in pre-therapy specimens. At both times points, such clonally expanded populations were found predominantly in effector memory T-cells from peripheral blood and lymph node tissue. CONCLUSIONS: Memory T-cells maintained a relatively constant HIV-1 DNA integrant pool that was genetically stable during long-term effective ART. These integrants appear to be maintained by cellular proliferation and longevity of infected cells rather than by ongoing viral replication.
    The Journal of Infectious Diseases 02/2015; DOI:10.1093/infdis/jiv092 · 5.78 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate the changes in running biomechanics after training in Form-Focused running using ChiRunning vs. Not-Form focused training and Self-Directed training in untrained individuals.Design: Pilot study - Randomized controlled trial. Setting: Research Institution with Tertiary Care Medical Center. Participants: Seventeen subjects (9 males, 8 females) with pre-hypertension. METHODS: Twenty-two participants were randomized to three study arms but 17 completed the study. The study arms were: 1) group-based Form-Focused running using ChiRunning (enrolled, n =10; completed, n=7); 2) group-based conventional running (enrolled, n =6; completed, n=4); 3) self-directed training with educational materials (enrolled, n =6; completed, n=6). The training schedule was prescribed for 8 weeks with 4 weeks of follow-up. All subjects completed overground running motion analyses before and after training. OUTCOMES: Ankle, knee, hip joint peak moments and powers; Average vertical loading rate (AVLR), impact peak, cadence, stride length, strike index, and stride reach. Paired T-tests were used to compare differences with-in groups over-time. RESULTS: Form-Focused group reduced their Stride Reach (P = .047) after the training but not the other groups. Form-Focused group showed a close to significant reduction in knee adduction moment (P = .051) and a reduction in the peak ankle eversion moment (P = .027). Self-Directed group showed an increase in the running speed, (P =.056) and increases in ankle and knee joint powers and moments. CONCLUSIONS: There are differences in the changes in running biomechanics between individuals trained in running form that emphazies mid-foot strike, higher cadence, and shorter stride compared to those not trained in the thise technique. These differences may be associated with reduced lower extremity stress in individuals trained in this running form but future studies are needed to confirm these findings in larger samples.
    PM&R 01/2015; DOI:10.1016/j.pmrj.2015.01.010 · 1.66 Impact Factor
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    ABSTRACT: The eradication of HIV necessitates elimination of the HIV latent reservoir. Identifying host determinants governing latency and reservoir size in the setting of antiretroviral therapy (ART) is an important step in developing strategies to cure HIV infection. We sought to determine the impact of cell-intrinsic immunity on the HIV latent reservoir. We investigated the relevance of a comprehensive panel of established anti-HIV-1 host restriction factors to multiple established virologic and immunologic measures of viral persistence in HIV-1-infected, ART-suppressed individuals. We measured the mRNA expression of 42 anti-HIV-1 host restriction factors, levels of cell-associated HIV-1 RNA, levels of total pol and 2-long terminal repeat (2-LTR) circle HIV-1 DNA and immunophenotypes of CD4 T cells in 72 HIV-1-infected individuals on suppressive ART (23 individuals initiated ART less than 1 year postinfection, and 49 individuals initiated ART greater than 1 year post-infection). Correlations were analysed using nonparametric tests. The enhanced expression of a few select host restriction factors, p21, schlafen 11 and PAF1, was strongly associated with reduced CD4 T-cell associated HIV RNA during ART (P < 0.001). In addition, our data suggested that ART perturbs the regulatory relationship between CD4 T-cell activation and restriction factor expression. Lastly, cell-intrinsic immune responses were significantly enhanced in individuals who initiated ART during early versus chronic infection and may contribute to the reduced reservoir size observed in these individuals. Intrinsic immune responses modulate HIV persistence during suppressive ART and may be manipulated to enhance the efficacy of ART and promote viral eradication through reversal of latency in vivo.
    AIDS (London, England) 01/2015; 29(4). DOI:10.1097/QAD.0000000000000572 · 6.56 Impact Factor
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    ABSTRACT: We estimate the relative transmission rate in early versus later infection amongst men who have sex with men (MSM) in San Francisco, USA, by studying the characteristics of a sample of transmitters, recruited through newly infected MSM between 1996 and 2009. Of 36 transmitters identified, 9 were recently infected based on testing history and serologic testing. The odds ratio of transmitting during early infection was 15.2 (95% CI 6.3-33.4, p<0.001) unadjusted and 8.9 (95% CI 4.1-19.4) when adjusting for self-reported antiretroviral treatment. This high transmissibility could be due to both high infectiousness and high rates of partner change or concurrency. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
    The Journal of Infectious Diseases 12/2014; DOI:10.1093/infdis/jiu831 · 5.78 Impact Factor
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    ABSTRACT: Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean = 35.4, SD = 3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b = -56.8 base pairs per one point increase in PSQI, SE = 20.4, p=0.007) and CD4+ T cells (b = -37.2, SE = 15.9, p = 0.022). Among separate aspects ofglobal sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres.In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and disease risk in obese individuals. Copyright © 2014. Published by Elsevier Inc.
    Brain Behavior and Immunity 12/2014; 47. DOI:10.1016/j.bbi.2014.12.011 · 6.13 Impact Factor
  • W.E. Mehling · A.L Avins · M.C Acree · T.S Carey · F.M. Hecht
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    ABSTRACT: Background The 9-item STarT-Back screening tool was developed in primary care patients with low back pain (LBP) to identify those at greatest risk for chronic pain and requiring targeted treatment. We conducted a secondary data analysis study to examine the performance of comparable questionnaire items in a sample of primary care patients with well-defined acute LBP.Methods In a prospective cohort study, 605 primary care patients with LBP of less than 30 days answered a questionnaire with 6 items identical and 3 items analogous to the 9-item STarT-Back. Participants were followed up at 6 months and 2 years. STarT-Back rules were applied to classify participant's risk of chronic LBP, and the performance of the screening items in predicting outcomes was assessed using likelihood ratios.ResultsThe proportion of patients with chronic pain at follow-up was considerably lower (6 months: 22%; 2 years: 25%) than in the STarT-Back validation cohort (40%) of patients with pain of any duration. The probability of developing chronic pain given a high-risk designation by items similar to the STarT-Back increased the pre-test probability to 31% and 35%. Likelihood ratios were close to 1.ConclusionsA risk classification schema using the recommended cut-off scores with items similar to the STarT-Back in a primary care population with strictly defined acute LBP had limited ability to identify persons who progressed to chronic pain. The results suggest caution when applying the STarT-Back in patients with acute LBP and a need to consider a modification of its cut-offs.
    European journal of pain (London, England) 12/2014; 19(3). DOI:10.1002/ejp.615 · 3.22 Impact Factor
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    ABSTRACT: The association between the host immune environment and the size of the HIV reservoir during effective antiretroviral therapy is not clear. Progress has also been limited by the lack of a well-accepted assay for quantifying HIV during therapy. We examined the association between multiple measurements of HIV and T cell activation (as defined by markers including CD38, HLA-DR, CCR5 and PD-1) in 30 antiretroviral-treated HIV-infected adults. We found a consistent association between the frequency of CD4+ and CD8+ T cells expressing HLA-DR and the frequency of resting CD4+ T cells containing HIV DNA. This study highlights the need to further examine this relationship and to better characterize the biology of markers commonly used in HIV studies. These results may also have implications for reactivation strategies.
    PLoS ONE 10/2014; 9(10):e110731. DOI:10.1371/journal.pone.0110731 · 3.23 Impact Factor
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    ABSTRACT: HLA-B*5701 is the host factor most strongly associated with slow HIV-1 disease progression, although risk of progression may vary among patients carrying this allele. The interplay between HIV-1 evolutionary rate variation and risk of progression to AIDS in HLA-B*5701 subjects was studied using longitudinal viral sequences from high-risk progressors (HRPs) and low-risk progressors (LRPs). Posterior distributions of HIV-1 genealogies assuming a Bayesian relaxed molecular clock were used to estimate the absolute rates of nonsynonymous and synonymous substitutions for different set of branches. Rates of viral evolution, as well as in vitro viral replication capacity assessed using a novel phenotypic assay, were correlated with various clinical parameters. HIV-1 synonymous substitution rates were significantly lower in LRPs than HRPs, especially for sets of internal branches. The viral population infecting LRPs was also characterized by a slower increase in synonymous divergence over time. This pattern did not correlate to differences in viral fitness, as measured by in vitro replication capacity, nor could be explained by differences among subjects in T cell activation or selection pressure. Interestingly, a significant inverse correlation was found between baseline CD4+ T cell counts and mean HIV-1 synonymous rate (which is proportional to the viral replication rate) along branches representing viral lineages successfully propagating through time up to the last sampled time point. The observed lower replication rate in HLA-B*5701 subjects with higher baseline CD4+ T cell counts provides a potential model to explain differences in risk of disease progression among individuals carrying this allele.
    PLoS Computational Biology 09/2014; 10(9):e1003830. DOI:10.1371/journal.pcbi.1003830 · 4.83 Impact Factor
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    ABSTRACT: Events during primary HIV-1 infection have been shown to be critical for the subsequent rate of disease progression. Early control of viral replication, resolution of clinical symptoms and development of a viral setpoint have been associated with the emergence of HIV-specific CD8 T cell responses. Here we assessed which particular HIV-specific CD8 T cell responses contribute to long-term control of HIV-1.
    Journal of Virology 08/2014; 88(21). DOI:10.1128/JVI.02016-14 · 4.65 Impact Factor
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    ABSTRACT: Objective: Cross-sectional HIV incidence surveillance, using assays that distinguish ‘recent’ from ‘nonrecent’ infections, has been hampered by inadequate performance and characterization of incidence assays. In this study, the Consortium for the Evaluation and Performance of HIV Incidence Assays presents results of the first independent evaluation of five incidence assays (BED, Limiting Antigen Avidity, Less-sensitive Vitros, Vitros Avidity and BioRad Avidity). Design: A large repository of diverse specimens from HIV-positive patients was established, multiple assays were run on 2500 selected specimens, and data were analyzed to estimate assay characteristics relevant for incidence surveillance. Methods: The mean duration of recent infection (MDRI, average time ‘recent’ while infected for less than some time cut-off T) was estimated from longitudinal data on seroconverters by regression. The false-recent rate (FRR, probability of testing ‘recent’ when infected for longer than T) was explored by measuring the proportions of ‘recent’ results in various subsets of patients. Results: Assays continue to fail to attain the simultaneously large MDRI and small FRR demanded by existing performance guidelines. All assays produce high FRRs amongst virally suppressed patients (>40%), including elite controllers and treated patients. Conclusions: Results from this first independent evaluation provide valuable information about the current performance of assays, and suggest the need for further optimization. Variation of ‘recent’/‘nonrecent’ thresholds and the use of multiple antibody-maturation assays, as well as other biomarkers, can now be explored, using the rich data generated by the Consortium for the Evaluation and Performance of HIV Incidence Assays. Consistently high FRRs amongst those virally suppressed suggest that viral load will be a particularly valuable supplementary marker. Video abstract:
    AIDS (London, England) 08/2014; 28(16). DOI:10.1097/QAD.0000000000000429 · 6.56 Impact Factor
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    ABSTRACT: A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated ("putative progressors", PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = -0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.
    PLoS Pathogens 08/2014; 10(8):e1004345. DOI:10.1371/journal.ppat.1004345 · 8.14 Impact Factor

Publication Stats

10k Citations
1,246.15 Total Impact Points

Institutions

  • 2000–2015
    • University of California, San Francisco
      • • Department of Medicine
      • • Division of HIV/AIDS
      • • Division of Hospital Medicine
      • • Department of Family and Community Medicine
      San Francisco, California, United States
  • 2012
    • Karolinska Institutet
      • Department of Microbiology, Tumor and Cell Biology (MTC)
      Stockholm, Stockholm, Sweden
  • 2008–2012
    • CSU Mentor
      • Department of Medicine
      Long Beach, California, United States
    • Henry M Jackson Foundation
      Maryland City, Maryland, United States
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, CA, United States
  • 2011
    • University of Hawaiʻi at Mānoa
      • Department of Tropical Medicine, Medical Microbiology and Pharmacology
      Honolulu, Hawaii, United States
  • 2001–2011
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2006–2010
    • University of California, San Diego
      • Department of Medicine
      San Diego, California, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Blood Systems Research Institute
      San Francisco, California, United States
  • 2009
    • Ragon Institute of MGH, MIT and Harvard
      Charlestown, Maryland, United States
  • 2003
    • Blood Centers of the Pacific
      San Francisco, California, United States