BackgroundVirus-specific CD8+ T lymphocytes play a key role in the initial reduction of peak viremia during acute viral infections, but display signs of increasing dysfunction and exhaustion under conditions of chronic antigen persistence. It has been suggested that virus-specific CD8+ T cells with a “polyfunctional” profile, defined by the capacity to secrete multiple cytokines or chemokines, are most competent in controlling viral replication in chronic HIV-1 infection. We used HIV-1 infection as a model of chronic persistent viral infection to investigate the process of exhaustion and dysfunction of virus-specific CD8+ T cell responses on the single-epitope level over time, starting in primary HIV-1 infection.Methods and FindingsWe longitudinally analyzed the polyfunctional epitope-specific CD8+ T cell responses of 18 patients during primary HIV-1 infection before and after therapy initiation or sequence variation in the targeted epitope. Epitope-specific CD8+ T cells responded with multiple effector functions to antigenic stimulation during primary HIV-1 infection, but lost their polyfunctional capacity in response to antigen and up-regulated programmed death 1 (PD-1) expression with persistent viremic infection. This exhausted phenotype significantly decreased upon removal of stimulation by antigen, either in response to antiretroviral therapy or by reduction of epitope-specific antigen load in the presence of ongoing viral replication, as a consequence of in vivo selection of cytotoxic T lymphocyte escape mutations in the respective epitopes. Monofunctionality increased in CD8+ T cell responses directed against conserved epitopes from 49% (95% confidence interval 27%–72%) to 76% (56%–95%) (standard deviation [SD] of the effect size 0.71), while monofunctionality remained stable or slightly decreased for responses directed against escaped epitopes from 61% (47%–75%) to 56% (42%–70%) (SD of the effect size 0.18) (p < 0.05).ConclusionThese data suggest that persistence of antigen can be the cause, rather than the consequence, of the functional impairment of virus-specific T cell responses observed during chronic HIV-1 infection, and underscore the importance of evaluating autologous viral sequences in studies aimed at investigating the relationship between virus-specific immunity and associated pathogenesis.

Overall, the rate of GBV, particularly intimate partner violence, increased within the year following Hurricane Katrina and did not return to baseline during the protracted phase of displacement. Disaster planning efforts should incorporate plans to decrease the incidence of GBV following a disaster, and to ensure adequate services to people with postdisaster GBV experience.

BACKGROUND: Physicians are increasingly asked to improve the delivery of clinical services and patient experiences of care. OBJECTIVE:We evaluated the association between clinical performance and patient experiences in a statewide sample of physician practice sites and a sample of physicians within a large physician group. DESIGN, SETTING, PARTICIPANTS:We separately identified 373 practice sites and 119 individual primary care physicians in Massachusetts. MEASUREMENTS: Using Health Plan Employer Dataand Information Set data, we produced two composites addressing processes of care (prevention, disease management) and one composite addressing outcomes. Using Ambulatory Care Experiences Survey data, we produced seven composite measures summarizing the quality of clinical interactions and organizational features of care. For each sample (practice site and individual physician), we calculated adjusted Spearman correlation coefficients to assess the relationship between the composites summarizing patient experiences of care and those summarizing clinical performance.RESULTS: Among 42 possible correlations (21 correlations involving practice sites and 21 involving individual physicians), the majority were positive in site level (71%) and physician level (67%) analyses. For the 28 possible correlations involving patient experiences and clinical process composites, 8 (29%) were significant and positive, and only 2 (7%) were significant and negative. The magnitude of the significant positive correlations ranged from 0.13 to 0.19 at the site level and from 0.28 to 0.51 at the physician level. There were no significant correlations between patient experiences and the clinical outcome composite. CONCLUSIONS:The modest correlations suggest that clinical quality and patient experience are distinct, but related domains that may require separate measurement and improvement initiatives.KEY WORDS: quality of care; patient centered care; primary care; quality measurement; quality improvement.

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Background: Physicians and medical educators have repeatedly acknowledged the inadequacy of communication skills training in the medical school curriculum and opportunities to improve these skills in practice. This study of a controlled intervention evaluates the effect of teaching practicing physicians the skill of "agenda-setting" on patients' experiences with care. The agenda-setting intervention aimed to engage clinicians in the practice of initiating patient encounters by eliciting the full set of concerns from the patient's perspective and using that information to prioritize and negotiate which clinical issues should most appropriately be dealt with and which (if any) should be deferred to a subsequent visit.