Delayed-type hypersensitivity and hepatitis B vaccine responses, in vivo markers of cellular and humoral immune function, and the risk of AIDS or death

Background: Delayed-type hypersensitivity (DTH) test responsiveness is associated with HIV disease progression; however it is unknown whether other immune markers, such as hepatitis B virus (HBV) vaccine seroresponse, also predict HIV outcomes. Methods: Eligible participants received HBV vaccine after HIV diagnosis, had non-anergic DTH testing at the time of last HBV vaccination, and available post-vaccine HBV antibody responses. The risk of progression to AIDS or death from the time of last HBV vaccination was evaluated. Results: Of 369 eligible participants with non-anergic DTH responses, 148 (40%) were HBV vaccine responders. In a multivariate model adjusted for age, CD4 count, viral load, and number of vaccinations, HBV vaccine non-responders had an increased risk of progression to AIDS or death (HR 1.81; 95% CI, 1.03–3.19). Conclusions: HBV vaccine seroresponses were independent of DTH responses which suggest that nonresponse to HBV vaccine is not solely due to cell-mediated immune dysfunction in HIV-infected persons

Spontaneous virologic suppression in HIV controllers is independent of delayed-type hypersensitivity test responsiveness

<p>Abstract</p> <p>Background</p> <p>Delayed-type hypersensitivity (DTH) testing, an in vivo assessment of cell-mediated immunity, is a predictor of HIV disease progression beyond CD4 cell count. We investigated whether preserved DTH responsiveness was characteristic of HIV controllers compared to non-controllers and individuals on suppressive HAART.</p> <p>Findings</p> <p>DTH testing consisted of ≥ 3 recall antigens applied approximately every 6 months. DTH responses were classified by the number of positive skin tests: anergic (0), partial anergic (1), or non-anergic (≥ 2). HIV controllers were compared to treatment naïve non-controllers (n = 3822) and a subgroup of non-controllers with VL < 400 copies/mL on their initial HAART regimen (n = 491). The proportion of non-anergic results at first DTH testing was similar for HIV controllers compared to non-controllers (81.9% vs. 77.6%; P = 0.22), but tended to be greater in HIV controllers compared to the HAART subgroup (81.9% vs. 74.5%; P = 0.07). Complete anergy was observed in 14 (10.1%) HIV controllers with CD4 counts ≥ 400 cells/uL. For longitudinal testing, the average percentage of non-anergic DTH determinations per participant was higher in HIV controllers compared to non-controllers (81.2 ± 31.9% vs. 70.7 ± 36.8%; P = 0.0002), however this difference was eliminated with stratification by CD4 count: 200-399 (83.4 ± 35.6% vs. 71.9 ± 40.9%; P = 0.15) and > 400 cells/uL (81.2 ± 31.5% vs. 80.4 ± 32.7%; P = 0.76).</p> <p>Conclusions</p> <p>Spontaneous virologic control was not associated with DTH responsiveness, and several HIV controllers were anergic despite having elevated CD4 counts. These findings suggest that cellular immunity assessed by DTH is not a principal factor contributing to spontaneous virologic suppression in HIV controllers.</p

Virologic outcomes of HAART with concurrent use of cytochrome P450 enzyme-inducing antiepileptics: a retrospective case control study

<p>Abstract</p> <p>Background</p> <p>To evaluate the efficacy of highly-active antiretroviral therapy (HAART) in individuals taking cytochrome P450 enzyme-inducing antiepileptics (EI-EADs), we evaluated the virologic response to HAART with or without concurrent antiepileptic use.</p> <p>Methods</p> <p>Participants in the US Military HIV Natural History Study were included if taking HAART for ≥6 months with concurrent use of EI-AEDs phenytoin, carbamazepine, or phenobarbital for ≥28 days. Virologic outcomes were compared to HAART-treated participants taking AEDs that are not CYP450 enzyme-inducing (NEI-AED group) as well as to a matched group of individuals not taking AEDs (non-AED group). For participants with multiple HAART regimens with AED overlap, the first 3 overlaps were studied.</p> <p>Results</p> <p>EI-AED participants (n = 19) had greater virologic failure (62.5%) compared to NEI-AED participants (n = 85; 26.7%) for the first HAART/AED overlap period (OR 4.58 [1.47-14.25]; P = 0.009). Analysis of multiple overlap periods yielded consistent results (OR 4.29 [1.51-12.21]; P = 0.006). Virologic failure was also greater in the EI-AED versus NEI-AED group with multiple HAART/AED overlaps when adjusted for both year of and viral load at HAART initiation (OR 4.19 [1.54-11.44]; P = 0.005). Compared to the non-AED group (n = 190), EI-AED participants had greater virologic failure (62.5% vs. 42.5%; P = 0.134), however this result was only significant when adjusted for viral load at HAART initiation (OR 4.30 [1.02-18.07]; P = 0.046).</p> <p>Conclusions</p> <p>Consistent with data from pharmacokinetic studies demonstrating that EI-AED use may result in subtherapeutic levels of HAART, EI-AED use is associated with greater risk of virologic failure compared to NEI-AEDs when co-administered with HAART. Concurrent use of EI-AEDs and HAART should be avoided when possible.</p

The Effect of Human Immunodeficiency Virus on Hepatitis B Virus Serologic Status in Co-Infected Adults

Factors associated with serologic hepatitis B virus (HBV) outcomes in HIV-infected individuals remain incompletely understood, yet such knowledge may lead to improvements in the prevention and treatment of chronic HBV infection.HBV-HIV co-infected cohort participants were retrospectively analyzed. HBV serologic outcomes were classified as chronic, resolved, and isolated-HBcAb. Chronic HBV (CHBV) was defined as the presence of HBsAg on two or more occasions at least six months apart. Risk factors for HBV serologic outcome were assessed using logistic regression. Of 2037 participants with HBV infection, 281 (14%) had CHBV. Overall the proportions of HBV infections classified as CHBV were 11%, 16%, and 19% for CD4 cell count strata of > or =500, 200-499, and <200, respectively (p<0.0001). Risk of CHBV was increased for those with HBV infection occurring after HIV diagnosis (OR 2.62; 95% CI 1.78-3.85). This included the subset with CD4 count > or =500 cells/microL where 21% of those with HBV after HIV diagnosis had CHBV compared with 9% for all other cases of HBV infection in this stratum (p = 0.0004). Prior receipt of HAART was associated with improved HBV serologic outcome overall (p = 0.012), and specifically among those with HBV after HIV (p = 0.002). In those with HBV after HIV, HAART was associated with reduced risk of CHBV overall (OR 0.18; 95% CI 0.04-0.79); including reduced risk in the subsets with CD4 > or =350 cells/microL (p<0.001) and CD4 > or =500 cells/microL (p = 0.01) where no cases of CHBV were seen in those with a recent history of HAART use.Clinical indicators of immunologic status in HIV-infected individuals, such as CD4 cell count, are associated with HBV serologic outcome. These data suggest that immunologic preservation through the increased use of HAART to improve functional anti-HBV immunity, whether by improved access to care or earlier initiation of therapy, would likely improve HBV infection outcomes in HIV-infected individuals

Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. (HR 3.40; 95% CI, 1.39–8.32).

Patient and physician factors associated with participation in cervical and uterine cancer trials: An NRG/GOG247 study

AbstractPurposeThe aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials.MethodsProspective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial. Odds ratios (OR) and 95% confidence intervals (CI) for significant (p<0.05) results reported.ResultsSixty institutions, 781 patients, and 150 physicians participated, 300/780 (38%) had a trial available, 290/300 had known participation status. Of these, 150 women enrolled (59.5%), 102 eligible did not enroll (35%), 38 (13%) were ineligible. Ethnicity and specialty of physician, practice type, data management availability, and patient age were significantly associated with trial availability. Patients with >4 comorbidities (OR 4.5; CI 1.7–11.8) had higher odds of trial ineligibility. Non-White patients (OR 7.9; CI 1.3–46.2) and patients of Black physicians had greater odds of enrolling (OR 56.5; CI 1.1–999.9) in a therapeutic trial. Significant patient therapeutic trial enrollment factors: belief trial may help (OR 76.9; CI 4.9–>1000), concern about care if not on trial (OR12.1; CI 2.1–71.4), pressure to enroll (OR .27; CI 0.12–.64), caregiving without pay (OR 0.13; CI .02–.84). Significant physician beliefs were: patients would not do well on standard therapy (OR 3.6; CI 1.6–8.4), and trial would not be time consuming (OR 3.3; CI 1.3–8.1).ConclusionsTrial availability, patient and physician beliefs were factors identified that if modified could improve enrollment in cancer cooperative group clinical trials

Outcomes of highly active antiretroviral therapy in the context of universal access to healthcare: the U.S. Military HIV Natural History Study

<p>Abstract</p> <p>Background</p> <p>To examine the outcomes of highly-active antiretroviral therapy (HAART) for individuals with free access to healthcare, we evaluated 2327 patients in a cohort study composed of military personnel and beneficiaries with HIV infection who initiated HAART from 1996 to the end of 2007.</p> <p>Methods</p> <p>Outcomes analyzed were virologic suppression (VS) and failure (VF), CD4 count changes, AIDS and death. VF was defined as never suppressing or having at least one rebound event. Multivariate (MV) analyses stratified by the HAART initiation year (before or after 2000) were performed to identify risk factors associated with these outcomes.</p> <p>Results</p> <p>Among patients who started HAART after 2000, 81% had VS at 1 year (N = 1,759), 85% at 5 years (N = 1,061), and 82% at 8 years (N = 735). Five years post-HAART, the median CD4 increase was 247 cells/ml and 34% experienced VF. AIDS and mortality rates at 5 years were 2% and 0.3%, respectively. In a MV model adjusted for known risk factors associated with treatment response, being on active duty (versus retired) at HAART initiation was associated with a decreased risk of AIDS (HR = 0.6, 95% CI 0.4-1.0) and mortality (0.6, 0.3-0.9), an increased probability of CD4 increase ≥ 50% (1.2, 1.0-1.4), but was not significant for VF.</p> <p>Conclusions</p> <p>In this observational cohort, VS rates approach those described in clinical trials. Initiating HAART on active duty was associated with even better outcomes. These findings support the notion that free access to healthcare likely improves the response to HAART thereby reducing HIV-related morbidity and mortality.</p

Patient and physician factors associated with participation in cervical and uterine cancer trials: An NRG/GOG247 study

To identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials

Avoidable readmission in Hong Kong - system, clinician, patient or social factor?

<p>Abstract</p> <p>Background</p> <p>Studies that identify reasons for readmissions are gaining importance in the light of the changing demographics worldwide which has led to greater demand for hospital beds. It is essential to profile the prevalence of avoidable readmissions and understand its drivers so as to develop possible interventions for reducing readmissions that are preventable. The aim of this study is to identify the magnitude of avoidable readmissions, its contributing factors and costs in Hong Kong.</p> <p>Methods</p> <p>This was a retrospective analysis of 332,453 inpatient admissions in the Medical specialty in public hospital system in Hong Kong in year 2007. A stratified random sample of patients with unplanned readmission within 30 days after discharge was selected for medical record reviews. Eight physicians reviewed patients' medical records and classified whether a readmission was avoidable according to an assessment checklist. The results were correlated with hospital inpatient data.</p> <p>Results</p> <p>It was found that 40.8% of the 603 unplanned readmissions were judged avoidable by the reviewers. Avoidable readmissions were due to: clinician factor (42.3%) including low threshold for admission and premature discharge etc.; patient factor (including medical and health factor) (41.9%) such as relapse or progress of previous complaint, and compliance problems etc., followed by system factor (14.6%) including inadequate discharge planning, inadequate palliative care/terminal care, etc., and social factor (1.2%) such as carer system, lack of support and community services. After adjusting for patients' age, gender, principal diagnosis at previous discharge and readmission hospitals, the risk factors for avoidable readmissions in the total population i.e. all acute care admissions irrespective of whether there was a readmission or not, included patients with a longer length of stay, and with higher number of hospitalizations and attendance in public outpatient clinics and Accident and Emergency departments in the past 12 months. In the analysis of only unplanned readmissions, it was found that the concordance of the principal diagnosis for admission and readmission, and shorter time period between discharge and readmission were associated with avoidable readmissions.</p> <p>Conclusions</p> <p>Our study found that almost half of the readmissions could have been prevented. They had been mainly due to clinician and patient factors, in particular, both of which were intimately related to clinical management and patient care. These readmissions could be prevented by a system of ongoing clinical review to examine the clinical practice/decision for discharge, and improving clinical care and enhancing patient knowledge of the early warning signs for relapse. The importance of adequate and appropriate ambulatory care to support the patients in the community was also a key finding to reduce avoidable readmissions. Education on patient self-management should also be enhanced to minimize the patient factors with regard to avoidable readmission. Our findings thus provide important insights into the development of an effective discharge planning system which should place patients and carers as the primacy focus of care by engaging them along with the healthcare professionals in the whole discharge planning process.</p