Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.Trial RegistrationClinicalTrials.gov NCT01365065

Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology-Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.

BackgroundRates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART.MethodsWe conducted a nested case-control study of suicide and accidental or violent death in the Australian HIV Observational Database (AHOD) between January 1999 and March 2012. For each case, 2 controls were matched by clinic, age, sex, mode of exposure and HIV-positive date to adjust for potential confounding by these covariates. Risk of suicide and accidental or violent death was estimated using conditional logistic regression.ResultsWe included 27 cases (17 suicide and 10 violent/accidental death) and 54 controls. All cases were men who have sex with men (MSM) or MSM/ injecting drug use (IDU) mode of exposure. Increased risk was associated with unemployment (Odds Ratio (OR) 5.86, 95% CI: 1.69–20.37), living alone (OR 3.26, 95% CI: 1.06–10.07), suicidal ideation (OR 6.55, 95% CI: 1.70–25.21), and >2 psychiatric/cognitive risk factors (OR 4.99, 95% CI: 1.17–30.65). CD4 cell count of >500 cells/µL (OR 0.25, 95% CI: 0.07–0.87) and HIV-positive date ≥1990 (1990–1999 (OR 0.31, 95% CI: 0.11–0.89), post-2000 (OR 0.08, 95% CI: 0.01–0.84)) were associated with decreased risk. CD4 cell count ≥500 cells/µL remained a significant predictor of reduced risk (OR 0.15, 95% CI: 0.03–0.70) in a multivariate model adjusted for employment status, accommodation status and HIV-positive date.ConclusionsAfter adjustment for psychosocial factors, the immunological status of HIV-positive patients contributed to the risk of suicide and accidental or violent death. The number of psychiatric/cognitive diagnoses contributed to the level of risk but many psychosocial factors were not individually significant. These findings indicate a complex interplay of factors associated with risk of suicide and accidental or violent death.

Objectives To describe hospitalization rates, risk factors and associated diagnoses in people with HIV in Australia between 1999 and 2007. Design Retrospective cohort study of people with HIV (n = 842) using data linkage between the Australian HIV Observational Database and administrative hospital morbidity data collections. Methods Incidence rate ratios with 95% confidence intervals were estimated using Poisson regression models to assess risk factors for hospitalization. Predictors of length of stay were assessed using generalized mixed models. The association between hospitalization and mortality was assessed using Cox regression. Results In 4519 person-years of observation, there were 2667 hospital admissions; incidence rate of 59 per 100 person-years. Hospitalization rates were 50–300% higher in this cohort than comparable age and sex strata in the general population. Older age (incidence rate ratio 1.46, 95% confidence interval 1.28–1.65 per 10-year increase) and prior AIDS (incidence rate ratio 1.71, 95% confidence interval 1.24–2.35) were significantly associated with hospitalization. Other predictors of hospitalization included lower CD4 cell counts, higher HIV RNA, longer duration of HIV infection and experience with more drug classes. Lower CD4 cell counts, older age and hepatitis C virus antibody positivity were independently associated with longer hospital stay. Non-AIDS diseases were the principle reason for admission in the majority of cases. Mortality was associated with more frequent hospitalization during the study period. Conclusion Hospitalization rates are higher in people with HIV than the general population in Australia and are associated with markers of advanced HIV disease despite the widespread use of combination antiretroviral therapy.

IntroductionHIV-positive (HIV+) temporary residents living in Australia legally are unable to access government subsidized antiretroviral treatment (ART) which is provided via Medicare to Australian citizens and permanent residents. Currently, there is no information systematically being collected on non-Medicare eligible HIV+ patients in Australia. The objectives of this study are to describe the population recruited to the Australian HIV Observational Database (AHOD) Temporary Residents Access Study (ATRAS) and to determine the short- and long-term outcomes of receiving (subsidized) optimal ART and the impact on onwards HIV transmission.MethodsATRAS was established in 2011. Eligible patients were recruited via the AHOD network. Key HIV-related characteristics were recorded at baseline and prospectively. Additional visa-related information was also recorded at baseline, and updated annually. Descriptive statistics were used to describe the ATRAS cohort in terms of visa status by key demographic characteristics, including sex, region of birth, and HIV disease status. CD4 cell count (mean and SD) and the proportion with undetectable (<50 copies/ml) HIV viral load are reported at baseline, 6 and 12 months of follow-up. We also estimate the proportion reduction of onward HIV transmission based on the reduction in proportion of people with detectable HIV viral load.ResultsA total of 180 patients were recruited to ATRAS by June 2012, and by July 2013 39 patients no longer required ART via ATRAS, 35 of whom became eligible for Medicare-funded medication. At enrolment, 63% of ATRAS patients were receiving ART from alternative sources, 47% had an undetectable HIV viral load (<50 copies/ml) and the median CD4 cell count was 343 cells/µl (IQR: 222–479). At 12 months of follow-up, 85% had an undetectable viral load. We estimated a 75% reduction in the risk of onward HIV transmission with the improved rate of undetectable viral load.ConclusionsThe immunological and virological improvements highlight the importance of supplying optimal ART to this vulnerable population. The increase in proportion with undetectable HIV viral load shows the potentially significant impact on HIV transmission in addition to the personal health benefit for each individual.