Addressing social influences reduces antibiotic duration in complicated abdominal infection: a mixed methods study.

BACKGROUND: Antimicrobial therapy for intra-abdominal infections is often inappropriately prolonged. An intervention addressing factors influencing the duration of intravenous antibiotic use was undertaken. This study reports the antibiotic prescribing patterns before and after the intervention and a qualitative analysis of the experience of the intervention. METHODS: Quantitative: A retrospective audit of patients with complicated intra-abdominal infection before and after a multifaceted persuasive intervention was performed. Qualitative: Semi-structured interviews were performed to evaluate which elements of the intervention were perceived to be effective. RESULTS: An intervention including collaborative inter-specialty and inter-professional educational meetings, and education of all professional streams was undertaken. Quantitative: Twenty-three patients before and 22 patients after the intervention were included. The total duration of antibiotics decreased significantly following the intervention (9.2 versus 6.6 days P = 0.02). The duration of intravenous antibiotics did not change significantly (5.4 versus 4.5 days, P = 0.06). Qualitative: Eighteen health-care professionals participated. Thematic analysis indicated that a collaborative approach between senior surgical and infectious disease specialists in the pre-intervention stage led to perceived ownership and leadership of the intervention by the surgical team, which was thought critical to the success of the intervention. Conversely, the ability of nurses and pharmacists to influence antibiotic practice was considered limited and a poster promoting the intervention was perceived as ineffective. CONCLUSION: Consultant leadership and specialty ownership of the process were perceived to be critical in the success of the intervention. Antibiotic stewardship programs which address social factors may have greater efficacy to optimize antimicrobial prescribing.

Risk of cardiovascular disease in HIV-positive Queensland men receiving combined antiretroviral therapy.

UNLABELLED: Background Cardiovascular disease (CVD) is a major cause of death among HIV-positive individuals receiving combination antiretroviral therapy (cART). The risk of CVD is estimated using a variety of risk calculations, however, currently there is no specific CVD risk calculator endorsed for Australians receiving cART. METHODS: A retrospective study of 210 Queensland men older than 35 years with cART-treated HIV was conducted to estimate the prevalence of CVD and the risk of a cardiovascular event occurring within 5 years. The weighted Cohen's kappa coefficient was used to estimate the agreement between the Australian Absolute CVD Risk Calculator and the Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D) 5-year Estimated CVD Risk Equation. RESULTS: The prevalence of CVD was 31.9%. Hypertensive disease was the most prevalent CVD (25.2%). Queensland men with cART-treated HIV were at moderate risk (5%) of a cardiovascular event in the next 5 years. There was a substantial agreement (κ=0.63) between the Australian Absolute CVD Risk Calculator and the D:A:D 5-year Estimated CVD Risk Equation. CONCLUSIONS: Queensland men with cART-treated HIV are experiencing high prevalence of CVD and are at moderate risk of a CVD event in the next 5 years. Primary care guidelines should emphasise CVD prevention as a keystone for the treatment of people living with HIV.

Recent trends in early stage response to combination antiretroviral therapy in Australia.

BACKGROUND: There have been improvements in combination antiretroviral therapy (cART) over the past 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome. METHODS: Patients in the Australian HIV Observational Database who initiated treatment using mono/duo therapy prior to 1996, or using cART from 1996 onwards, were included in the analysis. Patients were stratified by era of ART initiation. Median changes in CD4(+) T-cell count and the proportion of patients with detectable HIV viral load (>400 copies/ml) were calculated over the first 4 years of treatment. Probabilities of treatment switch were estimated using the Kaplan-Meier method. RESULTS: A total of 2,753 patients were included in the analysis: 28% initiated treatment <1996 using mono/duo therapy and 72% initiated treatment ≥1996 using cART (30% 1996-1999, 12% 2000-2003, 11% 2004-2007 and 19% ≥2008). Overall CD4(+) T-cell count response improved by later era of initiation (P<0.001), although 2000-2003 CD4(+) T-cell count response was less than that for 1996-1999 (P=0.007). The average proportion with detectable viral load from 2 to 4 years post-treatment commencement by era was: <1996 mono/duo 0.69 (0.67-0.71), 1996-1999 cART 0.29 (0.28-0.30), 2000-2003 cART 0.22 (0.20-0.24), 2004-2007 cART 0.09 (0.07-0.10) and ≥2008 cART 0.04 (0.03-0.05). Probability of treatment switch at 4 years after initiation decreased from 53% in 1996-1999 to 29% after 2008 (P<0.001). CONCLUSIONS: Across the five time-periods examined, there have been incremental improvements for patients initiated on cART, as measured by overall response (viral load and CD4(+) T-cell count) and also increased durability of first-line ART regimens.

Determinants of suicide and accidental or violent death in the Australian HIV Observational Database.

BACKGROUND: Rates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: After 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.

Co-morbidity, ageing and predicted mortality in antiretroviral treated Australian men: a quantitative analysis.

BACKGROUND: Life expectancy has increased in HIV-positive individuals receiving combination antiretroviral therapy (cART); however, they still experience increased mortality due to ageing-associated comorbidities compared with HIV-negative individuals. METHODS: A retrospective study of 314 Queensland HIV-infected males on cART was conducted. The negative impact of ageing was assessed by estimating the probability of 5-year mortality; comparisons were made between an HIV-specific predictive tool (VACS index) and the Australian Bureau of Statistics (ABS) life-tables to examine potential differences attributed to HIV. The negative impact of ageing was also assessed by the prevalence of comorbidities. Associations between comorbidity and estimates of predicted mortality by regression analysis were assessed. RESULTS: The mean predicted 5-year mortality rate was 6% using the VACS index compared with 2.1% using the ABS life-table (p<0.001). The proportion of patients at predicted high risk of mortality (>9%) using the VACS index or ABS life-table were 17% and 1.8% respectively. Comorbidities were also more prevalent in this cohort compared with rates of comorbidities in age-matched Australian men from the general population. Metabolic disease (38.2%) was the most prevalent comorbidity followed by renal (33.1%) and cardiovascular disease (23.9%). Multivariate analysis demonstrated that patients with a history of cardiovascular disease had a higher predicted risk of mortality (OR=1.69;95%CI:1.17-2.45) whereas ex-smokers had a lower predicted risk of mortality (OR=0.61;95%CI:0.41-0.92). CONCLUSIONS: Using the VACS Index there is an increased predicted risk of mortality in cART-treated HIV infected Australian men compared with age-matched men using the ABS data. This increased predicted mortality risk is associated with cardiovascular disease and the number of comorbidities per subject; which suggests that the VACS Index may discriminate between high and low predicted mortality risks in this population. However, until the VACS Index is validated in Australia this data may suggest the VACS Index overestimates predicted mortality risk in this country.

Tenofovir-associated proteinuria.

Proteinuria was observed in 27% of 153 patients taking tenofovir for more than 1 year. Concomitant protease inhibitor therapy and cumulative tenofovir exposure were independently associated with proteinuria in this cohort. Proteinuria was reversible in 11 of 12 patients who ceased tenofovir because of proteinuria without altering other medications. Clinicians should be aware that tenofovir can cause reversible proteinuria in patients with HIV.

Alterations in immune function are associated with liver enzyme elevation in HIV and HCV co-infection after commencement of combination antiretroviral therapy.

The cause of liver enzyme elevation during combination antiretroviral therapy in people with human immunodeficiency virus and hepatitis C virus co-infection is unclear. We followed 12 subjects (five with alanine transaminase elevation) for 24 weeks after combination antiretroviral therapy commencement. Immune responses against hepatitis C virus, human immunodeficiency virus and other viruses were assessed by interferon-γ ELISpot. Plasma cytokines, chemokines and anti-hepatitis C virus antibody levels were measured. Those with liver enzyme elevation had higher ELISpot responses both against hepatitis C virus non-structural regions and other viral antigens, and their anti-hepatitis C virus antibody levels were consistently higher, suggesting that reconstitution of both hepatitis C virus-specific and non-hepatitis C virus-specific immune responses may be associated with liver transaminase elevation during combination antiretroviral therapy.