Kathleen Falster

Long-Term Patterns in CD4 Response Are Determined by an Interaction Between Baseline CD4 Cell Count, Viral Load, and Time: The Asia Pacific HIV Observational Database (APHOD)

Background:Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time and, in particular, the role of baseline and follow-up covariates. Methods:Patients in Asia Pacific HIV Observational Database who first commenced cART after January 1, 1997, and who had a baseline CD4 cell count and viral load measure and at least 1 follow-up measure between 6 and 24 months, were included. CD4 cell counts were determined at every 6-month period after the commencement of cART for up to 6 years. Results:A total of 1638 patients fulfilled the inclusion criteria with a median follow-up time of 58 months. Lower post-cART mean CD4 cell counts were found to be associated with increasing age (P < 0.001), pre-cART hepatitis C coinfection (P = 0.038), prior AIDS (P = 0.019), baseline viral load ≤100,000 copies per milliliter (P < 0.001), and the Asia Pacific region compared with Australia (P = 0.005). A highly significant 3-way interaction between the effects of time, baseline CD4 cell count, and post-cART viral burden (P < 0.0001) was demonstrated. Higher long-term mean CD4 cell counts were associated with lower baseline CD4 cell count and consistently undetectable viral loads. Among patients with consistently detectable viral load, CD4 cell counts seemed to converge for all baseline CD4 levels. Conclusions:Our analyses suggest that the long-term shape of post-cART CD4 cell count changes depends only on a 3-way interaction between baseline CD4 cell count, viral load response, and time.

Hepatitis C Virus Acquisition among Injecting Drug Users: A Cohort Analysis of a National Repeated Cross-sectional Survey of Needle and Syringe Program Attendees in Australia, 1995–2004

High hepatitis C virus (HCV) prevalence has been documented among many injecting drug user (IDU) populations worldwide; however, there is limited published data on trends in incidence of infection in these epidemics over time. To address this, we used a novel method of analyzing data collected via repeat, cross-sectional sero-surveys by injection initiation cohorts to investigate trends in HCV seropositivity among a population of needle and syringe program (NSP) attendees in Australia between 1995 and 2004, and thereby infer annual incidence trends. Injection initiation cohorts were defined by their time of entry into the IDU population. We also investigated the associations between HCV antibody seroprevalence and risk factor data, and trends in risk factor data over the decade. Approximately 20,000 NSP attendees participated in the study over the 10-year period. Within each injection initiation cohort, we found an increase in HCV prevalence over time, with prevalence appearing to reach saturation around 90%. There was little indication that the slopes of increase had changed with more recent initiation cohorts. While duration of injecting was most strongly associated with HCV seropositivity in this study, we also found that self-reported history of needle and syringe sharing and imprisonment were independently associated with higher HCV prevalence regardless of duration of injecting, with the exception of IDUs who have 15 or more years injecting experience. In this group, recent risk behavior had no relationship to prevalence. In summary, our findings suggest a persistent HCV epidemic despite significant harm reduction efforts in Australia since the mid-1980s, with HIV incidence effectively constant in successive initiation cohorts.

Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment

OBJECTIVES To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006. METHODS We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts. RESULTS We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81-92%) and two large, community-based surveys in Australia (69-85% and 49-83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria; however, the sample size was very small. CONCLUSIONS For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.

Poor baseline immune function predicts an incomplete immune response to combination antiretroviral treatment despite sustained viral suppression.

Objectives:To determine the prevalence and predictors of an incomplete immune response in patients with sustained viral suppression after starting their first or second combination antiretroviral treatment (cART) regimen. Methods:All patients were recruited to the Australian HIV Observational Database (AHOD) by March 2006. Data were analyzed to assess the prevalence of an incomplete immune response (<350 cells/μL) in the 12-24 months after starting the first or second cART regimen. Factors associated with an incomplete immune response were assessed using logistic regression and time to AIDS/death was assessed using survival analysis. Results:Of the 2493 patients recruited to AHOD by March 2006, 590 were eligible for the analysis. Twenty-eight percent of patients with a baseline CD4 count <350 cells per microliter had an incomplete immune response 12-24 months after starting their first or second cART regimen. Lower baseline CD4 count before starting the cART regimen was predictive of an incomplete immune response. There was a nonsignificant trend toward faster AIDS or death in incomplete immune responders. Conclusions:An incomplete immune response in patients with sustained viral suppression is associated with poorer immune function before starting cART. Type of cART or individual antiretroviral drug was not associated with an incomplete immune response.

AIDS-related and non-AIDS-related mortality in the Asia-Pacific region in the era of combination antiretroviral treatment

Objective:Although studies have shown reductions in mortality from AIDS after the introduction of combination antiretroviral treatment (cART), little is known about cause-specific mortality in low-income settings in the cART era. We explored predictors of AIDS and non-AIDS mortality and compared cause-specific mortality across high-income and low-income settings in the Asia-Pacific region. Methods:We followed patients in the Asia Pacific HIV Observational Database from the date they started cART (or cohort enrolment if cART initiation was identified retrospectively), until the date of death or last follow-up visit. Competing risks methods were used to estimate the cumulative incidence, and to investigate predictors, of AIDS and non-AIDS mortality. Results:Of 4252 patients, 215 died; 89 from AIDS, 97 from non-AIDS causes and 29 from unknown causes. Age more than 50 years [hazard ratio 4.29; 95% confidence interval (CI) 2.10–8.79] and CD4 cell counts less than or equal to 100 cells/μl (hazard ratio 8.59; 95% CI 5.66–13.03) were associated with an increased risk of non-AIDS mortality. Risk factors for AIDS mortality included CD4 cell counts less than or equal to 100 cells/μl (hazard ratio 34.97; 95% CI 18.01–67.90) and HIV RNA 10 001 or more (hazard ratio 4.21; 95% CI 2.07–8.55). There was some indication of a lower risk of non-AIDS mortality in Asian high-income, and possibly low-income, countries compared to Australia. Conclusion:Immune deficiency is associated with an increased risk of AIDS and non-AIDS mortality. Older age predicts non-AIDS mortality in the cART era. Less conclusive was the association between country-income level and cause-specific mortality because of the relatively high proportion of unknown causes of death in low-income settings.

Hospitalizations in a cohort of HIV patients in Australia, 1999―2007

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.

Inequalities in unintentional injuries between indigenous and non-indigenous children: a systematic review

Background Indigenous children suffer a disproportionally high burden of unintentional injuries. A more detailed understanding of the underlying causes, risk factors and gaps in research is required to inform prevention efforts and direct future research. The aim of this review was to systematically assess the evidence regarding differences in rates of unintentional injuries between indigenous and non-indigenous children and to identify leading causes and underlying risk factors contributing to these differences. Method We systematically searched the literature including 10 electronic databases, institutional websites and reference lists of relevant studies. Due to the substantial heterogeneity between studies, results were summarised in a narrative synthesis and no meta-analysis was carried out. Results A total of 39 studies were included in this review. Most studies were descriptive and only five adjusted for potential confounding in the analysis. Indigenous to non-indigenous rate ratios for morbidity and mortality for unintentional injury ranged from 1.2 to 2.3 and 1.8 to 8.2, respectively. The difference varied greatly by cause of injury and between studies, ranging from a reduced risk of hospitalisation due to fall injuries to a 17-fold increased risk of mortality due to pedestrian injuries. Burns, poisoning and transport injuries were the major contributors to the increased injury burden in indigenous children. The studies offered only limited insight into the underlying causes of these differences, but socioeconomic status and parents’ educational attainment were contributing factors. Conclusions Indigenous children experience a significantly higher burden of morbidity and mortality from unintentional injuries across different indigenous communities worldwide. Most of these injuries are highly preventable, presenting substantial potential to improve indigenous child health. However, there is limited evidence to illuminate the underlying risk factors for unintentional injuries in indigenous children, and this is a priority for further research.

What factors contribute to positive early childhood health and development in Australian Aboriginal children? Protocol for a population-based cohort study using linked administrative data (The Seeding Success Study)

Introduction Australian Aboriginal children are more likely than non-Aboriginal children to have developmental vulnerability at school entry that tracks through to poorer literacy and numeracy outcomes and multiple social and health disadvantages in later life. Empirical evidence identifying the key drivers of positive early childhood development in Aboriginal children, and supportive features of local communities and early childhood service provision, are lacking. Methods and analysis The study population will be identified via linkage of Australian Early Development Census data to perinatal and birth registration data sets. It will include an almost complete population of children who started their first year of full-time school in New South Wales (NSW), Australia, in 2009 and 2012. Early childhood health and development trajectories for these children will be constructed via linkage to a range of administrative data sets relating to birth outcomes, congenital conditions, hospital admissions, emergency department presentations, receipt of ambulatory mental healthcare services, use of general practitioner services, contact with child protection and out-of-home care services, receipt of income assistance and fact of death. Using multilevel modelling techniques, we will quantify the contributions of individual-level and area-level factors to variation in early childhood development outcomes in Aboriginal and non-Aboriginal children. Additionally, we will evaluate the impact of two government programmes that aim to address early childhood disadvantage, the NSW Aboriginal Maternal and Infant Health Service and the Brighter Futures Program. These evaluations will use propensity score matching methods and multilevel modelling. Ethics and dissemination Ethical approval has been obtained for this study. Dissemination mechanisms include engagement of stakeholders (including representatives from Aboriginal community controlled organisations, policy agencies, service providers) through a reference group, and writing of summary reports for policy and community audiences in parallel with scientific papers.

Inequalities in hospitalized unintentional injury between Aboriginal and non-Aboriginal children in New South Wales, Australia

OBJECTIVES To quantify inequalities in rates of unintentional injury-related hospitalizations between Australian Aboriginal and non-Aboriginal children. METHODS We used linked hospital and mortality data to construct a retrospective whole-of-population birth cohort including 1,124,717 children born in the state of New South Wales, Australia, between July 1, 2000 and December 31, 2012. We adjusted hazard ratios (HRs) of first injury hospitalization for geographic clustering and individual- and area-level factors. RESULTS Aboriginal children were 1.6 times more likely than were non-Aboriginal children to be hospitalized for an unintentional injury. The largest inequalities were for poisoning (HR = 2.7; 95% CI = 2.4, 3.0) and injuries stemming from exposure to fire, flames, heat, and hot substances (HR = 2.4; 95% CI = 2.1, 2.7). Adjustment reduced the inequality for all unintentional injury overall (HR = 1.4; 95% CI = 1.3, 1.4) and within leading injury mechanisms. CONCLUSIONS Australian Aboriginal children suffer a disproportionately high burden of unintentional injury.

Closing the Aboriginal child injury gap: targets for injury prevention

Objective: To describe the leading mechanisms of hospitalised unintentional injury in Australian Aboriginal children and identify the injury mechanisms with the largest inequalities between Aboriginal and non‐Aboriginal children.