Summary Background Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs—so-called triple-class ...virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000–09. Methods In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF. Findings 28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000–09. The proportion of patients with virological response after TCVF increased from 19·5% in 2000 to 57·9% in 2009 (adjusted p<0·0001). Incidence of AIDS decreased from 7·7 per 100 person-years in 2000–02 to 2·3 in 2008 and 1·2 in 2009 (adjusted p<0·0001). Mortality decreased from 4·0 per 100 person-years between 2000 and 2002 to 1·9 in 2007 and 1·4 in 2008 (unadjusted p=0·023), but the trend was not significant after adjustment (p=0·22). Interpretation A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000–09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs. Funding UK Medical Research Council.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study ...includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86–0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74–0.95) and death from infections (HR 0.86 per year, 95% CI 0.77–0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective: To report the prevalence of markers for HIV infection, hepatitis B and hepatitis C among Australian prison entrants.
Design: Cross‐sectional survey conducted over 2‐week periods in 2004, ...2007 and 2010.
Setting: Reception prisons in New South Wales, Queensland, Tasmania and Western Australia.
Participants: Individuals entering prison from the community during the survey periods.
Main outcome measure: Prevalence of anti‐HIV antibody (anti‐HIV), hepatitis B surface antigen (HBsAg), anti‐hepatitis B core antibody (anti‐HBc) and anti‐hepatitis C virus antibody (anti‐HCV).
Results: The study included 1742 prison entrants: 588 (33.8%) in 2004, 536 (30.8%) in 2007 and 618 (35.5%) in 2010. The age‐standardised prevalence estimates for anti‐HIV, HBsAg and anti‐HBc were 0.4%, 2.3% and 21.7% respectively, and remained stable over the three survey periods. The age‐standardised prevalence estimate for anti‐HCV was 29.0%; it decreased over time (33.3% in 2004 v 23.2% in 2010; P = 0.001), and this coincided with a decrease in prison entrants reporting injecting drug use (58.3% 343/588 in 2004 v 45.3% 280/618 in 2010; P < 0.001). Among injecting drug users, the prevalence of anti‐HCV was 57.2% and did not change significantly over time. Of those who were anti‐HCV positive, 33.7% (140/415) were unaware of their infection status, and 74.3% (185/249) of those who tested positive for anti‐HBc reported that they had never had hepatitis B.
Conclusions: HIV prevalence is low in the Australian prisoner population but transmission remains a risk. Despite a decrease in the proportion of prison entrants reporting injecting drug use, prevalence of hepatitis B and hepatitis C has remained high. Treatment and prevention initiatives should be prioritised for this population.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To investigate whether HIV-infected patients on a stable and fully suppressive combination antiretroviral therapy (cART) regimen could safely be monitored less often than the current recommendations ...of every 3 months.
Two thousand two hundred and forty patients from the EuroSIDA study who maintained a stable and fully suppressed cART regimen for 1 year were included in the analysis.
Risk of treatment failure, defined by viral rebound, fall in CD4 cell count, development of new AIDS-defining illness, serious opportunistic infection or death, in the 12 months following a year of a stable and fully suppressed regimen was assessed.
One hundred thirty-one (6%) patients experienced treatment failure in the 12 months following a year of stable therapy, viral rebound occurred in 99 (4.6%) patients. After 3, 6 and 12 months, patients had a 0.3% 95% confidence interval (CI) 0.1-0.5, 2.2% (95% CI 1.6-2.8) and 6.0% (95% CI 5.0-7.0) risk of treatment failure, respectively. Patients who spent more than 80% of their time on cART with fully suppressed viraemia prior to baseline had a 38% reduced risk of treatment failure, hazard ratio 0.62 (95% CI 0.42-0.90, P = 0.01).
Patients who have responded well to cART and are on a well tolerated and durably fully suppressive cART regimen have a low chance of experiencing treatment failure in the next 3-6 months. Therefore, in this subgroup of otherwise healthy patients, it maybe reasonable to extend visit intervals to 6 months, with cost and time savings to both the treating clinics and the patients.
Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and ...mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio aOR 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio aIRR 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP. Please see later in the article for the Editors' Summary
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Traumatic brain injury (TBI) may be a risk factor for criminal behaviour however multiple factors potentially confound the association. Methods Record linkage and Cox proportional hazards ...regression analyses were used to examine the association between hospital-recorded TBI (n = 7,694) and subsequent first criminal conviction in a retrospective cohort matched 1:3 with 22,905 unaffected community controls and full-sibling controls (n = 2,397). Aboriginality, substance abuse, social disadvantage, and mental illness were included in analyses as potential confounders Results In multivariable models, relative to general population controls, TBI was associated with any conviction (males: Hazard Ratio (HR) = 1.58 (95% CI 1.46 to 1.72); females: HR = 1.52 (95% CI 1.28 to 1.81)); and similar Hazard Ratios were obtained for the sibling analyses in males (HR = 1.68 (95% CI 1.31-2.18)) and females (HR 1.27 (95% CI 0.71-2.29)). TBI was also associated with violent convictions relative to the general population, (males: HR = 1.65 (95% CI 1.42 to 1.92); females HR = 1.73 (95% CI 1.21 to 2.47)), and in analyses with sibling controls in men (HR = 1.89 (95% CI 1.20-3.00)), but not in women (HR 0.73, 95% CI 0.29-1.81)). Conclusion The results support a modest causal link between TBI and criminality after comprehensive adjustment for confounding. Reducing the rate of TBI, a major public health imperative, might have benefits in terms of crime reduction.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Individuals from the ...Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 ...L between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up PYFU) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/...L. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/...L among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval CI, 20.0-21.1 per 1000 PYFU) with current CD4 200-349 cells/...L to 4.1 per 1000 PYFU (95% CI, 3.6-4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/...L. Persons with a current CD4 of 500-749 cells/...L had a significantly higher rate of ADIs (adjusted incidence rate ratio aIRR, 1.20; 95% CI, 1.10-1.32), whereas those with a current CD4 of ≥1000 cells/...L had a similar rate (aIRR, 0.92; 95% CI, .79-1.07), compared to a current CD4 of 750-999 cells/...L. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25-1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01-1.25), comparing persons with a current CD4 of 500-749 cells/...L to 750-999 cells/...L. The incidence of ADIs was higher in individuals with a current CD4 count of 500-749 cells/...L compared to those with a CD4 count of 750-999 cells/...L, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/... (ProQuest: ... denotes formulae/symbols omitted.)
Full text
Available for:
BFBNIB, NUK, PNG, UL, UM, UPUK
Objectives The presence and severity of pelvic inflammatory disease (PID) symptoms are thought to vary by microbiological etiology but there is limited empirical evidence. We sought to estimate and ...compare the rates of hospitalisation for PID temporally related to diagnoses of gonorrhoea and chlamydia. Methods All women, aged 15-45 years in the Australian state of New South Wales (NSW), with a diagnosis of chlamydia or gonorrhoea between 01/07/2000 and 31/12/2008 were followed by record linkage for up to one year after their chlamydia or gonorrhoea diagnosis for hospitalisations for PID. Standardised incidence ratios compared the incidence of PID hospitalisations to the age-equivalent NSW population. Results A total of 38,193 women had a chlamydia diagnosis, of which 483 were hospitalised for PID; incidence rate (IR) 13.9 per 1000 person-years of follow-up (PYFU) (95%CI 12.6-15.1). In contrast, 1015 had a gonorrhoea diagnosis, of which 45 were hospitalised for PID (IR 50.8 per 1000 PYFU, 95%CI 36.0-65.6). The annual incidence of PID hospitalisation temporally related to a chlamydia or gonorrhoea diagnosis was 27.0 (95%CI 24.4-29.8) and 96.6 (95%CI 64.7-138.8) times greater, respectively, than the age-equivalent NSW female population. Younger age, socio-economic disadvantage, having a diagnosis prior to 2005 and having a prior birth were also associated with being hospitalised for PID. Conclusions Chlamydia and gonorrhoea are both associated with large increases in the risk of PID hospitalisation. Our data suggest the risk of PID hospitalisation is much higher for gonorrhoea than chlamydia; however, further research is needed to confirm this finding.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
