Hypersensitivity reactions, hepatotoxicity, and other discontinuations in persons receiving integrase strand transfer inhibitors: results from the EuroSIDA study.

Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use.Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort.Methods: We compared individuals ≥18 years and starting combination antiretroviral therapy (ART, ≥3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed.Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7-2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106-124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160-188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04-1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18-2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00-0.99/1000 PYFU).Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs.

Towards healthier food choices for hospital staff and visitors: impacts of a healthy food and drink policy implemented at scale in Australia.

OBJECTIVE: To determine the impact of a healthy food and drink policy on hospital staff and visitors' food purchasing behaviours, and their awareness and support for the changes introduced. DESIGN: Two repeated cross-sectional surveys, consisting of intercept interviews and observations of food items purchased, were conducted before (March-July 2018) and after (April-June 2019) the target date for implementation of thirteen food and drink practices (31 December 2018). Food purchases were coded as 'Everyday' (healthy) or 'Occasional' (unhealthy). SETTING: Ten randomly selected New South Wales public hospitals, collection sites including hospital entrances and thirteen hospital cafés/cafeterias. PARTICIPANTS: Surveys were completed by 4808 hospital staff and visitors (response rate 85 %). The majority were female (63 %), spoke English at home (85 %) and just over half had completed tertiary education (55 %). RESULTS: Significant increases from before to after the implementation target date were found for policy awareness (23 to 42 %; P < 0·0001) and support (89 to 92 %; P = 0·01). The proportion of 'Everyday' food purchases increased, but not significantly (56 to 59 %; P = 0·22); with significant heterogeneity between outlets (P = 0·0008). Overall, younger, non-tertiary-educated adults, visitors and those that spoke English at home were significantly less likely to purchase 'Everyday' food items. Support was also significantly lower in males. CONCLUSIONS: The findings provide evidence of strong policy support, an increasing awareness of related changes and a trend towards increased 'Everyday' food purchasing. Given the relatively early phase of policy implementation, and the complexity of individual food purchasing decisions, longer-term follow-up of purchasing behaviour is recommended following ongoing implementation efforts.

Is Cohort Representativeness Passé? Poststratified Associations of Lifestyle Risk Factors with Mortality in the UK Biobank.

BACKGROUND: The UK Biobank (UKB) has been used widely to examine associations between lifestyle risk factors and mortality outcomes. It is unknown whether the extremely low UKB response rate (5.5%) and lack of representativeness materially affects the magnitude and direction of effect estimates. METHODS: We used poststratification to match the UKB sample to the target population in terms of sociodemographic characteristics and prevalence of lifestyle risk factors (physical inactivity, alcohol intake, smoking, and poor diet). We compared unweighted and poststratified associations between each lifestyle risk factor and a lifestyle index score with all-cause, cardiovascular disease (CVD), and cancer mortality. We also calculated the unweighted to poststratified ratio of HR (RHR) and 95% confidence interval as a marker of effect-size difference. RESULTS: Of 371,974 UKB participants with no missing data, 302,009 had no history of CVD or cancer, corresponding to 3,298,958 person years of follow-up. Protective associations between alcohol use and CVD mortality observed in the unweighted UKB were substantially altered after poststratification, for example, from a hazard ratio (HR) of 0.63 (0.45-0.87) unweighted to 0.99 (0.65-1.50) poststratified for drinking ≥5 times/week versus never drinking. The magnitude of the poststratified all-cause mortality hazard ratio comparing least healthy with healthiest tertile of lifestyle risk factor index was 9% higher (95% confidence interval: 4%, 14%) than the unweighted estimates. CONCLUSIONS: Lack of representativeness may distort the associations of alcohol with CVD mortality, and may underestimate health hazards among those with cumulatively the least healthy lifestyles.

Glycemic Control Following GLP-1 RA or Basal Insulin Initiation in Real-World Practice: A Retrospective, Observational, Longitudinal Cohort Study.

INTRODUCTION: Injectable therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and basal insulin (BI) are well-established agents for people with type 2 diabetes (T2D). This study aimed to investigate real-world effectiveness of GLP-1 RAs or BI in adults with T2D poorly controlled on oral antihyperglycemic drugs (OADs). METHODS: This was a retrospective, observational, longitudinal cohort study of adults with T2D from the US Optum Humedica® database and UK Clinical Practice Research Datalink, who initiated either injectable between January 1, 2010, and June 30, 2016. Baseline characteristics, glycated hemoglobin (HbA1c) change, and cumulative percentage reaching HbA1c < 7% in 24 months after initiation were analyzed in four patient cohorts. RESULTS: In the US and UK databases, respectively, 20,836 and 5508 patients initiated GLP-1 RAs and 60,598 and 5083 initiated BI. Baseline mean HbA1c at initiation ranged between 8.8% and 10.3% across all cohorts. In all cohorts, a decrease of HbA1c occurred 3-6 months after initiation. The cumulative percentage of patients reaching HbA1c < 7% showed the greatest probability in the first 12 months (15-40% of patients across cohorts at 12 months), particularly in the first 6 months after initiation. The probability of reaching glycemic control diminished after the second quarter. The proportion of patients reaching HbA1c < 7% in both GLP-1 RA and BI cohorts at 12 months was < 25% if baseline HbA1c was ≥ 9%. CONCLUSIONS: For adults with T2D inadequately controlled on OADs, this analysis reveals an unmet clinical need. Initiation of first injectable therapy did not occur until HbA1c was considerably above target, when control is harder to achieve. Results suggest that in individuals with baseline HbA1c ≥ 9.0%, only a minority are likely to achieve an HbA1c < 7% with a GLP-1 RA or BI alone.

Weight change among repeat participants of an Aboriginal community-based weight loss program.

BACKGROUND: Community-based weight loss programs may have potential to address overweight and obesity at the population level. However, participation patterns and individual outcomes from these programs are understudied. This study examined repeat participation patterns and participant weight change between contests over seven years of an Aboriginal Australian team-based program in order to identify (1) predictors of repeat participation and (2) associations with weight change between contests. METHODS: Data for the 12 contests from 2012 to 2018 were merged, with probabilistic record matching. A total of 7510 enrolments were registered for the 12 contests, representing 4438 unique people. Contest lengths varied from 10 to 16 weeks in duration. Non-repeat participants were those who only competed once in the program by the end of 2018, and repeaters were those who competed in at least two contests. Associations between repeat participation and participant baseline (i.e., first participation occasion) characteristics, change in diet and physical activity and percent change in weight during the first participation occasion were examined using crossed random effects (for person and team) regression adjusted for exposure to the program. Weight percentage change between contests was calculated for consecutive participation occasions occurring at least three months apart, converted to percent change per month. Weight change was regressed on number of repeat participation occasions adjusted for age, gender, baseline weight at first participation occasion, and weight percent change in the immediately preceding contest. RESULTS: One-third of the 4433 participants participated more than once, with women more likely than men to repeat. A 1% reduction in weight during a competition was associated with an increase in weight of 0.05% per month between competition end and subsequent participation. Regain was smaller the heavier participants were at their first participation. CONCLUSIONS: While individuals benefit from weight loss through program participation, strengthening strategies for weight loss maintenance within or following the program could improve long-term weight outcomes and reduce weight cycling.

Sociodemographic factors associated with food insecurity: data from the 2003-2014 New South Wales Population Health Survey.

OBJECTIVE: To determine the prevalence and sociodemographic factors associated with food insecurity in the state of New South Wales (NSW), Australia. DESIGN: Cross-sectional analysis of food insecurity data collected by the NSW Population Health Survey between 2003 and 2014. Multiple logistic regression was used to examine associations with key sociodemographic variables. SETTING: NSW, Australia. PARTICIPANTS: 212 608 survey participants responded to the food insecurity survey question between 2003 and 2014. 150 767 of them were aged ≥16 years. The survey sample was randomly selected and weighted to be representative of the NSW population. RESULTS: On average 6 % of adults aged ≥16 years experienced food insecurity in NSW. The odds of food insecurity appeared to increase from one survey year to the next by a factor of 1·05. Food insecurity was found to be independently associated with age, sex, marital status, household size, education, employment status, household income, smoking status, alcohol intake and self-rated health. The association with income, smoking status and self-rated health appeared to be the strongest among all covariates and showed a gradient effect. Food insecurity appeared to increase significantly between the age of 16 and 19 years. CONCLUSIONS: The prevalence of food insecurity appears to be rising over time. Given the negative health consequences of food insecurity, more rigorous measurement and monitoring of food insecurity in NSW and nationally is strongly recommended. The findings provide support for interventions targeting low-income and younger population groups.

Beyond weight loss: Impact of a weight management programme for mid-older Australians in private health insurance.

Weight-loss maintenance and lifestyle behaviour necessary to manage weight are undisputedly challenging. We evaluated a secondary prevention weight-loss maintenance programme for participants (n = 490) with weight-related chronic disease in the Australian private health insurance setting. This study investigated the impact of the maintenance programme on anthropometric and lifestyle risk behaviour changes after 6 and 12 months, and trends in weight-loss maintenance after 1 year. Using a pre- and post-test design, data were analysed with generalized linear mixed models for repeated measures to determine the effect of the programme on weight loss and lifestyle behaviour outcomes. After initially losing a clinically significant amount of weight (mean 9.1 kg), maintenance-programme participants maintained clinically significant weight loss (mean 7.6 kg) at 12 months. Rates of discontinuation in the programme were high (47% at 6 months and 73% at 12 months). Weight-loss maintenance was achieved by 76% of participants at 3 months and 62% at 6 months, stabilizing at 55% and 56% at 9 and 12 months, respectively. Greater initial weight loss was associated with weight-loss maintenance at 12 months. Participants <55 years demonstrated consistent weight-loss maintenance over this time but the odds for successful weight-loss maintenance for those ≥55 years continued to decrease over time. At maintenance-baseline, 68.3% of participants had sufficient physical activity for health; 61.4% and 19.8% met recommended fruit and vegetable consumption, respectively. All lifestyle risk behaviours were maintained at 12 months. A programme extending support strategies for maintaining weight-related behaviour shows promise to successfully support these changes over 12 months. There is a potentially important opportunity for targeted intervention at 6 to 9 months.

Cause-specific mortality after diagnosis of cancer among HIV-positive patients: A collaborative analysis of cohort studies.

People living with HIV (PLHIV) are more likely than the general population to develop AIDS-defining malignancies (ADMs) and several non-ADMs (NADMs). Information is lacking on survival outcomes and cause-specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996-2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause-specific mortality rates (MR) after diagnosis of specific cancers and compared 5-year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006-2015: ADMs 102 (95% CI 92-113) per 1,000 years versus 88 (78-100), viral NADMs 134 (106-169) versus 111 (93-133) and nonviral NADMs 264 (232-300) versus 226 (206-248). Estimated 5-year survival for PLHIV diagnosed with liver (29% [19-39%]), lung (18% [13-23%]) and cervical (75% [63-84%]) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% [67-81%]). Among ART-treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS.

Differences between patients with type 1 diabetes with optimal and suboptimal glycaemic control: A real-world study of more than 30 000 patients in a US electronic health record database.

AIMS: To use electronic health record data from real-world clinical practice to assess demographics, clinical characteristics and disease burden of adults with type 1 diabetes (T1D) in the United States. MATERIALS AND METHODS: Retrospective observational study of adults with T1D for ≥24 months at their first visit with a T1D diagnosis code ("index date") between July 2014 and June 2016 in the Optum Humedica database. Demographic characteristics, acute complications (severe hypoglycaemia [SH], diabetic ketoacidosis [DKA]), microvascular complications, cardiovascular (CV) events and health care resource utilization during the 12 months before the index date ("baseline period") were compared between patients with optimal versus suboptimal glycaemic control (glycated haemoglobin [HbA1c] <7.0% vs. ≥7.0% [53 mmol/mol]) at the closest measurement to the index date. RESULTS: Of 31 430 adults with T1D, 79.9% had suboptimal glycaemic control (mean HbA1c 8.8% [73 mmol/mol]). These patients were more likely to be younger, African American, uninsured or on Medicaid, obese, smokers, have uncontrolled hypertension and have depression. Despite worse glycaemic control and increased CV risk factors of uncontrolled hypertension, obesity and smoking, rates of coronary heart disease and stroke were not higher in these patients. Patients with suboptimal glycaemic control also experienced more diabetes complications (including SH, DKA and microvascular disease) and utilized more emergency care, with more emergency department visits and inpatient stays. CONCLUSION: This real-world study of >30 000 adults with T1D showed that individuals with suboptimal versus optimal glycaemic control differed significantly in terms of health care coverage, comorbidities, diabetes-related complications, health care utilization and CV risk factors. However, suboptimal control was not associated with increased risk of CV outcomes.

Incidences of Severe Hypoglycemia and Diabetic Ketoacidosis and Prevalence of Microvascular Complications Stratified by Age and Glycemic Control in U.S. Adult Patients With Type 1 Diabetes: A Real-World Study.

OBJECTIVE: To assess the burden of disease for adults with type 1 diabetes in a U.S. electronic health record database by evaluating acute and microvascular complications stratified by age and glycemic control. RESEARCH DESIGN AND METHODS: This is a retrospective observational study of adults with type 1 diabetes (1 July 2014-30 June 2016) classified using a validated algorithm, with disease duration ≥24 months and, during a 12-month baseline period, not pregnant and having one or more insulin prescriptions and one or more HbA1c measurements. Demographic characteristics, acute complications (severe hypoglycemia [SH], diabetic ketoacidosis [DKA]), and microvascular complications (neuropathy, nephropathy, retinopathy) were stratified by age (18-25, 26-49, 50-64, ≥65 years) and glycemic control (HbA1c <7%, 7% to <9%, ≥9%). RESULTS: Of 31,430 patients, ∼20% had HbA1c <7%. Older patients had lower HbA1c values than younger patients (P < 0.001). Patients with poor glycemic control had the highest annual incidence of SH (4.2%, 4.0%, and 8.3%) and DKA (1.3%, 2.8%, and 15.8%) for HbA1c <7%, 7% to <9%, and ≥9% cohorts, respectively (both P < 0.001), and a higher prevalence of neuropathy and nephropathy (both P < 0.001). CONCLUSIONS: For adults with type 1 diabetes, glycemic control appears worse than previously estimated. Rates of all complications increased with increasing HbA1c. Compared with HbA1c <7%, HbA1c ≥9% was associated with twofold and 12-fold higher incidences of SH and DKA, respectively. Younger adults had more pronounced higher risks of SH and DKA associated with poor glycemic control than older adults.

Cessation of Cigarette Smoking and the Impact on Cancer Incidence in Human Immunodeficiency Virus-infected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study.

Background: Cancers are a major source of morbidity and mortality for human immunodeficiency virus (HIV)-infected persons, but the clinical benefits of smoking cessation are unknown. Methods: Participants were followed from 1 January 2004 until first cancer diagnosis, death, or 1 February 2016. Smoking status was defined as ex-smoker, current smoker, and never smoker. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression, adjusting for demographic and clinical factors. Results: In total 35442 persons from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study contributed 309803 person-years of follow-up. At baseline, 49% were current smokers, 21% were ex-smokers, and 30% had never smoked. Incidence of all cancers combined (n = 2183) was highest <1 year after smoking cessation compared to never smokers (aIRR, 1.66 [95% confidence interval {CI}, 1.37-2.02]) and not significantly different from never smokers 1-1.9 years after cessation. Lung cancer incidence (n = 271) was elevated <1 year after cessation (aIRR, 19.08 [95% CI, 8.10-44.95]) and remained 8-fold higher 5 years after smoking cessation (aIRR, 8.69 [95% CI, 3.40-22.18]). Incidence of other smoking-related cancers (n = 622) was elevated in the first year after cessation (aIRR, 2.06 [95% CI, 1.42-2.99]) and declined to a level similar to nonsmokers thereafter. Conclusions: Lung cancer incidence in HIV-infected individuals remained elevated >5 years after smoking cessation. Deterring uptake of smoking and smoking cessation efforts should be prioritised to reduce future cancer risk.

Determinants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1-Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapy.

BACKGROUND: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. METHODS: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. RESULTS: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm. DISCUSSION: Starting ART with a CD4 cell count of ≥500 cells/mm makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals because of persisting high CD8 cell counts. To what extent these subnormal immunological responses affect specific clinical endpoints requires further investigation.

Variation in antiretroviral treatment coverage and virological suppression among three HIV key populations.

OBJECTIVES: We assessed differences in antiretroviral treatment (ART) coverage and virological suppression across three HIV key populations, as defined by self-reported HIV transmission category: sex between men, injection drug use (IDU) and heterosexual transmission. DESIGN: A multinational cohort study. METHODS: Within the EuroSIDA study, we assessed region-specific percentages of ART-coverage among those in care and virological suppression (<500 copies/ml) among those on ART, and analysed differences between transmission categories using logistic regression. RESULTS: Among 12 872 participants followed from 1 July 2014 to 30 June 2016, the percentages of ART-coverage and virological suppression varied between transmission categories, depending on geographical region (global P for interaction: P = 0.0148 for ART-coverage, P = 0.0006 for virological suppression). In Western [adjusted odds ratio (aOR) 1.41 (95% confidence interval 1.14-1.75)] and Northern Europe [aOR 1.68 (95% confidence interval 1.25-2.26)], heterosexuals were more likely to receive ART than MSM, while in Eastern Europe, there was some evidence that infection through IDU [aOR 0.60 (95% confidence interval 0.31-1.14)] or heterosexual contact [aOR 0.58 (95% confidence interval 0.30-1.10)] was associated with lower odds of receiving ART. In terms of virological suppression, people infected through IDU or heterosexual contact in East Central and Eastern Europe were around half as likely as MSM to have a suppressed viral load on ART, while we observed no differences in virological suppression across transmission categories in Western and Northern Europe. CONCLUSION: In our cohort, patterns of ART-coverage and virological suppression among key populations varied by geographical region, emphasizing the importance of tailoring HIV programmes to the local epidemic.

Persistent disparities in antiretroviral treatment (ART) coverage and virological suppression across Europe, 2004 to 2015.

BACKGROUND: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection. AIM: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA < 500 copies/mL) across Europe and explored temporal trends. METHODS: In three cross-sectional analyses in 2004-05, 2009-10 and 2014-15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression. RESULTS: Overall, the percentage of people on ART increased from 2004-05 (67.8%) to 2014-15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004-05, 87.7% in 2014-15). However, the rate of improvement over time varied significantly between regions (p < 0.01). In 2014-15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014-15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13-0.21) in Eastern Europe. CONCLUSIONS: Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA.

Cascade of care and factors associated with virological suppression among HIV-positive persons linked to care in the Test and Keep in Care (TAK) project.

INTRODUCTION: Early treatment remains the most effective HIV prevention strategy; poor linkage to care after HIV diagnosis may compromise this benefit. We sought to better understand patient characteristics and their association with virological suppression (VS) following cART initiation. METHODS: The TAK project collects pre-linkage to care and clinical data on patients diagnosed with HIV in voluntary testing facilities in central Poland. Data collected for persons diagnosed in 2010-2013 were linked with HIV clinic records. Individuals linked to care who commenced cART were followed from until the earliest of first VS (HIV RNA < 50 copies/ml), last visit, death or 6 January 2016. Cox-proportional hazard models were used to identify factors associated with first viral suppression. RESULTS: 232 persons were HIV positive, 144 (62%, 95% CI 55, 68%) linked to care, 116 (81% of those linked to care, 95% CI 73, 87%) started cART during follow up, of which 113 (97%, 95% CI 93, 99%) achieved VS. Non-PI based regimen (for integrase inhibitors aHR: 5.03: 1.90, 13.32) and HLA B5701-positive (aHR: 3.97: 1.33, 11.85) were associated with higher chance of VS. Unknown syphilis status (aHR: 0.27: 0.13, 0.57) and higher HIV RNA (aHR a tenfold increase: 0.56: 0.42, 0.75) remained associated with lower chance of VS. CONCLUSIONS: Although a low proportion of persons were linked to care, almost all those linked to care started cART and achieved rapid VS. The high rates of VS were irrespective of prior HIV-associated risk behaviours. Linkage to care remains the highest priority in prevention strategies in central Poland.

Increased non-AIDS mortality among persons with AIDS-defining events after antiretroviral therapy initiation.

INTRODUCTION: HIV-1 infection leads to chronic inflammation and to an increased risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining events (ADEs) were associated with increased overall and cause-specific non-AIDS related mortality after antiretroviral therapy (ART) initiation. METHODS: We included HIV treatment-naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model. RESULTS: The adjusted hazard of overall non-AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause-specific non-AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL). CONCLUSIONS: In this large multi-centre cohort collaboration with standardized assignment of causes of death, non-AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non-AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma.

Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided. Results: Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate = 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] = 1.06 to 1.30) and 149 developed HL (incidence rate = 0.44/1000 PYFU, 95% CI = 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 = 8.08, 95% CI = 5.63 to 11.61; HL = 4.58, 95% CI = 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL = 1.97, 95% CI = 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile = 2.91, 95% CI = 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL. Conclusions: CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.

CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: a multinational, multicohort European study.

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2.

Poor Linkage to Care Despite Significant Improvement in Access to Early cART in Central Poland - Data from Test and Keep in Care (TAK) Project.

BACKGROUND: The main objective of the TAK project is investigating barriers in accessing HIV care after HIV-diagnosis at the CBVCTs of central Poland. Here we describe factors associated with and changes over time in linkage to care and access to cART. METHOD: Data collected in 2010-2013 in CBVCTs were linked with HIV clinics records using unique identifiers. Individuals were followed from the day of CBVCTs visit until first clinical visit or 4/06/2014. Cox-proportional hazard models were used to identify factors associated with being linked to care and starting cART. RESULTS: In total 232 persons were diagnosed HIV-positive and 144 (62.1% 95%CI: 55.5-68.3) persons were linked to care. There was no change over time in linkage to care (p = 0.48), while time to starting cART decreased (p = 0.02). Multivariate factors associated with a lower rate of linkage to care were hetero/bisexual sexual orientation, lower education, not having an HIV-positive partner and not using condoms in a stable relationship. Multivariate factors associated with starting cART were lower education, recent year of linked to care, and first HIV RNA and CD4 cell count. CONCLUSIONS: Benefits of linkage to care, measured by access to early treatment, steadily improved in recent years. However at least 1 in 3 persons aware of their HIV status in central Poland remained outside professional healthcare. Persons at higher risk of remaining outside care, thus target population for future interventions, are bi/heterosexuals and those with lower levels of education.