Keith Chan

Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database

ObjectiveTo provide population-based estimates of the prevalence of lipodystrophy syndrome and constituent symptoms and to identify correlates of prevalent symptomology. MethodsParticipants in a province-wide HIV/AIDS treatment programme reported morphological and metabolic abnormalities. Probable lipodystrophy was defined as self-report of at least one morphological abnormality or both high cholesterol and triglyceride levels. Explanatory variables investigated included: age; sex; ethnicity; transmission risk group; CD4 cell count; plasma viral load; AIDS diagnosis; duration of infection; alternative therapy use; past, current and duration of use of antiretroviral therapy (ART) by class and specific drug; total duration of ART; and current adherence. Stepwise logistic regression identified possible determinates of lipodystrophy. ResultsOf 1035 participants, 50% appeared to have probable lipodystrophy, with 36% reporting peripheral wasting, 33% abdominal weight gain, 6% buffalo hump, and 10 and 12% increased triglyceride or cholesterol levels, respectively. In multivariate analysis, lipodystrophy was associated with older age (per year) (AOR 1.03; 95% CI 1.01, 1.04), the use of ingested alternative therapies (AOR 1.46; 95% CI 1.06, 2.01), having ever used protease inhibitors (PI) (AOR 2.63; 95% CI 1.89, 3.66), and duration of stavudine treatment (per year) (AOR 1.35; 95% CI 1.15, 1.58). In analysis limited to participants exposed to PI, after similar adjustment, the duration of lamivudine rather than stavudine treatment was associated with lipodystrophy (AOR 1.32; 95% CI 1.13, 1.53). ConclusionIncreased risk of abnormalities is associated with the use of PI, and the duration of stavudine and lamivudine treatment after adjustment for personal characteristics, clinical disease stage, duration of infection and detailed treatment history.

The cascade of HIV care in British Columbia, Canada, 1996-2011: a population-based retrospective cohort study

BACKGROUND The cascade of HIV care has become a focal point for implementation efforts to maximise the individual and public health benefits of antiretroviral therapy. We aimed to characterise longitudinal changes in engagement with the cascade of HIV care in British Columbia, Canada, from 1996 to 2011. METHODS We used estimates of provincial HIV prevalence from the Public Health Agency of Canada and linked provincial population-level data to define, longitudinally, the numbers of individuals in each of the eight stages of the cascade of HIV care (HIV infected, diagnosed, linked to HIV care, retained in HIV care, highly active antiretroviral therapy (HAART) indicated, on HAART, adherent to HAART, and virologically suppressed) in British Columbia from 1996 to 2011. We used sensitivity analyses to determine the sensitivity of cascade-stage counts to variations in their definitions. FINDINGS 13,140 people were classified as diagnosed with HIV/AIDS in British Columbia during the study period. We noted substantial improvements over time in the proportions of individuals at each stage of the cascade of care. Based on prevalence estimates, the proportion of unidentified HIV-positive individuals decreased from 49·0% (estimated range 36·2-57·5%) in 1996 to 29·0% (11·6-40·7%) in 2011, and the proportion of HIV-positive people with viral suppression reached 34·6% (29·0-43·1%) in 2011. INTERPRETATION Careful mapping of the cascade of care is crucial to understanding what further efforts are needed to maximise the beneficial effects of available interventions and so inform efforts to contain the spread of HIV/AIDS. FUNDING British Columbia Ministry of Health, US National Institute on Drug Abuse (National Institutes of Health).

Socioeconomic status, access to triple therapy, and survival from HIV-disease since 1996.

Background: In the era before highly active antiretroviral therapy (HAART), socioeconomic status was associated with survival from HIV disease. We have explored socioeconomic status, access to triple therapy (HAART), and mortality in the context of a universal healthcare system. Methods: We evaluated 1408 individuals who initiated double or triple therapy between 1 August 1996 and 31 December 1999, and were followed until 31 March 2000. Cumulative HIV-related mortality rates were estimated using Kaplan–Meier methods and Cox proportional hazards regression. Results: In the overall Cox model, we found that adherence [risk ratio (RR) 0.83; per 10% increase], CD4 cell count (RR 1.53; per 100 cell decrease), and lower socioeconomic status (RR 2.19; high versus low), were associated with HIV-related mortality. However, socioeconomic status was not significant among patients prescribed triple therapy in a stratified analysis, or in a sub-analysis restricted to patients prescribed HAART in the initial regimen. When we investigated if inequitable access to HAART by socio-economic status could explain the discrepancy, we found that persons in the lower socio-economic strata were less likely to be prescribed triple therapy even after adjustment for clinical characteristics. Conclusion: In a universal healthcare system, socioeconomic status was strongly associated with HIV-related mortality. When we investigated possible explanations for this association, we found that individuals of lower socioeconomic status were less likely to receive triple therapy after adjustment for clinical characteristics. Our findings highlight the need for the monitoring of therapeutic guidelines to ensure equitable access, as treatment strategies are updated.

Impairments, activity limitations and participation restrictions: Prevalence and associations among persons living with HIV/AIDS in British Columbia

BackgroundTo measure the prevalence of and associations among impairments, activity limitations and participation restrictions in persons living with HIV in British Columbia to inform support and care programs, policy and research.MethodsA cross-sectional population-based sample of persons living with HIV in British Columbia was obtained through an anonymous survey sent to members of the British Columbia Persons With AIDS Society. The survey addressed the experience of physical and mental impairments, and the experience and level of activity limitations and participation restrictions. Associations were measured in three ways: 1) impact of types of impairment on social restriction; 2) impact of specific limitations on social restriction; and 3) independent association of overall impairments and limitations on restriction levels. Logistic regression was used to measure associations with social restriction, while ordinal logistic regression was used to measure associations with a three-category measure of restriction level.ResultsThe survey was returned by 762 (50.5%) of the BCPWA participants. Over ninety percent of the population experienced one or more impairments, with one-third reporting over ten. Prevalence of activity limitations and participation restrictions was 80.4% and 93.2%, respectively. The presence of social restrictions was most closely associated with mental function impairments (OR: 7.0 for impairment vs. no impairment; 95% CI: 4.7 – 10.4). All limitations were associated with social restriction. Among those with ≤ 200 CD4 cells/mm3, odds of being at a higher restriction level were lower among those on antiretrovirals (OR: 0.3 for antiretrovirals vs. no antiretrovirals; 95% CI: 0.1–0.9), while odds of higher restriction were increased with higher limitation (OR: 3.6 for limitation score of 1–5 vs. no limitation, 95%CI: 0.9–14.2; OR: 24.7 for limitation score > 5 vs. no limitation, 95%CI: 4.9–125.0). Among those with > 200 CD4 cells/mm3, the odds of higher restriction were increased with higher limitation (OR: 2.7 for limitation score of 1–5 vs. no limitation, 95%CI: 1.4–5.1; OR: 8.6 for limitation score > 5 vs. no limitation, 95%CI: 3.9–18.8), as well as by additional number of impairments (OR:1.2 for every additional impairment; 95% CI:1.1–1.3).ConclusionsThis population-based sample of people living with HIV has been experiencing extremely high rates of impairments, activity limitations and participation restrictions. Furthermore, the complex inter-relationships identified amongst the levels reveal lessons for programming, policy and research in terms of the factors that contribute most to a higher quality of life.

Depressive symptoms decline among persons on HIV protease inhibitors.

Objective: To ascertain whether initiation of protease inhibitors was associated with a change in depressive symptoms among persons infected with HIV. Methods: Study subjects included men and women who were enrolled in the HIV/AIDS Drug Treatment Program and who had completed an annual participant survey before and after initiating triple combination therapy with a protease inhibitor. Depressive symptoms were assessed using the Centre for Epidemiologic Studies‐Depression scale (CES‐D). Statistical analyses to determine the change in CES‐D total and subscale scores before and after protease inhibitor use were conducted using parametric and multivariate methods. Results: Our analysis was restricted to 453 participants. Of these 234 (52%) were depressed at baseline (CES‐D score ≥ 16). Compared with nondepressed participants, depressed participants were slightly younger (p = .048), less likely to be employed (p < .001) and more likely to have an annual income less than

Antiretroviral treatment patterns and incident HIV-associated morphologic and lipid abnormalities in a population-based cohort

10,000 per annum (p < .001). After adjusting for CD4 count, employment status, income, age, and CES‐D total or subscale score at baseline, we found a significant improvement in total scale score (p = .001) and depressive mood (p = .002), positive affects (p = .005), and somatic symptoms (p = .011) subscale scores at follow‐up. There was no significant change in the interpersonal relations score over the study period. Conclusion: Our findings indicate that in addition to conferring impressive clinical benefits, protease inhibitor use is associated with a significant improvement in HIVpositive individuals’ mental health.

Non-consensual sex experienced by men who have sex with men: prevalence and association with mental health

This study provides population-based estimates of the incidence of constituent symptoms associated with HIV-related lipodystrophy syndrome. Possible predictors of symptomatology based on analysis of accrued cases are provided after adjustment for a broad range of personal, clinical, and treatment characteristics. Patients enrolled in a province-wide HIV/AIDS treatment program reported annually on the occurrence of lipoatrophy, lipohypertrophy, and elevated triglyceride and cholesterol levels. Of 1261 individuals who provided baseline data, 745 were available at follow-up, among whom incidence was 27% for lipoatrophy, 21% for lipohypertrophy, and 10% and 16% for increased triglyceride and cholesterol levels, respectively. In logistic multivariate modeling, incident lipoatrophy was associated with duration of stavudine (per quarter) (adjusted odds ratio [AOR] 1.18; 95% confidence interval [CI] 1.09-1.27) and having been diagnosed with AIDS (AOR 2.07; 95% CI 1.20-3.56). Lipohypertrophy risk increased with use of protease inhibitor (AOR 3.53; 95% CI 1.81-6.86) and stavudine (AOR 3.67; 95% CI 1.61-8.38). Incident cholesterol or triglyceride abnormalities were associated with protease inhibitor use (AOR 7.17; 95% CI 2.46-20.96) and duration of ritonavir (per quarter) (AOR 1.12; 95% CI 1.04-1.21). Our findings suggest high annual rates of incidence and a role of first line antiretroviral therapies in symptom development. These outcomes, in conjunction with the findings of others have important implications for evolving treatment patterns.

Intensive care unit admission has minimal impact on long-term mortality

Little is known about the psychosocial factors associated with sexual assault experienced by males. Men (N=358), 19-35 years of age, recruited by community outreach, completed questionnaires. Eligibility criteria included: being HIV-negative and self-identifying as gay or bisexual. Lifetime prevalence rates of childhood sexual abuse, juvenile prostitution, and adult sexual assault were determined. The mental health of this population was explored including associations between sexual victimization and mental health disorders (alcohol abuse, suicidal ideation and attempts, mood disorders, and poor self-esteem). Almost 1 in 10 of the men had engaged in juvenile prostitution, 14% were forced into sexual activity before 14 years of age, and 14% were sexually victimized after the age of 14. Those exposed to non-consensual sex were 2.9 (95% CI: 1.8-4.7) times more likely to abuse alcohol than those free of victimization. Those who reported childhood sexual abuse were 3.3 (95% CI: 1.7-6.4) times more likely to have attempted suicide. Juvenile prostitution was associated with current depression (OR=6.4; 95% CI: 2.8-14.9). Health professionals have the responsibility to respond competently and sensitively to victims of sexual violence. To do this, many need to recognize the prevalence of male sexual trauma, to deconstruct their personal beliefs about same-sex sexual violence, and to learn to ask sensitive questions in their assessment interviews.

HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort.

OBJECTIVE To measure the association between intensive care unit (ICU) admission and both hospital and long-term mortality, separate from the effect of hospital admission alone. DESIGN Retrospective cohort study. SETTING All hospitals in British Columbia, Canada, during 3 fiscal years, 1994 to 1996. PATIENTS A total of 27,103 patients admitted to ICU and 41,308 (5% random sample) patients admitted to hospital but not to ICU. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS Although ICU admission was an important factor associated with hospital mortality (odds ratio: 9.12; 95% confidence interval: 8.34-9.96), the association between ICU admission and mortality after discharge was relatively minimal (hazard ratio: 1.21; 95% confidence interval: 1.17-1.27) and was completely overshadowed by the effect of age, gender, and diagnosis. CONCLUSIONS After controlling for the effect of hospital admission, admission to ICU has minimal independent effect on mortality after discharge.

Willingness to participate and enroll in a phase 3 preventive HIV-1 vaccine trial.

ObjectiveTo assess the effect of baseline HIV reverse transcriptase (RT) and protease sequence variation on virologic outcomes in a large cohort of antiretroviral-naive patients in British Columbia, Canada. MethodsPopulation sequencing of RT and protease was performed on baseline viral RNA of all antiretroviral-naive patients first seeking treatment in British Columbia between June 1997 and August 1998 (n = 479). Relative risks of virological failure associated with genotypic differences from a ‘standard’ HIV strain (HXB2) were assessed for up to 18 months. ResultsThe prevalence of key baseline mutations known to confer resistance to RT and protease inhibitors (PI) was 3.4 and 3.8%, respectively. No statistically significant impact on virologic outcomes could be established for these patients. However, the data suggest that some individuals (harboring a M184V mutation in RT or a V82I in protease) may have benefited from pre-therapy resistance tests. ‘Secondary’ mutations in the protease associated with resistance (e.g. codons 10, 36 or 63) were common, but the presence of these secondary mutations, either alone or in combination, did not appear to result in early loss of therapeutic virological suppression. Preliminary analyses suggest that an amino acid change at codon 35 in the protease may be associated with early treatment failure. ConclusionsThe results suggest that routine genotyping of naive patients about to start antiretroviral therapy would be of benefit to a relatively small proportion of the population. Secondary mutations associated with resistance to PI alone were not found to affect virologic outcomes significantly.