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Objectives We sought to compare all-cause mortality of people living with HIV and accessing care in Canada and the UK. Methods Individuals from the Canadian Observational Cohort ( CANOC) collaboration and UK Collaborative HIV Cohort ( UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy ( ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow-up as a competing risk. Results A total of 19 960 participants were included in the analysis ( CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older [median age 39 years (interquartile range ( IQR): 33, 46 years) vs. 36 years ( IQR: 31, 43 years) for UK CHIC participants], to be male (86 vs. 73%, respectively), and to report men who have sex with men ( MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person-years ( PY) of follow-up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence interval ( CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow-up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72-1.03). Conclusions Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO)'s HIV drug resistance (HIVDR) early warning indicators (EWIs) measure antiretroviral therapy (ART)-site factors associated with HIVDR prevention, without HIVDR laboratory testing. We assessed the relationship between EWIs and HIVDR acquisition using data from British Columbia, Canada. Methods Eligible patients were ART-naïve, were ≥ 19 years old, had initiated ART between 1 January 2000 and 31 December 2012, had ≥ 15 months of follow-up, and were without transmitted HIVDR. Patients were followed for acquired HIVDR until 31 March 2014, the last contact date, or death. We built logistic regression models to assess the associations and predictive ability of individual indicators and of the EWI Score (the number of indicators for which a patient did not meet the criteria) on HIVDR acquisition (to any class of HIVDR, lamivudine (3TC)/emtricitabine (FTC), nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs)]). Results All explored EWIs were associated with at least one class of HIVDR, with the exception of 'ART prescribing practices'. We observed a dose--response relationship between acquiring HIVDR to any antiretroviral class and an increasing EWI score in our predictive logistic regression model. The area under the curve was 0.848 (excellent discrimination). The adjusted odds ratios for acquiring any class of HIVDR for an EWI score of 1, 2 and ≥ 3 versus 0 were 2.30 [95% confidence Interval (CI) 1.21-4.38], 3.35 (95% CI: 1.86-6.03) and 7.26 (95% CI: 4.18-12.61), respectively. Conclusions Several EWIs were associated with and predictive of HIVDR, supporting the WHO EWIs as a component of the HIVDR prevention method in settings where HIVDR testing is not routinely or widely available. [ABSTRACT FROM AUTHOR]

Objectives To document the quality of initial HIV care in Canada using the Programmatic Compliance Score ( PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. Methods We analysed data from the Canadian Observational Cohort Collaboration ( CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy ( ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm3; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. Results Of the 7460 participants (18% female), the median score was 1.0 (Q1−Q3 1.0−2.0); 21% scored 0 and 8% scored ≥ 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio ( AHR) 1.64; 95% confidence interval ( CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score ≥ 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus ( HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000−2003) had poorer scores. Conclusions Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible. [ABSTRACT FROM AUTHOR]

Objectives Nonoccupational post-exposure prophylaxis ( nPEP) is a strategy to reduce the risk of HIV infection in those with high-risk exposure. This study characterized nPEP awareness among gay, bisexual and other men who have sex with men ( MSM) in Metro Vancouver, British Columbia, Canada after a pilot nPEP programme established in 2012. Methods Momentum Health Study participants were MSM aged ≥16 years recruited via respondent-driven sampling ( RDS) who completed a computer-assisted self-interview. Stratifying patients by HIV status, we used multivariable logistic regression with backward selection to identify factors associated with nPEP awareness. All analyses were RDS-adjusted. Results A total of 51.9% (112 of 173) of HIV-positive and 48.5% (272 of 500) of HIV-negative participants had heard of nPEP. Only 3% (five of 106) of HIV-negative participants who reported recent high-risk sex used nPEP. Generally, nPEP awareness was higher for participants who engaged in sexual activities with increased HIV transmission potential. Factors associated with greater awareness among HIV-negative participants included recent alcohol use, higher communal sexual altruism, previous sexually transmitted infection diagnosis, and greater perceived condom use self-efficacy. Other factors associated with greater awareness among HIV-negative participants included white race/ethnicity, gay sexual identity, more formal education, lower personal sexual altruism, and Vancouver residence. Greater nPEP awareness among HIV-positive participants was associated with greater perceived agency to ask sexual partners' HIV status and more frequently reporting doing so, a higher number of lifetime receptive sex partners, and greater access to condoms. Conclusions Following implementation of an nPEP pilot programme, nPEP awareness among HIV-negative MSM was 51% and use was 3%. These data support the need to expand access to and actively promote nPEP services. [ABSTRACT FROM AUTHOR]

Objectives Since 2006, the British Columbia HIV/ AIDS Drug Treatment Program ( DTP) has expanded enrolment and dramatically increased its number of participants. We examined the effect this expansion has had on the underlying cause of death in HIV-infected individuals. Methods We analysed data from participants aged 18 years and older in the DTP to measure 2-year mortality rates and causes of death from 2001 to 2012. We conducted tests of trend for all-cause and cause-specific mortality, and compared demographics and characteristics of individuals. Cox proportional hazard models were used to determine the risk of death. Results A total of 8185 participants received antiretroviral therapy ( ART) during the study period. Mortality declined from 3.88 per 100 person-years ( PY) in 2001-2002 to 2.15 per 100 PY in 2011-2012 ( P = 0.02). There were significant decreases in HIV-related deaths (2.34 to 0.56 per 100 PY; P = 0.02) and deaths attributable to chronic liver disease (0.20 to 0.09 per 100 PY; P = 0.01), cardiovascular disease (0.24 to 0.05 per 100 PY; P = 0.03) and suicides (0.47 to 0 per 100 PY; P = 0.003). Multivariate models, adjusted for age, gender, history of injecting drug use, AIDS diagnoses and baseline CD4 cell counts, demonstrated that initiation of ART in all time periods after 2001-2002 was independently associated with reduced mortality ( P < 0.001). Conclusions We observed declines in HIV-related mortality and certain non- HIV-related causes of death among participants in the BC DTP from 2001 to 2012. These findings suggest that there may be broader benefits to the increasingly liberal HIV treatment guidelines, including reductions in death caused by cardiovascular disease and chronic liver disease. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to explore non- HIV-related health care service ( NHRHS) utilization, demographic, clinical and laboratory factors associated with timely initial 'retention' in HIV care among individuals 'linked' to HIV care in British Columbia ( BC), Canada. Methods We conducted a Weibull time-to-initial-retention analysis among BC Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort participants linked in 2000-2010, who had ≥ 1 year of follow-up. We defined 'linked' as the first HIV-related service accessed following HIV diagnosis and 'retained' as having, within a calendar year, either: (i) at least two HIV-related physician visits/diagnostic tests or (ii) at least two antiretroviral therapy ( ART) dispensations, ≥ 3 months apart. Individuals were followed until they were retained, died, their last contact date, or until 31 December 2011, whichever occurred first. Results Of 5231 linked individuals (78% male; median age 39: ( Q1− Q3: 32-46) years], 4691 (90%) were retained [median time to initial retention of 9 (Q1-Q3: 5-13) months] by the end of follow-up and 540 (10%) were not. Eighty-four per cent of not retained and 96% of retained individuals used at least one type of NHRHS during follow-up. Individuals who saw a specialist for NHRHS during follow-up had a shorter time to initial retention than those who did not [adjusted hazard ratio ( aHR) 2.79; 95% confidence interval ( CI): 2.47-3.16]. However, those who saw a general practitioner ( GP) for NHRHS ( aHR 0.79; 95% CI: 0.74-0.84) and those admitted to the hospital for NHRHS ( aHR 0.60; 95% CI: 0.54-0.67), versus those who did/were not, respectively, had longer times to initial retention, as did female patients, people who inject drugs ( PWID) and individuals < 40 years old. Conclusions Overall, 84% of not retained individuals used some type of NHRHS during follow-up. Given that 71% of not retained individuals used GP NHRHS, our results suggest that GP-targeted interventions may be effective in improving time to initial retention. [ABSTRACT FROM AUTHOR]

Objectives We used population-based data to identify incident cancer cases and correlates of cancer among women living with HIV/ AIDS in British Columbia ( BC), Canada between 1994 and 2008. Methods Data were obtained from a retrospective population-based cohort created from linkage of two province-wide databases: (1) the database of the BC Cancer Agency, a province-wide population-based cancer registry, and (2) a database managed by the BC Centre for Excellence in HIV/ AIDS, which contains data on all persons treated with antiretroviral therapy in BC. This analysis included women (≥ 19 years old) living with HIV in BC, Canada. Incident cancer diagnoses that occurred after highly active antiretroviral therapy ( HAART) initiation were included. We obtained a general population comparison of cancer incidence among women from the BC Cancer Agency. Bivariate analysis ( Pearson χ2, Fisher's exact or Wilcoxon rank-sum test) compared women with and without incident cancer across relevant clinical and sociodemographic variables. Standardized incidence ratios ( SIRs) were calculated for selected cancers compared with the general population sample. Results We identified 2211 women with 12 529 person-years ( PY) of follow-up who were at risk of developing cancer after HAART initiation. A total of 77 incident cancers (615/100 000 PY) were identified between 1994 and 2008. HIV-positive women with cancer, in comparison to the general population sample, were more likely to be diagnosed with invasive cervical cancer, Hodgkin's lymphoma, non- Hodgkin's lymphoma and Kaposi's sarcoma and less likely to be diagnosed with cancers of the digestive system. Conclusions This study observed elevated rates of cancer among HIV-positive women compared to a general population sample. HIV-positive women may have an increased risk for cancers of viral-related pathogenesis. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to examine trends in initiating highly active antiretroviral therapy ( HAART) with a CD4 count ≤ 200 cells/μL and the contribution of having a CD4 count ≤ 200 cells/μL at the time of diagnosis to these trends, in British Columbia ( BC), Canada. Methods We included in the analysis treatment-naïve BC residents aged ≥ 19 years who initiated HAART from 2003 to 2012. Participants were classified as follows: Group 1: diagnosed and initiated HAART with a CD4 count > 200 cells/μL; Group 2: diagnosed with a CD4 count > 200 cells/μL and initiated HAART with a CD4 count ≤ 200 cells/μL; and Group 3: diagnosed and initiated HAART with a CD4 count ≤ 200 cells/μL. We measured trends in initiating HAART with a CD4 count ≤ 200 cells/μL and used logistic regression models to measure factors associated with initiating HAART with a CD4 count ≤ 200 cells/μL, stratified by having a CD4 count ≤ 200 cells/μL or > 200 cells/μL at the time of diagnosis. Results Between 2003 and 2012, 3506 BC residents initiated HAART. Of these, 44% (1558 of 3506) initiated HAART with a CD4 count ≤ 200 cells/μL. This proportion declined from 69% (198 of 287) in 2003 to 21% (81 of 330) in 2012 ( P < 0.001). The proportion of those in Group 3 increased from 49% (97 of 198) in 2003 to 69% (56 of 81) in 2012 ( P < 0.001). Overall, 56% (1948), 22% (776) and 22% (782) made up Groups 1, 2, and 3, respectively. In adjusted analyses, seeing a specialist was significantly associated with being in Group 3. Using injection drugs and seeing a specialist were associated with being in Group 2. Conclusions In recent years, among individuals who ever initiated HAART in BC, being diagnosed with low CD4 cell counts has become a greater contributor to initiating HAART with low CD4 cell counts. [ABSTRACT FROM AUTHOR]

Objectives Sustained optimal use of combination antiretroviral therapy ( cART) has been shown to decrease morbidity, mortality and HIV transmission. However, incomplete adherence and treatment interruption ( TI) remain challenges to the full realization of the promise of cART. We estimated trends and predictors of treatment interruption and resumption among individuals in the Canadian Observational Cohort ( CANOC) collaboration. Methods cART-naïve individuals ≥ 18 years of age who initiated cART between 2000 and 2011 were included in the study. We defined TIs as ≥ 90 consecutive days off cART. We used descriptive analyses to study TI trends over time and Cox regression to identify factors predicting time to first TI and time to treatment resumption after a first TI. Results A total of 7633 participants were eligible for inclusion in the study, of whom 1860 (24.5%) experienced a TI. The prevalence of TI in the first calendar year of cART decreased by half over the study period. Our analyses highlighted a higher risk of TI among women [adjusted hazard ratio ( aHR) 1.59; 95% confidence interval ( CI) 1.33-1.92], younger individuals ( aHR 1.27; 95% CI 1.15-1.37 per decade increase), earlier treatment initiators ( CD4 count ≥ 350 vs. < 200 cells/μL: aHR 1.46; 95% CI 1.17-1.81), Aboriginal participants ( aHR 1.67; 95% CI 1.27-2.20), injecting drug users ( aHR 1.43; 95% CI 1.09-1.89) and users of zidovudine vs. tenofovir in the initial cART regimen ( aHR 2.47; 95% CI 1.92-3.20). Conversely, factors predicting treatment resumption were male sex, older age, and a CD4 cell count < 200 cells/μL at cART initiation. Conclusions Despite significant improvements in cART since its advent, our results demonstrate that TIs remain relatively prevalent. Strategies to support continuous HIV treatment are needed to maximize the benefits of cART. [ABSTRACT FROM AUTHOR]

Objectives The extent to which clinical progression of HIV-positive patients leads to an increase in health care utilization, especially prior to their death, is unknown. Thus, we modelled trends in CD4 cell count and emergency department utilization and the likelihood of an emergency department visit leading to a transfer to an acute care-level facility prior to a patient's death from nonaccidental causes. Methods Eligible patients initiated highly active antiretroviral therapy ( HAART) in British Columbia between August 1996 and June 2006 ( n = 457). Patients were followed until their death, which occurred on or before 30 June 2007 (period in which the emergency department visit data were available). Trends were modelled using generalized mixed effects. Results Patients experienced a significantly steep decline in CD4 cell count and a corresponding increase in the number of emergency department visits and transfers to acute-level facilities in the 5 years prior to death. For every 6-month interval prior to death, the CD4 cell count decreased by 13.22 cells/μL, the risk of experiencing an emergency department visit increased by 9%, and among those ever admitted, the odds ratio of being transferred to an acute care-level facility increased by 3%. Conclusions We showed that patients experienced a steep decline in CD4 cell count, which was associated with an increase in health care utilization prior to their death. These findings highlight the substantial residual avoidable burden that unsuccessfully managed HIV disease poses, even in the HAART era. Further strategies to enhance sustained and successful engagement in care are urgently needed to mitigate high health care utilization. [ABSTRACT FROM AUTHOR]

Objectives Although combination antiretroviral therapy ( cART) can restore CD4 T-cell numbers in HIV infection, alterations in T-cell regulation and homeostasis persist. We assessed the incidence and predictors of reversing these alterations with cART. Methods ART-naïve adults (n = 4459) followed within the Canadian Observational Cohort and exhibiting an abnormal T-cell phenotype ( TCP) prior to cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T-cell count (< 532 cells/μ L), (2) lost T-cell homeostasis ( CD3 < 65% or > 85%) or (3) CD4: CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP, CD4 and CD8 T-cell percentages and absolute counts were also analysed for a median duration of 3.14 years [interquartile range ( IQR) 1.48-5.47 years]. Predictors of TCP normalization were assessed using adjusted Cox proportional hazards models. Results At baseline, 96% of pateints had CD4 depletion, 32% had lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third of patients had normalized CD4 T-cell counts, but only 85 individuals (2%) had normalized their TCP. In a multivariable model adjusted for age, measurement frequency and baseline regimen, higher baseline CD4 T-cell counts and time-dependent viral suppression independently predicted TCP normalization [hazard ratio ( HR) for baseline CD4 T-cell count = 1.42 (1.31-1.54) per 100 cells/μ L increase; P ≤ 0.0001; HR for time-dependent suppressed viral load = 3.69 (1.58-8.61); P-value ≤ 0.01]. Conclusions Despite effective cART, complete TCP recovery occurred in very few individuals and was associated with baseline CD4 T-cell count and viral load suppression. HIV-induced alterations of the TCP are incompletely reversed by long-term ART. [ABSTRACT FROM AUTHOR]

Objectives There is growing concern about access to HIV/AIDS care among injection drug users (IDUs). We examined rates of CD4 cell count monitoring and correlates among HIV-infected IDUs. Methods This prospective observational cohort study of 460 community-recruited HIV-infected IDUs was situated in a Canadian city where all medical care is provided free of charge. Over a median follow-up period of 76 months, we evaluated factors associated with CD4 cell count monitoring through a linkage with a centralized CD4 registry. Results Overall, <5% of IDUs had CD4 monitoring consistent with local therapeutic guidelines. In multivariate analyses, after adjustment for being on antiretroviral therapy [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.84–2.70, P<0.001] female gender (OR 0.71, 95% CI 0.57–0.89, P=0.003), non-White ethnicity (OR 0.75, 95% CI 0.60–0.94, P=0.014), use of methadone maintenance therapy (OR 1.66, 95% CI 1.42–1.94, P<0.001) and daily heroin use (OR 0.72, 95% CI 0.61–0.85, P<0.001) were independently associated with CD4 monitoring. Conclusions Strategies to improve CD4 surveillance among IDUs are critically important, particularly for female and non-White IDUs. Expanded treatment for heroin dependence appears to have the greatest potential for improved care. [ABSTRACT FROM AUTHOR]

We undertook this study to provide a profile of Aboriginal people initiating antiretroviral therapy and their response to treatment. Aboriginal peoples were identified through self-report. Baseline socio-demographics and risk factors were compared between Aboriginal and non-Aboriginal participants as were baseline factors associated with two consecutive plasma viral load measures below 500 copies/ml using contingency table analysis. Multivariate survival analysis of the prognostic factors associated with time to two consecutive plasma viral load measures below 500 copies/ml among eligible participants was undertaken to characterize response to antiretroviral therapy. There were 892 participants with available data for this analysis, of those 146 (16%) self-identified as Aboriginal. Aboriginal participants were more likely to be female (p 10K CDN (p

Background: High levels of antiretroviral therapy adherence are important for human immunodeficiency virus type 1 (HIV-1) suppression, yet the magnitude of adherence required to maintain it is less well characterized. Furthermore, methods to accommodate changes in adherence over time are lacking. In the present study, our objective was to determine the magnitude of antiretroviral therapy adherence needed to maintain HIV-1 suppression by use of a time-updated adherence measure that has the potential to be of use in a clinical setting.Methods: We examined a population-based cohort of HIV-1-infected subjects > or =18 years of age, residing in British Columbia, Canada, who started receiving antiretroviral therapy between 1 August 1996 and 30 September 2003, who had at least 2 consecutive viral loads <500 copies/mL and who had prescriptions filled at least 3 times during a follow-up period ending 30 September 2004. Virological failure was defined as the second of 2 consecutive viral loads >1000 copies/mL. Cox proportional hazards model was used to determine the relationship between virological failure and refill-based, time-updated surrogate measure of adherence.Results: Among the 1634 participants > or =18 years of age who initiated triple combination therapy during the study, 606 virological failure events were identified. In multivariate analyses, subjects with < or =95% adherence were 1.66 (95% confidence interval, 1.38-2.01) times more likely to experience virological failure than those with >95% adherence.Conclusions: The highest levels of antiretroviral therapy adherence are associated with higher rates of maintained virological suppression. This simple, dynamic surrogate measure of adherence overcomes the limitation of single-point-in-time calculations of adherence and may be useful in real time to determine whether an individual is exhibiting incomplete adherence. [ABSTRACT FROM AUTHOR]

Context: Guidelines for antiretroviral therapy are important for clinicians worldwide given the complexity of the field and the varied clinical situations in which these agents are used. The International AIDS Society-USA panel has updated its recommendations as warranted by new developments in the field.Objective: To provide physicians and other human immunodeficiency virus (HIV) clinicians with current recommendations for the use of antiretroviral therapy in HIV-infected adults in circumstances for which there is relatively unrestricted access to drugs and monitoring tools. The recommendations are centered on 4 key issues: when to start antiretroviral therapy; what to start; when to change; and what to change. Antiretroviral therapy in special circumstances is also described.Data Sources and Study Selection: A 16-member noncompensated panel was appointed, based on expertise in HIV research and patient care internationally. Data published or presented at selected scientific conferences from mid 2004 through May 2006 were identified and reviewed by all members of the panel.Data Extraction and Synthesis: Data that might change previous guidelines were identified and reviewed. New guidelines were drafted by a writing committee and reviewed by the entire panel.Conclusions: Antiretroviral therapy in adults continues to evolve rapidly, making delivery of state-of-the-art care challenging. Initiation of therapy continues to be recommended in all symptomatic persons and in asymptomatic persons after the CD4 cell count falls below 350/microL and before it declines to 200/microL. A nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with low-dose ritonavir each combined with 2 nucleoside (or nucleotide) reverse transcriptase inhibitors is recommended with choice being based on the individual patient profile. Therapy should be changed when toxicity or intolerance mandate it or when treatment failure is documented. The virologic target for patients with treatment failure is now a plasma HIV-1 RNA level below 50 copies/mL. Adherence to antiretroviral therapy in the short-term and the long-term is crucial for treatment success and must be continually reinforced. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy (HAART) adherence research has focused predominantly on individuals with less than optimal clinical outcomes; therefore, little is known about the experiences of individuals who sustain undetectable viral loads. The present study used a qualitative method to explore how individuals who have sustained undetectable viral loads account for their success, and to identify challenges, as well as possible needs, for continued success. Participants were 20 patients at an outpatient infectious disease clinic in an urban center. Participants completed two 60-minute interviews. The Critical Incident Technique was used to identify and classify critical incidents linked with sustaining treatment success. Of the 438 critical incidents collected, 316 were identified as helpful and 122 were identified as unhelpful. Helpful categories included resolving ambivalence, using personal strengths, and fostering helpful relationships. Unhelpful categories were mood, lack of social support, financial difficulties, and medication factors. Doing well on antiretroviral therapy is a dynamic process that requires ongoing attention from both the patient and care provider. The results of this study highlight the efforts of patients to maintain their health and remind care providers not to assume that patients are not facing continuous challenges. Findings from the present study suggest that psychosocial factors do contribute to improved clinical outcomes in patients taking HAART. [ABSTRACT FROM AUTHOR]

BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

BACKGROUND: The goal of the present study was to characterize outcome and predictors of outcome of treatment interruption (TI) in highly active antiretroviral therapy (HAART)-treated patients. METHODS: A systematic chart/database review was conducted to identify patients with nadir CD4 cell counts >200 cells/mm(3) and without acquired immunodeficiency syndrome-defining illnesses who underwent a TI. Collected data included duration and reason for TI, demographic characteristics, CD4 cell count, and plasma viral load. Human immunodeficiency virus (HIV) envelope (V3) loop genotyping was performed on plasma HIV RNA. The presence of basic residues at aa 11 and/or 25 (the '11/25' genotype) was a further possible prognostic variable of interest. Cox proportional hazards models were used to assess characteristics associated with time to HAART reinitiation after TI. RESULTS: A total of 208 of 4461 (4.7%) patients underwent TI. The study group consisted of 197 (94.7%) of 208 participants for whom V3 genotyping was successful. The median CD4 cell count at time of the initiation of TI was 620 cells/mm(3). A total of 59 (29.9%) patients reinitiated HAART after a median of 15 months. At the time of the reinitiation of HAART, the median plasma viral load was >100,000 copies/mL, and the median CD4 cell count was 260 cells/mm(3). Among the 197 study patients, there were 6 deaths, none of which was attributable to the TI. A total of 81% had plasma viral loads <50 copies/mL by 15 months of follow-up after reinitiation of HAART. In multivariate analysis, a nadir CD4 cell count < or =250 cells/mm(3) (risk ratio [RR], 2.79 [95% confidence interval [CI], 1.60-4.86]; P < .001) and the presence of the 11/25 genotype (RR, 2.07 [95% CI, 1.07-4.02]; P = .031) were positively and independently associated with faster time to HAART reinitiation, after adjusting for age and plasma virus load at the start of TI. CONCLUSIONS: Our study suggests that TI is a viable option for HIV-positive adults with nadir CD4 cell counts >250 cells/mm(3). A nadir CD4 cell count of 200-250 cells/mm(3) and the 11/25 viral genotype were found to be associated with a faster HAART reinitiation. Copyright © 2005 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. [ABSTRACT FROM AUTHOR]

Background: The safety of delaying highly active antiretroviral therapy (HAART) in HIV-infected patients is uncertain when the CD4+ cell count declines below 0.350 x 10(9) cells/L.Objective: To evaluate the effect of baseline CD4+ cell count and adherence to HAART on survival rates.Design: Prospective observational study.Setting: Province-wide Canadian HIV/AIDS treatment program.Patients: 1422 HIV-infected persons initiating HAART between 1 August 1996 and 31 July 2000 and followed through 31 March 2002.Measurements: Patients were stratified by baseline CD4+ cell count and adherence level. Cumulative mortality rates were evaluated by using Kaplan-Meier methods and Cox regression-estimated adjusted relative hazards.Results: Kaplan-Meier analyses showed no survival benefit of starting HAART at a CD4+ count of 0.200 x 10(9) cells/L or greater among adherent patients. Adjusted analysis showed that compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, nonadherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically elevated mortality rates (adjusted relative hazard, 2.56 [95% CI, 1.36 to 4.84]; P = 0.004). However, compared with adherent patients who initiated HAART at a CD4+ cell count of 0.350 x 10(9) cells/L or greater, adherent patients who initiated HAART when the CD4+ cell count was 0.200 to 0.349 x 10(9) cells/L had statistically similar mortality rates (adjusted relative hazard, 0.82 [CI, 0.45 to 1.49]; P > 0.2).Conclusions: Delaying HAART until the CD4+ cell count falls to 0.200 x 109 cells/L does not increase the mortality rate in HIV-infected patients with good medication adherence. Mortality rates increase if HAART is initiated below 0.200 x 10(9) cells/L. Also, nonadherent patients have higher mortality rates than adherent patients with similar CD4+ cell counts. Above a CD4+ cell count of 0.200 x 10(9) cells/L, medication adherence is the critical determinant of survival, not the CD4+ cell count at which HAART is begun. [ABSTRACT FROM AUTHOR]

Objective To assess the effect of adherence to antiretroviral therapy on the duration of virological suppression after controlling for whether or not the patient ever attained a plasma viral load below the limit of detection of sensitive HIV-1 RNA assays. Methods Data were combined from three randomized, blinded clinical trials (INCAS, AVANTI-2, and AVANTI-3) that compared the antiviral effects of two- and three-drug antiretroviral regimens. Virological suppression was defined as maintaining a plasma viral load below 1000 copies/mL. Adherence was defined prospectively and measured by patient self-report. Results Adherence did not have a major impact on the probability of achieving virological suppression for patients receiving dual therapy. However, for patients receiving triple therapy, adherence increased the probability of virological suppression, whether the plasma viral load nadir was above or below the lower limit of quantification. Compared to adherent patients with a plasma viral load nadir below the lower limit of quantification, the relative risk of virological failure was 3.0 for non-adherent patients with a nadir below the limit, 18.1 for adherent patients with a nadir above the limit, and 32.1 for non-adherent patients with a nadir above the limit. Conclusion For patients receiving current three-drug antiretroviral regimens, adherence to therapy and plasma viral load nadir are important factors determining the duration of virological suppression. [ABSTRACT FROM AUTHOR]

Objective: To provide current recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease.Participants: The original International AIDS Society-USA 13-member panel representing international expertise in antiretroviral research and care of patients with HIV infection.Evidence: The following were considered: Newly available clinical and basic science study results, including phase 3 controlled trials; clinical, virological, and immunologic end-point data; interim analyses of studies presented at national and international research conferences; studies of HIV pathophysiology; and expert opinions of panel members. Recommendations were limited to the drugs available in mid 1997.Process: The full panel met on a regular basis (July 1996, September 1996, November 1996, January 1997, and April 1997) since the publication of its initial recommendations in mid 1996 to review new research reports and interim results. The panel discussed whether and how new information changed its initial recommendations. The recommendations contained herein were determined by group consensus.Conclusions: New data have provided a stronger rationale for earlier initiation of more aggressive therapy than previously recommended and reinforce the importance of careful selection of initial drug regimen for each patient for optimal long-term clinical benefit and adherence. The plasma viral load is a crucial element of clinical management for assessing prognosis and the effectiveness of therapy, and such testing must be done properly. Treatment failure is most readily indicated by a rising plasma HIV RNA level and should be confirmed prior to a change of treatment. Therapeutic approaches must be updated as new data, particularly on the long-term clinical effect of aggressive antiretroviral treatment, continue to emerge. [ABSTRACT FROM AUTHOR]

Objective: To provide clinical recommendations for antiretroviral therapy for human immunodeficiency virus (HIV) disease with currently (mid 1996) available drugs. When to start therapy, what to start with, when to change, and what to change to were addressed.Participants: A 13-member panel representing international expertise in antiretroviral research and HIV patient care was selected by the international AIDS Society-USA.Evidence: Available clinical and basic science data, including phase 3 controlled trials, clinical endpoint data, virologic and immunologic endpoint data, interim analyses, studies of HIV pathophysiology, and expert opinions of panel members were considered. Recommendations were limited to drugs available in mid 1996.Process: For each question posed, 1 or more member(s) reviewed and presented available data. Recommendations were determined by group consensus (January 1996); revisions as warranted by new data were incorporated by group consensus (February-May 1996).Conclusions: Recent data on HIV pathogenesis, methods to determine plasma HIV RNA, clinical trial data, and availability of new drugs point to the need for new approaches to treatment. Therapy is recommended based on CD4+ cell count, plasma HIV RNA level, or clinical status. Preferred initial drug regimens include nucleoside combinations; at present protease inhibitors are probably best reserved for patients at higher progression risk. For treatment failure or drug intolerance, subsequent regimen considerations include reasons for changing therapy, available drug options, disease stage, underlying conditions, and concomitant medication(s). Therapy for primary (acute) infection, high-risk exposures to HIV, and maternal-to-fetal transmission are also addressed. Therapeutic approaches need to be updated as new data continue to emerge. [ABSTRACT FROM AUTHOR]

We studied the association between socioeconomic status and survival in a prospective study of 364 HIV-infected homosexual men who were recruited during 1982-84. The participants were divided by annual income; those earning above Canadian $10,000 (high-income; n = 274) and those below $10,000 (low-income; n = 90) at recruitment. The latter threshold closely approximated to the poverty level for this population. Low income men were significantly younger than high income men but the groups were similar with respect to baseline CD4 counts, subsequent use of anti-retrovirals and prophylaxis against Pneumocystis carinii pneumonia (PCP), and number of visits attended during follow-up. Subjects were followed for a median of 9.5 years (range 1.8-13.1). By Dec 31, 1993, there were 135 deaths yielding a cumulative mortality rate of mean 45% (SD 4.0) at 11.5 years. Men aged 30 or more at infection had poorer survival than those under 30 (mortality risk ratio 1.56; 95% CI 1.09-2.24; p = 0.015), and longer survival was significantly associated with a higher CD4 count at the earliest seropositive visit. The age-adjusted mortality risk ratio for low income men compared with high income men was significantly increased at 1.63 (95% CI 1.11-2.40; p = 0.013). The significant risk of death for low income men persisted despite adjustment for age at infection, CD4 count, use of zidovudine, dideoxyinosine, and dideoxycytidine, use of PCP prophylaxis, and year of infection. We cannot attribute our findings to income loss as a result of more rapid HIV progression because the same effect was present in people who provided income data before seroconversion. Similarly, our findings are not due to differential access to care because the study was done within the context of a universal health care system, and the two income groups received treatments equally. This finding is consistent with the association of lower socioeconomic status with increased morbidity and mortality observed within large populations and in other diseases. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the rate changes of new HIV infections in British Colombia.

OBJECTIVES: We examined the significance of plasma HIV-1 RNA levels (or viral load alone) in predicting CD4 cell decline in untreated HIV-infected individuals. METHODS: Data were obtained from the British Columbia Centre for Excellence in HIV/AIDS. Participants included all residents who ever had a viral load determination in the province and who had never taken antiretroviral drugs (N = 890). We analyzed a total of 2074 viral load measurements and 2332 CD4 cell counts. Linear mixed-effects models were used to predict CD4 cell decline over time. RESULTS: Longitudinal viral load was strongly associated with CD4 cell decline over time; an average of 1 log(10) increase in viral load was associated with a 55-cell/mm(3) decrease in CD4 cell count. CONCLUSIONS: Our results support the combined use of CD4 cell count and viral load as prognostic markers in HIV-infected individuals before the introduction of antiretroviral therapy. [ABSTRACT FROM AUTHOR]