Cohort profile: the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
Robert S Hogg
Publications and source records attributed to Robert S Hogg.
Rates of inappropriate antiretroviral prescription among injection drug users.
BACKGROUND: Although the survival benefits of antiretroviral therapy (ART) for the treatment of HIV infection are well established, the clinical management of HIV disease continues to present major challenges. There are particular concerns regarding access to appropriate HIV treatment among HIV-infected injection drug users (IDU). METHODS: In a prospective cohort study of HIV-infected IDU in Vancouver, Canada, we examined initial ART regimens vis-à-vis the provincial government's therapeutic guidelines at the time ART was initiated. Briefly, there have been four sets of guidelines: Era 1 (1992 to November 1995; double-drug (dual NRTIs) ART for patients with a CD4 cell count of 350 or less); Era 2 (December 1995 to May 1996; double-drug therapy for patients with a CD4+ cell count of 500 or less); Era 3 (June 1996 to June 1997; triple-drug therapy (dual NRTIs with a PI or NNRTI) for patients who had a plasma viral load of > 100,000 HIV-1 RNA copies/mL; dual therapy with two NRTIs for those with a plasma viral load of 5,000 to 100,000 HIV-1 RNA copies/mL); Era 4 (since July 1997; universal use of triple drug therapy as first-line treatment). RESULTS: Between May 1996 and May 2003, 431 HIV-infected individuals were enrolled into the cohort. By May 31, 2003, 291 (67.5%) individuals had initiated ART. We noted instances of inappropriate antiretroviral prescription in each guideline era, with 9 (53%) in Era 1, 3 (12%) in Era 2, 22 (28%) in Era 3, and 23 (15%) in Era 4. Of the 57 subjects who received an inappropriate ART regimen initially, 14 never received the appropriate therapy; among the remaining 43, the median time to the initiation of a guideline-appropriate ART regimen was 12 months (inter-quartile range 5-20). CONCLUSION: The present study identified measurable rates of guideline-inappropriate ART prescription for patients who were injection drug users. Rates were highest in the era of dual therapy, although high rates persisted into the triple-therapy era. As therapeutic guidelines continue to evolve, it is critical that mechanisms be put in place to ensure prescription of ART combinations for IDU that are consistent with current expert recommendations.
Journal Article↗
Performance of immunologic responses in predicting viral load suppression: implications for monitoring patients in resource-limited settings.
BACKGROUND: World Health Organization (WHO) guidelines for the use of antiretroviral therapy (ART) in resource-limited settings state that CD4 cell counts may be used to indicate when ART regimens should be changed because of treatment failure. The performance of immunologic monitoring for this purpose has not been evaluated, however. METHODS: Participants aged > or =18 years from the British Columbia HIV/AIDS Drug Treatment Program who had CD4 cell counts < or =200 cells/microL or an AIDS diagnosis at baseline had CD4 cell counts measured at 6 and 12 months after treatment initiation. Logistic regression analysis was used to calculate sensitivity, specificity, and positive and negative predictive values for immunologic responses in terms of predicting failure to achieve 2 viral load measurements < 500 copies/mL within 1 year. RESULTS: Viral load suppression occurred in 674 (60%) of 1125 subjects. Using no increase in CD4 cell counts at 6 months as a definition of treatment failure had a sensitivity of 34%, specificity of 94%, positive predictive value of 75%, and negative predictive value of 71% for predicting failure to achieve virologic suppression. Using 12-month CD4 cell count values, the measurements were 35%, 95%, 79%, and 73%, respectively. CONCLUSION: Immunologic criteria to predict which patients have not achieved virologic suppression results in significant misclassification of therapeutic responses.
Anti-HIV Agents↗
A simple, dynamic measure of antiretroviral therapy adherence predicts failure to maintain HIV-1 suppression.
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.
Adult↗
HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis.
BACKGROUND: Highly active antiretroviral therapy (HAART) for the treatment of HIV infection was introduced a decade ago. We aimed to examine trends in the characteristics of patients starting HAART in Europe and North America, and their treatment response and short-term prognosis. METHODS: We analysed data from 22,217 treatment-naive HIV-1-infected adults who had started HAART and were followed up in one of 12 cohort studies. The probability of reaching 500 or less HIV-1 RNA copies per mL by 6 months, and the change in CD4 cell counts, were analysed for patients starting HAART in 1995-96, 1997, 1998, 1999, 2000, 2001, and 2002-03. The primary endpoints were the hazard ratios for AIDS and for death from all causes in the first year of HAART, which were estimated using Cox regression. RESULTS: The proportion of heterosexually infected patients increased from 20% in 1995-96 to 47% in 2002-03, and the proportion of women from 16% to 32%. The median CD4 cell count when starting HAART increased from 170 cells per muL in 1995-96 to 269 cells per muL in 1998 but then decreased to around 200 cells per muL. In 1995-96, 58% achieved HIV-1 RNA of 500 copies per mL or less by 6 months compared with 83% in 2002-03. Compared with 1998, adjusted hazard ratios for AIDS were 1.07 (95% CI 0.84-1.36) in 1995-96 and 1.35 (1.06-1.71) in 2002-03. Corresponding figures for death were 0.87 (0.56-1.36) and 0.96 (0.61-1.51). INTERPRETATION: Virological response after starting HAART improved over calendar years, but such improvement has not translated into a decrease in mortality.
Adolescent↗
Complementary and alternative medicine use in British Columbia--a survey of HIV positive people on antiretroviral therapy.
In 2002, the British Columbia (BC) Centre for Excellence in HIV/AIDS collected final detailed data on complementary and alternative medicine (CAM) use in their HIV treatment program. This cross-sectional study of 682 participants examines types and determinants of CAM use in this program, and examines adverse effects associated with CAM use and antiretroviral therapy (ART). Among the 47% ever CAM users in the included population, vitamins/minerals (81%), meditation/yoga (36%), massage (31%), marijuana (30%), dietary supplements (24%), and herbal medicines (19%), were most commonly used. Multivariate analysis indicated CAM users were less likely to have low education (AOR=0.51), more likely to be unemployed (AOR=1.52), more likely to have been on ART longer (AOR=1.19), and more likely to experience objective, action-requiring (OA) side effects (AOR=1.45). CAM use is common. Both patients and health professionals should be aware of potential toxicities and drug interactions related to the use of CAM and HIV/AIDS treatment.
Adult↗
Aboriginal status is a prognostic factor for mortality among antiretroviral naïve HIV-positive individuals first initiating HAART.
BACKGROUND: Although the impact of Aboriginal status on HIV incidence, HIV disease progression, and access to treatment has been investigated previously, little is known about the relationship between Aboriginal ethnicity and outcomes associated with highly active antiretroviral therapy (HAART). We undertook the present analysis to determine if Aboriginal and non-Aboriginal persons respond differently to HAART by measuring HIV plasma viral load response, CD4 cell response and time to all-cause mortality. METHODS: A population-based analysis of a cohort of antiretroviral therapy naïve HIV-positive Aboriginal men and women 18 years or older in British Columbia, Canada. Participants were antiretroviral therapy naïve, initiated triple combination therapy between August 1, 1996 and September 30, 1999. Participants had to complete a baseline questionnaire as well as have at least two follow-up CD4 and HIV plasma viral load measures. The primary endpoints were CD4 and HIV plasma viral load response and all cause mortality. Cox proportional hazards models were used to determine the association between Aboriginal status and CD4 cell response, HIV plasma viral load response and all-cause mortality while controlling for several confounder variables. RESULTS: A total of 622 participants met the study criteria. Aboriginal status was significantly associated with no AIDS diagnosis at baseline (p = 0.0296), having protease inhibitor in the first therapy (p = 0.0209), lower baseline HIV plasma viral load (p < 0.001), less experienced HIV physicians (P = 0.0133), history of IDU (p < 0.001), not completing high school (p = 0.0046), and an income of less than $10,000 per year (p = 0.0115). Cox proportional hazards models controlling for clinical characteristics found that Aboriginal status had an increased hazard of mortality (HR = 3.12, 95% CI: 1.77-5.48) but did not with HIV plasma viral load response (HR = 1.15, 95% CI: 0.89-1.48) or CD4 cell response (HR = 0.95, 95% CI: 0.73-1.23). CONCLUSION: Our study demonstrates that HIV-infected Aboriginal persons accessing HAART had similar HIV treatment response as non-Aboriginal persons but have a shorter survival. This study highlights the need for continued research on medical interventions and behavioural changes among HIV-infected Aboriginal and other marginalized populations.
Journal Article↗
Impact of baseline viral load and adherence on survival of HIV-infected adults with baseline CD4 cell counts > or = 200 cells/microl.
BACKGROUND: Baseline plasma HIV RNA levels > 100 000 copies/ml have been associated with elevated mortality rates after the initiation of HAART. There is uncertainty regarding the optimal strategy for patients with high plasma HIV RNA but CD4 cell count > or = 200 cells/microl. OBJECTIVE: To evaluate the impact of baseline plasma HIV RNA on survival among patients with CD4 cell counts > or = 200 cells/microl. METHODS: Patients were stratified by plasma HIV RNA, CD4 cell count and adherence level. Mortality rates were evaluated using Kaplan-Meier methods and Cox regression. RESULTS: Among 1166 patients initiating HAART with a CD4 cell count > or = 200 cells/microl, a baseline HIV RNA > or = 100 000 copies/ml was statistically associated with elevated mortality among non-adherent patients (log-rank P = 0.032), but not for adherent patients (log-rank P = 0.690). In a multivariate Cox model comparing patients with a baseline CD4 cell count > or = 200 cells/microl and a baseline plasma HIV RNA < 100 000 copies/ml, the mortality rate was statistically similar among patients with a baseline CD4 cell count > or = 200 cells/microl and a baseline plasma HIV RNA > or = 100 000 copies/ml (relative hazard, 1.21; 95% confidence interval, 0.89-1.65; P = 0.232). CONCLUSION: HIV RNA > or = 100 000 copies/ml was only associated with mortality among HIV-infected patients initiating HAART with CD4 cell counts > or= 200 cells/microl if the patients were non-adherent.
Adolescent↗
Validity of self-reported antiretroviral therapy use among injection drug users.
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Anti-HIV Agents↗
Antiretroviral adherence and HIV treatment outcomes among HIV/HCV co-infected injection drug users: the role of methadone maintenance therapy.
OBJECTIVE: We examined the association of methadone maintenance therapy (MMT) with highly active antiretroviral therapy (HAART) adherence and HIV treatment outcomes among a cohort of HIV/HCV co-infected injection drug users (IDUs). METHODS: We obtained demographic, drug use, and addiction care history from the Vancouver Injection Drug User Study (VIDUS), which is an open cohort study of IDUs. The questionnaires were longitudinally linked to the British Columbia HIV/AIDS Drug Treatment Program to obtain HAART adherence and HIV treatment outcome data. There were 278 VIDUS participants who accessed HAART from August 1, 1996 to November 24, 2003. We constructed longitudinal logistic models using generalized estimating equations to examine the independent associations between methadone maintenance therapy and the following outcomes: HAART adherence; plasma HIV-1 RNA suppression; and CD4 cell rise of 100cells/mm(3). RESULTS: Among participants who reported at least weekly heroin use, MMT was independently associated with lower odds of subsequent weekly heroin use during the follow-up period (adjusted odds ratio; 95% confidence interval [AOR; 95% CI]: 0.24; 0.14-0.40). We also found that MMT was positively associated with adherence (AOR 1.52; 95% CI 1.16-2.00), HIV-1 RNA suppression (AOR 1.34; 95% CI 1.00-1.79), and CD4 cell count rise (AOR 1.58; 95% CI 1.26-1.99). CONCLUSIONS: Among HIV/HCV co-infected IDUs on HAART, enrollment in MMT was associated with reduced heroin use, and improved adherence, HIV-1 RNA suppression and CD4 cell count response. Integrating opiate addiction care and HIV care may provide improved health outcomes for this vulnerable population and should be further explored.
Adult↗
Randomized clinical evaluation of self-screening for anal cancer precursors in men who have sex with men.
BACKGROUND: Self-collection of anorectal swab specimens could greatly facilitate the completion of prerequisite studies and future implementation of anal cancer screening among men who have sex with men (MSM). We therefore compared self- versus clinician- collection procedures with respect to specimen adequacy for cytological evaluation, concordance of paired cytological results, and concordance of cytological with biopsy results. METHODS: Paired self- and clinician- collected anorectal Dacron swabs for liquid-based (Thin Prep) cytological evaluation were collected in random sequence from a mostly HIV-1 seronegative cohort of young MSM in Vancouver. Slides were reviewed by one cytopathologist. Presence of any cytological abnormality (atypical squamous cells of uncertain significance, ASCUS, or above) prompted referral for high-resolution anoscopy and possible biopsy. RESULTS: Among 222 patient-clinician specimen pairs, most were adequate for cytological evaluation, though self-collected specimens were less likely to be so (83% versus 92%, McNemar's test p < 0.001). Cytological abnormalities, noted in 47 (21%) of self-collected and 47 (21%) of clinician-collected specimens (with fair agreement, kappa = 0.414) included, respectively: ASCUS (5%, 5%), and low-grade (13%, 13%) and high-grade (3%, 3%) squamous intraepithelial lesions. Among 12 men with biopsy-confirmed high-grade neoplasia, most had abnormal cytological results (including 6 patient and 9 clinician swabs) but few (2 patient and 1 clinician swab) were high-grade. CONCLUSION: Self-collection of anorectal swab specimens for cytologic screening in research and possibly clinical settings appears feasible, particularly if specimen adequacy can be further improved. The severity of biopsy-confirmed anorectal disease is seriously underestimated by cytological screening, regardless of collector.
Journal Article↗
Disease progression in patients with virological suppression in response to HAART is associated with the degree of immunological response.
OBJECTIVE: To determine if immunological response is associated with disease progression in patients with virological suppression after initiating HAART. DESIGN: A cohort study of 1084 treatment-naive participants in the British Columbia HIV/AIDS Drug Treatment Program who had achieved viral loads < 500 copies/ml at 3-9 months after initiating triple-drug therapy. METHODS: Cox proportional hazards was used to model the association with disease progression of baseline variables, change in CD4 cell counts and CD4 cell count strata at 6 months. Logistic regression analysis was used to examine associations with two definitions of poor immunological response. RESULTS: Patients were followed for a median of 51.4 months. In univariate analyses, increases in CD4 cell counts of < 25 cells/microl and absolute CD4 cell counts of < 200 cells/microl were associated with an increased risk of death or new AIDS events. Two mulitivariate models, one including baseline CD4 cell count and change in CD4 cell count from baseline and the other including only absolute CD4 cell counts at 6 months, were found to predict disease progression in this setting. Increases in CD4 cell count of < 25 cells/microl were associated with increasing age and inversely associated with low baseline CD4 cell counts, high baseline viral loads and good adherence to therapy. CD4 cell counts of < 200 cells/microl at 6 months were associated with low baseline CD4 cell counts and having AIDS at baseline. CONCLUSION: Patients with virological suppression are still at risk for HIV disease progression if adequate immunological responses are not achieved.
Adult↗
Hepatitis C coinfection is independently associated with decreased adherence to antiretroviral therapy in a population-based HIV cohort.
OBJECTIVE: To characterize the impact of hepatitis C (HCV) serostatus on adherence to antiretroviral treatment (ART) among HIV-infected adults initiating ART. METHODS: The British Columbia HIV/AIDS Drug Treatment Program distributes, at no cost, all ART in this Canadian province. Eligible individuals used triple combination ART as their first HIV therapy and had documented HCV serology. Statistical analyses used parametric and non-parametric methods, including multivariate logistic regression. The primary outcome was > or = 95% adherence, defined as receiving > or = 95% of prescription refills during the first year of antiretroviral therapy. RESULTS: There were 1186 patients eligible for analysis, including 606 (51%) positive for HCV antibody and 580 (49%) who were negative. In adjusted analyses, adherence was independently associated with HCV seropositivity [adjusted odds ratio (AOR), 0.48; 95% confidence interval (CI), 0.23-0.97; P = 0.003], higher plasma albumin levels (AOR, 1.07; 95% CI, 1.01-1.12; P = 0.002) and male gender (AOR, 2.53; 95% CI, 1.04-6.15; P = 0.017), but not with injection drug use (IDU), age or other markers of liver injury. There was no evidence of an interaction between HCV and liver injury in adjusted analyses; comparing different strata of HCV and IDU confirmed that HCV was associated with poor adherence independent of IDU. CONCLUSIONS: HCV-coinfected individuals and those with lower albumin are less likely to be adherent to their ART.
Adult↗
Impact of HAART and injection drug use on life expectancy of two HIV-positive cohorts in British Columbia.
BACKGROUND: The introduction of HAART has led to consistent improvements in survival among HIV-infected individuals. However, there is evidence that not all populations have benefited equally from HAART and that mortality rates are higher in HIV-infected injection drug users than in non-users. OBJECTIVE: To model life expectancies for HIV-positive individuals subdivided according to history of injection drug use and treatment with HAART. DESIGN: Population-based study of HIV-positive persons in British Columbia's HIV/AIDS treatment program. METHODS: The primary outcome measures in this study were life expectancy at exact age 20 and potential years of life lost. RESULTS: The highest life expectancy (38.9 years) and lowest potential years of life lost were measured for individuals taking HAART and without a history of injection drug use. The lowest life expectancy (19.1 years) and highest potential years of life lost were measured in HIV-positive injection drug users who were not taking HAART. CONCLUSIONS: There are substantial disparities in life expectancy for persons living with HIV in British Columbia. Members of the injection drug community, particularly those who are not taking HAART, experience elevated mortality in comparison with those without a history of drug use.
Adult↗
Self-screening for rectal sexually transmitted infections: human papillomavirus.
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Adult↗
The impact of sex partners' HIV status on HIV seroconversion in a prospective cohort of injection drug users.
OBJECTIVE AND DESIGN: The identification of individuals at highest risk of HIV infection is critical for targeting prevention strategies. We evaluated the HIV status of the sex partners of injection drug users (IDUs) and rates of subsequent HIV seroconversion among a prospective cohort study of IDUs. METHODS: We performed an analysis of the time to HIV infection among baseline HIV-negative IDUs enrolled in the Vancouver Injection Drug Users Study. IDUs were stratified based on whether or not they reported having an HIV-positive sex partner. Kaplan-Meier methods were used to estimate cumulative HIV incidence rates, and Cox regression was used to determine adjusted relative hazards (RHs) for HIV seroconversion. RESULTS: Of 1013 initially HIV-negative IDUs, 4.8% had an HIV-positive partner at baseline. After 18 months, the cumulative HIV incidence rate was significantly elevated among those who reported having an HIV-positive sex partner (23.4% vs. 8.1%; log-rank P < 0.001). In a Cox regression model adjusting for all variables that were associated with the time to HIV infection in univariate analyses, including drug use characteristics, having an HIV-positive sex partner (RH = 2.42 [95% confidence interval: 1.30 to 4.60]; P = 0.005) remained independently associated with time to HIV seroconversion. CONCLUSIONS: Having an HIV-positive sex partner was strongly and independently associated with seroconversion after adjustment for risk factors related to drug use. Our findings may aid public health workers in their efforts to identify IDUs who should be targeted with education and prevention efforts and indicate the need for ongoing development of prevention interventions for IDU sex partners who are HIV discordant.
AIDS Serodiagnosis↗
Estimated numbers of men and women infected with HIV/AIDS in Tijuana, Mexico.
Tijuana, Mexico, just south of San Diego, California, is located by the busiest land border crossing in the world. Although UNAIDS considers Mexico to be a country of "low prevalence, high risk," recent surveillance data among sentinel populations in Tijuana suggests HIV prevalence is increasing. The aim of this study was to estimate the number of men and women aged 15 to 49 years infected with HIV in Tijuana. Gender and age-specific estimates of the Tijuana population were obtained from the 2000 Mexican census. Population and HIV prevalence estimates for at-risk groups were obtained from published reports, community based studies, and data from the Centro Nacional para la Prevención y Control del VIH/SIDA (CENSIDA). Age-specific fertility rates for Mexico were used to derive the number of low and high-risk pregnant women. Numbers of HIV-positive men and women were estimated for each at-risk group and then aggregated. A high growth scenario based on current HIV prevalence and a conservative, low growth estimate were determined. A total of 686,600 men and women in Tijuana were aged 15 to 49 years at the time of the 2000 census. Considering both scenarios, the number of infected persons ranged from 1,803 to 5,472 (HIV prevalence: 0.26 to 0.80%). The majority of these persons were men (>70%). The largest number of infected persons were MSM (N = 1,146 to 3,300) and IDUs (N = 147 to 650). Our data suggest that up to one in every 125 persons aged 15-49 years in Tijuana is HIV-infected. Interventions to reduce ongoing spread of HIV are urgently needed.
Acquired Immunodeficiency Syndrome↗
High prevalence of smoking among urban-dwelling Canadian men who have sex with men.
A small but consistent literature from the United States suggests increased risk for smoking among lesbians and men who have sex with men (MSM). Few studies have investigated smoking among MSM in other countries where different social norms and restrictions on smoking in public apply. We measured smoking behaviours in a convenience sample of urban-dwelling young Canadian MSM (median age 28 years). We compared the prevalence of smoking among MSM with that among other men in British Columbia (BC) using National Population Health Survey data to compute an age-adjusted standardized prevalence ratio (SPR). Independent predictors of smoking among MSM were identified using adjusted odds ratios (OR) with 95% confidence intervals (CI). Smoking during the previous year was reported by twice as many MSM (54.5% of 354) as other men in BC (25.9%) (SPR = 1.94, 95% CI 1.48-2.59), with largest differentials observed among men under 25 years of age. In multivariable analyses, smoking among MSM was significantly associated with younger age (OR 0.94, CI 0.88-1.00 per year), greater number of depressive symptoms (OR 1.12, CI 1.06-1.19 per symptom) and Canadian Aboriginal ethnicity (OR 2.64, CI 1.05-6.60). In summary, MSM in our study were twice as likely to smoke as other men in BC; the greatest differences were observed among the youngest men. The design of effective prevention and cessation programs for MSM will require identification of the age-dependent determinants of smoking initiation, persistence, and attempts to quit.
Adolescent↗