Acquired Immunodeficiency Syndrome: Montaner JS

Yeni PG, Hammer SM, Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Volberding PA. · Hôpital Bichat-Claude Bernard, Department of Infectious Diseases, 46 Rue Henri-Huchard, Paris, Cedex 18 France 75877. · JAMA. · Pubmed #12095387 No free full text.

Abstract: OBJECTIVE: New information warrants updated recommendations for the 4 central issues in antiretroviral therapy: when to start, what drugs to start with, when to change, and what to change to. These updated recommendations are intended to guide practicing physicians actively involved in human immunodeficiency virus (HIV)- and acquired immunodeficiency syndrome (AIDS)-related care. PARTICIPANTS: In 1995, physicians with specific expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care were invited by the International AIDS Society-USA to serve on a volunteer panel. In 1999, others were invited to broaden international representation. The 17-member panel met regularly in closed meetings between its last report in 2000 and April 2002 to review current data. The effort was sponsored and funded by the International AIDS Society-USA, a not-for-profit physician education organization. EVIDENCE AND CONSENSUS PROCESS: The full panel was convened in late 2000 and assigned 7 section committees. A section writer and 3 to 5 section committee members (each panel member served on numerous sections) identified relevant evidence and prepared draft recommendations. Basic science, clinical research, and epidemiologic data from the published literature and abstracts from recent (within 2 years) scientific conferences were considered by strength of evidence. Extrapolations from basic science data and expert opinion of the panel members were included as evidence. Draft sections were combined and circulated to the entire panel and discussed in a series of full-panel conference calls until consensus was reached. Final recommendations represent full consensus agreement of the panel. CONCLUSIONS: Because of increased awareness of the activity and toxicity of current drugs, the threshold for initiation of therapy has shifted to a later time in the course of HIV disease. However, the optimal time to initiate therapy remains imprecisely defined. Availability of new drugs has broadened options for therapy initiation and management of treatment failure, which remains a difficult challenge.

Montaner JS, Mellors JW. · No affiliation provided · Antivir Ther. · Pubmed #10682149 No free full text.

This publication has no abstract.

Levy AR, James D, Johnston KM, Hogg RS, Harrigan PR, Harrigan BP, Sobolev B, Montaner JS. · Department of Health Care and Epidemiology, University of British Columbia, Vancouver, BC, Canada. · Lancet Infect Dis. · Pubmed #16500598 No free full text.

Abstract: We reviewed published studies reporting the direct medical costs of treating HIV-infected people in countries using highly active antiretroviral therapy (HAART). Of 543 potentially relevant studies, only nine provided adequate data to make a meaningful statement about costs. Within studies, people with more advanced disease incurred higher total costs. Valid comparisons of total direct medical costs between studies were not possible because of differences in the specific components included, the heterogeneous nature of study populations in terms of disease stage, the sources and methods used to estimate unit costs, and the level of aggregation at which results were reported. The advent of HAART has major implications for the cost of treating HIV-infected individuals. Although this information is important for planning purposes, only a small number of published studies provide useful estimates of the direct cost. A useful method of estimating resource use and costs is computer simulation.

Raboud JM, Rae S, Hogg RS, Yip B, Sherlock CH, Harrigan PR, O'Shaughnessy MV, Montaner JS. · Data and Methodology Program, Canadian HIV Trials Network, Vancouver, Canada. · J Infect Dis. · Pubmed #10479170 No free full text.

Abstract: Suppression of human immunodeficiency virus type 1 plasma virus load (PVL) to <20 copies/mL is associated with a longer virologic response after initiation of antiretroviral therapy. The relationship between duration of virologic response and PVL nadir according to a less sensitive assay was explored. When compared with subjects with a PVL nadir >500 copies/mL, the relative risks of PVL rising above 1000 copies/mL for participants in the INCAS trial and the British Columbia Drug Treatment Program with a PVL nadir below the limit of detection (LOD) were 0.04 (95% confidence interval [CI], 0.02-0.09) and 0.06 (95% CI, 0.03-0.12), respectively. The corresponding relative risks for persons with a detectable but not quantifiable PVL nadir were 0.25 (95% CI, 0.13-0.50) and 0.54 (95% CI, 0.25-1.19). The relative risks of virologic failure associated with a PVL nadir detectable but not quantifiable and a PVL nadir below the LOD were statistically different (P<.0001) in both data sets.

Tam LW, Chui CK, Brumme CJ, Bangsberg DR, Montaner JS, Hogg RS, Harrigan PR. · British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Vancouver, Canada. · J Acquir Immune Defic Syndr. · Pubmed #18845950 No free full text.

Abstract: OBJECTIVE: To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada. METHODS: Plasma samples with plasma viral load >1,000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables. RESULTS: The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50% per additional mutation. At 80%-90% adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95% confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0, 95% CI: 3.3 to 10.9; P < 0.0001) compared with the >or=95% refill reference group. In a multivariate model, individuals with <95% refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95% CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95% CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of >or=95% refills with consistently detectable drug levels. Adherence-resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs. CONCLUSION: The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.

Lima VD, Hogg RS, Harrigan PR, Moore D, Yip B, Wood E, Montaner JS. · BC Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, British Columbia, Canada. · AIDS. · Pubmed #17413689 No free full text.

Abstract: OBJECTIVE: To characterize the temporal changes in mortality and life expectancy among HIV-positive individuals initiating antiretroviral therapy in British Columbia, Canada, from 1993 to 2004. METHODS: This analysis was restricted to 2238 antiretroviral-naive HIV-positive individuals who started antiretroviral therapy between January 1993 and September 2004. The primary analysis endpoint was all-cause mortality stratified by four time periods: 1993-1995, 1996-1998, 1999-2001, and 2002-2004. Cox proportional hazard models, with associated 95% confidence intervals (CI), were used to estimate the hazard of death. Abridged life tables were constructed to compare life expectancies at the age of 20 years. RESULTS: Product limit estimates of the cumulative mortality rate at 12 months after therapy initiation decreased from 15.8% (+/- 1.6%) in 1993-1995 to 6.1% (+/- 1.1%) in 2002-2004. Life expectancy at the age of 20 years has increased from 9.1 years (+/- 2.3 years) in 1993-1995 to 23.6 years (+/- 4.4 years) in 2002-2004. Subjects in 1993-1995 were more likely to die than those who started therapy in 2002-2004 (hazard ratio 2.78; 95% CI 1.92-3.85). Patients who initiated dual therapy or therapies containing three or more antiretroviral drugs were, respectively, 1.49 (95% CI 1.23-1.82) and 2.56 (95% CI 2.13-3.13) times less likely to die than those who started on monotherapy. CONCLUSION: A significant and progressive decrease in mortality and increase in life expectancy were observed over the 12-year study period. The increase in life expectancy and decrease in mortality were directly associated with the use of modern forms of HAART.

Christie T, Asrat GA, Jiwani B, Maddix T, Montaner JS. · BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada. · Dev World Bioeth. · Pubmed #17355326 No free full text.

Abstract: OBJECTIVE: To contrast relief efforts for the 26 December 2004 tsunami with current global HIV/AIDS relief efforts and analyse possible reasons for the disparity. METHODS: Literature review and ethical analysis. RESULTS: Just over 273,000 people died in the tsunami, resulting in relief efforts of more than US$10 bn, which is sufficient to achieve the United Nation's long-term recovery plan for South East Asia. In contrast, 14 times more people died from HIV/AIDS in 2004, with UNAIDS predicting a US$8 bn funding gap for HIV/AIDS in developing nations between now and 2007. This disparity raises two important ethical questions. First, what is it that motivates a more empathic response to the victims of the tsunami than to those affected by HIV/AIDS? Second, is there a morally relevant difference between the two tragedies that justifies the difference in the international response? The principle of justice requires that two cases similarly situated be treated similarly. For the difference in the international response to the tsunami and HIV/AIDS to be justified, the tragedies have to be shown to be dissimilar in some relevant respect. Are the tragedies of the tsunami disaster and the HIV/AIDS pandemic sufficiently different, in relevant respects, to justify the difference in scope of the response by the international community? CONCLUSION: We detected no morally relevant distinction between the tsunami and the HIV/AIDS pandemic that justifies the disparity. Therefore, we must conclude that the international response to HIV/AIDS violates the fundamental principles of justice and fairness.

Wood E, Tyndall MW, Montaner JS, Kerr T. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, and the Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC. · CMAJ. · Pubmed #17116909 links to  free full text

Abstract: In many cities, infectious disease and overdose epidemics are occurring among illicit injection drug users (IDUs). To reduce these concerns, Vancouver opened a supervised safer injecting facility in September 2003. Within the facility, people inject pre-obtained illicit drugs under the supervision of medical staff. The program was granted a legal exemption by the Canadian government on the condition that a 3-year scientific evaluation of its impacts be conducted. In this review, we summarize the findings from evaluations in those 3 years, including characteristics of IDUs at the facility, public injection drug use and publicly discarded syringes, HIV risk behaviour, use of addiction treatment services and other community resources, and drug-related crime rates. Vancouver's safer injecting facility has been associated with an array of community and public health benefits without evidence of adverse impacts. These findings should be useful to other cities considering supervised injecting facilities and to governments considering regulating their use.

Kuyper LM, Kerr T, Li K, Hogg RS, Tyndall MW, Montaner JS, Wood E. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, and Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada. · Subst Use Misuse. · Pubmed #16809177 No free full text.

Abstract: We performed analyses of syringe buying and syringe selling among Vancouver injection drug users, recruited from May 1996 and followed up between November 2002 and August 2003, in the context of one of North America's largest syringe exchange programs (SEPs). An interviewer-administered questionnaire, approximately 45 minutes in duration, was used to collect information regarding risk factors for HIV infection and sources of sterile syringes. Seventy participants (15%) reported syringe selling and 122 (26%) reported syringe buying. Syringe sellers were more likely to be female, reside in unstable housing, need help injecting, and have visited the SEP at least once weekly. Syringe buyers were more likely to need help injecting, have difficulty finding new syringes, have binged on drugs, and have visited the SEP at least once weekly. Syringe buying most frequently occurred when the SEP was closed.

Braitstein P, Zala C, Yip B, Brinkhof MW, Moore D, Hogg RS, Montaner JS. · British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, Canada. · J Infect Dis. · Pubmed #16362890 No free full text.

Abstract: 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.

Toulson AR, Harrigan R, Heath K, Yip B, Brumme ZL, Harris M, Hogg RS, Montaner JS. · BC Centre for Excellence in HIV/AIDS, Faculty of Medicine, University of British Columbia, Vancouver, Canada. · J Infect Dis. · Pubmed #16235178 No free full text.

Abstract: 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.

Anis AH, Guh D, Hogg RS, Wang XH, Yip B, Craib KJ, O'Shaughnessy MV, Schechter MT, Montaner JS. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada. · Pharmacoeconomics. · Pubmed #15344307 No free full text.

Abstract: OBJECTIVE: To estimate survival, the number of life-years gained and cost effectiveness of antiretroviral therapy (ART) regimens, denoted as ERA-I [zidovudine + (didanosine or zalcitabine)]; ERA-II [stavudine + (didanosine or zalcitabine) or lamivudine + (zidovudine or didanosine or zalcitabine or stavudine)]; and ERA-III [2 nucleoside reverse transcriptase inhibitors + (1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor)]. DESIGN: Modelling of drug cost, cost of opportunistic diseases and survival of HIV positive men and women in the province of British Columbia who were first prescribed any ART between October 1992 and June 1996. A 'reference cohort' was modelled upon individuals in a longitudinal cohort of homosexual men followed since 1982. PERSPECTIVE AND SETTING: Third-party payer perspective in British Columbia, Canada. PATIENTS: All HIV-positive men and women aged > or =18 years with CD4+ counts < or =350 cells/microL who were enrolled in the province-wide drug treatment programme. MAIN OUTCOME MEASURES: Annual costs, survival and cost-effectiveness ratios of successive ART regimens. RESULTS: Total costs [1997 Canadian dollars ($Can)] at 12 months under ERA-I, -II and -III were $Can4897, $Can6620 and $Can 11 914, respectively. Survival at 12 months under ERA-I, -II and -III was 89.6%, 91.0% and 97.6%, respectively. The annual incremental cost (estimated by the total incremental cost at 12 months) between ERA-II and ERA-I was $Can1723. The incremental cost-effectiveness ratios between ERA-III and ERA-I, and between ERA-III and ERA-II were $Can58 806 and $Can46 971 per life-year gained, respectively. CONCLUSION: We found the cost effectiveness of ERA-III ART regimens well within the range of currently funded therapies for the treatment of other chronic diseases.

Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC, Canada. · J Acquir Immune Defic Syndr. · Pubmed #15076240 No free full text.

Abstract: BACKGROUND: There have been concerns that irreversible immune damage may result if highly active antiretroviral therapy (HAART) is initiated after the CD4 cell count declines to below 350 cells/microL; however, the role of antiretroviral adherence on CD4 cell count responses has not been well evaluated. METHODS: We evaluated CD4 cell count responses of 1522 antiretroviral-naive patients initiating HAART who were stratified by baseline CD4 cell count (<50, 50-199, and >or=200 cells/microL) and adherence. RESULTS: Among patients starting HAART with <50 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 200 cells/microL (interquartile range [IQR]: 130-290) for adherent patients versus 60 cells/microL (IQR: 10-130) for nonadherent patients. Similarly, among patients starting HAART with 50 to 199 cells/microL, during the fifth 15-week period after the initiation of HAART, absolute CD4 cell counts were 300 cells/microL (IQR: 180-390) versus 125 cells/microL (IQR: 40-210) for nonadherent patients. In Cox regression analyses, adherence was the strongest independent predictor of the time to a gain of >or=50 cells/microL from baseline (relative hazard [RH] = 2.88, 95% confidence interval [CI]: 2.46-3.37). Among patients with baseline CD4 cell counts <200 cells/microL, adherence was the strongest independent predictor of the time to a CD4 cell count >200 cells/microL (RH = 4.85, 95% CI: 3.15-7.47). CONCLUSIONS: These data demonstrate that substantial CD4 gains are possible among highly advanced adherent patients and should contribute to the ongoing debate over the optimal time to initiate HAART.

Wood E, Tyndall MW, Spittal PM, Li K, Anis AH, Hogg RS, Montaner JS, O'Shaughnessy MV, Schechter MT. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, BC. · CMAJ. · Pubmed #12538544 links to  free full text

Abstract: BACKGROUND: More than 93% of the nearly $500 million spent annually on Canada's drug strategy goes toward efforts to reduce the illicit drug supply. However, little is known about the effectiveness of this strategy. On Sept. 2, 2000, Canadian police seized approximately 100 kg of heroin in one of the nation's largest-ever seizures of this drug. An ongoing prospective cohort study of injection drug users afforded an opportunity to evaluate the impact of this seizure. METHODS: The Vancouver Injection Drug User Study is a prospective cohort study of injection drug users that began in 1996. The present study relied primarily on data acquired from participants who were seen during the 30-day periods immediately before and after the seizure. We compared drug use and behavioural characteristics, heroin and cocaine prices, and participants' reports of whether law enforcement had affected their source of drugs or the types of drugs available on the street, as well as overdoses, in these 2 periods. RESULTS: The 138 participants seen before the seizure were similar to the 123 participants seen after the seizure with respect to age, sex, ethnic background, education, HIV serostatus, neighbourhood residence, instability of housing, employment status, use of methadone maintenance therapy and all other measured potential confounders (all p > 0.10). We found no difference in the extent to which participants in the 2 groups reported daily use of heroin, frequency of nonfatal overdoses, or whether law enforcement had affected their source of drugs or the types of drugs available on the street (all p > 0.10). Although we detected no difference in the price of cocaine, the median reported price of heroin went down after the seizure (p = 0.034), which suggests that other shipments compensated for the seizure. External evaluations of deaths from overdoses and heroin purity indicated that the seizure had no impact, nor was any impact seen when the periods of analysis were extended. INTERPRETATION: The massive heroin seizure appeared to have no measurable public health benefit. Closer scrutiny of enforcement efforts is warranted to ensure that resources are delivered to the most efficient and cost-effective public health programs.

Heath KV, Chan KJ, Singer J, O'Shaughnessy MV, Montaner JS, Hogg RS. · Centre for Excellence in HIV/AIDS, Vancouver, Canada. · Int J Epidemiol. · Pubmed #12435777 links to  free full text

Abstract: OBJECTIVE: To provide population-based incidence estimates for constituent symptoms of human immundeficiency virus (HIV)-related lipodystrophy syndrome and to identify possible independent predictors of accrued cases. DESIGN: Prospective population-based cohort. Methods Study subjects were antiretroviral-naïve individuals who initiated treatment between October 1998 and May 2001 and provided completed self-reported data regarding the occurrence of lipoatrophy, lipohypertrophy and increased triglyceride and cholesterol levels. Possible predictors of incident lipoatrophy, lipohypertrophy, dyslipidaemia and mixed lipodystrophy (symptoms of both lipoatrophy and lipohypertrophy) were identified using logistic regression modelling. A sub-analysis restricted to subjects retaining original treatment at study completion was conducted using similar methods. RESULTS: Among the 366 study subjects, cumulative incidence was 29% for lipoatrophy, 23% for lipohypertrophy, 9% for dyslipidaemia, and 13% for mixed lipodystrophy after a median duration of 12 months of antiretroviral therapy. In an intentto-treat analysis incident lipoatrophy and lipohypertrophy were independently associated with initiation of protease inhibitor (PI)-containing regimens, (adjusted odds ratio [AOR] = 1.94; 95% CI: 1.25-3.03 and AOR = 1.76; 95% CI: 1.09-2.85, respectively) and female gender (AOR = 2.06; 95% CI: 1.03-4.12 and AOR = 2.36; 95% CI: 1.17-4.74, respectively). Both mixed lipodystrophy and reported dyslipidaemia were associated only with PI inclusion in the initial regimen (AOR = 2.27; 95% CI: 1.14-4.53 and AOR = 2.14; 95% CI: 1.26-3.65, respectively). Similar results were obtained in analysis of individuals retained in initial treatment groups throughout follow-up. CONCLUSION: Incident morphological and lipid abnormalities are common among individuals initiating first-time antiretroviral therapy. Use of PI was consistently associated with all lipodystrophy-related abnormalities after adjustment for a broad range of patient personal, clinical and treatment characteristics.

Alexander CS, Montessori V, Wynhoven B, Dong W, Chan K, O'Shaughnessy MV, Mo T, Piaseczny M, Montaner JS, Harrigan PR. · Department of Medicine, University of British Columbia, Vancouver, Canada. · Antivir Ther. · Pubmed #12008785 No free full text.

Abstract: In North America, the B subtype of the major group (M) of HIV-1 predominates. Phylogenetic analysis of HIV reverse transcriptase and protease sequences isolated from 479 therapy-naive patients, first seeking treatment in British Columbia between June 1997 and August 1998, revealed a prevalence of 4.4% non-B virus. A range of different subtypes was identified, including one subtype A, 11 C, two D, five CRF01_AE, and one sample that could not be reliably subtyped. Baseline CD4 courts were significantly lower in individuals harbouring the non-B subtypes (P = 0.02), but baseline viral loads were similar (P = 0.80). In this study, individuals infected with non-B variants did not have a significantly different virological response to therapy after up to 18 months.

Hogg RS, Yip B, Chan KJ, Wood E, Craib KJ, O'Shaughnessy MV, Montaner JS. · Director, AIDS Research Programme, St Paul's Hospital/University of British Columbia, 667-1081 Burrard St, Vancouver, British Columbia V6Z 1Y6, Canada. · JAMA. · Pubmed #11722271 links to  free full text

Abstract: CONTEXT: Current recommendations for initiation of antiretroviral therapy in patients infected with human immunodeficiency virus type 1 (HIV) are based on CD4 T-lymphocyte cell counts and plasma HIV RNA levels. The relative prognostic value of each marker following initiation of therapy has not been fully characterized. OBJECTIVE: To describe rates of disease progression to death and AIDS or death among patients starting triple-drug antiretroviral therapy, stratified by baseline CD4 cell count and HIV RNA levels. DESIGN, SETTING, AND PARTICIPANTS: Population-based analysis of 1219 antiretroviral therapy-naive HIV-positive men and women aged 18 years or older in British Columbia who initiated triple-drug therapy between August 1, 1996, and September 30, 1999. MAIN OUTCOME MEASURE: Cumulative mortality rates from the initiation of triple-drug antiretroviral therapy to September 30, 2000, determined using various CD4 cell and plasma HIV RNA thresholds. RESULTS: As of September 30, 2000, 82 patients had died of AIDS-related causes, for a crude AIDS-related mortality rate of 6.7%. The product limit estimate (SE) of the cumulative mortality rate at 12 months was 2.9% (0.5%). In univariate analyses, a prior diagnosis of acquired immunodeficiency syndrome (AIDS), CD4 cell count, use of protease inhibitors, and HIV RNA level were associated with mortality. There was no difference in mortality by age or sex. Only CD4 cell count remained statistically significant in the multivariate analysis. After controlling for AIDS, protease inhibitor use, and plasma HIV RNA level at baseline, patients with CD4 cell counts of less than 50/microL were 6.67 (95% confidence interval [CI], 3.61-12.34) times and those with counts of 50/microL to 199/microL were 3.41 (95% CI, 1.93-6.03) times more likely to die than those with counts of at least 200/microL. CONCLUSION: Our data demonstrate uniformly low rates of disease progression to death and AIDS or death among patients starting antiretroviral therapy with CD4 cell counts of at least 200/microL. In our study, disease progression to death and AIDS or death was clustered among patients starting therapy with CD4 cell counts less than 200/microL.

Wood E, Braitstein P, Montaner JS, Schechter MT, Tyndall MW, O'Shaughnessy MV, Hogg RS. · British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, Canada. · Lancet. · Pubmed #10902622 No free full text.

Abstract: BACKGROUND: Despite growing international pressure to provide HIV-1 treatment to less-developed countries, potential demographic and epidemiological impacts have yet to be characterised. We modelled the future impact of antiretroviral use in South Africa from 2000 to 2005. METHODS: We produced a population projection model that assumed zero antiretroviral use to estimate the future demographic impacts of the HIV-1 epidemic. We also constructed four antiretroviral-adjusted scenarios to estimate the potential effect of antiretroviral use. We modelled total drug cost, cost per life-year gained, and the proportion of per-person health-care expenditure required to finance antiretroviral treatment in each scenario. FINDINGS: With no antiretroviral use between 2000 and 2005, there will be about 276,000 cumulative HIV-1-positive births, 2,302,000 cumulative new AIDS cases, and the life expectancy at birth will be 46.6 years by 2005. By contrast, 110,000 HIV-1-positive births could be prevented by short-course antiretroviral prophylaxis, as well as a decline of up to 1 year of life expectancy. The direct drug costs of universal coverage for this intervention would be US$54 million--less than 0.001% of the per-person health-care expenditure. In comparison, triple-combination treatment for 25% of the HIV-1-positive population could prevent a 3.1-year decline in life expectancy and more than 430,000 incident AIDS cases. The drug costs of this intervention would, however, be more than $19 billion at present prices, and would require 12.5% of the country's per-person health-care expenditure. INTERPRETATION: Although there are barriers to widespread HIV-1 treatment, limited use of antiretrovirals could have an immediate and substantial impact on South Africa's AIDS epidemic.

Wood E, Schechter MT, Tyndall MW, Montaner JS, O'Shaughnessy MV, Hogg RS. · British Columbia Centre for Excellence in HIV/AIDS, St Paul's Hospital, Vancouver, Canada. · AIDS. · Pubmed #10894288 No free full text.

Abstract: OBJECTIVE: To model the potential impact of HIV infection rates and the use of antiretroviral medication on life expectancy and mortality in the Downtown Eastside of Vancouver, British Columbia, Canada, from 1999 to 2006. DESIGN: Population projections were made to estimate the population of the Downtown Eastside in the year 2006. METHODS: Two scenarios were modelled to predict the impact of HIV infection and antiretroviral use on mortality and life expectancy. The use of antiretroviral therapy was estimated to be 80% in the first scenario and 20% in the second. The prevalence of HIV by age and sex, and by year infected was estimated using data from the Vancouver Injection Drug User Study. RESULTS: If the level of antiretroviral therapy use among HIV-positive individuals was 80% at baseline, then we estimate that the life expectancy at birth in the year 2006 will be 60.8 years for men and 72.8 years for women, and 172 AIDS deaths will occur between 1999 and 2006. In contrast, if the present level of antiretroviral medication use persists, the life expectancy at birth in the year 2006 will be 56.9 years for men and 68.6 years for women, and 503 AIDS deaths will occur between 1999 and 2006. CONCLUSION: Our analysis suggests that if the low levels of antiretroviral therapy use persist, life expectancy in Vancouver's Downtown Eastside will soon be on a par with many of the world's least developed countries. Our findings highlight the large health status decline that can be expected in many inner city neighbourhoods if low levels of antiretroviral use persist. Although reasonable coverage targets for injection drug users (IDU) have not been established, the expanded use of antiretroviral medication is urgently needed to avert a drastic decline in health status.

Weber AE, Yip B, O'Shaughnessy MV, Montaner JS, Hogg RS. · British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital. · CMAJ. · Pubmed #10750463 links to  free full text

Abstract: BACKGROUND: This study was initiated to evaluate the demographic and clinical determinants of admission to hospital among HIV-positive men and women receiving antiretroviral therapy in British Columbia. METHODS: The analysis was restricted to participants enrolled in the HIV/AIDS Drug Treatment Program between September 1992 and March 1997 who had completed an annual participant survey, had a viral load determination and had signed a consent form allowing electronic access to their inpatient hospital records. A record linkage was conducted with the BC Ministry of Health to obtain all records of hospital admissions from April 1991 to March 1997. Statistical analyses were carried out using parametric and nonparametric methods and multivariate logistic analyses. RESULTS: The study sample comprised 947 participants (859 men, 88 women). Of these, 165 (17%) were admitted to hospital during the study period from May 1, 1996, to Mar. 31, 1997. The median number of admissions was 1 (interquartile range [IQR] 1-2 admissions), and the median length of stay per admission was 3 days (IQR 1-8 days). Admission to hospital was associated with being unemployed (82% of those admitted v. 58% of those not admitted), being an injection drug user (24% v. 17%), reporting a fair or poor health status (46% v. 29%) and having a physician experienced in the management of HIV/AIDS (31% v. 24%). Examination of clinical determinants demonstrated that hospital admission was associated with a previous admission (72% v. 46%), a high viral load (median 74,000 v. 14,000 HIV-1 RNA copies/mL), a low CD4 count (median 0.16 v. 0.27 x 10(9)/L) and an AIDS diagnosis (44% v. 24%). Multivariate logistic regression analysis revealed that being admitted to hospital was independently associated with being unemployed (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.66-4.20), having been previously admitted to hospital (OR 2.30, 95% CI 1.53-3.46), having a high viral load at baseline (OR 1.45, 95% CI 1.16-1.80), being an injection drug user (OR 1.63, 95% CI 1.02-2.62) and having an experienced physician (OR 1.98, 95% CI 1.29-3.03). INTERPRETATION: Hospital admission among participants in this study was found to be associated with marginalization and poor health status.

Kirstein LM, Mellors JW, Rinaldo CR, Margolick JB, Giorgi JV, Phair JP, Dietz E, Gupta P, Sherlock CH, Hogg R, Montaner JS, Muñoz A. · Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA. · J Clin Microbiol. · Pubmed #10405379 links to  free full text

Abstract: We conducted two studies to determine the potential influence of delays in blood processing, type of anticoagulant, and assay method on human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma. The first was an experimental study in which heparin- and EDTA-anticoagulated blood samples were collected from 101 HIV-positive individuals and processed to plasma after delays of 2, 6, and 18 h. HIV-1 RNA levels in each sample were then measured by both branched-DNA (bDNA) and reverse transcriptase PCR (RT-PCR) assays. Compared to samples processed within 2 h, the loss (decay) of HIV-1 RNA in heparinized blood was significant (P < 0.05) but small after 6 h (bDNA assay, -0.12 log(10) copies/ml; RT-PCR, -0.05 log(10) copies/ml) and after 18 h (bDNA assay, -0.27 log(10) copies/ml; RT-PCR, -0.15 log(10) copies/ml). Decay in EDTA-anticoagulated blood was not significant after 6 h (bDNA assay, -0.002 log(10) copies/ml; RT-PCR, -0.02 log(10) copies/ml), but it was after 18 h (bDNA assay, -0.09 log(10) copies/ml; RT-PCR, -0.09 log(10) copies/ml). Only 4% of samples processed after 6 h lost more than 50% (>/=0.3 log(10) copies/ml) of the HIV-1 RNA, regardless of the anticoagulant or the assay that was used. The second study compared HIV-1 RNA levels in samples from the Multicenter AIDS Cohort Study (MACS; samples were collected in heparin-containing tubes in 1985, had a 6-h average processing delay, and were assayed by bDNA assay) and the British Columbia Drug Treatment Program (BCDTP) (collected in EDTA- or acid citrate dextrose-containing tubes in 1996 and 1997, had a 2-h maximum processing delay, and were assayed by RT-PCR). HIV-1 RNA levels in samples from the two cohorts were not significantly different after adjusting for CD4(+)-cell count and converting bDNA assay values to those corresponding to the RT-PCR results. In summary, the decay of HIV-1 RNA measured in heparinized blood after 6 h was small (-0.05 to -0.12 log(10) copies/ml), and the minor impact of this decay on HIV-1 RNA concentrations in archived plasma samples of the MACS was confirmed by the similarity of CD4(+)-cell counts and assay-adjusted HIV-1 RNA concentrations in the MACS and BCDTP.

Forrest DM, Zala C, Djurdjev O, Singer J, Craib KJ, Lawson L, Russell JA, Montaner JS. · British Columbia Center for Excellence in HIV/AIDS, Division of Critical Care Medicine, University of British Columbia, Vancouver, Canada. · Arch Intern Med. · Pubmed #10218755 links to  free full text

Abstract: OBJECTIVES: To determine (1) predictors of in-hospital mortality and long-term survival in patients with acute respiratory failure (ARF) caused by acquired immunodeficiency syndrome-related Pneumocystis carinii pneumonia (PCP) and (2) long-term survival for patients with ARF relative to those without ARF. METHODS: A retrospective medical chart review was conducted of all cases of PCP-related ARF for which the patient was admitted to the intensive care unit of a single tertiary care institution between 1991 and 1996. Data were extracted regarding physiologic scores, relevant laboratory values, and duration of previous maximal therapy with combined anti-PCP agents and corticosteroids at entry to the intensive care unit. Duration of survival was determined by Kaplan-Meier methods from date of first hospital admission and compared for patients with and without ARF. RESULTS: There were 41 admissions to the intensive care unit among 39 patients, with 56.4% in-hospital mortality. Higher physiologic scores (Acute Physiology and Chronic Health Evaluation II [APACHE II], Acute Lung Injury, and modified Multisystem Organ Failure scores) were predictive of in-hospital mortality. Duration of previous maximal therapy also predicted in-hospital mortality (45% for patients with <5 days of previous maximal therapy vs 88% for those with > or =5 days of previous maximal therapy; P = .03). Combining physiologic scores and duration of previous maximal therapy enhanced prediction of in-hospital mortality. There was no difference in long-term survival between patients with PCP with ARF and those without ARF (P = .80), and baseline characteristics did not predict long-term survival. CONCLUSIONS: In-hospital mortality of patients with acquired immunodeficiency syndrome-related PCP and ARF is predicted by duration of previous maximal therapy and physiologic scores, and their combination enhances predictive accuracy. Long-term survival of patients with ARF caused by PCP is comparable to that of patients with PCP who do not develop ARF, and determinants of in-hospital mortality do not predict long-term survival.

Hogg RS, Yip B, Kully C, Craib KJ, O'Shaughnessy MV, Schechter MT, Montaner JS. · No affiliation provided · CMAJ. · Pubmed #10102000 links to  free full text

Abstract: BACKGROUND: The efficacy of triple-drug antiretroviral regimens in the treatment of patients infected with HIV has been established in several randomized clinical trials. However, the effectiveness of these new regimens in patient populations outside clinical trials remain unproven. This study compared mortality and AIDS-free survival among HIV-infected patients in British Columbia who were treated with double- and triple-drug regimens. METHODS: The authors used a prospective, population-based cohort design to study a population of HIV-positive men and women 18 years or older for whom antiretroviral therapy was first prescribed between Oct. 1, 1994, and Dec. 31, 1996; all patients were from British Columbia. Rates of progression from the initiation of antiretroviral therapy to death or to diagnosis of primary AIDS were determined for patients who initially received an ERA-II regimen (2 nucleoside analogue reverse transcriptase inhibitors [NRTIs] including lamivudine or stavudine, or both) and for those who initially received an ERA-III regimen (triple-drug regimen consisting of 2 NRTIs and a protease inhibitor [indinavir, ritonavir or saquinavir] or a non-NRTI [nevirapine]). RESULTS: A total of 500 men and women (312 receiving an ERA-III regimen and 188 an ERA-III regimen) were eligible. Patients in the ERA-III group survived significantly longer than those in the ERA-II group. As of Dec. 31, 1997, 40 patients had died (35 in the ERA-II group and 5 in the ERA-III group), for a crude mortality rate of 8.0%. The cumulative mortality rates at 12 months were 7.4% (95% confidence interval [CI] 5.9% to 8.9%) for patients in the ERA-II group and 1.6% (95% CI 0.7% to 2.5%) for those in the ERA-III group (log rank p = 0.003). The likelihood of death was more than 3 times higher among patients in the ERA-II group (mortality risk ratio 3.82 [95% CI 1.48% to 9.84], p = 0.006). After adjustment for prophylaxis for Pneumocystis carinii pneumonia or Mycobacterium avium infection, AIDS diagnosis, CD4+ cell count, sex and age at initiation of therapy, the likelihood of death among patients in the ERA-II group was 3.21 times higher (95% CI 1.24 to 8.30, p = 0.016) than in the ERA-III group. Cumulative rates of progression to AIDS or death at 12 months were 9.6% (95% CI 7.7% to 11.5%) in the ERA-II group and 3.3% (95% CI 1.8% to 4.8%) in the ERA-III group (log rank p = 0.006). After adjustment for prognostic variables (prophylaxis for P. carinii pneumonia or M. avium infection, CD4+ cell count, sex and age at initiation of treatment), the likelihood of progression to AIDS or death at 12 months among patients in the ERA-II group was 2.37 times higher (95% CI 1.04 to 5.38, p = 0.040) than in the ERA-III group. INTERPRETATION: This population-based cohort study confirms that patients initially treated with a triple-drug antiretroviral regimen comprising 2 NRTIs plus protease inhibitor or a non-NRTI have a lower risk of morbidity and death than patients treated exclusively with 2 NRTIs.

Christie TK, Montaner JS. · No affiliation provided · CMAJ. · Pubmed #16754908 links to  free full text

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