Mitochondrial toxicity in the era of HAART: evaluating venous lactate and peripheral blood mitochondrial DNA in HIV-infected patients taking antiretroviral therapy.

Nucleoside analogs can induce mitochondrial toxicity by inhibiting the human DNA polymerase gamma. This can lead to a wide range of clinical toxicities, from asymptomatic hyperlactatemia to death. Despite their technical and physiological variability, we propose that random venous lactate measurements can be useful to monitor the development of nucleoside-related mitochondrial toxicity.

Prevalence and correlates of untreated human immunodeficiency virus type 1 infection among persons who have died in the era of modern antiretroviral therapy.

We evaluated all human immunodeficiency virus (HIV)-related deaths over the period 1 January 1995-31 December 2001 in a Canadian province in which all HIV care and antiretroviral therapy are provided free of charge. Persons who had received antiretroviral drugs before death were compared with those who had died without ever receiving HIV treatment, by fitting a logistic model. Overall, 1239 deaths were attributed to HIV infection during the study period.

Adherence and plasma HIV RNA responses to highly active antiretroviral therapy among HIV-1 infected injection drug users.

Background: The benefits of highly active antiretroviral therapy (HAART) for the treatment of HIV infection are well documented, but concerns regarding access and adherence to HAART are growing. We evaluated virological responses to HAART among HIV-1 infected patients who were injection drug users (IDUs) in a population-based setting where HIV/AIDS care is delivered free of charge.

Methods: We evaluated previously untreated HIV-1 infected men and women who initiated HAART between Aug.

Interventional cardiovascular procedures among HIV-infected individuals on antiretroviral therapy 1995-2000.

Objective: To calculate the rate of interventional cardiac procedures (ICP) among HIV-infected individuals ever treated with antiretroviral therapy (ART) and to describe clinical and sociodemographic characteristics associated with ICP.

Methods: Since 1992, ART in British Columbia (BC) has been centrally distributed by the BC Centre for Excellence in HIV/AIDS. The BC Cardiac Registry maintains information regarding all cardiac procedures performed in BC.

Antiretroviral concentrations in untimed plasma samples predict therapy outcome in a population with advanced disease.

This study was designed to examine the relationship between untimed antiretroviral concentrations measured in plasma samples collected for virus-load testing and response to highly active antiretroviral therapy. Plasma nonnucleoside reverse-transcriptase-inhibitor and protease-inhibitor concentrations were retrospectively measured in all virus-load plasma samples collected during the first year of therapy, for 122 patients in British Columbia, Canada, who initiated therapy between August 1996 and September 1999 and who had CD4 counts <50 cells/micro L. Drug levels were designated a priori as "low" if the concentrations were below the published Ctrough-SD.

Rates of disease progression among human immunodeficiency virus-infected persons initiating multiple-drug rescue therapy.

To characterize survival and to compare rates of disease progression to death of human immunodeficiency virus (HIV)-infected patients, between those initiating multiple-drug rescue therapy (MDRT) and those antiretroviral-inexperienced initiating triple-drug antiretroviral therapy (ART), we conducted a population-based analysis of HIV-infected men and women aged > or =18 years in British Columbia, Canada. Cumulative mortality rates were estimated by use of Kaplan-Meier methods, and Cox-proportional hazard regression was used to model the simultaneous effect of prognostic variables on survival. Cumulative mortality at 36 months was 14.

Mitochondrial:nuclear DNA ratios in peripheral blood cells from human immunodeficiency virus (HIV)-infected patients who received selected HIV antiretroviral drug regimens.

Mitochondrial:nuclear DNA (mtDNA:nDNA) ratios in blood cells were investigated in relation to selected human immunodeficiency virus antiretroviral drug regimens. Patients (n = 214) continually received a regimen consisting of either (1) saquinavir (SAQ) + ritonavir (RTV) + either nevirapine (NVP) or lamivudine (3TC) (n=32) or (2) SAQ+RTV (+/- either NVP or 3TC) + either stavudine (d4T) (n=127), didanosine (ddI) (n=19), d4T+ddI (n=21), or zidovudine (ZDV) (n=15), for >/=4 months. NVP- or 3TC-only regimens were associated with median mtDNA:nDNA ratios that were significantly higher than those for ddI- and d4T+ddI-containing regimens (P<.

Sexual violence among a cohort of injection drug users.

The objective of this study was to determine the prevalence of, and factors associated with, sexual violence in childhood, adolescence and adulthood, among injection drug using men and women. The Vancouver Injection Drug User Study is a prospective cohort of injection drug users (IDU) begun in 1996. The analysis included all individuals who completed the baseline questionnaire who responded to a question about sexual assault.

Prevalence and clinical implications of insertions in the HIV-1 p6Gag N-terminal region in drug-naive individuals initiating antiretroviral therapy.

We assessed the prevalence and clinical impact of insertions within the HIV-1 p6Gag proline-rich (PTAP) region on initial antiretroviral therapy response in 461 HIV-infected, drug-naive individuals initiating therapy in British Columbia, Canada between June 1996 and August 1998. HIV p6Gag insertions were detected by nested RT-PCR of extracted patient plasma followed by direct DNA sequencing. Insertions were observed in 70 of 423 successfully genotyped samples (16.

Impaired virologic response to highly active antiretroviral therapy associated with ongoing injection drug use.

Injection drug users who continue to use drugs may not respond to highly active antiretroviral therapy (HAART) as well as other HIV-infected individuals, even after adjusting for a reliable measure of adherence. We therefore compared the virologic response among participants in a population-based HIV/AIDS Drug Treatment Program in British Columbia, Canada, by injection drug use activity. Participants who were HIV infected and naive to antiretroviral therapy and who were prescribed antiretroviral treatment between August 1996 and December 2000 were eligible for this study.

Health and socioeconomic status differences among antibody hepatitis C positive and negative transfusion recipients, 1986-1990.

Objective: To characterize the socioeconomic and health status, disease symptoms of anti-HCV-positive and negative transfusion recipients.

Methods: A cross-sectional interviewer-administered survey of subjects identified through the British Columbia Blood Recipient Program. Study subjects were 18 years and over and had to have had a transfusion between August 1, 1986 and June 30, 1990 and completed an interview of satisfactory quality.

Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?

Objective: Therapeutic guidelines advise that 200-350 x 106 cells/l may approximate an irreversible threshold beyond which response to therapy is compromised. We evaluated whether non-immune-based factors such as physician experience and adherence could affect survival among HIV-infected adults starting HAART.

Methods: Analysis of 1416 antiretroviral naive patients who initiated triple therapy between 1 August 1996 and 31 July 2000, and were followed until 31 July 2001.

Length of ICU stay for chronic obstructive pulmonary disease varies among large community hospitals.

Objective: To determine whether differences exist among large community hospitals in length of Intensive Care Unit (ICU) stay, hospital stay or hospital mortality for patients admitted to ICU and whose most responsible diagnosis was chronic obstructive pulmonary disease (COPD).

Design: Retrospective cohort study.

Setting: All seven large community hospitals in British Columbia, Canada.

Virologic and immunologic response, clinical progression, and highly active antiretroviral therapy adherence.

A growing body of evidence suggests that a high degree of adherence is required to achieve and maintain a successful virologic response both in the short and long term. This holds true despite the definition of adherence or how it is measured. Reported differences in the degree of adherence required are likely due to differences in study design, difficulty measuring patient adherence, patient population studied, and the antiretroviral regimen studied.

Influence of polymorphisms within the CX3CR1 and MDR-1 genes on initial antiretroviral therapy response.

Objective: Single nucleotide polymorphisms (SNP) in the genes encoding the human CX3CR1 chemokine receptor and the P-glycoprotein multidrug transporter have been associated with accelerated disease progression in untreated individuals and implicated in therapeutic response, respectively. This retrospective study assessed the influence of SNP in the CX3CR1 and MDR-1 genes on initial virological and immunological response in 461 HIV-infected, antiretroviral-naive individuals initiating antiretroviral therapy in British Columbia, Canada.

Methods: CX3CR1 and MDR-1 SNP were determined by PCR amplification of human DNA from plasma, followed by DNA sequencing.

Impact of supply-side policies for control of illicit drugs in the face of the AIDS and overdose epidemics: investigation of a massive heroin seizure.

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.

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

Little is known about the psychosocial factors associated with sexual assault experienced by males. Men (N=358), 19-35 years of age, recruited by community outreach, completed questionnaires. Eligibility criteria included: being HIV-negative and self-identifying as gay or bisexual.

Risk factors for elevated HIV incidence among Aboriginal injection drug users in Vancouver.

Background: Because of established links between entrenched poverty and risk of HIV infection, there have long been warnings that HIV/AIDS will disproportionately affect Aboriginal people in Canada. We compared HIV incidence rates among Aboriginal and non-Aboriginal injection drug users (IDUs) in Vancouver and studied factors associated with HIV seroconversion among Aboriginal participants.

Methods: This analysis was based on 941 participants (230 Aboriginal people) recruited between May 1996 and December 2000 who were seronegative at enrollment and had completed at least one follow-up visit.

The potential public health and community impacts of safer injecting facilities: evidence from a cohort of injection drug users.

Background: Although medically supervised safer injecting facilities (SIFs) remain untested in North America, their implementation is currently being debated. Reluctance of health policy makers to initiate a pilot study of SIFs may in part be hindered by outstanding questions regarding the potential community and public health impact of the intervention. Specifically, it is presently unknown if those at greatest risk of overdose and HIV transmission or those responsible for community impact of injection drug use will be willing to attend.

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

Objectives: To assess the extent to which HIV-negative cohort study participants would be willing to participate (WTP) in future HIV vaccine trials, to explore enrollment into an ongoing phase 3 HIV vaccine trial, and to assess changing WTP in such trials over time.

Methods: The Vanguard Project is a prospective study of gay and bisexual men in the greater Vancouver region, British Columbia, Canada. Sociodemographic characteristics, sexual risk behavior, beliefs around HIV, and reasons for not participating in the AIDSVAX B/B trial were collected from self-administered questionnaires.

Incidence of morphological and lipid abnormalities: gender and treatment differentials after initiation of first antiretroviral therapy.

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.