Jsg Montaner

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

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

Rates of antiretroviral resistance among HIV-infected patients with and without a history of injection drug use.

Background:There exist concerns regarding the potential for elevated rates of antiretroviral resistance among HIV-infected injection drug users (IDUs) prescribed highly active antiretroviral therapy (HAART), however, no population-based study has examined if IDUs have elevated rates of antiretroviral resistance in comparison to non-IDUs. Objective:To evaluate the time to the development of antiretroviral resistance among antiretroviral-naive patients with and without a history of injection drug use. Methods:In British Columbia there is a province-wide HIV/AIDS treatment program that provides antiretrovirals free of charge. We examined all antiretroviral-naive patients initiating HAART between 1 August 1996 and 30 September 2000 and who were followed to 31 March 2002. The main outcome measure was the time to class-specific antiretroviral resistance. Cumulative antiretroviral resistance rates among IDUs and non-IDUs were evaluated using Kaplan–Meier methods and relative hazards were estimated using Cox regression. Results:Overall, 1191 antiretroviral-naive patients initiated HAART during the study period. Resistance mutations were observed in 298 (25%) subjects during the first 30 months of HAART. In comparison with non-IDUs, the risk of protease inhibitor resistance [relative hazard (RH), 0.9; 95% confidence interval (CI), 0.5–1.6] and non-nucleoside reverse transcriptase inhibitor resistance (RH, 1.5; 95% CI, 1.0–2.2) were similar among IDUs, and there were no differences in the rates of resistance to the sub-classes of nucleoside reverse transcriptase inhibitors. Conclusions:Resistance to all major classes of antiretrovirals were similar among IDUs and non-IDUs after 30 months of follow-up. These findings should help to allay fears that prescribing HAART to IDUs may result in elevated rates of resistance.

Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort

The aim of the study was to evaluate time to virological suppression in a cohort of individuals who started highly active antiretroviral therapy (HAART), and to explore the factors associated with suppression.

CD4 percentage is an independent predictor of survival in patients starting antiretroviral therapy with absolute CD4 cell counts between 200 and 350 cells/μL

To determine the prognostic value of baseline CD4 percentage in terms of patient survival in comparison to absolute CD4 cell counts for HIV‐positive patients initiating highly active antiretroviral therapy (HAART).

Impact of adherence on duration of virological suppression among patients receiving combination antiretroviral therapy

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.

Superior virological response to boosted protease inhibitor-based highly active antiretroviral therapy in an observational treatment programme.

The use of boosted protease inhibitor (PI)‐based antiretroviral therapy has become increasingly recommended in international HIV treatment consensus guidelines based on the results of randomized clinical trials. However, the impact of this new treatment strategy has not yet been evaluated in community‐treated cohorts.

Initiation of antiretroviral therapy at high CD4+ cell counts is associated with positive treatment outcomes.

Objective:There is limited research investigating the possible mechanisms of how starting combination antiretroviral therapy (cART) at a higher CD4+ cell count decreases mortality. This study investigated the association between initiating cART with short-term and long-term achievement of viral suppression; emergence of any drug resistance and of an AIDS-defining illness (ADI); long-term treatment adherence; and all-cause mortality. Methods:This retrospective cohort study included 4120 naive patients who initiated cART between 2000 and 2012. Patients were followed until 2013, death or until the last contact date (varied by outcome). The main exposure was the interaction between period of cART initiation (2000–2006 and 2007–2012) and CD4+ cell count at cART initiation (<500 versus ≥500 cells/&mgr;l). We considered both baseline and longitudinal covariates. We fitted different multivariable models using cross-sectional and longitudinal statistical methods, depending on the outcome. Results:Patients who initiated cART with a CD4+ cell count at least 500 cells/&mgr;l in 2007–2012 had an increased likelihood of achieving viral suppression at 9 months and of maintaining an adherence level of at least 95% over time, and the lowest probability of developing any resistance and an ADI during follow-up. These patients were not the ones with the highest likelihood of maintaining viral suppression over time, most likely due to viral load blips experienced during the follow-up. Conclusion:The outcomes in this study likely play an important role in explaining the positive impact of early cART initiation on mortality. These results should alleviate some of the concerns clinicians may have when initiating cART in patients with high CD4+s as recommended by current treatment guidelines.

Poor adherence to HIV monitoring and treatment guidelines for HIV-infected injection drug users

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.

Performance of a World Health Organization first-line regimen (stavudine/lamivudine/nevirapine) in antiretroviral-naïve individuals in a Western setting

In 2003, the World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) introduced the ‘3 by 5 Initiative’ to treat 3 million individuals by the end of 2005. This study evaluates the time to treatment termination, viral load suppression, and detection of drug resistance among antiretroviral‐naïve individuals initiating stavudine/lamivudine/nevirapine (d4T/3TC/NVP) in British Columbia, Canada, to provide a context for future programme planning.

Regimen-dependent variations in adherence to therapy and virological suppression in patients initiating protease inhibitor-based highly active antiretroviral therapy.

To examine differences among four protease inhibitor (PI)‐based drug regimens in adherence to therapy and rate of achievement of virological suppression in a cohort of antiretroviral‐naive patients initiating highly active antiretroviral therapy (HAART).