Eric Druyts

Impact of neighborhood-level socioeconomic status on HIV disease progression in a universal health care setting.

Objectives:The objectives of this study were to examine neighborhood measures of socioeconomic status and their effect on the risk of mortality among HIV-positive persons accessing and not accessing treatment, the effects of late access to treatment by CD4 cell count, and survival among those who accessed treatment. Methods:We limited our analysis to the era of highly active antiretroviral therapy (HAART). We used individual-level patient and clinical characteristics and neighborhood-level socioeconomic data to address our objectives. The Pearson χ2 and Wilcoxon sign rank tests were used to compare mortality among HIV-positive persons accessing and not accessing treatment, logistic regression models were used to compare persons who accessed treatment with low CD4 cell counts (<50 cells/mm3) with those who accessed treatment earlier (CD4 count ≥50 cells/mm3), and Weibull survival models were used to compare mortality among those who accessed treatment. Results:Forty percent of people who died from HIV/AIDS-related causes never accessed treatment. Among those who accessed treatment, 16% did so when their CD4 counts were <50 cells/mm3. Unemployment was associated with delayed access to treatment (odds ratio = 1.41, 95% confidence interval [CI]: 1.14 to 1.74). Postsecondary education (hazard ratio [HR] = 0.80, 95% CI: 0.71 to 0.91) and percent of residents below the poverty line (HR = 1.07, 95% CI: 1.01 to 1.13) were associated with mortality. Conclusions:In a setting where treatment for HIV is free of charge, a significant number of HIV-positive persons did not access HAART. Low socioeconomic status was associated with this delay and with increased mortality among persons receiving HAART. Social and health policy initiatives, beyond free and universal health care, are required to optimize access to HAART.

Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: A systematic review and meta-analysis

Background:HIV/AIDS has historically had a sex and gender-focused approach to prevention and care. Some evidence suggests that HIV-positive men have worse treatment outcomes than their women counterparts in Africa. Methods:We conducted a systematic review and meta-analysis of the effect of sex on the risk of death among participants enrolled in antiretroviral therapy (ART) programs in Africa since the rapid scale-up of ART. We included all cohort studies evaluating the effect of sex (male, female) on the risk of death among participants enrolled in regional and national ART programs in Africa. We identified these studies by searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird random-effects method to pool the proportions of men receiving ART and the hazard ratios for death by sex. Results:Twenty-three cohort studies, including 216 008 participants (79 892 men) contributed to our analysis. The pooled proportion of men receiving ART was 35% [95% confidence interval (CI): 33–38%]. The pooled hazard ratio estimate indicated a significant increase in the risk of death for men when compared to women [hazard ratio: 1.37 (95% CI: 1.28–1.47)]. This was consistent across sensitivity analyses. Interpretation:The proportion of men enrolled in ART programs in Africa is lower than women. Additionally, there is an increased risk of death for men enrolled in ART programs. Solutions that aid in reducing these sex inequities are needed.

Descriptive review and evaluation of the functioning of the International Health Regulations (IHR) Annex 2

BackgroundThe International Health Regulations (IHRs) (2005) was developed with the aim of governing international responses to public health risks and emergencies. The document requires all 194 World Health Organization (WHO) Member States to detect, assess, notify and report any potential public health emergency of international concern (PHEIC) under specific timelines. Annex 2 of the IHR outlines decision-making criteria for State-appointed National Focal Points (NFP) to report potential PHEICs to the WHO, and is a critical component to the effective functioning of the IHRs.MethodsThe aim of the study was to review and evaluate the functioning of Annex 2 across WHO-reporting States Parties. Specific objectives were to ascertain NFP awareness and knowledge of Annex 2, practical use of the tool, activities taken to implement it, its perceived usefulness and user-friendliness. Qualitative telephone interviews, followed by a quantitative online survey, were administered to NFPs between October, 2009 and February, 2010.ResultsA total of 29 and 133 NFPs participated in the qualitative and quantitative studies, respectively. Qualitative interviews found most NFPs had a strong working knowledge of Annex 2; perceived the tool to be relevant and useful for guiding decisions; and had institutionalized management, legislation and communication systems to support it. NFPs also perceived Annex 2 as human and disease-centric, and emphasized its reduced applicability to potential PHEICs involving bioterrorist attacks, infectious diseases among animals, radio-nuclear and chemical spills, and water- or food-borne contamination. Among quantitative survey respondents, 88% reported having excellent/good knowledge of Annex 2; 77% reported always/usually using Annex 2 for assessing potential PHEICs; 76% indicated their country had some legal, regulatory or administrative provisions for using Annex 2; 95% indicated Annex 2 was always/usually useful for facilitating decisions regarding notifiability of potential PHEICs.ConclusionThis evaluation, including a large sample of WHO-reporting States Parties, found that the IHRs Annex 2 is perceived as useful for guiding decisions about notifiability of potential PHEICs. There is scope for the WHO to expand training and guidance on application of the IHRs Annex 2 to specific contexts. Continued monitoring and evaluation of the functioning of the IHR is imperative to promoting global health security.

HIV/AIDS in Vancouver, British Columbia: A Growing Epidemic

The prevalence of HIV in Vancouver, British Columbia was subject to two distinct periods of rapid increase. The first occurred in the 1980s due to high incidence among men who have sex with men (MSM), and the second occurred in the 1990s due to high incidence among injection drug users (IDU). The purpose of this study was to estimate and model the trends in HIV prevalence in Vancouver from 1980 to 2006. HIV prevalence data were entered into the UNAIDS/WHO Estimation and Projection Package (EPP) where prevalence trends were estimated by fitting an epidemiological model to the data. Epidemic curves were fit for IDU, MSM, street-based female sex trade workers (FSW), and the general population. Using EPP, these curves were then aggregated to produce a model of Vancouvers overall HIV prevalence. Of the 505 000 people over the age of 15 that reside in Vancouver, 6108 (ranging from 4979 to 7237) were living with HIV in the year 2006, giving an overall prevalence of 1.21 percent (ranging from 0.99 to 1.43 percent). The subgroups of IDU and MSM account for the greatest proportion of HIV infections. Our model estimates that the prevalence of HIV in Vancouver is greater than one percent, roughly 6 times higher than Canadas national prevalence. These results suggest that HIV infection is having a relatively large impact in Vancouver and that evidence-based prevention and harm reduction strategies should be expanded.

Efficacy and Safety of Pegylated Interferon Alfa-2a or Alfa-2b Plus Ribavirin for the Treatment of Chronic Hepatitis C in Children and Adolescents: A Systematic Review and Meta-analysis

BACKGROUND A systematic review and meta-analysis were conducted to examine the efficacy and safety of pegylated interferon (peg-IFN) alfa-2a and peg-IFN alfa-2b plus ribavirin (RBV) in children and adolescents with chronic hepatitis C virus (HCV). METHODS Medline, Embase, and Cochrane Central Register of Controlled Trials were searched. Clinical trials examining peg-IFN alfa-2a or peg-IFN alfa-2b plus RBV among persons ages 3-18 years with HCV were included. Data were abstracted for complete early virologic response (EVR), sustained virologic response (SVR), relapse, treatment discontinuations, hematologic and dermatologic adverse events, and growth inhibition. RESULTS Eight trials met the inclusion criteria. Results indicate that 70% of subjects (95% confidence interval [CI], 58%-81%) achieved EVR, and 58% (95% CI, 53%-64%) achieved SVR. EVR and SVR were higher for those with HCV genotypes 2/3 than 1/4. Discontinuation due to adverse events and discontinuation due to viral breakthrough were each 4%, discontinuation due to a lack of response was 15%, and relapse was 7%. Anemia, neutropenia, leukopenia, and thrombcytopenia were 11%, 32%, 52%, and 5%, respectively. Alopecia, injection site erythema, and pruritus were 13%, 27%, and 10%, respectively. Small growth inhibitions were observed during treatment. CONCLUSION The results of this meta-analysis indicate that peg-IFN/RBV combination treatment is effective and safe in treating children and adolescents with HCV.

Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis

Background: Most patients with moderate and severe chronic obstructive pulmonary disease (COPD) receive long-acting bronchodilators (LABA) for symptom control. It is, however, unclear if and what drug treatments should be added to LABAs to reduce exacerbations, which is an important goal of COPD management. Since current guidelines cannot make strong recommendations yet, our aim was to determine the relative efficacy of existing treatments and combinations to reduce the risk for COPD exacerbations. Methods: We included randomized clinical trials (RCTs) evaluating long-acting β2 agonists (LABA), long-acting muscarinic antagonists (LAMA), inhaled glucocorticosterioids (ICS), and the phosphodiesterase-4 (PDE4) inhibitor roflumilast, and combinations of these interventions in moderate to severe COPD populations. Our primary outcome was the event rate of exacerbations. We conducted a random-effects Bayesian mixed-treatment comparison (MTC) and applied several sensitivity analyses. In particular, we confirmed our findings using a binomial MTC analysis examining whether a patient experienced at least one exacerbation event or not during the trial. We also used an additive assumption to calculate the combined effects of treatments that were not included in the systematic review. Results: Twenty-six studies provided data on the total number of exacerbations and/or the mean annual rate of exacerbations among a combined 36,312 patients. There were a total of 10 treatment combinations in the MTC and 15 in the additive analysis. Compared with all other treatments, the combination of roflumilast plus LAMA exhibited the largest treatment effects, and had the highest probability (45%) of being the best first-line treatment. This was consistent whether applying the incidence rate analysis or the binomial analysis. When applying the additive assumption, most point estimates suggested that roflumilast may provide additional benefit by further reducing exacerbations. Conclusions: Using various meta-analytic approaches, our study demonstrates that depending on the choice of drug, combined treatments offer a therapeutic advantage.

Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naïve to anti-TNF therapy: An indirect treatment comparison meta-analysis

OBJECTIVE To compare the efficacy of adalimumab and infliximab for the treatment of moderate to severe ulcerative colitis using indirect treatment comparison meta-analysis. METHODS A systematic review and Bayesian indirect treatment comparison meta-analyses were performed for seven patient-important clinical outcomes at 8 weeks and 52 weeks. Odds ratio (OR) estimates and associated 95% credible intervals (CrIs) were produced. RESULTS Five eligible RCTs informed clinical remission, response, mucosal healing, quality of life, colectomy, serious adverse events, and discontinuation due to adverse events at 8 weeks and 52 weeks. At 8 weeks of induction therapy, clinical remission (OR=0.42, 95% CrI 0.17-0.97), clinical response (OR=0.45, 95% CrI 0.23-0.89) and mucosal healing (OR=0.46, 95% CrI 0.25-0.86) statistically favored infliximab. However, after 52 weeks of maintenance therapy OR estimates showed no significant difference between infliximab and adalimumab. For serious adverse events and discontinuations due to adverse events, adalimumab and infliximab were similar to placebo. Further, the indirect treatment comparison of adalimumab and infliximab yielded odds ratios close to 1.00 with wide credible intervals. CONCLUSION The findings of this indirect treatment comparison meta-analysis suggest that both infliximab and adalimumab are superior to placebo in the treatment of moderate to moderately severe ulcerative colitis. While infliximab is statistically more effective than adalimumab in the induction of remission, response and mucosal healing at 8 weeks, infliximab and adalimumab are comparable in efficacy at 52 weeks of maintenance treatment.

Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a multiple treatment comparison meta-analysis.

Background: New direct-acting antiviral agents for hepatitis C genotype 1 infection, boceprevir and telaprevir, offer enhanced sustained virologic response (SVR) among both treatment-naïve and treatment-experienced patients. Aim: To determine the relative efficacy of the new direct-acting antiviral agents by applying a multiple treatment comparison meta-analysis. Design: We included published Phase II and III randomized controlled trials evaluating head-to-head comparisons between boceprevir, telaprevir, peg-interferon alpha-2a with ribavirin and peg-interferon alpha-2b with ribavirin in hepatitis C genotype 1 patients. We applied Bayesian multiple treatment comparison meta-analysis. Results: We included data from four boceprevir, three telaprevir and six peg-interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin randomized controlled trials. Both boceprevir and telaprevir offer statistically superior outcomes for SVR, relapse and discontinuation due to adverse events than either peg-interferons among both treatment-naïve and treatment-experienced patients. Among treatment-naïve patients, clinical outcomes were similar for boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval (95% CrI) 0.41–1.91] and for relapse (OR 1.09, 95% CrI 0.19–4.84). Similarly, among treatment-experienced patients, clinical outcomes were similar for boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70–3.08) and for relapse (OR 0.35, 95% CrI 0.13–1.02). For treatment-naïve patients receiving standard-duration therapy, telaprevir yielded lower rates of anemia and neutropenia, but higher rates of rash and pruritus. For treatment-experience patients, all adverse event rates were higher with telaprevir. Discussion: Boceprevir and telaprevir exhibit similar effects among hepatitis C genotype 1 treatment-naïve and treatment-experienced patients.

Comparative efficacy of triptans for the abortive treatment of migraine: A multiple treatment comparison meta-analysis

Background Migraine is the most common neurological condition in developed countries. The abortive treatment of migraine attacks is important both for quality of life and costs associated with illness. Triptans, serotonin 5-HT1B/1D receptor agonists, effectively relieve the pain, disability, and associated symptoms of migraine while improving health-related quality of life. Although a number of direct head-to-head triptan comparisons have been made, data for all possible permutations are not available, and unlikely to ever be so, although in clinical practice such information would be useful. Objective We aimed to determine the relative efficacy of all available triptans to abort migraine headache among patients with previous adequate response to migraine treatments. Methods We included only double-blinded randomized clinical trials comparing triptans to either placebo or another triptan. Our primary outcomes were pain-free response at two hours and 24-hour sustained pain-free response, and our secondary outcomes were headache response at two hours and 24-hour sustained headache response. We used Bayesian multiple treatment comparison meta-analyses of seven triptans used in adult patients to abort migraine attacks. We applied a random-effects analysis with meta-regression adjusting for dose. Results are reported as odds ratios with 95% credible intervals. Results We included data from 74 randomized clinical trials. All triptans were significantly superior to placebo for all outcomes, with the exception of naratriptan for 24-hour sustained pain-free response. Eletriptan consistently yielded the highest treatment effect estimates. For the two-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, almotriptan, naratriptan, and frovatriptan for at least one of the two outcomes. Rizatriptan yielded the second highest treatment effects followed by zolmitriptan. For the 24-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, rizatriptan, almotriptan, and naratriptan for at least one of the two outcomes. Frovatriptan data were not available at that endpoint. Further, the probability that eletriptan is the most likely of all triptans to produce a favorable outcome was 68% for pain-free response at two hours, and 54% for 24-hour sustained pain-free response. Conclusion Triptans appear to offer differing treatment effects. In the populations studied eletriptan was most likely to produce pain-free responses that were sustained.

Comparative efficacy of golimumab, infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs

Aim: To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). Design: A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). Results: After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. Conclusion: The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.