Melanie Murray

Differential impact of adherence on long-term treatment response among naive HIV-infected individuals.

Objectives: To examine the long-term impact of adherence on virologic, immunologic, and dual response stratified by type of HAART regimen in treatment-naive patients starting HAART in British Columbia, Canada; and to assess the degree of virologic and immunologic response associated with emergence of drug resistance, progression to AIDS, and mortality. Methods: Eligible participants initiated HAART between 1 January 2000 and 30 November 2004, were followed until 30 November 2005, and had at least 2 years of follow-up. Virologic and immunologic responses were dichotomized at their median values. Virologic response was defined as at least 65% of follow-up time with plasma viral load (pVL) of less than 50 copies/ml. Immunologic response was defined as a CD4 cell count increase of at least 145 cells/μl. Adherence measures were based on prescription refill compliance. Proportional odds models and logistic regression were used to address our objectives. Results: The distribution of patient responses was 394 (44.9%) for CD4+/pVL+ (best), 350 (39.9%) for CD4−/pVL+ or CD4+/pVL− (incomplete), and 134 (15.3%) for CD4−/pVL− (worst). We found a positive correlation between adherence and virologic and immunologic responses (P < 0.01). Having worst compared with best response (reference group) was associated with higher odds of mortality (odds ratio: 6.09; 95% confidence interval: 2.57–14.42) and emergence of drug resistance (odds ratio: 10.56; 95% confidence interval: 5.93–18.81) even after adjusting for adherence and HAART regimen. Conclusion: Patients not attaining the best virologic and immunologic responses are at a high risk for emergence of drug resistance and mortality, and these responses are highly dependent on the adherence level and initial HAART regimen. Patients on protease inhibitor-single did worse no matter the adherence level.

The effect of injecting drug use history on disease progression and death among HIV-positive individuals initiating combination antiretroviral therapy: collaborative cohort analysis

We examined whether determinants of disease progression and causes of death differ between injecting drug users (IDUs) and non‐IDUs who initiate combination antiretroviral therapy (cART).

Association Between Short Leukocyte Telomere Length and HIV Infection in a Cohort Study: No Evidence of a Relationship With Antiretroviral Therapy

BACKGROUND Individuals infected with human immunodeficiency virus (HIV) appear to age faster than the general population, possibly related to HIV infection, antiretroviral therapy, and/or social/environmental factors. We evaluated leukocyte telomere length (LTL), a marker of cellular aging, in HIV-infected and uninfected adults. METHODS Clinical data and blood were collected from Children and women: AntiRetrovirals and the Mechanism of Aging (CARMA) cohort study participants. Variables found to be important in univariate analysis were multivariate model candidates. RESULTS Of the 229 HIV-infected and 166 HIV-uninfected participants, 76% were women, and 71% were current/previous smokers. In a multivariate model of all participants, older age (P < .001), HIV infection (P = .04), active hepatitis C virus (HCV) infection (P = .02), and smoking (P < .003) were associated with shorter LTL. An interaction was detected, whereby smoking was associated with shorter LTL in HIV-uninfected subjects only. Among those, age and smoking (P ≤ .01) were related to shorter LTL. In 2 models of HIV-infected individuals, age (P ≤ .002) and either active HCV infection (P = .05) or peak HIV RNA ≥100 000 copies/mL (P = .04) were associated with shorter LTL, whereas other HIV disease or treatment parameters were unrelated. CONCLUSIONS Our results suggest that acquisition of HIV and viral load are primarily responsible for the association between HIV-positive status and shorter LTL. The lack of association between LTL and time since HIV diagnosis, antiretroviral treatment, or degree of immune suppression would implicate HIV infection-related factors rather than disease progression or treatment. Smoking effects on LTL appear masked by HIV, and HCV infection may accelerate LTL shortening, particularly in coinfected individuals. The effect of early therapeutic intervention on LTL in HIV and HCV infections should be evaluated.

HIV Incidence and Prevalence Among Aboriginal Peoples in Canada

We examined incidence, prevalence, and correlates of HIV infection in Aboriginal peoples in Canada and found that among most risk groups both Aboriginal and non-Aboriginal participants showed similar levels of HIV prevalence. Aboriginal peoples who use illicit drugs were found to have higher HIV incidence and prevalence when compared to their non-Aboriginal drug-using peers. Aboriginal street youth and female sex workers were also found to have higher HIV prevalence. Among Aboriginal populations, correlates of HIV-positive sero-status include syringe sharing and frequently injecting drugs, as well as geographic and social factors such as living in Vancouver or having a history of non-consensual sex. This study is relevant to Canada and elsewhere, as Indigenous populations are disproportionately represented in the HIV epidemic worldwide.

A Qualitative Study Investigating the Use of a Mobile Phone Short Message Service Designed to Improve HIV Adherence and Retention in Care in Canada (WelTel BC1)

&NA; Patient engagement in care and adherence to medication are critical to achieving the full benefits of antiretroviral therapy (ART) among people with HIV infection. A randomized controlled trial in Kenya, WelTelKenya1, showed that an interactive mobile phone text‐messaging intervention can improve adherence and viral load suppression. We conducted a pilot study to adapt the WelTel intervention for HIV‐infected clients (n = 25) at an HIV clinic in Vancouver, British Columbia. Between April and June 2012, we recruited five participants from five groups: youth (14–24 years), mature (≥50 years), English as a second language, remote (≥3 hours travel time to clinic), and nonsuppressed (CD4+ T cell count <200 cells/mm3 and viral load ≥250 copies/mL on two consecutive occasions). Participants described the intervention as a useful way to communicate with health care providers, thus increasing the ability to access services, report side effects, and attend appointments.

Select Neurocognitive Impairment in HIV-Infected Women: Associations with HIV Viral Load, Hepatitis C Virus, and Depression, but Not Leukocyte Telomere Length

Background Through implementation of combination antiretroviral therapy (cART) remarkable gains have been achieved in the management of HIV infection; nonetheless, the neurocognitive consequences of infection remain a pivotal concern in the cART era. Research has often employed norm-referenced neuropsychological scores, derived from healthy populations (excluding many seronegative individuals at high risk for HIV infection), to characterize impairments in predominately male HIV-infected populations. Methods Using matched-group methodology, we assessed 81 HIV-seropositive (HIV+) women with established neuropsychological measures validated for detection of HIV-related impairments, as well as additional detailed tests of executive function and decision-making from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Results On validated tests, the HIV+ women exhibited impairments that were limited to significantly slower information processing speed when compared with 45 HIV-seronegative (HIV−) women with very similar demographic backgrounds and illness comorbidities. Additionally, select executive impairments in shifting attention (i.e., reversal learning) and in decision-making quality were revealed in HIV+ participants. Modifiers of neurocognition in HIV-infected women included detectable HIV plasma viral load, active hepatitis C virus co-infection, and self-reported depression symptoms. In contrast, leukocyte telomere length (LTL), a marker of cellular aging, did not significantly differ between HIV+ and HIV− women, nor was LTL associated with overall neurocognition in the HIV+ group. Conclusions The findings suggest that well-managed HIV infection may entail a more circumscribed neurocognitive deficit pattern than that reported in many norm-referenced studies, and that common comorbidities make a secondary contribution to HIV-related neurocognitive impairments.

Hepatitis C virus treatment rates and outcomes in HIV/ hepatitis C virus co-infected individuals at an urban HIV clinic

Objectives The factors associated with hepatitis C virus (HCV) treatment uptake and responses were assessed among HCV/HIV co-infected individuals referred for HCV therapy at an urban HIV clinic. Methods Retrospective review of HIV/HCV patients enrolled in the HCV treatment program at the John Ruedy Immunodeficiency Clinic in Vancouver. The factors associated with treatment uptake were assessed using multivariate analysis. Results A total of 134 HCV/HIV co-infected individuals were recalled for assessment for HCV therapy. Overall 64 (48%) initiated treatment, and of those treated 49 (76.6%) attained end treatment response, whereas 35 (57.8%) achieved sustained virological response (SVR). When evaluated by genotype, 53% (17/32) of those with genotype 1, and 65% (20/31) of those with genotype 2 or 3 infections attained SVR. In treated individuals, alanine aminotransferase dropped significantly after treatment (P<0.001). During treatment, CD4 counts dropped significantly (P<0.001) in all patients. The counts recovered to baseline in patients who achieved SVR, but remained lower in patients who failed the therapy (P=0.015). On multivariate analysis, history of injection drug use (odds ratio: 3.48; 95% confidence interval: 1.37–8.79; P=0.009) and low hemoglobin levels (odds ratio: 4.23; 95% confidence interval: 1.36–13.10; P=0.013) were associated with those who did not enter the treatment. Conclusion Only half of treatment-eligible co-infected patients referred for the therapy initiated treatment. Of those referred for the therapy, history of injection drug use was associated with lower rates of treatment uptake. Treated HIV/HCV co-infected individuals benefitted from both decreased alanine aminotransferase (independent of SVR), and rates of SVR similar to those described in HCV monoinfected patients.

Identifying Barriers and Facilitators of 13 mHealth Projects in North America and Africa: Protocol for a 5-Year Implementation Science Study

Background Although many mHealth interventions have shown efficacy in research, few have been effectively implemented and sustained in real-world health system settings. Despite this programmatic gap, there is limited conclusive evidence identifying the factors that affect the implementation and successful integration of mHealth into a health system. Objective The aim of this study is to examine the individual, organizational, and external level factors associated with the effective implementation of WelTel, an mHealth intervention designed to support outpatient medication adherence and engagement in care in Africa and North America. Methods We will adopt the Consolidated Framework for Implementation Research (CFIR) constructs for evaluation of mHealth implementation including a scoring and monitoring system. We will apply the adapted tool to identify facilitators and barriers to implementation of the WelTel mHealth intervention in order to determine how the technology platform is perceived, diffused, adapted, and used by different mHealth project teams and health system actors in Africa and North America. We will use a mixed-methods approach to quantitatively test whether the factors identified in the CFIR framework are associated with the successful uptake of the mHealth intervention toward implementation goals. We will triangulate these data through interviews and focus group discussion with project stakeholders, exploring factors associated with successful implementation and sustainment of these interventions. Results The development of the customized CFIR is finalized and currently is in pilot testing. The initial results of the use of the tool in those 13 implementations will be available in 2019. Continuous conference and peer- reviewed publications will be published in the coming years. Conclusions The results of this study will provide an in-depth understanding of individual, organizational, and external level factors that influence the successful implementation of mHealth in different health systems and geographic contexts over time. Via the tool’s unique scoring system connected to qualitative descriptors, these data will inform the most critical implementation targets and contribute to the tailoring of strategies that will assist the health system in overcoming barriers to implementation, and ultimately, improve treatment adherence and engagement in care. Registered Report Identifier RR1-10.2196/9633

Premature Spinal Bone Loss in Women Living with HIV is Associated with Shorter Leukocyte Telomere Length

With advances in combination antiretroviral therapy (cART), people living with HIV are now surviving to experience aging. Evidence suggests that individuals living with HIV are at greater risk for low bone mineral density (BMD), osteoporosis, and fractures. Better understanding of the pathophysiology of bone health in women living with HIV (WLWH) is important for treatment strategies. The goal of this study was to explore new biological factors linked to low BMD in WLWH. Standardized BMD measures of WLWH were compared to reference values from an unselected population of women from the same geographical region of the same age range. Linear regression analysis was used to assess relationships among health-related characteristics, cellular aging (measured by leukocyte telomere length; LTL), cART, and BMD of WLWH. WLWH (n = 73; mean age 43 ± 9 years) had lower BMD Z-scores at the lumbar spine (LS) (mean difference = −0.39, p < 0.001) and total hip (TH) (−0.29, p = 0.012) relative to controls (n = 290). WLWH between 50 and 60 years (n = 17) had lower Z-scores at the LS (p = 0.008) and TH (p = 0.027) compared to controls (n = 167). Among WLWH, LS BMD was significantly associated with LTL (R2 = 0.09, p = 0.009) and BMI (R2 = 0.06, p = 0.042). Spinal BMD was adversely affected in WLWH. Reduction of LTL was strongly associated with lower BMD and may relate to its pathophysiology and premature aging in WLWH.

Operationalizing mHealth to improve patient care: a qualitative implementation science evaluation of the WelTel texting intervention in Canada and Kenya

BackgroundMobile health (mHealth) applications have proliferated across the globe with much enthusiasm, although few have reached scale and shown public health impact. In this study, we explored how different contextual factors influenced the implementation, effectiveness and potential for scale-up of WelTel, an easy-to-use and evidence-based mHealth intervention. WelTel uses two-way SMS communication to improve patient adherence to medication and engagement in care, and has been developed and tested in Canada and Kenya.MethodsWe used a comparative qualitative case study design, which drew on 32 key informant interviews, conducted in 2016, with stakeholders involved in six WelTel projects. Our research was guided by the Consolidated Framework for Implementation Research (CFIR), a meta-theoretical framework, and our analysis relied on a modified approach to grounded theory, which allowed us to compare findings across these projects.ResultsWe found that WelTel had positive influences on the “culture of care” at local clinics and hospitals in Canada and Kenya, many of which stretched beyond the immediate patient-client relationship to influence wider organizational systems. However, these were mediated by clinician norms and practices, the availability of local champion staff, the receptivity and capacity of local management, and the particular characteristics of the technology platform, including the ability for adaptation and co-design. We also found that scale-up was influenced by different forms of data and evidence, which played important roles in legitimization and partnership building. Even with robust research evidence, scale-up was viewed as a precarious and uncertain process, embedded within the wider politics and financing of Canadian and Kenyan health systems. Challenges included juggling different interests, determining appropriate financing pathways, maintaining network growth, and “packaging” the intervention for impact and relevance.ConclusionsOur comparative case study, of a unique transnational mobile health research network, revealed that moving from mHealth pilots to scale is a difficult, context-specific process that couples social and technological innovation. Fostering new organizational partnerships and ways of learning are paramount, as mHealth platforms straddle the world of research, industry and public health. Partnerships need to avoid the perils of the technological fix, and engage the structural barriers that mediate people’s health and access to services.