The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic

British Columbia Centre for Excellence in HIV/AIDS, Providence Health Care, University of British Columbia, Vancouver, Canada.
The Lancet (Impact Factor: 39.21). 09/2006; 368(9534):531-6. DOI: 10.1016/S0140-6736(06)69162-9
Source: PubMed
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    ABSTRACT: Realizing the full individual and population-wide benefits of antiretroviral therapy for human immunodeficiency virus (HIV) infection requires an efficient mechanism of HIV-related health service delivery. We developed a system dynamics model of the continuum of HIV care in Vancouver, Canada, which reflects key activities and decisions in the delivery of antiretroviral therapy, including HIV testing, linkage to care, and long-term retention in care and treatment. To measure the influence of operational interventions on population health outcomes, we incorporated an HIV transmission component into the model. We determined optimal resource allocations among targeted and routine testing programs to minimize new HIV infections over five years in Vancouver. Simulation scenarios assumed various constraints informed by the local health policy. The project was conducted in close collaboration with the local health care providers, Vancouver Coastal Health Authority and Providence Health Care.
    Health Care Management Science 01/2015; DOI:10.1007/s10729-014-9312-0 · 1.05 Impact Factor
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    ABSTRACT: The "cascade of care" displays the proportion of individuals who are infected with human immunodeficiency virus (HIV), diagnosed, linked, retained, on antiretroviral treatment, and HIV suppressed. We examined the implications of including death in the use of this cascade for program and public health performance metrics. Individuals newly diagnosed with HIV and living in Calgary between 2006 and 2013 were included. Through linkage with Public Health and death registries, the deaths (ie, all-cause mortality) and their distribution within the cascade were determined. Mortality rates are reported per 100 person-years. Estimated new HIV infections were 680 (543 confirmed and 137 unknown cases). Forty-three individuals, after diagnosis, were never referred for HIV care. Despite referral(s), 88 individuals (18%) never attended the clinic for HIV care. Of individuals retained in care, 87% received antiretroviral therapy and 76% achieved viral suppression. Thirty-six deaths were reported (mortality rate, 1.50/100 person-years). One diagnosis was made posthumously. Deaths (20 of 35; 57%) occurred for individuals linked but not retained in care (6.93/100 person-years), and 70% were HIV-related. Mortality rate for patients in care was 0.79/100 person-years. Retained patients with detectable viremia had a death rate of 2.49/100, which contrasted with 0.28/100 person-years in those with suppressed viremia. Eight of these 15 deaths (53%) were HIV-related. Over half of deaths occurred in those referred but not effectively linked or retained in HIV care, and these cases may be easily overlooked in standard HIV mortality studies. Inclusion of deaths into the cascade may further enhance its value as a public health metric.
    03/2014; 1(1):ofu011. DOI:10.1093/ofid/ofu011
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    ABSTRACT: Sequencing human immunodeficiency virus type 1 (HIV-1) for drug resistance mutations and viral tropism is crucial to the current HIV/AIDS personalized treatment approach. This thesis addresses particular areas where clinical utility data is lacking: First, current methods were validated as clinically useful with plasma viral RNA primarily from patients infected with subtype B HIV-1, the dominant strain in developed countries; however, globally most patients are infected with non-subtype B variants. Secondly, there is insufficient data available with respect to the newest classes of antiretroviral drugs (i.e. CCR5-antagonist and integrase inhibitors). Finally, modern antiretroviral therapies often lead to “undetectable plasma viremia” (i.e. successful ongoing treatment) which make plasma-based genotypic testing impossible; the utility of examining alternative sample types is being actively explored. The overall objective of this thesis is to evaluate genotypic assessment of HIV-1 using standard and “second generation” DNA sequencing methods for guiding clinical decisions in nonconventional sample types. Specifically, it is hypothesized that genotypic assessment of subtype A, C and D HIV-1, plasma viral RNA collected pre-therapy, and viral DNA archived in blood cells are useful predictors of in vitro phenotype and/or clinical outcomes. Chapter 1 and 2 examine the clinical utility of current genotyping approaches when applied to non-subtype-B HIV-1. Results suggest that (1) transmitted genotypic drug resistance predicted small but negative treatment outcomes in non-B infections, and (2) current genotypic tools for predicting viral tropism had poor sensitivities and/or specificities in subtypes A and D, but not C HIV-1. Chapter 3 and 4 examine the clinical utility of current genotypic approaches coupled with alternative sample types. Results suggest that (3) pre-therapy plasma sample tropism results predicted post-therapy post-suppression tropism in 90% of subjects, and (4) viral DNA archived in blood and plasma RNA had similar integrase inhibitor-associated mutations, but mutations in DNA were detected substantially later and were substantially less prevalent. In conclusion, genotypic assessment of HIV-1 using nonconventional sample types is clinically relevant, but has specific limitations. Further methodological research and clinical validation studies are needed to ensure proper interpretation of results.
    01/2015, Degree: PhD, Supervisor: Dr. Richard Harrigan

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