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HIV-1 disease progression during highly active antiretroviral therapy: an application using population-level data in British Columbia: 1996-2011.

ABSTRACT: BACKGROUND:Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011. METHODS:We used population-level data on disease progression and antiretroviral treatment utilization from the BC HIV Drug Treatment Program. Disease progression was captured using longitudinal CD4 and plasma viral load testing data, linked with data on antiretroviral treatment. The study outcome was categorized into (CD4 count ? 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state continuous-time Markov model was used to estimate covariate-specific probabilities of CD4 progression, focusing on temporal changes during the study period. RESULTS:A total of 210,083 CD4 measurements among 7421 individuals with HIV/AIDS were included in the study. Results of the multivariate model suggested that current highly active antiretroviral treatment at baseline, lower baseline CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were each associated with accelerated progression. Immunological improvement was accelerated significantly from 2004 onward, with 23% and 46% increases in the probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004-2008 and 2008-2011, respectively. CONCLUSION:Our results demonstrate the impact of innovations in antiretroviral treatment and treatment delivery at the population level. These results can be used to estimate a transition probability matrix flexible to changes in the observed mix of clients in different clinical stages and treatment regimens over time.

SUBMITTER: Nosyk B

PROVIDER: S-EPMC3800281 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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HIV-1 disease progression during highly active antiretroviral therapy: an application using population-level data in British Columbia: 1996-2011.

Nosyk Bohdan B Min Jeong J Lima Viviane D VD Yip Benita B Hogg Robert S RS Montaner Julio S G JS

Journal of acquired immune deficiency syndromes (1999) 20130801 5

<h4>Background</h4>Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011.<h4>Methods</h4>We used population-level data on disease progression and antiretroviral treatment util ...[more]

PMID: 24135777

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Project description:BackgroundWidespread HIV screening and access to highly active antiretroviral treatment (ART) were cost effective in mathematical models, but population-level implementation has led to questions about cost, value, and feasibility. In 1996, British Columbia, Canada, introduced universal coverage of drug and other health-care costs for people with HIV/AIDS and and began extensive scale-up in access to ART. We aimed to assess the cost-effectiveness of ART scale-up in British Columbia compared with hypothetical scenarios of constrained treatment access.MethodsUsing comprehensive linked population-level data, we populated a dynamic, compartmental transmission model to simulate the HIV/AIDS epidemic in British Columbia from 1997 to 2010. We estimated HIV incidence, prevalence, mortality, costs (in 2010 CAN$), and quality-adjusted life-years (QALYs) for the study period, which was 1997-2010. We calculated incremental cost-effectiveness ratios from societal and third-party-payer perspectives to compare actual practice (true numbers of individuals accessing ART) to scenarios of constrained expansion (75% and 50% probability of accessing ART). We also investigated structural and parameter uncertainty.FindingsActual practice resulted in 263 averted incident cases compared with 75% of observed access and 676 averted cases compared with 50% of observed access to ART. From a third-party-payer perspective, actual practice resulted in incremental cost-effectiveness ratios of $23 679 per QALY versus 75% access and $24 250 per QALY versus 50% access. From a societal perspective, actual practice was cost saving within the study period. When the model was extended to 2035, current observed access resulted in cumulative savings of $25·1 million compared with the 75% access scenario and $65·5 million compared with the 50% access scenario.InterpretationART scale-up in British Columbia has decreased HIV-related morbidity, mortality, and transmission. Resulting incremental cost-effectiveness ratios for actual practice, derived within a limited timeframe, were within established cost-effectiveness thresholds and were cost saving from a societal perspective.FundingBC Ministry of Health, National Institute of Drug Abuse at the US National Institutes of Health.

Project description:Antiretroviral therapy (ART) and harm reduction services have been cited as key contributors to control of HIV epidemics; however, the specific contribution of ART has been questioned due to uncertainty of its true efficacy on HIV transmission through needle sharing. We aimed to isolate the independent effects of harm reduction services (opioid agonist treatment uptake and needle distribution volumes) and ART on HIV transmission via needle sharing in British Columbia, Canada, from 1996 to 2013.We used comprehensive linked individual health administrative and registry data for the population of diagnosed people living with HIV in British Columbia to populate a dynamic, compartmental transmission model to simulate the HIV/AIDS epidemic in British Columbia from 1996 to 2013. We estimated HIV incidence, mortality, and quality-adjusted life-years (QALYs). We also estimated scenarios designed to isolate the independent effects of harm reduction services and ART, assuming 50% (10-90%) efficacy, in reducing HIV incidence through needle sharing, and we investigated structural and parameter uncertainty.We estimate that 3204 (upper bound-lower bound 2402-4589) incident HIV cases were averted between 1996 and 2013 as a result of the combined effect of the expansion of harm reduction services and ART coverage on HIV transmission via needle sharing. In a hypothetical scenario assuming ART had zero effect on transmission through needle sharing, we estimated harm reduction services alone would have accounted for 77% (upper bound-lower bound 62-95%) of averted HIV incidence. In a separate hypothetical scenario where harm reduction services remained at 1996 levels, we estimated ART alone would have accounted for 44% (10-67%) of averted HIV incidence. As a result of high distribution volumes, needle distribution predominantly accounted for incidence reductions attributable to harm reduction but opioid agonist treatment provided substantially greater QALY gains.If the true efficacy of ART in preventing HIV transmission through needle sharing is closer to its efficacy in sexual transmission, ART's effect on incident cases averted could be greater than that of harm reduction. Nonetheless, harm reduction services had a vital role in reducing HIV incidence in British Columbia, and should be viewed as essential and cost-effective tools in combination implementation strategies to reduce the public health and economic burden of HIV/AIDS.BC Ministry of Health; National Institutes of Health (R01DA041747); Genome Canada (142HIV).

Dataset Information

HIV-1 disease progression during highly active antiretroviral therapy: an application using population-level data in British Columbia: 1996-2011.

Publications

HIV-1 disease progression during highly active antiretroviral therapy: an application using population-level data in British Columbia: 1996-2011.

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