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      Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada

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          Abstract

          Background

          Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000–2007 in the U.S. and Canada.

          Methods

          Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables.

          Results

          The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000–2002 to 2006–2007. Men and women had comparable life expectancies in all periods except the last (2006–2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm 3.

          Conclusions

          A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.

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          Most cited references12

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          Correcting for noncompliance and dependent censoring in an AIDS Clinical Trial with inverse probability of censoring weighted (IPCW) log-rank tests.

          AIDS Clinical Trial Group (ACTG) randomized trial 021 compared the effect of bactrim versus aerosolized pentamidine (AP) as prophylaxis therapy for pneumocystis pneumonia (PCP) in AIDS patients. Although patients randomized to the bactrim arm experienced a significant delay in time to PCP, the survival experience in the two arms was not significantly different (p = .32). In this paper, we present evidence that bactrim therapy improves survival but that the standard intent-to-treat comparison failed to detect this survival advantage because a large fraction of the subjects either crossed over to the other therapy or stopped therapy altogether. We obtain our evidence of a beneficial bactrim effect on survival by artificially regarding the subjects as dependently censored at the first time the subject either stops or switches therapy; we then analyze the data with the inverse probability of censoring weighted Kaplan-Meier and Cox partial likelihood estimators of Robins (1993, Proceedings of the Biopharmaceutical Section, American Statistical Association, pp. 24-33) that adjust for dependent censoring by utilizing data collected on time-dependent prognostic factors.
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            The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time.

            To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens. Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N = 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective. The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value <0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and boosted protease inhibitor-based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality. Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.
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              HIV and aging: time for a new paradigm.

              The population of patients with HIV infection achieving viral suppression on combination antiretroviral therapy is growing, aging, and experiencing a widening spectrum of non-AIDS diseases. Concurrently, AIDS-defining conditions are becoming less common and are variably associated with outcome. Nonetheless, the spectrum of disease experienced by those aging with HIV remains strongly influenced by HIV, its treatment, and the behaviors, conditions, and demographics associated with HIV infection. Our focus must shift from a narrow interest in CD4 counts, HIV-RNA, and AIDS-defining illnesses to determining the optimal management of HIV infection as a complex chronic disease in which the causes of morbidity and mortality are multiple and overlapping. We need a new paradigm of care with which to maximize functional status, minimize frailty, and prolong life expectancy. A composite index that summarizes a patient's risk of morbidity and mortality could facilitate this work and help chart its progress.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                18 December 2013
                : 8
                : 12
                : e81355
                Affiliations
                [1 ]British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada
                [2 ]Simon Fraser University, Burnaby, British Columbia, Canada
                [3 ]Johns Hopkins University, Baltimore, Maryland, United States of America
                [4 ]Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                [5 ]Ontario HIV Treatment Network, Toronto, Ontario, Canada
                [6 ]The Core Center, Bureau of Health Services of Cook County, Chicago, Illinois, United States of America
                [7 ]University of Calgary, Calgary, Alberta, Canada
                [8 ]Veterans Administration Connecticut Healthcare System and Yale University, West Haven, Connecticut, United States of America
                [9 ]McGill University Health Centre, Montreal, Quebec, Canada
                [10 ]Oregon Health and Science University, Portland, Oregon, United States of America
                [11 ]University of California San Francisco, San Francisco, California, United States of America
                [12 ]University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
                [13 ]Vanderbilt University, Nashville, Tennessee, United States of America
                [14 ]Kaiser Permanente Northern California, Oakland, California, United States of America
                [15 ]San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America
                [16 ]Harvard School of Public Health, Boston, Massachusetts, United States of America
                [17 ]University of Washington, Seattle, Washington, United States of America
                [18 ]National Cancer Institute, Rockville, Maryland, United States of America
                Infectious Disease Service, United States of America
                Author notes

                ¶ Membership for The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA is provided in Appendix S1.

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: RSH HS AC. Analyzed the data: SPM RSH HS AC KA. Wrote the manuscript: RSH HS AC SPM KA. Critical revision of the article for important intellectual content: HS RSH AC SPM KA KB ANB MC KAG MJG AJ GK MBK PTK JM SN SBR TRS MJS SD LPJ RJB MMK JJG RM SJG.

                Article
                PONE-D-13-20154
                10.1371/journal.pone.0081355
                3867319
                24367482
                b7cd708f-1b09-4dc3-9134-bee47b040340
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 May 2013
                : 11 October 2013
                Page count
                Pages: 8
                Funding
                This work was supported by grants U01-AI069918, U10-AA13566, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, U01-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-HD32632, U10-EY08057, U10-EY08052, U10-EY08067, UL1-RR024131, UL1-RR024131, M01-RR-00052, M01-RR00071, M01-RR00079, M01-RR00083, M01-RR00722, M01-RR025747, P30-AI27757, P30-AI27767, P30-AI27763, P30-AI50410, P30-AI54999, R01-DA04334, R01-DA12568, R01-DA11602, R01-AA16893, R24-AI067039, Z01-CP010176, AHQ290-01-0012, N02-CP55504, AI-69432, AI-69434, K01-AI071725, K23-AI610320, K23-EY013707, K24-DA00432, K24 AI65298 and K01-AI093197 from the National Institutes of Health; contract 290-01-0012 from the Agency for Healthcare Research and Quality; contract CDC200-2006-18797 from the CDC; grants TGF-96118, HCP-97105, CBR-86906, CBR-94036, KRS-86251, and 169621 from the Canadian Institutes of Health Research; the Canadian HIV Trials Network, project 24; and the government of British Columbia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Epidemiology
                Epidemiological Methods
                Infectious Disease Epidemiology
                Infectious Diseases
                Sexually Transmitted Diseases
                AIDS
                Viral Diseases
                HIV
                HIV diagnosis and management
                HIV epidemiology
                Non-Clinical Medicine
                Health Care Policy
                Health Statistics
                Public Health

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