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      Trends in reported AIDS defining illnesses (ADIs) among participants in a universal antiretroviral therapy program: an observational study

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          Abstract

          Background

          We examined trends in AIDS-defining illnesses (ADIs) among individuals receiving highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada to determine whether declines in ADIs could be contributing to previously observed improvements in life-expectancy among HAART patients in BC since 1996.

          Methods

          HAART-naïve individuals aged ≥ 18 years who initiated treatment in BC each of the following time-periods 1996 - 1998; 1999 - 2001; 2002 - 2004; 2005 - 2007 were included. The proportion of participants with reported ADIs were examined for each time period and trends were analyzed using the Cochran-Armitage Trend Test. Cox proportional hazards models were used to examine factors associated with ADIs.

          Results

          A total of 3721 individuals (81% male) initiated HAART during the study period. A total of 251 reports of ADIs were received from 214 unique patients. These occurred in a median of 4 months (IQR = 1-19 months) from HAART initiation. The proportion of individuals with a reported ADI did not change significantly from 4.6% in the earliest time period to 5.8% in the latest period (p = 0.181 for test of trend). There were no significant declines in any specific ADI over the study period. Multivariable Cox models found that individuals initiating HAART during 2002-04 were at an increased risk of ADIs (AHR = 1.55; 95% CI 1.04-2.32) in comparison to 1996 - 98, but there were no significant differences in other time periods.

          Conclusions

          Trends in reported ADIs among individuals receiving HAART since 1996 in BC do not appear to parallel improvements in life-expectancy over the same period.

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          Most cited references13

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          Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.

          Orlando Gutiérrez, Gary Allred, Gary Chamness … (2003)
          Systemic chemotherapy for operable breast cancer substantially decreases the risk of death. Patients often have de novo resistance or incomplete response to docetaxel, one of the most active agents in this disease. We postulated that gene expression profiles of the primary breast cancer can predict the response to docetaxel. We took core biopsy samples from primary breast tumours in 24 patients before treatment and then assessed tumour response to neoadjuvant docetaxel (four cycles, 100 mg/m2 daily for 3 weeks) by cDNA analysis of RNA extracted from biopsy samples using HgU95-Av2 GeneChip. From the core biopsy samples, we extracted sufficient total RNA (3-6 microg) for cDNA array analysis using HgU95-Av2 GeneChip. Differential patterns of expression of 92 genes correlated with docetaxel response (p=0.001). Sensitive tumours had higher expression of genes involved in cell cycle, cytoskeleton, adhesion, protein transport, protein modification, transcription, and stress or apoptosis; whereas resistant tumours showed increased expression of some transcriptional and signal transduction genes. In leave-one-out cross-validation analysis, ten of 11 sensitive tumours (90% specificity) and 11 of 13 resistant tumours (85% sensitivity) were correctly classified, with an accuracy of 88%. This 92-gene predictor had positive and negative predictive values of 92% and 83%, respectively. Correlation between RNA expression measured by the arrays and semiquantitative RT-PCR was also ascertained, and our results were validated in an independent set of six patients. If validated, these molecular profiles could allow development of a clinical test for docetaxel sensitivity, thus reducing unnecessary treatment for women with breast cancer.
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            AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study.

            Susan K. Wood, O. Baker, Richard Novak … (2010)
            To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era. A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S. HIV clinics. We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994-2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period. Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/microl) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994-1997, 1998-2002, and 2003-2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003-2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% opportunistic illness events occurred at CD4 cell counts at least 200 cells/microl. Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003-2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/microl.
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              Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City.

              Lucia V Torian, R Pfeiffer, Judith E Sackoff … (2006)
              Monitoring the full spectrum of causes of death among persons with AIDS is increasingly important as survival improves because of highly active antiretroviral therapy. To describe recent trends in deaths due to HIV-related and non-HIV-related causes among persons with AIDS, identify factors associated with these deaths, and identify leading causes of non-HIV-related deaths. Population-based cohort analysis. New York City. All adults (age > or =13 years) living with AIDS between 1999 and 2004 who were reported to the New York City HIV/AIDS Reporting System and Vital Statistics Registry through 2004 (n = 68,669). Underlying cause of death on the death certificate. Between 1999 and 2004, the percentage of deaths due to non-HIV-related causes increased by 32.8% (from 19.8% to 26.3%; P = 0.015). The age-adjusted mortality rate decreased by 49.6 deaths per 10,000 persons with AIDS (P < 0.001) annually for HIV-related causes but only by 7.5 deaths per 10 000 persons with AIDS (P = 0.004) annually for non-HIV-related causes. Of deaths due to non-HIV-related causes, 76% could be attributed to substance abuse, cardiovascular disease, or a non-AIDS-defining type of cancer. Compared with men who have sex with men, injection drug users had a statistically significantly increased risk for death due to HIV-related causes (hazard ratio, 1.59 [95% CI, 1.49 to 1.70]) and non-HIV-related causes (hazard ratio, 2.54 [CI, 2.24 to 2.87]). Compared with autopsy and chart review, death certificates may lack specificity in the underlying cause of death or detailed clinical and treatment-related information. Non-HIV-related causes of death account for one fourth of all deaths of persons with AIDS. Cardiovascular disease, non-AIDS-defining cancer, and substance abuse account for most non-HIV-related deaths. Reducing deaths from these causes requires a shift in the health care model for persons with AIDS from a primary focus on managing HIV infection to providing care that addresses all aspects of physical and mental health.
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                Author and article information

                Journal
                Journal ID (nlm-ta): AIDS Res Ther
                Title: AIDS Research and Therapy
                Publisher: BioMed Central
                ISSN (Electronic): 1742-6405
                Publication date Collection: 2011
                Publication date (Electronic): 5 September 2011
                Volume: 8
                Page: 31
                Affiliations
                [1 ]School of Population and Public Health, University of British Columbia, Vancouver, Canada
                [2 ]British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, Canada
                [3 ]Medical Undergraduate Program, University of British Columbia, Vancouver, Canada
                [4 ]Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada
                [5 ]Faculty of Health Sciences, Simon Fraser University, Vancouver, Canada
                Article
                Publisher ID: 1742-6405-8-31
                DOI: 10.1186/1742-6405-8-31
                PMC ID: 3180248
                PubMed ID: 21892955
                SO-VID: d23b650e-4e4b-45d4-a9e8-04b9b5ae9260
                Copyright © Copyright ©2011 Jafari et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 29 April 2011
                Date accepted : 5 September 2011
                Categories
                Subject: Research

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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