Finally, for comparison with data for decedents, we undertook further analyses of all substantially treated HOPS participants with index CD4 cell counts at least 200 cells/μl and found that publicly insured participants were more likely (P < 0.05) than privately insured participants to have HCV or chronic HBV infection (28.5 vs. 8.5%), hypertension (35.3 vs. 18.7%), cardiovascular disease (6.8 vs. 2.2%), diabetes (6.8 vs. 2.3%), and chronic obstructive pulmonary disease (5.8 vs. 1.2%) at index date.
In this large prospective observational study of a diverse cohort of HIV-infected patients seen in the United States during the contemporary HAART era, substantially HAART-treated patients with a CD4 cell count of at least 200 cells/μl whose principal access to medical care payment was through publicly funded sources experienced a greater than two-fold adjusted mortality rate compared with similar patients whose healthcare costs were paid by private entities. Significant differences in adjusted mortality rates by payor among similar patients with CD4 cell count less than 200 cells/μl were not apparent. In these adjusted analyses, race/ethnicity was not associated with increased mortality once CD4 cell counts, insurance/payor, and other factors were taken into account. Among participants who died, several modifiable comorbid conditions and related causes of death were more prevalent among publicly than privately insured participants and among blacks than whites.
Our decision to focus this analysis on substantially treated patients was based upon preliminary findings (data not shown) of marked differences in the prevalence and persistence of HAART use among patient groups (e.g., publicly insured compared with privately insured, blacks compared with whites). We sought to minimize the impact of differential HAART exposure by evaluating more optimally treated patients. The substantially treated group differed from the overall cohort (see Acknowledgements section); in the substantially treated group, there was a somewhat lower proportion of black and publicly insured patients, median baseline and nadir CD4 were lower, and there was a higher prevalence of AIDS.
The independent association of public insurance with increased mortality risk was noted only in patients with either an index CD4 or a CD4 cell count at HAART initiation at least 200 cells/μl. This finding suggests that the increased risk of death was not a consequence of HIV-related morbidity per se but rather was associated with differences between the two groups in the rates or types of comorbid conditions or differences in the quality of medical care provided. We believe our analysis is the first to document an association between the types of medical coverage to which HIV-infected patients have access and patient survival.
In multivariate models, differences were observed among patients with CD4 cell counts more than of at least 200 cells/μl when stratified by insurance type, in the prevalence of factors shown to be associated with mortality risk. In univariate models these included hepatitis C virus co-infection (which correlates with IDU and history of substance abuse) and tobacco smoking.
We acknowledge that these factors could have contributed to observed mortality differences between publicly and privately insured persons in this higher CD4 stratum; nevertheless, the independent and significant association of public insurance with increased mortality in adjusted models persisted after adjusting for key variables prognostic of the mortality in the HOPS.
Recent reports indicate that deaths and comorbidities during the contemporary treatment era are less likely to involve AIDS-defining (immunodeficiency-related or opportunistic) illnesses and are increasingly likely to occur as a consequence of complications from chronic non-AIDS comorbidities [2,12–16]. In our cohort, nearly half of deaths were due to non-AIDS causes. Some of the most prevalent non-AIDS causes of death (e.g. cardiovascular, renal, and liver disease)  and comorbidities (e.g. viral hepatitis coinfection, obesity) occurred with greater frequency among both publicly insured and black participants who died. Obesity and viral hepatitis coinfection as well as many of the other comorbidities that were differentially increased among publicly insured and black participants represent preventable, often treatable conditions. Hence, timely identification and treatment of comorbidities has emerged as an important component of HIV medical care .
We urge caution in interpreting our findings. We believe it would be improper to consider these findings as evidence that the quality of publicly funded healthcare provided was inferior and that it was primarily this inferiority that contributed to the greater mortality observed among publicly insured persons. Although we did not specifically examine the quality of healthcare delivered, our findings have important implications for healthcare reform because the population of persons whose access to healthcare was principally through public sources was significantly enriched in patients diagnosed with comorbidities – usually treatable and often preventable – that are known to be causes of the diseases that predominated as causes of death, especially for the publicly insured. Although the associations between mortality and type of insurance among these HIV-infected adults may have been influenced by subtle differences in the quality of care, none were readily apparent in any comparisons of care indices [e.g., frequency of visits (data not shown)] among privately vs. publicly funded patients at any HOPS site; it is more likely that the mortality/insurance associations were driven by an excess of underlying non-HIV-related comorbid disease among persons whose healthcare was publicly funded. The extent to which having publicly funded healthcare was a marker for socioeconomic issues which themselves engendered greater risk for death (and disease) is unclear.
Our study has limitations. As insurance/payor status was ascertained only at the time of clinic visits, we could not ascertain the precise timing of transition from private to public insurance/payor or vice-versa in the relatively small proportion of patients who had more than one primary payor type while under observation. For the same reason, we could not estimate percentage of follow-up time spent in each insurance category, and instead we assigned insurance/payor category based upon its presence at more than 75% of the visits. We believe that it is unlikely that this impacted our overall findings as the vast majority of patients analyzed had only one insurance/payor type throughout their observation. Furthermore, we could not find evidence that the association between public-coverage and increased mortality among patients with CD4 cell count at least 200 cells/μl was due to a systematic shift of patients from privately to publicly funded health coverage over time in association with advancing age or progression of their HIV disease. Although we adjusted for key variables associated with mortality in our final parsimonious model, unmeasured or other unaccounted for confounders might exist that could explain the association of public insurance with increased mortality among patients with CD4 cell count at least 200 cells/μl. For instance, we lack systematically collected data on antiretroviral adherence, clinical encounter length, missed clinical visits, or comorbid disease prevention counseling administration. Also, we have tried to consider other aspects of care or sociodemographics for which ‘insurance payor’ may be a proxy. Included among these were issues for which did not have sufficient data available to us to specifically address, such as data regarding quality of life or patient income. Indeed, our findings suggest further research is needed to investigate these and other qualitative differences in HIV care that might be payor-based and their causal associations with mortality. Also, information on causes of death was not complete for all patients and could have been inaccurately documented on death certificates in some cases, as has been observed in prior studies [18–20].
Nevertheless, important strengths of our analysis include the use of data from a longitudinal observational cohort in which there were sufficient numbers of deaths to allow for relevant comparisons using sociodemographic variables. HOPS patients were cared for in real-world clinical settings (i.e. observations were not derived from clinical trials or interval cohorts) by their own medical care providers and were sufficiently diverse in terms of sex, race/ethnicity, and type of health insurance to permit meaningful analysis of factors that impacted survival.
The extent to which mortality rates among HIV-infected patients treated with HAART can be further reduced by routine and timely screening for and treatment of non-HIV-associated comorbid illnesses is not yet clear. Although it is unknown at present whether such measures should commence at earlier ages for HIV-infected persons than HIV-uninfected persons, as HIV-infected patients live longer the incidence of these conditions will almost certainly increase. Preemptive risk reduction, early detection, and aggressive treatment of chronic comorbid diseases increasingly comprise routine medical care for HIV infection. Adoption of such measures as standard-of-care may bring us closer to ‘closing the gap’ in survival expectancy that exists between diverse populations of HIV-infected persons, and between HIV-infected and HIV-uninfected patients in the United States.
In conclusion, among contemporary HIV-infected US patients substantially treated with HAART whose CD4 cell counts were at least 200 cells/μl, we observed higher mortality among persons whose only access to medical care was through publicly funded sources, compared to persons who received privately funded medical care. After adjusting for type of healthcare insurance and other factors that impact survival, risk of mortality among substantially HAART-treated patients did not differ by race/ethnicity. Further, we found significantly higher frequencies of often preventable chronic comorbid conditions among publicly insured patients who died; however, further research is warranted to characterize how these factors may explain our principal observation. As our nation undergoes healthcare reform, we need to better understand how healthcare delivery and its financial reimbursement affect quality of care (including routine well health screening and preemptive care) and mortality risk, particularly among groups of persons who have higher prevalence of illnesses that ultimately contribute to mortality regardless of insurance status. In the interim, screening for and addressing modifiable health risks associated with preventable and treatable medical conditions should guide clinical practice and inform public health measures in our efforts to further improve survival and enhance overall health for all patients.
F.J.P., K.B., and J.T.B. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
The HOPS is funded by the Centers for Disease Control and Prevention (CDC, contract no. 200-2006-18797). CDC authors listed on the masthead were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data, and preparation, review, or approval of the article as indicated below in the section detailing specific author contributions.
The findings and conclusions in this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
F.J.P., K.B., J.S.C., E.M.T., R.M.N., M.D.D., and J.T.B. contributed to study concept, design, data interpretation, and manuscript preparation.
R.K.B. contributed to data collection, analysis and interpretation, and manuscript preparation.
Reproducible Research Statement: Study protocol and statistical code: available from the authors. Data set: the HOPS is a public-use dataset and is available to non-HOPS investigators. However, confidentiality protections that govern the HOPS data require HOPS authors to strip all record identifiers; it will therefore take some time to make these data available if requested. In addition, the CDC's heightened security procedures require persons who want to analyze HOPS data to prepare a written proposal for CDC review and approval; sign confidentiality and data use agreements; conduct analyses with the CDC in Atlanta; and go through CDC security clearance for access to facilities. The authors would be happy to facilitate these procedures for persons interested in conducting analyses with HOPS project data and welcome these requests.
The HIV Outpatient Study (HOPS) Investigators include the following persons and sites: John T. Brooks, Kate Buchacz, Marcus Durham, Tony Tong, Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention (NCHSTP), Centers for Disease Control and Prevention (CDC), Atlanta, GA; Kathleen C. Wood, Rose K. Baker, James T. Richardson, Darlene Hankerson, and Carl Armon, Cerner Corporation, Vienna, VA; Frank J. Palella, Joan S. Chmiel, Onyinye Enyia, and Caroline Studney, Northwestern University Feinberg School of Medicine, Chicago, IL; Kenneth A. Lichtenstein and Cheryl Stewart, National Jewish Medical and Research Center Denver, CO; John Hammer, Benjamin Young, Kenneth S. Greenberg, Barbara Widick, and Joslyn D. Axinn, Rose Medical Center, Denver, CO; Bienvenido G. Yangco and Kalliope Halkias, Infectious Disease Research Institute, Tampa, FL; Douglas J. Ward and Charles A. Fiorentino, Dupont Circle Physicians Group, Washington, DC; Jack Fuhrer, Linda Ording-Bauer, Rita Kelly, and Jane Esteves, State University of New York (SUNY), Stony Brook, NY; Ellen M. Tedaldi, Ramona A. Christian, Faye Ruley and Atiya Nimmons, Temple University School of Medicine, Philadelphia, PA; Richard M. Novak and Andrea Wendrow, University of Illinois at Chicago, Chicago, IL.
Conflicts of interest
No potential conflicts of interest have been identified by any of the authors.
1. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators
. N Engl J Med
2. Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, Holmberg SD. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study
. J Acquir Immune Defic Syndr
3. Hessol NA, Kalinowski A, Benning L, Mullen J, Young M, Palella F, et al. Mortality among participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study
. Clin Infect Dis
4. Bhaskaran K, Hamouda O, Sannes M, Boufassa F, Johnson AM, Lambert PC, Porter K. Changes in the risk of death after HIV seroconversion compared with mortality in the general population
5. Welch KJ, Morse A. Survival patterns among HIV + individuals based on healthcare utilization
. J Natl Med Assoc
6. Losina E, Schackman BR, Sadownik SN, Gebo KA, Walensky RP, Chiosi JJ, et al. Racial and sex disparities in life expectancy losses among HIV-infected persons in the United States: impact of risk behavior, late initiation, and early discontinuation of antiretroviral therapy
. Clin Infect Dis
7. Lemly DC, Shepherd BE, Hulgan T, Rebeiro P, Stinnette S, Blackwell RB, et al. Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care
. J Infect Dis
8. Mugavero MJ, Lin HY, Allison JJ, Giordano TP, Willig JH, Raper JL, et al. Racial disparities in HIV virologic failure: do missed visits matter?
. J Acquir Immune Defic Syndr
9. Silverberg MJ, Leyden W, Quesenberry CP Jr, Horberg MA. Race/ethnicity and risk of AIDS and death among HIV-infected patients with access to care
. J Gen Intern Med
10. Weintrob AC, Grandits GA, Agan BK, Ganesan A, Landrum ML, Crum-Cianflone NF, et al. Virologic response differences between African Americans and European Americans initiating highly active antiretroviral therapy with equal access to care
. J Acquir Immune Defic Syndr
11. Mugavero MJ, Lin HY, Willig JH, Westfall AO, Ulett KB, Routman JS, et al. Missed visits and mortality among patients establishing initial outpatient HIV treatment
. Clin Infect Dis
12. Buchacz K, Baker RK, Moorman AC, Richardson JT, Wood KC, Holmberg SD, Brooks JT. Rates of hospitalizations and associated diagnoses in a large multisite cohort of HIV patients in the United States, 1994–2005
13. Crum NF, Riffenburgh RH, Wegner S, Agan BK, Tasker SA, Spooner KM, et al. Comparisons of causes of death and mortality rates among HIV-infected persons: analysis of the pre, early, and late HAART (highly active antiretroviral therapy) eras
. J Acquir Immune Defic Syndr
14. Sabin CA, Smith CJ, Youle M, Lampe FC, Bell DR, Puradiredja D, et al. Deaths in the era of HAART: contribution of late presentation, treatment exposure, resistance and abnormal laboratory markers
15. Marin B, Thiebaut R, Bucher HC, Rondeau V, Costagliola D, Dorrucci M, et al. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy
16. Neuhaus J, Angus B, Kowalska JD, La Rosa A, Sampson J, Wentworth D, Mocroft A. Risk of all-cause mortality associated with nonfatal AIDS and serious non-AIDS events among adults infected with HIV
17. Justice AC. Prioritizing primary care in HIV: comorbidity, toxicity, and demography
. Top HIV Med
18. Centers for Disease Control and Prevention (CDC). Electronic record linkage to identify deaths among persons with AIDS – District of Columbia, 2000-2005.MMWR Morb Mortal Wkly Rep
19. Hooshyar D, Hanson DL, Wolfe M, Selik RM, Buskin SE, McNaghten AD. Trends in perimortal conditions and mortality rates among HIV-infected patients
20. Lau B, Gange SJ, Moore RD. Risk of non-AIDS-related mortality may exceed risk of AIDS-related mortality among individuals enrolling into care with CD4+ counts greater than 200 cells/mm3
. J Acquir Immune Defic Syndr
Keywords:© 2011 Lippincott Williams & Wilkins, Inc.
HAART; insurance; mortality; race/ethnicity