Impact of HIV/AIDS on care and outcomes of severe sepsis

With the advent of highly active antiretroviral therapy (HAART) in the late 1990s, opportunistic infection and mortality rates for patients with HIV/AIDS have dramatically decreased, thus transforming HIV/AIDS from a uniformly fatal condition to a more manageable chronic illness [1‐5]. Improvement in care and survival have also extended to HIV/AIDS patients with severe infections and those who receive care in the intensive care unit (ICU) [6‐9]. While studies have shown dramatic improvement in survival related to intensive care for patients with HIV/AIDS in the HAART era, some studies in patients with HIV/AIDS and serious illness have reported continued low rates of intensive care [9, 10].

In 1992, the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference arrived at the current definition of severe sepsis (SS) as a systemic inflammatory syndrome in response to infection that is associated with acute organ dysfunction [11]. Subsequent studies have shown that SS results in substantial morbidity and mortality for all patients, especially for patients with comorbid illnesses, including HIV/AIDS [12‐14]. However, those data pre-date the HAART era, and there are few data directly comparing outcomes and resource use for patients with SS and HIV/AIDS versus patients with SS but without HIV/AIDS. Thus, the purpose of this study was two-fold: to examine patterns of care and outcomes for patients with SS and HIV/AIDS; and to assess differences in patterns of care and outcomes for those with SS and HIV/AIDS versus those with SS without HIV/AIDS.

We identified 74,020 cases of severe sepsis, 10.3% (n = 7,638) with HIV/AIDS (Table 1). Those with SS and HIV/AIDS were significantly younger on average (41.9 years versus 49.9 years); more likely to be male (66% versus 54%); less likely to be white (20% versus 56%); less likely to have commercial insurance (16% versus 42%); more likely to be admitted for medical reasons (88% versus 69%); more likely to be admitted at a teaching hospital (76% versus 61%); less likely to have comorbid illnesses (30% versus 51%); and more likely to have respiratory (45% versus 42%) and opportunistic infections (53% versus 9%) than those without HIV/AIDS (p ≤ 0.0001 for all comparisons; Table 1).

In this HAART-era study, we found that patients with SS and HIV/AIDS overall had less costly hospitalizations, were less likely to be admitted to the ICU, and had a greater in-hospital mortality than those without HIV/AIDS. HIV/AIDS patients had similar LOS, lower hospitalization costs, and greater mortality than those without HIV/AIDS whether they lived, died, or were admitted to the ICU. However, for patients with SS not in the ICU, the trends were different. Specifically, those with HIV/AIDS had significantly longer LOS and had somewhat higher mean hospitalization costs (and continued higher mortality rates) than those without HIV/AIDS. We also found that when compared with those with SS and HIV/AIDS, patients with SS without HIV/AIDS were universally more likely to be admitted to the ICU, even when they had comorbid illnesses with equal or worse expected in-hospital mortality (e.g., metastatic cancer). Those results were robust with qualitatively similar results in univariate, multivariable, and subgroup analyses.

Despite having higher mortality rates, patients with SS and HIV/AIDS were significantly less likely to be admitted to the ICU than patients with SS without HIV/AIDS. Nicolau and colleagues [22] studied patients with Pneumocystis carinii pneumonia with and without HIV/AIDS and had similar findings. What is unclear and cannot be discerned from our data is whether that difference in care is inappropriate because of physician or healthcare system bias or whether the difference is appropriate and based on differences in patient preference (e.g., advanced directives) or clinical differences between patients with and without HIV/AIDS. Existing evidence suggests there may be clinical biases against aggressive treatment of patients with SS and HIV/AIDS [23‐26]. In our analysis, for patients with SS who were not admitted to the ICU, one could argue that those with HIV/AIDS were 'sicker' than those without HIV/AIDS because they had longer LOS, higher mean hospitalization costs, and higher mortality (in contrast to the overall trends that showed that, in general, patients with HIV/AIDS had similar LOS and lower hospitalization costs) and should have had more ICU utilization. Sasse and Wachter and colleagues [24‐26] speculated that there is clinical bias that stems from a conception of HIV as a 'terminal' condition with poor overall long-term survival resulting in a provider-imposed limitation on medical care. We performed a limited exploration of this explanation with our data. If systematic withholding of ICU admission was indeed happening based on expected survival, then patients in our database with other comorbid illnesses with equal or higher in-hospital mortality rates (i.e., metastatic cancer) could also have been expected to have lower ICU admission rates. However, patients with SS without HIV/AIDS were universally more likely to be admitted to the ICU regardless of their comorbidities and associated mortality (including those with metastatic cancer).

The explanation for differences in ICU use may also lie in patient preferences. Given the emphasis on advanced directives in patients with HIV/AIDS that began before the HAART era [27‐34], it is likely that more patients with HIV/AIDS than without HIV may have their wishes known vis-à-vis aggressive care and, thus, may have had their care decelerated, decreasing the use of aggressive measures and increasing use of palliative measures like hospice. Nonetheless, physicians caring for in-patients with HIV/AIDS, as well as the patients themselves, should be made aware of improvements in outcomes for critically ill patients with HIV/AIDS before making decisions about withholding or withdrawing aggressive care [7‐9].

In regards to our cost results, we suspected that the cost differences might be explained by the differences in ICU admission and mortality (i.e., patients with SS and HIV/AIDS may die quickly outside the ICU thus using less resources); however, the difference in cost persisted even after stratifying by mortality, and in fact, for those not admitted to the ICU, costs were similar for those with and without HIV/AIDS. Furthermore, the difference in cost persisted even in our adjusted analyses that accounted for additional issues such as LOS, comorbidities, and failing organ systems, as well as in our 'matched' subgroup analyses. Others have compared resource use between patients with and without HIV/AIDS [35‐37]. In those studies, patients with HIV/AIDS had significantly higher overall resource use. However, we found only one study that compared resource use in patients with and without HIV but with a similar discharge diagnosis, Pneumocystis carinii pneumonia [22]. The results of that study were similar to our current study in that patients with HIV/AIDS were less likely to be admitted to the ICU and had lower overall hospital costs.

The major limitations of our study relate to the use of administrative data. The general issues with using administrative data for research have been well documented by others [38, 39]. Specifically in our study, we could only define severe sepsis and HIV using ICD-9-CM codes, rather than by clinical, laboratory, or physiological parameters. In these administrative data, we were unable to discern differences in patient preferences and pathophysiology between those with SS with and without HIV/AIDS that likely exist and might thereby explain the differences we found in care, resource use, and mortality. Additionally, we were unable to discern HIV disease severity other than coexisting presence of opportunistic infection (there are not separate ICD-9-CM codes for HIV and AIDS) and we lacked the treatment (antiretroviral therapy) and laboratory staging (viral load and CD4 cell count) data that could also have provided insight into the differences we found. Furthermore, by using ICD-9-CM codes to identify severe sepsis, the temporal overlap between infection and organ dysfunction was not confirmed. However, we did use validated approaches for identifying both HIV [17] and severe sepsis [13], and our results are consistent with other clinical studies that report outcomes for patients with severe sepsis (or sepsis syndrome) and HIV/AIDS [7, 8, 13, 40]. Finally, treatment, ICU utilization, and mortality expectations have evolved over time for patients with HIV/AIDS. Thus, studying a fluid situation at one period in time (1999) is not optimal, and more recent longitudinal data would be useful and should be pursued as future work.

Despite the limitations, our study has several notable strengths. First, our finding of less aggressive care (lower cost of hospitalization and less ICU care) were robust with consistent findings using different analysis assumptions and methodologies. Second, using a large, multi-state administrative database allows us to easily generate reliable estimates of outcomes obviating the need for a large multi-center study and permits examination of care patterns and resource use simultaneously. Furthermore, our study has more power and generalizability than the small, single-site studies that have provided much of the evidence base for care of critically ill patients with HIV/AIDS [7, 8, 40‐44]. Lastly, our study has a broad perspective that is not limited in focus to only HIV patients [6‐10, 40‐44] or to patients receiving care in the ICU [7, 8, 10, 41‐43] but, rather, includes all patients with severe sepsis regardless of site of care within the acute care hospital thus permitting examination and comparison of care and outcomes in patients with and without HIV/AIDS with similar serious disease processes.

In conclusion, we found a difference in care and outcome for patients with SS and HIV/AIDS, in that they had less costly hospitalizations, were less likely to be admitted to the ICU, and had greater in-hospital mortality than those without HIV/AIDS. Further research is needed to examine whether that difference in care persists over time and if it is inappropriate because of physician or healthcare system bias or whether the difference is appropriate and based on differences in patient preference or clinical differences between patients with and without HIV/AIDS.