In this study, we observed a high rate of mortality in ICU, a majority of admissions not primarily related to opportunistic infections and only a few discoveries of HIV infection after ICU admission. In this HIV-infected population, we showed that mortality in ICU and during the first year following admission were related to the acute illness severity and immunovirological statuses at ICU admission and that introduction or pursuit of HAART seemed to be associated with a better outcome. The 1-year mortality contrasted with the ICU mortality (62.2% and 36.7% respectively), suggesting that the long-term survival of critically ill HIV-infected patients was still poor. Our in-ICU mortality was similar to other centers in industrialized countries [12
], but our 1-year survival rate was lower compared with the few studies reporting long-term outcomes, in which antiretroviral-naïve subjects were the vast majority [15
]. This last point can be explained by the fact that the HIV-infected subjects in our study had a long history of HIV infection and treatment and that morbid outcomes after ICU discharge were independent of immune restoration under HAART (i.e., non-AIDs defining cancers, decompensated cirrhosis).
As in several other studies, use of vasopressive agents, mechanical ventilation, and severity scores at the admission were the main prognostic factors of ICU mortality [9
HIV-infected patients admitted to ICU do not form a homogenous population and should be considered according to their immunovirological status. For example, patients with HAART failure and deep immunological deficiency, patients with AIDS classifying diseases but who never had antiretroviral therapy, or patients in the early stage of the HIV infection with high CD4 cell count will probably have very different outcomes. These different situations are not entirely captured by analyzing separately plasma HIV RNA viral load and CD4+ cell count. In our study, death at 1
year after admission was not directly related to a CD4+ cell count <200/mm3
. We thus decided to classify patients into four groups according to viral load and CD4 counts at the admission and showed that patients from the groups [CD4low
] or [CD4low
] had a very bad outcome at 1
year compared with the group [CD4high
]. The group [CD4low
] contained patients with viral replication suppressed by HAART but without immune reconstitution and the group [CD4low
] patients with HAART failure, whereas the group [CD4high
] corresponded to patients with a good response to HAART. To our knowledge, combined plasma HIV RNA viral load and CD4+ cell count have never been evaluated as prognostic factor in HIV-infected patients admitted to ICU.
In the general HIV-infected population presenting an opportunistic infection, early HAART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred HAART [29
]. Moreover, it is now recommended to prescribe HAART in the majority of HIV-infected patients even for high CD4 level [26
]. Management of antiretroviral therapy is a challenge in ICU, and introducing HAART in a patient with no HAART at admission is a difficult decision. There are no pharmacologic and pharmacokinetic data concerning antiretroviral therapy in hemodynamically unstable patients. Drug-to-drug interactions are expected with antiarrhythmics, anticonvulsants, antifungal, antibiotics, gastrointestinal drugs, or sedative drugs, such as midazolam. Only AZT can be used for intravenous administration, and pharmacokinetics of administration using nasogastric tubes for others compounds are uncertain and could lead to poor drug absorption and further development of resistance. In our study, we showed that introducing or continuing HAART in HIV-infected patients in ICU seems to be protective in the short-term and introducing HAART in a patient with no HAART at admission seems to be associated with a better long-term outcome. One must probably discriminate HIV-related situations in which immune restoration is crucial for clinical response or to prevent other complications (especially in case of long period of ICU) from other situations.
Only four retrospective studies analyzed the impact of HAART in ICU and showed discordant results. A study of 281 patients admitted to ICU in the San Francisco General Hospital found that HAART use at ICU admission was not associated with a better hospital survival but was associated with predictors of better outcome, such as higher serum albumin concentrations [8
]. The second study from São Paulo University Hospital analyzed predictive factors of mortality for 278 HIV patients admitted to ICU; 193 of them (69.4%) died before 6
]. They demonstrated that HAART use in ICU was negatively predictive of 6-month mortality, especially if this therapy was introduced during the first 4
days of admission in ICU. However, contrasting with our and other studies, 80.6% of the ICU admissions were due to AIDS-defining conditions, and all subjects had very low CD4 counts. The third study from Saint Louis hospital in Paris [9
] analyzed predictive factors of mortality for 284 HIV patients admitted to ICU and showed that comorbidities and organ dysfunctions, but not HIV-related variables, were associated with death. Among the 233 (82%) patients with known HIV infection before ICU admission, 64% were on HAART but HAART use at ICU admission was not associated with ICU mortality.
The most recent study, from the University Medical Center Utrecht in Netherlands [21
], analyzed characteristics from patients admitted to the ICU during the pre-HAART era (n
47), and during the HAART period (1996–2008, n
80). The 1-year mortality in the HAART era decreased to 51%. Predictors of short- and long-term (1
year and 5
years) mortality in the HAART era were older age, APACHE II score
20, and the use of mechanical ventilation, but neither HIV-related factors nor the use of HAART on ICU admission were significant.
Our study has several limitations. First, the design was retrospective. All patients were managed in two different ICU without standardized, written protocols, but all patients had a follow-up in the same Infectious Diseases Department and no data of ICU concern were missing. Loss of follow-up is less than 10%, which is usual in this pathology. During this period, we recorded only 104 admissions in this two medical ICU, but we have no data about HIV-infected patients hospitalized in surgical ICU. Second, the study period is very long (11
years), comprising progress in critical care practices during the past decade: use of low tidal volumes for patients with respiratory failure, adjuvant corticosteroids for certain conditions, and early goal-directed therapy for sepsis. Even if the admission policy of HIV-infected patients remains constant in our centers, antiretroviral therapy also has evolved and new combinations are supposed to enhance efficiency with fewer adverse events. However, number of admissions, age, and severity scores throughout the different periods were not significantly different (Table ). Third, numbers of patients in each immunovirological subgroup were too small to discriminate patients who really benefited from HAART use in ICU. Our results suggest that introduction of HAART is beneficial in some patients in the ICU, but this protective effect may be simply an association rather than a causative factor.