Survival trends in critically ill HIV-infected patients in the highly active antiretroviral therapy era

Introduction

The widespread use of highly active antiretroviral therapy (ART) has reduced HIV-related life-threatening infectious complications. Our objective was to assess whether highly active ART was associated with improved survival in critically ill HIV-infected patients.

Methods

A retrospective study from 1996 to 2005 was performed in a medical intensive care unit (ICU) in a university hospital specialized in the management of immunocompromised patients. A total of 284 critically ill HIV-infected patients were included. Differences were sought across four time periods. Risk factors for death were identified by multivariable logistic regression.

Results

Among the 233 (82%) patients with known HIV infection before ICU admission, 64% were on highly active ART. Annual admissions increased over time, with no differences in reasons for admission: proportions of patients with newly diagnosed HIV, previous opportunistic infection, CD4 counts, viral load, or acute disease severity. ICU and 90-day mortality rates decreased steadily: 25% and 37.5% in 1996 to 1997, 17.1% and 17.1% in 1998 to 2000, 13.2% and 13.2% in 2001 to 2003, and 8.6% in 2004 to 2005. Five factors were independently associated with increased ICU mortality: delayed ICU admission (odds ratio (OR), 3.04; 95% confidence interval (CI), 1.29 to 7.17), acute renal failure (OR, 4.21; 95% CI, 1.63 to 10.92), hepatic cirrhosis (OR, 3.78; 95% CI, 1.21 to 11.84), ICU admission for coma (OR, 2.73; 95% CI, 1.16 to 6.46), and severe sepsis (OR, 3.67; 95% CI, 1.53 to 8.80). Admission to the ICU in the most recent period was independently associated with increased survival: admission from 2001 to 2003 (OR, 0.28; 95% CI, 0.08 to 0.99), and between 2004 and 2005 (OR, 0.13; 95% CI, 0.03 to 0.53).

Conclusions

ICU survival increased significantly in the highly active ART era, although disease severity remained unchanged. Co-morbidities and organ dysfunctions, but not HIV-related variables, were associated with death. Earlier ICU admission from the hospital ward might improve survival.     

Osteonecrosis in six HIV-infected patients receiving highly active antiretroviral therapy

OBJECTIVE: To report 6 cases of osteonecrosis in HIV-infected patients treated with highly active antiretroviral therapy (HAART) and compare the observed risk factors with those of published cases. CASE SUMMARIES: Osteonecrosis was diagnosed between 1999 and 2002 in 6 of 417 HIV-infected patients in our department of infectious diseases. At the time of diagnosis, mean patient age was 42 years, and 5 patients had developed AIDS. Mean CD4+ lymphocyte count was 563.5 cells/mm(3) and viral load was undetectable (<50 copies/mL) in 5 patients. The patients' mean body mass index was 22.5 kg/m(2). Four had lipodystrophy. All were receiving HAART, including a protease inhibitor in 4 patients; the remaining 2 patients had a history of protease inhibitor treatment. Median time from the first antiretroviral therapy to osteonecrosis diagnosis was 46.5 months. Established risk factors were the use of corticosteroids in 2 patients and dyslipidemia in all patients. All of the patients developed pain and functional impotence of the hip or ankle joints. Osteonecrosis of the hip was bilateral in 4 cases. Three patients required surgical intervention, all of whom had favorable outcomes. DISCUSSION: HIV-infected patients are at a higher risk for the development of osteonecrosis and are more likely to be exposed to predisposing factors to its development. The HAART implication as a predisposing factor remains controversial. CONCLUSIONS: The pathogenesis of osteonecrosis in HIV-infected individuals may be multifactorial; the reasonable approach for clinicians consists of treating concomitant predisposing conditions that might further cause osteonecrosis.     

Admissions to intensive care unit of HIV-infected patients in the era of highly active antiretroviral therapy: etiology and prognostic factors

Introduction  

Although access to highly active antiretroviral therapy (HAART) has prolonged survival and improved life quality, HIV-infected patients with severe immunosuppression or comorbidities may develop complications that require critical care support in intensive care units (ICU). This study aimed to describe the etiology and analyze the prognostic factors of HIV-infected Taiwanese patients in the HAART era.     

HIV-infected patients' adherence to highly active antiretroviral therapy: a phenomenological study

Adherence to the treatment regimen is essential to the success of highly active antiretroviral therapy for patients who are infected with HIV. The evidence suggests that poor adherence to antiretroviral drug therapy is a major problem that has the potential to diminish effective viral suppression, promote viral resistance, and place patients at risk for hospitalization, opportunistic infections, and an increased risk of HIV transmission. The primary aim of this study was to understand patients' experiences regarding their adherence to antiretroviral drug therapy. Thus, 19 participants were recruited for in-depth interviews regarding their adherence to drug regimens. All the interviews were transcribed verbatim and analyzed by using Benner's phenomenological analysis approach. Four main themes emerged from the data: (i) choosing to live and the decision to start taking medications; (ii) strategies for adhering to the regimen and managing the side-effects; (iii) relationships with healthcare providers; and (iv) advantages of the medications as a motivator to continue one's adherence to the regimen. Studying and understanding the experiences of patients can provide new insights and strategies in order to enhance patients' adherence to highly active antiretroviral therapy.     

Characteristics and outcomes of HIV-infected patients in the ICU: impact of the highly active antiretroviral treatment era

Objective To examine whether the introduction of highly active antiretroviral therapy (HAART) has changed the rate of admission, the clinical spectrum, and the mortality of HIV-infected ICU patients.Design Observational study.Setting Infectious diseases ICU in a teaching hospital, Paris, France.Patients All HIV-infected patients admitted during a pre-HAART era (1995–1996; n=189) and a HAART era (1998–2000; n=236).Interventions None.Measurements and results At the HAART era, 79% of patients had derived no or little benefit from the availability of HAART at ICU admission: 44% had no history of antiretroviral (ARV) medications and 35% had failed to respond to ARV. As compared with the pre-HAART era, the rate of hospitalized HIV-infected patients requiring the ICU stay increased (HAART, 5.9% vs pre-HAART, 4.4%; p=0.004). The admission was more likely to occur through the emergency room (45 vs 29%, p=0.0004), and the patients to be foreigners (38.1 vs 28.6%; p=0.04). After adjustment for significant prognostic covariates (AIDS-related tumors at admission, CD4 count <50/mm³, poor functional status (Knaus score C or D), SAPSII, and need for mechanical ventilation), ICU survival was unchanged (adjusted OR=0.613, 95% CI=0.312–1.206), but 3-month survival was significantly improved (adjusted OR=0.57; 95% CI=0.32–0.99; p=0.045).Conclusion The number of HIV-infected patients admitted to the ICU remained high in the HAART era. Underutilization of HAART and limited access to health care are possible explanations. The ICU mortality has remained unchanged, but 3-month mortality has decreased.     

Histoplasmosis in two human immunodeficiency virus-positive immigrants to Italy: clinical features and management in the highly active antiretroviral therapy era

We report two cases of histoplasmosis occurring in human immunodeficiency virus-positive patients who immigrated to Italy, and focus our attention on the clinical features and therapeutic aspects, with particular emphasis on secondary prophylaxis. The patients had comparable human immunodeficiency virus baseline parameters, but had a completely different compliance over therapeutic regimens. The two patients were followed in two different city hospitals of our region, Padua and Verona, and the diagnosis was made on the basis of instrumental, histologic, and microbiologic findings. One of them was treated with corticosteroids because of nephrotic syndrome.     

Lipid-lowering and anti-inflammatory effects of tetradecylthioacetic acid in HIV-infected patients on highly active antiretroviral therapy

BACKGROUND: Highly active antiretroviral therapy (HAART) often leads to a dramatic improvement in clinical, viral and immunologic parameters in HIV-infected individuals. However, the emergence of long-term side-effects of HAART and in particular dylipidaemia is increasingly reported. Based on the potential lipid-lowering and immunomodulatory properties of tetradecylthioacetic acid (TTA) we examined whether TTA in combination with dietary intervention could modify lipid levels in peripheral blood in HIV-infected patients on HAART. MATERIALS AND METHODS: Ten HIV-infected patients on protease inhibitor-based HAART with hyperlipidaemia followed a cholesterol-lowering diet throughout the study period (8 weeks). During the last 4 weeks of the study all patients received TTA (1 g qd) in addition to the cholesterol-lowering diet. RESULTS: Our main and novel findings were: (i) TTA in combination with dietary intervention reduces total cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in these patients, and a particularly suppressing effect was observed during the TTA phase regarding total cholesterol. (ii) During the TTA phase, the cholesterol-lowering effect was accompanied by a significant reduction in plasma levels of tumour necrosis factor alpha. (iii) Our studies in peripheral blood mononuclear cells from these patients and in the liver from wild-type mice receiving TTA suggest that the hypolipidaemic effects of TTA may involve up-regulation of scavenger and LDL-receptor expression. CONCLUSIONS: Although few patients were studied, the present pilot study suggests that TTA combined with dietary intervention could be an interesting therapeutic approach in HIV-infected patients on HAART, potentially resulting in both hypolipidaemic and anti-inflammatory effects.     

Outcome of critically ill human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy

The purpose of this study was to determine the effect of prior use of highly active antiretroviral therapy (HAART) on outcome of human immunodeficiency virus (HIV)- patients admitted to intensive care units (ICUs). This study was a retrospective chart review of 242 HIV-infected patients who required 259 consecutive admissions to a university-affiliated hospital ICU during a 3-year period. Patient demographics, CD4 count, admission diagnosis, prior HAART, Pneumocystis jiroveci prophylaxis, length of stay, and ICU and hospital mortality were determined. Overall hospital mortality was 39%. Comparing patients who had received HAART before an ICU admission to those who had not, we found no difference between ICU or hospital mortality, need of mechanical ventilation, ICU and hospital length of stay, and incidence of P jiroveci. Pulmonary diagnosis was the most frequent ICU admission diagnosis (30%). Logistic regression analysis showed HIV-related illness and mechanical ventilation were significant independent predictors of increased hospital mortality.     

Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy

BACKGROUND: Limited data are available on the life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy (HAART). AIM: To provide such an estimate using a semi-parametric projection. DESIGN: Statistical analysis. METHODS: Follow-up data for patients newly diagnosed with HIV infection in Taiwan (HIV/AIDS Cohort) from 1 May 1997 to 30 April 2003 (n = 3351, only 1% are injecting drug users) were analysed using the Kaplan-Meier method. The survival function for an age- and gender-matched reference population was generated by the Monte Carlo method from the life-table of the general population. A constant excess hazard model was used to project long-term survival of HIV-infected patients, with linear extrapolation of a logit-transformed curve of survival ratio between HIV-infected patients and the reference population. RESULTS: The 5-year survival rate was 58% in patients who had already developed AIDS at diagnosis (AIDS group), and 89% in those who had not (non-AIDS group). Extrapolation yielded an expected mean survival time of 10.6 years after diagnosis for the AIDS group, and 21.5 years after diagnosis for the non-AIDS group. DISCUSSION: Our results support the expansion of HIV screening programs to minimize delay in diagnosis. With continuing advances in HAART, this estimate of survival in initially asymptomatic patients may be conservative. Their long life expectancy raises questions about what kind of preventive heath services should be offered. These should be addressed through further analysis of overall benefit and cost-effectiveness.     

Coronary artery calcium in HIV-infected men treated with highly active antiretroviral therapy

Calcium is a common component of an atherosclerotic plaque; therefore, the presence of coronary artery calcium (CAC) indicates atherosclerosis. This study investigated the difference in total CAC scores between HIV-infected patients treated with highly active antiretroviral therapy (HAART) and HIV-negative age-matched controls. HIV patients were 27 men treated with a protease inhibitor-containing HAART regimen for more than 1 year (M = 4.92 years, SD = 2.02), aged 30 to 60 years (M = 43.52 years, SD = 6.65), and not receiving lipid-lowering or hypoglycemic drugs. Controls were age-matched men randomly selected (three controls to one case, for a total of 81 controls) from our existing database of 25,250 men who self-referred for CAC screening (control database). Electron beam tomography was used to obtain CAC scores. The CAC scores were coded as above or below the age-specific (stratified in 5-year increments) 10th, 25th, 50th, 75th, or 90th percentile of our control database. Chi-square analyses for two independent samples indicated (1) a larger frequency of controls with CAC scores above the 10th (chi1= 8.32, P = .004) and 25th (chi1= 5.45, P = .02) percentiles than that of HIV patients, (2) no differences in CAC scores between groups above the 50th (chi = 0.85, P = .357) or 75th (chi = 0.46, P = .497) percentile, and (3) a larger frequency of HIV patients who were above the 90th percentile (chi = 4.5, P = .034). The strength of the relationship between group membership and scoring above the 90th percentile was significant (phi = 0.20, P = .034). These results tentatively suggest that there is an elevated level of subclinical atherosclerosis in HIV patients treated with HAART.     

Changes in leptin serum levels in HIV-infected children receiving highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) has significantly improved the prognosis of HIV(+) in children. Human immunodeficiency-associated lipodystrophy syndrome (HALS) is a side effect of HAART seen predominantly in adults and less often in children. Leptin is a protein thought to play an important role in body composition and has been shown to have immunomodulatory effects. We retrospectively studied serum levels of leptin in a cohort of eight HIV-infected children followed prospectively before and during HAART and investigated whether there is a correlation of these levels with the clinical, immunological, viral or nutritional changes observed during treatment in these children. None of our children developed HALS. In this small cohort of children, we found that serum leptin levels were appropriate to the nutritional status of the patient and that leptin/BMI increased in patients who responded to HAART. In conclusion, in HIV(+) children during HAART, leptin levels are related to the nutritional status of the child.     

Treatment and prognosis of AIDS-related lymphoma in the era of highly active antiretroviral therapy: findings from the Swiss HIV Cohort Study

OBJECTIVE: To assess the characteristics of combination antiretroviral therapy (cART) administered concomitantly with chemotherapy and to establish prognostic determinants of patients with AIDS-related non-Hodgkin's lymphoma. METHODS: The study included 91 patients with AIDS-related non-Hodgkin's lymphoma from the Swiss HIV Cohort Study enrolled between January 1997 and October 2003, excluding lymphomas of the brain. We extracted AIDS-related non-Hodgkin's lymphoma- and HIV-specific variables at the time of lymphoma diagnosis as well as treatment changes over time from charts and from the Swiss HIV Cohort Study database. Cox regression analyses were performed to study predictors of overall and progression-free survival. RESULTS: During a median follow up of 1.6 years, 57 patients died or progressed. Thirty-five patients stopped chemotherapy prematurely (before the sixth cycle) usually due to disease progression; these patients had a shorter median survival than those who completed six or more cycles (14 versus 28 months). Interruptions of cART decreased from 35% before chemotherapy to 5% during chemotherapy. Factors associated with overall survival were CD4+ T-cell count (<100 cells/microl) (hazard ratio [HR] 2.95 [95% confidence interval (CI) 1.53-5.67], hepatitis C seropositivity (HR 2.39 [95% CI 1.01-5.67]), the international prognostic index score (HR 1.98-3.62 across categories) and Burkitt histological subtypes (HR 2.56 [95% CI 1.13-5.78]). CONCLUSIONS: Interruptions of cART were usually not induced by chemotherapy. The effect of cART interruptions on AIDS-related non-Hodgkin's lymphoma prognosis remains unclear, however, hepatitis C seropositivity emerged-as a predictor of death beyond the well-known international prognostic index score and CD4+ T-cell count.     

Interrupting highly active antiretroviral therapy in patients with HIV

Scheduled treatment interruptions are preplanned interruptions of antiretroviral treatment, which may be directed by time (e.g., cycles of 8 weeks on treatment and 8 weeks off treatment); the concentration of CD4+ lymphocytes (the CD4 count); HIV-1 RNA concentration (viral load); or other factors. This review covers the rationale of scheduled treatment interruptions and the different strategies that have been explored. It examines the issue of autovaccination, resistance and other risks and benefits. Scheduled-treatment-interruption studies in three populations are discussed: patients who initiated highly active antiretroviral therapy during acute HIV infection; patients with successfully treated chronic HIV infection; and patients with highly active antiretroviral therapy failure.     

Point prevalence,microbiology and fluconazole susceptibility patterns of yeast isolates colonizing the oral cavities of HIV-infected patients in the era of highly active antiretroviral therapy

We conducted a prospective study to address the prevalence and microbiological characteristics of yeast isolates colonizing the oral cavities of HIV-infected patients undergoing highly active antiretroviral therapy. Sixty-eight patients (67%) from a total of 102 were found to be colonized with yeasts. Sixty-five patients carried a single species (60 Candida albicans, three Candida glabrata and two Candida krusei) and three patients had mixed colonization of C. albicans and C. krusei. The status of yeast carrier was not associated with the number of CD4 cells or the viral load. Similarly, the type of antiretroviral regimen was not associated with the carriage of Candida spp. The only predictor of Candida colonization was a previous history of oropharyngeal candidiasis (P = 0.009). Although many patients in this series had already been treated with repeated courses of fluconazole therapy for previous episodes of oropharyngeal candidiasis, fluconazole susceptibility patterns showed that 93% of yeasts were susceptible to this triazole in vitro (MIC < or = 8.0 mg/L).