Intensive care in patients with HIV infection in the era of highly active antiretroviral therapy

STUDY OBJECTIVES: The use of highly active antiretroviral therapy (HAART) has dramatically improved morbidity and mortality in patients with HIV infection. The types of critical illness and their outcomes in HIV-infected patients in recent years is unknown. DESIGN: We reviewed the medical records of all patients admitted to the Medical ICU of Beth Israel Medical Center, NY, from January to June 2001 and compared their characteristics with patients admitted to the same unit from November 1991 to October 1992. RESULTS: Of 441 admissions in the first half of 2001, 63 admissions (14%) were in 53 HIV-seropositive patients. There were 65 admissions to the Medical ICU during the 1-year period spanning 1991 to 1992. Compared with the earlier period, the 2001 patients were more likely to be black (52% vs 26%, respectively; p < 0.01) and injection drug users (75% vs 48%, respectively; p < 0.01), and were less likely to be white (11% vs 23%, respectively; difference not significant) and homosexual men (6% vs 26%, respectively; p < 0.01). In 2001, patients were less likely to be admitted with respiratory failure (22% vs 54%, respectively; p < 0.01) and with Pneumocystis jiroveci pneumonia (formerly referred to as Pneumocystis carinii) [3% vs 34%, respectively; p < 0.001], and were more likely to be admitted with non-HIV-related diseases (67% vs 12%, respectively; p < 0.001). Overall survival was much higher in the later period (71% vs 49%, respectively; p < 0.01). CONCLUSIONS: In the era of HAART, more patients with HIV infection were admitted to the ICU over a 12-month period than were 10 years previously. Patients were more likely to be injection drug users and were more likely to be admitted to the ICU because of non-HIV-associated conditions.     

Pulmonary manifestations of HIV infection in the era of highly active antiretroviral therapy.

STUDY OBJECTIVES: To determine whether the spectrum of HIV-related pulmonary disease seen by a university medical center Pulmonary and Critical Care Medicine Service has changed since the introduction of highly active antiretroviral therapy (HAART). DESIGN: Retrospective chart review. SETTING: A tertiary care university hospital. PATIENTS: All HIV-infected patients referred to the Pulmonary and Critical Care Medicine Service from January 1, 1993, through December 31, 1995 (era 1) and from July 1, 1997, through June 30, 2000 (era 2). INTERVENTIONS: Inpatient and outpatient charts were reviewed for data regarding patient demographics, CD4 cell counts, viral load levels, duration of HIV seropositivity, history of opportunistic infections, and final diagnosis. RESULTS: Pneumocystis carinii pneumonia (PCP) was less common in the HAART era than in the pre-HAART era, whereas bacterial pneumonia and non-Hodgkin's lymphoma (NHL) were more common in the HAART era than in the pre-HAART era. HAART was protective against PCP (odds ratio [OR], 0.37; confidence interval [CI], 0.16 to 0.89) in a manner dependent on the CD4 cell count. Patients receiving HAART were at increased risk for the development of bacterial pneumonia (OR, 2.41; CI, 1.12 to 5.17) and NHL (OR, 15.11; CI, 3.14 to 28.32). A history of PCP indicated a risk factor for bacterial pneumonia (OR, 2.14; CI, 1.13 to 4.04). A history of cytomegalovirus infection indicated a risk factor for NHL (OR, 6.0; CI, 1.27 to 28.32). CONCLUSIONS: There have been significant changes in the spectrum of HIV-related pulmonary complications seen by our Pulmonary and Critical Care Medicine Service in the HAART era.     

Nutrition in the era of highly active antiretroviral therapy.

Despite tremendous advances in treatment, persons with human immunodeficiency virus (HIV) infection commonly experience a variety of nutritional problems, such as weight loss, fat redistribution, and obesity. We discuss basic dietary and metabolic problems as they pertain to persons with HIV infection and provide practical suggestions for their management. In all persons, changes in weight are caused by disruptions of energy balance, which can be disturbed by alterations in energy intake (effective ingestion of calories), energy expenditure (use of calories), or both. Factors that contribute to the disturbance of energy balance are discussed in the context of HIV infection. Management of weight loss and weight gain may then be directed at the affected components of energy balance. This information is intended to raise health care providers' attention to nutrition in their patients, including monitoring of weight, dietary issues, and relevant symptoms, and to encourage liaisons with experienced dietitians and exercise trainers.     

HIV1 and the gut in the era of highly active antiretroviral therapy

The gut and its gut-associated lymphoid tissue serve as a preferential site for HIV1 entry, active viral replication, reservoir, and HIV-mediated CD4 cell apoptosis. The widespread use of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in the incidence of opportunistic enteric pathogens as a consequence of immune recovery. Nonetheless, patients with advanced HIV1 disease who were recently diagnosed or have poor response to HAART can still suffer from opportunistic infections with pathogens such as Cryptosporidium, microsporidia, Isospora belli, Cyclospora cayetanensis, Mycobacterium avium complex, and cytomegalovirus, among others. This review describes the impact of HIV1 infection on gut immune function, the salient features of the most common opportunistic enteric pathogens and HIV-associated enteropathy, and the effects of immune reconstitution after introduction of HAART.     

Inpatient care of the HIV infected patient in the highly active antiretroviral therapy (HAART) era

The inpatient presentation of the HIV infected patient has changed over the years. From the early years when patients presented with accumulating opportunistic infections that led to an early demise to the HAART era with reports of dramatic decreases in opportunistic infections and improvements in life expectancy, the evolution of inpatient HIV care has been a challenge to the clinician. In the HAART era the presentation of the HIV inpatient has diversified and in many ways is more challenging than the management of the HIV inpatient in the pre-HAART era. We will discuss the changing dynamics of HIV inpatient care from socioeconomic changes to changes in the presentation and reasons for hospitalization.     

HIV infection in the era of highly active antiretroviral therapy: the Malaga Study

We analyse the characteristics of patients diagnosed with HIV infection in the highly active antiretroviral therapy era in the southeast of Spain. Data were collected on 470 HIV patients diagnosed between January 1997 and December 2002. The number of cases fell over recent years and HIV transmission was sexual in 70.5%. The mean CD4 lymphocyte count was 302.1 x 10(6)/L and the mean viral load 4.70 log(10). Diagnosis of HIV coincided with an AIDS-defining opportunistic illness in 30.6% of patients and a late diagnosis (CD4 < 200 x 10(6)/L) was made in 48.3% of patients. A late diagnosis was related to male gender (OR 2.50; 95% CI 1.20-5.12; P < 0.001) and AIDS case (OR 18.80; 95% CI 10.50-33.80; P < 0.00001). These results suggest that there has been a progressive reduction in new cases of HIV-infected patients, with the main route of transmission being sexual and that the diagnosis was late in almost half the patients.     

Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy

BACKGROUND: Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. METHODS: We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. RESULTS: Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. CONCLUSION: Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.     

Cytomegalovirus disease in the highly active antiretroviral therapy era

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in AIDS patients. Epidemiologic studies indicate that until 10 years ago, nearly one half of HIV-infected patients eventually developed CMV end-organ disease, including chorioretinitis, esophagitis, colitis, pneumonia, and central nervous system disease. Since the introduction of highly active antiretroviral therapy (HAART) this incidence has declined dramatically. Nonetheless, patients still present with CMV disease and resistance or intolerance to HAART does develop, which may give rise to a resurgence of CMV syndromes in AIDS patients. Until recently, only intravenous ganciclovir and foscarnet were available for management of CMV infection. With the advent of additional agents, clinicians now face the challenge of optimizing therapy for individual patients. This paper reviews the most common clinical syndromes caused by CMV, the treatment options, as well as an approach to diagnosing and treating antiviral resistance.     

Isosporiasis in patients with HIV infection in the highly active antiretroviral therapy era in France

BACKGROUND: Isosporiasis, a rare cause of diarrhoea among HIV-infected patients in the pre-highly active antiretroviral therapy (HAART) era, seems to be re-emerging. METHODS: A retrospective study was carried out for the period 1995-2003 in two hospitals in Paris to describe the prevalence, clinical characteristics and therapeutic outcome of isosporiasis in HIV-infected patients, and to compare the findings with those for cryptosporidiosis and microsporidiosis. RESULTS: The prevalence of isosporiasis increased from 0.4 per 1000 patients in the pre-HAART era (1995-1996) to 4.4 per 1000 patients in the HAART era (2001-2003), whereas the prevalence of cryptosporidiosis and microsporidiosis decreased. Compared with patients with either cryptosporidiosis (n=91) or microsporidiosis (n=58), patients with isosporiasis (n=28) more frequently originated from sub-Saharan Africa (72%), were more frequently female and heterosexual, and had a higher median CD4 count at diagnosis (142 cells/microL). All patients with isosporiasis presented with diarrhoea, which was severe enough to lead to hospital admission for 60% of them. Fever was uncommon (7%). All patients were treated for isosporiasis, 27 of them with cotrimoxazole. Relapse of isosporiasis occurred in six of 16 patients (38%) despite maintenance cotrimoxazole therapy and HAART. CONCLUSION: Isosporiasis in France occurs mostly in patients emigrating from sub-Saharan Africa and can induce severe diarrhoea. Relapse is common despite cotrimoxazole maintenance therapy.     

Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy

Disseminated Mycobacterium avium complex (MAC) infection is a common complication of late-stage HIV-1 infection. Since the advent of highly active antiretroviral therapy (HAART), the rate of MAC infection has declined substantially, but patients with low CD4 cell counts remain at risk. Among patients in the Johns Hopkins cohort with advanced HIV disease, the proportion developing MAC has fallen from 16% before 1996 to 4% after 1996, with a current rate of less than 1% per year. Factors associated with developing MAC include younger age, no use of HAART, and enrollment before 1996. Prophylaxis with azithromycin or clarithromycin is recommended for all patients with CD4 counts less than 50 cells/mL. Optimum treatment for disseminated MAC includes clarithromycin and ethambutol, and another investigation suggests that the addition of rifabutin might reduce mortality. Both prophylaxis and treatment of disseminated MAC can be discontinued in patients who have responded to HAART, and specific guidelines for withdrawing treatment have been published. Although HAART has altered the frequency and outcome of MAC infection, it remains an important complication of AIDS.     

Pulmonary Kaposi sarcoma in the era of highly active antiretroviral therapy

OBJECTIVE: Since the introduction of highly active antiretroviral therapy (HAART) there has been a dramatic reduction in the incidence of Kaposi sarcoma (KS) and an improvement in survival. We wished to examine whether the outcome in pulmonary KS (pKS) has also altered. METHODS: In a single-institution cohort of 1140 HIV-positive patients with KS, 305 patients were diagnosed in the HAART era (1996-2004). We examined the clinicopathological features and outcomes of these patients, of whom 25 had pKS and 280 did not. RESULTS: Patients with pKS had lower CD4 cell counts at the time of KS diagnosis (Mann-Whitney U-test P=0.005). The incidence of pKS was higher in African patients than in non-African patients in this sample (Fisher's test, P=0.001). There were no significant differences in age, gender, plasma HIV-1 viral load or prior HAART treatment at the time of KS diagnosis. Five-year overall survival in the pKS group was 49% [95% confidence interval (CI) 26-73%] as compared with 82% (95% CI 76-87%) for the non-pKS group (log rank, P<0.0001). CONCLUSION: PKS remains an ominous diagnosis in the era of HAART, with a median survival of just 1.6 years.     

HIV-related lung cancer in the era of highly active antiretroviral therapy

OBJECTIVES: To address the impact of highly active antiretroviral therapy (HAART) on the incidence and outcome of patients with HIV-related lung cancer. DESIGN AND SUBJECTS: Patients with HIV-related lung cancer were identified from a prospective HIV data base of 8400 patients diagnosed between 1986 and 2001. Patients diagnosed with HIV-related lung cancer before 1996 were in the pre-HAART cohort whereas the remainder were in the post-HAART cohort. METHODS: The incidence of HIV-related lung cancer in the pre- and post-HAART cohorts was compared with the age and sex-matched population of south east England. Clinicopathological features, treatments and outcomes were also recorded. RESULTS: The incidence of HIV-related lung cancer increased from 0.8 (95% CI 0.2-3.2)/10(5) patient-years follow-up in the pre-HAART era to 6.7 (95% CI 3.1-13.9)/10(5) patient-years follow-up in the post-HAART era. The age and sex-matched incidence of lung cancer in south east England was 0.75 (95% CI 0.63-0.87)/10(5) patient-years, suggesting that HIV-related lung cancer only occurred more frequently in the post-HAART era (relative risk 8.93, 95% CI 4.92-19.98). The patient characteristics and outcomes were similar in the pre- and post-HAART eras, although the time interval between testing HIV positive and developing HIV-related lung cancer was longer in post-HAART patients. CONCLUSION: In this study HIV-related lung cancer occurred more frequently in the post-HAART era, when compared with the HIV-negative population. Unfortunately, the outcome of these patients remains poor despite HAART.     

Intensive care of human immunodeficiency virus-infected patients during the era of highly active antiretroviral therapy

Highly active antiretroviral therapy for human immunodeficiency virus (HIV) infection has produced significant declines in morbidity and mortality from acquired immunodeficiency syndrome (AIDS). Whether this therapy has resulted in changes in epidemiology and outcomes of intensive care among HIV-infected patients is unknown. We performed chart review of all intensive care unit admissions for HIV-infected patients at San Francisco General Hospital from 1996 through 1999. There were an average of 88.5 admissions per year with 71% survival to hospital discharge. Univariate analysis demonstrated that prior highly active antiretroviral therapy (odds ratio [OR] = 1.8, p = 0.04), a non-AIDS-associated admission diagnosis (OR = 3.7, p = 0.001), a lower Acute Physiology and Chronic Health Evaluation II score (OR = 5.4, p = 0.001), and higher serum albumin (OR = 4.4, p = 0.001) predicted improved survival. Pneumocystis carinii pneumonia (OR = 0.24, p = 0.001), mechanical ventilation (OR = 0.19, p = 0.001), or a pneumothorax (OR = 0.08, p = 0.001) were associated with worse survival. In multivariate logistic regression, all variables except prior use of highly active antiretroviral therapy and pneumothorax were significant independent predictors of outcome. At our institution, overall survival for HIV-infected intensive care unit patients has improved, especially among patients receiving highly active antiretroviral therapy. These patients may have an improved survival because of effects of therapy on variables such as likelihood of non-AIDS-associated admission diagnoses and serum albumin levels.