Samuel A. Bozzette

The Care of HIV-Infected Adults in the United States

BACKGROUND AND METHODS In order to elucidate the medical care of patients with human immunodeficiency virus (HIV) infection in the United States, we randomly sampled HIV-infected adults receiving medical care in the contiguous United States at a facility other than military, prison, or emergency department facility during the first two months of 1996. We interviewed 76 percent of 4042 patients selected from among the patients receiving care from 145 providers in 28 metropolitan areas and 51 providers in 25 rural areas. RESULTS During the first two months of 1996, an estimated 231,400 HIV-infected adults (95 percent confidence interval, 162,800 to 300,000) received care. Fifty-nine percent had the acquired immunodeficiency syndrome according to the case definition of the Centers for Disease Control and Prevention, and 91 percent had CD4+ cell counts of less than 500 per cubic millimeter. Eleven percent were 50 years of age or older, 23 percent were women, 33 percent were black, and 49 percent were men who had had sex with men. Forty-six percent had incomes of less than

A Controlled Trial of Early Adjunctive Treatment with Corticosteroids for Pneumocystis carinii Pneumonia in the Acquired Immunodeficiency Syndrome

10,000 per year, 68 percent had public health insurance or no insurance, and 30 percent received care at teaching institutions. The estimated annual direct expenditures for the care of the patients seen during the first two months of 1996 were

Health-related quality of life in patients with human immunodeficiency virus infection in the United States: results from the HIV cost and services utilization study

5.1 billion; the expenditures for the estimated 335,000 HIV-infected adults seen at least as often as every six months were

Prophylaxis against Disseminated Mycobacterium avium Complex with Weekly Azithromycin, Daily Rifabutin, or Both

6.7 billion, which is about

A Randomized Trial Comparing Fluconazole with Clotrimazole Troches for the Prevention of Fungal Infections in Patients with Advanced Human Immunodeficiency Virus Infection

20,000 per patient per year. CONCLUSIONS In this national survey we found that most HIV-infected adults who were receiving medical care had advanced disease. The patient population was disproportionately male, black, and poor. Many Americans with diagnosed or undiagnosed HIV infection are not receiving medical care at least as often as every six months. The total cost of medical care for HIV-infected Americans accounts for less than 1 percent of all direct personal health expenditures in the United States.

A Randomized Trial of Three Antipneumocystis Agents in Patients with Advanced Human Immunodeficiency Virus Infection

BACKGROUND Pneumocystis carinii pneumonia remains a common cause of serious morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). The extensive lung injury that accompanies pneumocystis-associated respiratory failure and the reports of clinical benefit from the use of adjunctive corticosteroids provided the rationale for this prospective multicenter trial. METHODS A total of 333 patients with AIDS and pneumocystis pneumonia received standard treatment and were randomly assigned to receive either corticosteroids (beginning with the equivalent of 40 mg of prednisone twice daily) or no additional therapy. The primary end points in this unblinded trial were the occurrence of respiratory failure (hypoxemia ratio [partial pressure of arterial oxygen divided by fraction of inspired oxygen] less than 75, intubation, or death), death, and dose-limiting toxicity of the initial standard therapy. RESULTS Of the patients with confirmed or presumed pneumocystis pneumonia (n = 225 and n = 26, respectively), those assigned to treatment with corticosteroids had a lower cumulative risk at 31 days of respiratory failure (0.14 vs. 0.30, P = 0.004) and of death (0.11 vs. 0.23, P = 0.009), as well as a lower risk of death within 84 days (0.16 vs. 0.26, P = 0.026). The frequency of dose-limiting toxicity of the standard therapy was similar in the two treatment groups. Intention-to-treat analyses of the entire cohort confirmed these findings. Clinical benefit could not be demonstrated, however, for patients with mild disease (hypoxemia ratio, greater than 350), equivalent to a partial pressure of oxygen greater than 75 torr on room air. The patients assigned to corticosteroid treatment had an excess of localized herpetic lesions (26 percent vs. 15 percent, P = 0.04) but not of other infections or of neoplasms. CONCLUSIONS Early adjunctive treatment with corticosteroids reduces the risks of respiratory failure and death in patients with AIDS and moderate-to-severe pneumocystis pneumonia. Because the adverse effects are few, corticosteroids should be included as part of the initial treatment for persons with AIDS who have moderate-to-severe pneumocystis pneumonia.

Expenditures for the Care of HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy

PURPOSE To measure health-related quality of life among adult patients with human immunodeficiency virus (HIV) disease; to compare the health-related quality of life of adults with HIV with that of the general population and with patients with other chronic conditions; and to determine the associations of demographic variables and disease severity with health-related quality of life. SUBJECTS AND METHODS We studied 2,864 HIV-infected adults participating in the HIV Cost and Services Utilization Study, a probability sample of adults with HIV receiving health care in the contiguous United States (excluding military hospitals, prisons, or emergency rooms). A battery of 28 items covering eight domains of health (physical functioning, emotional well-being, role functioning, pain, general health perceptions, social functioning, energy, disability days) was administered. The eight domains were combined into physical and mental health summary scores. SF-36 physical functioning and emotional well-being scales were compared with the US general population and patients with other chronic diseases on a 0 to 100 scale. RESULTS Physical functioning was about the same for adults with asymptomatic HIV disease as for the US population [mean (+/- SD) of 92+/-16 versus 90+/-17) but was much worse for those with symptomatic HIV disease (76+/-28) or who met criteria for the acquired immunodeficiency syndrome (AIDS; 58+/-31). Patients with AIDS had worse physical functioning than those with other chronic diseases (epilepsy, gastroesophageal reflux disease, clinically localized prostate cancer, clinical depression, diabetes) for which comparable data were available. Emotional well-being was comparable among patients with various stages of HIV disease (asymptomatic, 62+/-9; symptomatic, 59+/-11; AIDS, 59+/-11), but was significantly worse than the general population and patients with other chronic diseases except depression. In multivariate analyses, HIV-related symptoms were strongly associated with physical and mental health, whereas race, sex, health insurance status, disease stage, and CD4 count were at most weakly associated with physical and mental health. CONCLUSIONS There is substantial morbidity associated with HIV disease in adults. The variability in health-related quality of life according to disease progression is relevant for health policy and allocation of resources, and merits the attention of clinicians who treat patients with HIV disease.

The Impact of Competing Subsistence Needs and Barriers on Access to Medical Care for Persons with Human Immunodeficiency Virus Receiving Care in the United States

BACKGROUND Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing. METHODS We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex. RESULTS In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P = 0.008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, 0.28; P<0.001) or azithromycin alone (hazard ratio, 0.53; P = 0.03). Among the patients in whom azithromycin prophylaxis was not successful, 11 percent of M. avium complex isolates were resistant to azithromycin. Dose-limiting toxic effects were more common with the two-drug combination than with azithromycin alone (hazard ratio, 1.67; P=0.03). Survival was similar in all three groups. CONCLUSIONS For protection against disseminated M. avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated.

A Placebo-Controlled Trial of Maintenance Therapy with Fluconazole after Treatment of Cryptococcal Meningitis in the Acquired Immunodeficiency Syndrome

Background Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. Methods We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. Results After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the cl...

Comparison of Atovaquone (566C80) with Trimethoprim-Sulfamethoxazole to Treat Pneumocystis carinii Pneumonia in Patients with AIDS

BACKGROUND We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). METHODS In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4+ cells per cubic millimeter received zidovudine plus one of three randomly assigned prophylactic agents, beginning with trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of intolerance. RESULTS The estimated 36-month cumulative risks of P. carinii pneumonia were 18 percent, 17 percent, and 21 percent in the trimethoprim-sulfamethoxazole, dapsone, and aerosolized-pentamidine groups, respectively (P = 0.22). The difference in risk among treatment strategies was negligible in patients entering the study with 100 or more CD4+ lymphocytes per cubic millimeter. In those entering with fewer than 100 CD4+ cells per cubic millimeter, the risk was 33 percent with aerosolized pentamidine, as compared with 19 percent with trimethoprim-sulfamethoxazole and 22 percent with dapsone (P = 0.04). The lowest failure rates occurred in patients receiving trimethoprim-sulfamethoxazole, and failures were more common with 50 mg of dapsone than with 100 mg. Toxoplasmosis developed in less than 3 percent of patients. Of the patients assigned to the two systemic therapies, only 23 percent were receiving their assigned drug and dose when they completed the study. The median survival was approximately 39 months in all three groups, and the mortality attributable to P. carinii pneumonia was only 1 percent. CONCLUSIONS In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strategies that start with trimethoprim-sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.