Table of Contents

• Symptomatic Bone Disorders in HIV-Infected Patients: Incidence in the Aquitaine Cohort (1999-2002)
• Blood and Body Fluid Exposure Risks Among Health Care Workers: Results From the Duke Health and Safety Surveillance System
• Hepatitis C Virus Coinfection Increases Mortality in HIV-Infected Patients in the Highly Active Antiretroviral Therapy Era: Data From the HIV Atlanta VA Cohort Study
• Effect of Highly Active Antiretroviral Therapy (HAART) on Pharmacokinetics and Pharmacodynamics of Doxorubicin in Patients With HIV-Associated Non-Hodgkin's Lymphoma

Symptomatic Bone Disorders in HIV-Infected Patients: Incidence in the Aquitaine Cohort (1999-2002)

Martin K, Lawson-Ayayi S, Miremont-Salame G, et al.

Background: Since the inception of highly active antiretroviral therapy (HAART), mortality among HIV-infected patients has decreased, but this has been accompanied by the appearance of several complications.

Objectives: To estimate the incidence of symptomatic bone disorders in HIV-infected patients of the Aquitaine cohort (from southwest France) for the period 1999-2002, and to describe cases.

Methods: We retrospectively studied the records of 2,700 patients of the Aquitaine cohort, which was derived from a hospital-based surveillance system of HIV infection in France. All cases of symptomatic bone disorders diagnosed from 1 January 1999 to 30 June 2002 were reviewed.

Results: Fourteen cases of bone disorders were diagnosed; eight cases of aseptic osteonecrosis and six cases of severe osteoporosis, representing incidences of 0.3/1,000 patient-years [95 percent confidence interval (CI): 0.14-0.62] and 0.22/1,000 patient-years (95 percent CI: 0.09-0.52), respectively. All patients with aseptic osteonecrosis were male, while all but one with osteoporosis were female. The ages of patients ranged from 36 to 54 years for osteonecrosis and from 39 to 50 for severe osteoporosis. At the time of clinical diagnosis, all patients were treated with nucleoside reverse transcriptase inhibitors (duration of treatment ranging from 19 to 123 months for osteonecrosis and from 46 to 132 months for severe osteoporosis). Ten patients were treated with nonnucleoside reverse transcriptase inhibitors [duration of treatment ranging from six to 31 months for osteonecrosis (n=6) and from four to 29 months for severe osteoporosis (n=4)]. Thirteen patients were treated with protease inhibitors [duration of treatment ranging from 12 to 62 months for osteonecrosis (n=8) and from 3 to 44 months for severe osteoporosis (n=5)]. All osteonecrosis and five osteoporosis patients had at least one known risk factor or comorbidity associated with the bone disorder occurrence.

Conclusions: In our study, the etiology of clinical bone disorders seemed to be multifactorial, as almost all the patients had at least one possible risk factor in addition to HAART exposure. [HIV Med 2004;5(6):421-426.]

Blood and Body Fluid Exposure Risks Among Health Care Workers: Results From the Duke Health and Safety Surveillance System

Dement JM, Epling C, Ostbye T, et al.

Background: Healthcare workers (HCWs) are at risk of exposure to human blood and body fluids (BBF). Needlestick injuries and splashes place HCWs at risk for numerous blood-borne infections, including human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV). Utilizing a new comprehensive occupational health surveillance system, the objective of this research was to better define the BBF exposure risk and risk factors among employees of a large tertiary medical center.

Methods: A population of 24,425 HCWs employed in jobs with potential BBF exposure was followed for BBF exposure events from 1998 to 2002. BBF exposure rates were calculated for strata defined by age, race, gender, occupation, work location, and duration of employment. Poisson regression was used for detailed analyses of risk factors for BBF exposure.

Results: The study population reported 2,730 BBF exposures during the study period, resulting in an overall annual rate of 5.5 events/100 FTEs and a rate of 3.9 for percutaneous exposures. Higher rates were observed for males, persons employed less than four years, Hispanic employees, and persons less than 45 years of age. Much higher rates were observed for house staff, nurse anesthetists, inpatient nurses, phlebotomists, and surgical/operating room technicians. Poisson regression results strengthened and extended results from stratified analyses. Rates of percutaneous exposures from hollow needles were found to decrease over the study period; however, exposure rates from suture needles appear to be increasing.

Conclusion: While continued training efforts need to be directed toward new HCWs, our data also suggest that employees who have been in their job one to four years continue to be at higher risk of BBF exposures. This research also points to the need for better safety devices/products and work practices to reduce suture-related injuries. [Am J Ind Med 2004;46:637-648.]

Hepatitis C Virus Coinfection Increases Mortality in HIV-Infected Patients in the Highly Active Antiretroviral Therapy Era: Data From the HIV Atlanta VA Cohort Study

Anderson KB, Guest JL, Rimland D.

Background: We compared survival among patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) with that among patients infected solely with HIV.

Methods: Descriptive, bivariate, and survival analyses were conducted using data for all HIV-positive patients who were seen during the period of January 1997 through May 2001 in the HIV Atlanta VA Cohort Study (HAVACS) and who had been tested for HCV antibody since 1992 (n=970).

Results: The prevalence of HCV coinfection was 31.6 percent, and coinfected patients were significantly more likely to be older, black, and injection drug users. In multivariate analysis, the duration of survival from the time of diagnosis of acquired immunodeficiency syndrome (AIDS) was significantly shortened for HIV/HCV-coinfected patients (hazard ratio [HR]: 1.84; 95 percent confidence interval [CI]: 1.09-3.10), as was time from HIV diagnosis to death (HR: 2.47; 95 percent CI: 1.26-4.82). Recovery of CD4+ cell count from the time of initiation of HAART did not differ significantly by coinfection status.

Conclusions: HCV coinfection is common in this HIV-infected population and negatively affects survival from the time of both HIV and AIDS diagnoses, although this is apparently not associated with a difference in CD4+ cell recovery while receiving HAART. These findings differ from those of a previous study that was conducted in this cohort in the pre-HAART era, which found no association between HIV/HCV coinfection and HIV disease progression. [Clin Infect Dis 2004;39(10):1507-13.]

Effect of Highly Active Antiretroviral Therapy (HAART) on Pharmacokinetics and Pharmacodynamics of Doxorubicin in Patients With HIV-Associated Non-Hodgkin's Lymphoma

Toffoli G, Corona G, Cattarossi G, et al.

Background: We demonstrated that highly active antiretroviral therapy (HAART) increases the toxic effect of cyclophosphamide, vincristine, doxorubicin (DOX), and prednisone (CHOP) in HIV patients with non-Hodgkin's lymphoma (NHL). To ascertain the cause of increased toxicity, we investigated the pharmacokinetics of DOX in HIV patients with NHL treated with CHOP with and without HAART.

Methods: Complete pharmacokinetics and pharmacodynamic analysis was determined in 19 patients during 38 cycles of chemotherapy: 19 cycles with CHOP and 19 CHOP + HAART in a crossover-designed study. HAART included protease inhibitors indinavir (IDV) in nine patients, saquinavir (SQV) hard gel in six patients, and nelfinavir (NFV) in four patients.

Results: No significant effects of HAART on pharmacokinetics parameters of DOX were observed. Similarly, no differential effect on DOX pharmacokinetics among IDV, SQV, and NFV was evidenced. Significant associations (P = 0.012) were observed between DOX AUC (0-infinity) (area under the concentration curve) and G3-G4 WHO hematologic toxicity in patients treated with CHOP alone, but not in those treated with CHOP + HAART (P = not significant).

Conclusion: We demonstrated that HAART therapy has no significant effect on DOX pharmacokinetics. DOX AUC appears to be a predictor of toxicity only in patients treated with CHOP alone. Other factors besides DOX plasma levels are detrimental for toxicity after CHOP + HAART. Therefore, pharmacodynamic interactions between HAART and DOX should be considered. [Ann Oncol 2004;15(12):1805-1809.]