Portal de Periódicos da CAPES

Avascular necrosis of the bone in HIV-infected patients: incidence and associated factors

2002; Lippincott Williams & Wilkins; Volume: 16; Issue: 3 Linguagem: Inglês

10.1097/00002030-200202150-00021

1473-5571

Félix Gutiérrez, Sergio Padilla, Enrique Ortega, José A. Torres Garcia, Juan Flores, Carlos Galera, Esperanza Merino, Mar Masiá, P Roig, Vicente Boix, Joaquín Portilla, José Marı́a Cuadrado, J Gregori, José I. López,

Orthopedic Infections and Treatments

All cases of avascular necrosis of the bone (AVN) diagnosed in HIV-infected patients from 1990 to 2000 in two Spanish provinces were examined. The frequency of AVN has increased since 1996, reaching a high of 1.19 cases per 1000 HIV-infected patients in the year 2000. AVN was predominantly seen in patients with advanced HIV disease and 86% had at least one risk factor previously associated with AVN. Ninety-one percent had had previous exposure to antiretroviral drugs and 70% had been given HAART before developing AVN. Avascular necrosis of the bone (AVN), which is also referred to as osteonecrosis, is being increasingly reported in HIV-infected patients [1–8]. Whether AVN is an HIV-related complication, an adverse effect of antiretroviral therapy or is caused by another HIV-associated condition or therapy is unknown. Recent reports have associated AVN with metabolic complications of protease inhibitor (PI) therapy (i.e. hyperlipidaemia) [4,9,10] and with immunological and virological improvements resulting from highly active antiretroviral therapy (HAART) [5]. A link between AVN of the hip and the use of megestrol acetate has also been suggested [11]. Many of the previous studies on this issue have consisted of case reports or small series of cases in patients receiving HAART, and very few have provided data regarding frequency and patient characteristics. This study aims to describe the frequency and associated factors of AVN in a large Spanish cohort of HIV-infected patients before and after the HAART era. We reviewed all cases of AVN diagnosed in HIV-infected patients from 1990 to 2000 in the Valencian–Murcian HIV clinical cohort. This clinical cohort consists of clinical and demographic data from 19 HIV clinics in two provinces in south-eastern Spain. These clinics have provided medical care for a population of more than 10 000 HIV-infected patients since the beginning of the AIDS epidemic. Cases were identified from the records of HIV clinics by physicians caring for HIV-infected patients. A case was defined as having AVN when there was both a clinical and a radiographic diagnosis. A retrospective chart review was performed, and data were extracted using a standardized data collection sheet. The potential risk factors previously associated with AVN evaluated in this study included: a previous history of local trauma; the use of corticosteroids; alcohol abuse; the presence of anticardiolipin or antiphospholipid antibodies; a previous diagnosis of deep venous thrombosis or other hypercoagulable state; hyperlipaemia; and the use of megestrol acetate. To estimate trends in frequency, the annual incidence rates of AVN in AIDS patients were obtained from 1993 to 2000 using the total number of AIDS cases reported from all clinics to the Spanish National Registry of AIDS as the denominator. Incidence rates of AVN in HIV-infected patients were obtained for the years 1996, 1998, and 2000 in the Valencian community using the total number of HIV cases cared for in the clinics of this province (1996: 5705 patients; 1998: 6028 patients; 2000: 7572 patients) as the denominator. From 1990 to 2000, a total of 23 symptomatic cases of AVN were identified. There was a constant increase in the number of cases throughout the study period. Only four cases were diagnosed before 1996, nine additional cases from 1997 to 1999 and 10 cases in 2000. There was a marked increase in the annual incidence of AVN in AIDS patients since 1997 (1993: 3.7/1000 patients; 1994: 0/1000 patients; 1995: 1.6/1000 patients; 1996: 1.6/1000 patients; 1997: 4.1/1000 patients; 1998: 7.9/1000 patients; 1999: 12.9/1000 patients; 2000: 57.8/1000 patients). The frequency of AVN increased from 1.6 per 1000 AIDS patients during 1993–1996 to 14 per 1000 patients in 1997–2000 (P < 0.001 by chi-squared test). There was also a notable increase in the incidence of AVN in HIV-infected patients in the Valencian community from 0.18 per 1000 HIV-infected patients in 1996 to 1.19 per 1000 patients in 2000 (P = 0.0023 by chi-squared test). Demographic characteristics are shown in Table 1. Twenty-one of the 23 cases (91%) had had previous exposure to antiretroviral drugs. Sixteen out of 23 patients (70%) had been given HAART before developing AVN. At the time of diagnosis, 19 patients (83%) were receiving antiretroviral therapy with nucleoside analogue reverse transcriptase inhibitors, 13 (56%) were on treatment with PI, and three patients (13%) were on treatment with non-nucleoside analogue reverse transcriptase inhibitors as part of HAART regimens. Seven of the 23 patients (30%) had never received either PI or non-nucleoside analogue reverse transcriptase inhibitors before developing AVN. The median time from initiation of antiretroviral therapy to the diagnosis of AVN was 24 months (range 4 months to 8.5 years).Table 1: Demographic characteristics of 23 HIV-infected patients with avascular necrosis. Three patients (13%) had cholesterol levels higher than 240 mg/dl, and five had triglyceride levels greater than 200 mg/dl, but only one case had a cholesterol level greater than 300 mg/dl and another had a fasting triglyceride level higher than 300 mg/dl. Only two patients had clinical features consistent with lipodystrophy at diagnosis of AVN. Twenty out of 23 cases (86%) had at least one identifiable risk factor previously associated with AVN in HIV-negative individuals, and in 13 cases (57%) there were more than one of these predisposing factors (Table 1). Three out of 23 patients (14%) did not have any potential risk factor for developing AVN. All were on HAART and had a plasma HIV viral load below 500 copies/ml at diagnosis of AVN. This study confirmed that AVN is an emerging complication of HIV infection. In the year 2000, the incidence reached a high of 1.19 cases per 1000 patients, which is 29-fold higher than the population-based incidence [12]. An increasing trend in the incidence of new cases of AVN in HIV-infected patients has also been observed in some institutions in the USA [7,8], and a staggeringly high prevalence of asymptomatic AVN of the hip has recently been reported [13]. In the present study, the sharp increase in the frequency of AVN was observed since 1997, soon after PI were released in Spain and HAART became the standard of care for HIV-infected patients. However, HAART can not be the only explanation for AVN because 30% of our cases had not received HAART. Furthermore, our series do not suggest that either hyperlipidaemia or lipodystrophy are linked to AVN. In fact, only two of our patients had concurrent lipodystrophy, and although seven others had mild hypercholesterolaemia or hypertriglyceridaemia, none of them had marked hyperlipidaemia. Félix Gutiérreza Sergio Padillaa Enrique Ortegab J. Adolfo Garcíac Juan Floresd Carlos Galerae Esperanza Merinof Mar Masiáa Pablo Roigg Vicente Boixf Joaquín Portillaf José M. Cuadradog Joan Gregorih José Lopezi