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Keywords:

  • femoral necrosis;
  • hip arthroplasty;
  • HIV

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Background

Although HIV-infected patients are at greater risk of presenting with ischaemic necrosis of the femoral head, there have been concerns about whether total hip arthroplasty (THA) may have worse outcomes than expected.

Methods

From the Orthopedic and Trauma Surgery database we identified all patients who had undergone THA because of ischaemic necrosis of the femoral head from January 2001 until March 2010. Patient's diagnosis of HIV infection was confirmed at the time of arthroplasty by cross-matching with the HIV unit database. For every THA in HIV-infected patients, two THAs in patients not known to be HIV-infected, with the same diagnosis of ischaemic necrosis of the femoral head and having undergone surgery over the same period, were randomly selected. THAs were compared in HIV- and non-HIV-infected patients for surgical procedure, in-patient stay and long-term prognosis.

Results

There were 18 THAs in 13 HIV-infected patients and 36 THAs in 27 non-HIV-infected patients. No significant differences were observed in the mean time spent in surgery (106 vs. 109 minutes, respectively; P = 0.66), the need for red cell transfusion (1 vs. 4, respectively; P = 0.48) or the mean duration of hospitalization (7.8 vs. 9.4 days, respectively; P = 0.48). The two groups showed similar postoperative functional results, which were maintained until the end of the follow-up period (median 3.3 years in the HIV-positive group and 5.8 years in the HIV-negative group).

Conclusion

Our study suggests that the outcome of THA in HIV-positive patients is not worse than that of HIV-negative patients, although future research on larger numbers of patients is required to confirm this.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Ischaemic necrosis of the femoral head (INFH) is not a specific nosological entity but rather the common end-result of various disorders which lead to impaired blood supply to the bone [1]. The link between HIV infection and INFH was first established in 1990 [2]. Since then, numerous studies have identified HIV infection as a risk factor for the development of this problem [3-16]. It is unclear at the moment whether this risk is a consequence of the infection itself or an adverse effect of the drugs used by HIV-infected patients [7, 8, 10].

The introduction of combined antiretroviral therapy (cART) in the late 1990s dramatically improved the prognosis of HIV-positive patients, although associated morbimortality has remained higher than that of the general population [17-19]. In addition, prolonged use of cART has given rise to new complications. Compared with the HIV-uninfected population, patients treated with cART are at greater risk of suffering illnesses traditionally associated with ageing [20], such as diabetes, cardiovascular disease, chronic kidney failure, and neurocognitive and bone disorders (osteoporosis, osteopenia and osteonecrosis).

There is scarce recent information regarding the indication of total hip arthroplasty (THA) in HIV-positive patients. The first series of cases published 8–10 years ago showed an increased risk of infection and subsequent complication of the implant [21-23]. The objective of this study was to compare THA as INFH treatment in HIV-infected patients in the highly active antiretroviral therapy (HAART) era versus HIV-uninfected patients who received an implant during the same period by comparing epidemiological and intra-operative characteristics, hospitalization time and short- and long-term prognosis between the groups.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

We retrospective reviewed all patients diagnosed with INFH in our Orthopaedic and Trauma Surgery database between January 2001 and March 2010. We designed a retrospective, controlled study, in which cases were all those patients previously identified as HIV-positive by cross-matching with the HIV unit database. We identified 83 THAs in patients not known to be HIV-infected with the same diagnosis of INFH and having undergone the same intervention over the same period. For every THA in HIV-positive patients, two THAs in these HIV-negative patients were randomly selected by a person who was not involved in the study and who did not have knowledge of the hypothesis of the study. None of the controls were subsequently identified to be HIV positive after inclusion in the study. Throughout this period, there have been no variations in the type of surgery implemented for the treatment of this condition.

All preoperative, perioperative and postoperative data were obtained by reviewing standardized clinical dates. For HIV-positive patients, we collected the following information: date of diagnosis of HIV infection, total duration and types of antiretroviral treatment received, HIV stage [Centers for Disease Control and Prevention (CDC) classification] [24] and most recent CD4 T-lymphocyte count and viral load at the time of THA.

The mean time from the onset of INFH symptoms to INFH diagnosis was calculated. The diagnosis of INFH was established by conventional radiology (anteroposterior and axial) and, in specific cases, further confirmed by magnetic resonance imaging (MRI) or Technetium-99m (99mTC) gammagraphy.

The severity of the lesions was classified according to the Ficat and Arlet radiological classification system [25]. All patients underwent preanaesthetic assessment according to American Society of Anesthesiologists (ASA) guidelines [26]

Data on duration of hospitalization, time spent in surgery, postoperative drop in haemoglobin level and need for transfusion were collected. Preoperative and postoperative function was calculated according to the Merlé d'Aubigné and Postel scale [27] For the purposes of the study, we assessed the following postoperative complications: infection (pulmonary, urinary, surgical wound, joint, bone, septicaemia or fever of unknown origin), haemorrhage, surgical wound dehiscence, thromboembolic complications, cardiac complications (myocardial infarction, arrhythmia or heart failure), respiratory complications (atelectasia or pneumonia), renal complications and luxation or displacement of the implant.

Short-term (first year) and long-term (subsequent years) follow-up data obtained during regular visit check-ups (first visit 1 month after surgery, second visit 3 months after surgery, third visit 6 months after surgery, and then yearly) were reviewed for the purposes of the study, and clinically meaningful data were recorded for analysis.

Quantitative variables were described by the mean and standard deviation (SD) and the median and interquartile range (25th; 75th percentiles). Qualitative variables were described by absolute frequencies and percentages. The Mann–Whitney U-test and Fisher's exact test were used for statistical analyses in order to compare baseline homogeneity between groups. In order to evaluate the time to diagnosis, surgical duration, duration of hospitalization, evolution of haemoglobin and Merlé d'Aubigné functional scale, means and their 95% confidence intervals (CIs) were used. Odds ratios (ORs) and their 95% CIs were used to estimate risk for the Ficat and Arlet radiological classification system and the need for blood transfusion. All inferential analyses were performed by means of a generalized estimating equation (GEE) methodology using an unstructured matrix to account for intrasubject correlations. Baseline pretreatment values were used as a covariate for the evolution of values. Because this is a comparative observational study without a sample size calculation, all P-values were considered for descriptive purposes. All analyses were performed with spss v18 for Windows (SPSS Inc., Chicago, IL) and we considered a Type I error = 0.05.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Characteristics of the patients

A total of 18 THAs indicated for the treatment of INFH were identified in 13 HIV-positive patients (11 men and two women). Risk factors for HIV infection included sexual contact (n = 8; 62%), injecting drug use (IDU) (n = 4; 31%) and others (n = 1; 8%). At the time of HIV diagnosis, 67% of all patients were in stage C3, 11% in stage B3 and 22% in stage A2. The average duration of HIV infection prior to INFH diagnosis was 10 ± 6 years. The mean (± SD) duration of antiretroviral treatment at the time of INFH diagnosis was 9 ± 5 years. The most recent viral load within the 3 months prior to the intervention was <50 copies/ml in all patients, except for one case (1250 HIV-1 RNA copies/ml). The most recent CD4 T-lymphocyte count within the 3-month period prior to surgical intervention was (mean ± SD 434 ± 256 cells/μl (21 ± 10%). Patients had received treatment with a protease inhibitor (PI) for a mean (± SD) of 3.9 ± 2.7 years and with a nucleoside reverse transcriptase inhibitor (NRTI) for 8.1 ± 3.9 years.

The control group consisted of 36 THAs in 27 HIV-negative individuals (21 men and six women). The mean (± SD) age was 44.3 ± 9.1 years in the HIV-infected group and 47.0 ± 11.1 years in the control group (P = 0.45). The right/left hip ratio was 12/6 in the HIV-infected group and 15/17 in the control group (P = 0.15). The mean (± SD) duration of the follow-up period was 3.3 ± 2.5 years in the HIV-infected group and 5.5 ± 5.9 years in the control group (P = 0.08). All patients included in the study had at least 1 year of follow-up.

Table 1 shows comorbidities in each group. No differences were found with regard to body mass index or in the preanaesthetic assessment between the two groups. The frequency of chronic coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) was significantly higher in the HIV-positive group. HIV-positive patients more often had antecedents of IDU and coinfection with HBV/HCV. In general, patients from the HIV-negative group presented with more comorbidities than those from the HIV-positive group.

Table 1. Presentation of ischaemic femoral head necrosis (IFHN) and comorbidities in HIV-positive and HIV-negative patients
 HIV-negative patientsHIV-positive patientsP
  1. Results are mean (SD) and median [25; 75th percentiles] for body mass index, and absolute frequencies and percentages for the other variables. The Mann-Whitney U-test or Fisher's exact test was performed.

  2. ASA, American Society of Anesthesiologists.

Number of patients2713 
Body mass index25.4 (4.5)25.7 (6.7)0.94
25.1 [23; 28.1]25 [22.2; 28.7]
Preoperative ASAASA = 15 (19%)1 (8%)0.82
ASA = 214 (52%)9 (69%)
ASA = 38 (30%)2 (15%)
ASA = 40 (0%)1 (8%)
Other comorbidityHepatitis C or B0 (0%)4 (31%)0.01
Hypertension7 (26%)0 (0%)0.07
Dyslipaemia5 (19%)2 (15%)1
Diabetes mellitus2 (7%)1 (8%)1
Previous corticosteroid therapy9 (33%)2 (15%)0.29
Chronic kidney disease6 (22%)0 (0%)0.15
Chronic obstructive pulmonary disease10 (37%)3 (23%)0.48
Ischaemic coronary disease2 (7%)1 (8%)1
Alcohol abuse3 (11%)4 (31%)0.29
Tobacco smoking17 (63%)10 (77%)0.19
Other systemic illnesses9 (33%)2 (15%)0.48

Characteristics of INFH

No significant differences were found in the time from the onset of initial symptoms to the diagnosis of INFH or in the INFH radiological state at the time of diagnosis (Table 2). Of the 18 THAs in the HIV-positive group, at the time of diagnosis, three were found to be in state I–II (17%) and 15 in state III–IV (83%). In the control group, eight were found to be in state I–II (22%) and 28 in state III–IV (78%) (P = 0.70).

Table 2. Characteristics of surgery and total hip arthroplasty (THA) outcomes in HIV-positive and HIV-negative patients
 HIV-negative patientsHIV-positive patientsEstimated differences (or OR) and 95% CIP
  1. Estimated means (and differences between groups) or odds ratio (OR) were obtained by generalized estimating equation (GEE) models using the number of treated hips in order to considerate intra-subject correlations.

  2. CI, confidence interval.

  3. a

    Adjusted by baseline values as covariable.

Number of THAs3618  
Time from appearance of initial symptoms to diagnosis (months)19.1 (7.7; 30.5)14.9 (8.6; 21.2)4.2 (−8.8; 17.2)0.53
Radiological stateState I–II831.41 (0.24; 8.18)0.70
State III–IV28151
Duration of surgery109.1 min (101.8; 116.4)106.1 min (94.9; 117.3)3 (−10.4; 16.3)0.66
Days of hospitalization9.4 days (7.2; 11.7)7.8 days (6.9; 8.6)1.7 (−0.7; 4)0.16
Postoperative drop in haemoglobin (g/dl) 3.0 Hg/dL (2.7; 3.3)2.7 Hg/dL (2; 3.5)0.2 (−0.6; 1)0.56
Need for blood transfusion410.46 (0.05; 4.14)0.48
Functional resultsMerlé d'Aubigné: preoperative10.9 (9.7; 12.0)10.9 (9.4; 12.2)0.05 (−1.8; 1.9)0.96
Merlé d'Aubigné: postoperative17.4 (16.8; 18.0)16.7 (15.5; 17.8)0.73 (−0.6; 2.1)0.28
Merle d'Aubigné: change 6.5 (6; 7.1)5.9 (4.8; 6.9)0.46 (0.05; 4.14)0.26
ComplicationsIntrahospital (n)310.65 (0.06; 6.99)0.72
First year post-intervention (n)112.02 (0.13; 32.73)0.62
After first year (n)112.15 (0.13; 34,63)0.59

MRI was performed in five HIV-positive patients (38%) and in 18 HIV-negative patients (67%) (P = 0.09) Bone gammagraphy with 99mTC was carried out in five (39%) and 13 (53%) HIV-positive and HIV-negative patients, respectively (P = 0.29). Twenty-three per cent of HIV-positive patients and 33% of HIV-negative patients underwent both diagnostic tests (P = 0.39).

There were no significant differences in the bilaterality of osteonecrosis: 61% of the patients in the HIV-infected group and 55% of the control group had INFH in both hips (P = 0.49). We did, however, find significant differences in the involvement of other joints: 44% of HIV-positive patients had been diagnosed with osteonecrosis in areas other than the hip (mainly the humeral head, femoral condyli, tibia and talus). In contrast, only 7% of HIV-negative patients presented osteonecrosis in areas other than the hip (P = 0.008).

Comparisons of surgical and postoperative data

In all cases, a noncemented, total hip prosthesis was implanted. All interventions in both groups were performed by the same team of surgeons.

During the surgical procedure and hospitalization, no significant differences were observed in the time spent in surgery, the postoperative drop in haemoglobin level, the need for red cell transfusion or the duration of hospitalization (Table 2). The two groups presented similar postoperative functional results, which were maintained until the end of the follow-up period. (Table 2).

One HIV-positive patient presented with fever of unknown source on the third day following the procedure, which resolved spontaneously. In the control group, one patient with a history of alpha-antitrypsin deficit died on the 18th day following the procedure as a result of progressive respiratory failure, and two additional patients presented with minor complications: one patient developed immediate postoperative fever with wound exudation, and the other patient presented with partial dehiscence of the surgical wound and bleeding. Both complications resolved without the need for re-intervention.

During follow-up over the course of the first year, one patient in each group complained of persistent joint pain that persisted until the end of the follow-up period.

During long-term follow-up, 4 years after the intervention, a patient in the HIV-positive group presented with septic knee arthritis which required supracondylar amputation of the lower limb. In the control group, 5 years after the intervention and following a accidental fall, a patient presented with a periprosthetic fracture which required surgical intervention and replacement of the prosthesis.

In no cases were statistically significant differences found in the number of postoperative complications or the number of complications during short- and long-term follow-up.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

A THA implant is clearly indicated for advanced INFH. It has a very good postoperative functional outcome although existing data in HIV-infected patients are scarce and controversial. In the pre-HAART era, HIV-infected individuals were considered poor candidates for surgery because of its poor prognosis and concerns about potential HIV transmission to healthcare staff. The first case series of THA for INFH in HIV-positive patients was published in the early 21st Century and showed higher rates of subsequent infection and prosthesis complications than in the rest of the population. In 2003, a study by Parvizi et al. was published of 21 HIV-infected patients who underwent total hip replacement surgery between 1979 and 1998; all the patients died within 10 years of follow-up, with 13 re-interventions and six cases of deep infection [22]. A very similar study, carried out by Christopher Lehman et al. in 29 HIV-positive patients who underwent surgery between 1983 and 1995, also showed that this poor prognosis was even worse in patients with IDU antecedents [21].

More recent studies in the HAART era, however, have revealed lower infection rates in HIV-positive patients, but none of them compared the results with those for non-HIV-infected patients [28-33]. In 2005, Craig Mahoney et al. reported their results for a group of 40 HIV-infected patients in whom acute infection rates in the immediate postoperative stage had been lower than expected [28]. In 2008, Haberman et al. reported a series of 55 cases of THA in HIV-positive individuals; postoperative complications appeared mainly in patients with a difficult social background [29]. Also in 2008, Bahebeck et al. carried out a prospective study in the hospital of Yaoundé, Cameroon, in HIV-positive patients with CD4 counts >500 cells/μl without HAART and those with CD4 counts <500 cells/μl with HAART who underwent any traumatological intervention. In this study, postsurgical infection rates in HIV-infected patients were similar to those seen in non-HIV-infected patients, but HIV-infected patients need extended antibiotic prophylaxis [30].

INFH is a relatively infrequent THA indication [34]. According to the literature, 70% of all cases of necrosis of the femoral head are bilateral [35] and some authors even claim that these are always bilateral, although not always symptomatic. In our study, 61% of patients in the HIV-positive group and 55% of patients in the control group had been diagnosed with bilateral necrosis. We did, however, find differences between the two groups in the involvement of other joints. HIV-infected patients had been more frequently diagnosed with osteonecrosis in areas other than the hip, such as the humeral head, femoral condyle or tibia and talus.

Dudkiewicz et al. established that the aetiology of INFH did not affect initial THA results [36]. However, in cases in which INFH was induced by corticoid treatment, the longevity of the implant appeared more limited.

In our study we found that there were no significant differences in the delay in INFH diagnosis, time spent in surgery, duration of hospitalitzation or the functional outcome of arthroplasty. There were no significant differences in the number of complications or their severity.

Some authors recommend using antibiotic-loaded bone cement in patients with concomitant diseases which may predispose them to infection [37]. In our study, however, none of the prostheses was cemented. In all types of patient, it is advisable to always ensure the absence of any concomitant septic focus (e.g. dental, urinary or cutaneous). Similarly, the optimal time for surgery should be selected in accordance with the health state of the patient [38].

The main limitation of this study is the rather low number of HIV-infected patients included, despite our hospital being one of the biggest centres delivering HIV care in Spain. Although the incidence of INFH is higher in HIV-infected patients than in non-HIV-infected patients, the incidence remains low (0.65 cases per 100 person-years) [3]. In addition, only a few HIV-infected patients with INFH are symptomatic and a substantial proportion of them are treated conservatively for years before surgery. When the decision is made to perform surgery, there may be other conservative surgical options before a THA is indicated. Finally, we admit that some HIV-infected patients from our hospital with a surgical indication for THA had this surgery carried out in other centres. All these factors explain the relatively low number of HIV-infected patients with this intervention despite an extensive and accurate search of the hospital database. Given this low incidence of INFH and the reduced number of HIV-infected patients with this disease, this limitation is not easy to solve. Although a follow-up time of 4 or 5 years is sufficient to establish the functional evolution of a hip replacement and the occurrence of major complications, a time of longer than 4–5 years could provide additional data on the potential development of very long-term complications, although this seems unlikely.

In conclusion, the present study shows that THA for INFH in HIV-positive patients can produce similar, good results as in HIV-negative patients. With a mean follow-up time of 4 years, no complications inherent to THA implantation, whether in the early or late stages, were detected. Our study suggests that the outcome of THA in HIV-positive patients is not worse than that in HIV-negative patients, although future research on larger numbers of patients is required to confirm this.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
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