Femoral Neck Fractures in HIV-Positive Patients: Analysis of 10 Years Short-Term Post-operative Complications

Introduction: Aging and effect of antiretroviral therapy on bone mass could increase the risk of femoral neck fractures (FNF) in HIV patient. The aim of this study was specifically to determine whether intracapsular FNF in HIV-positive patients are more prone to short-term post-operative complications than similar fractures occurring in HIVnegative patients. Materials and methods: A group of 25 HIV-positive patients with intracapsular FNF were enrolled and matched to HIV-negative patient with similar fractures according to gender, age, a modified Charlson Comorbidity Index (CCI), fracture classification, surgical treatment and time interval between fracture event and surgery. For each group, length of stay, surgical time, early clinical outcomes and short-term surgical and medical complications were compared to determine the impact on the early outcome. Results: At the time of the fracture occurrence, 56% of HIVpositive patients were on antiretroviral therapy and 12% started with therapy in the perioperative period. At three months follow-up, there were no statistically significant differences between the two study groups in length of stay, Harris hip score and total number of early complications. However, a statistically significant increase in urinary tract infections and longer surgical time using hip sliding screw fixation were seen in the HIV-positive group. The poorest post-operative result was seen in a patient who failed to adequately adhere to the HIV therapy protocol. Conclusions: This study failed to show any statistically significant increase in short-term complications or worse clinical outcomes for intracapsular FNF in HIV-positive patients compared to HIV-negative patients to recommend their treatment in dedicated centres.


INTRODUCTION
Femoral neck fractures (FNF) are an increasing problem. An improvement in living standards and the greater effectiveness of treatments for chronic diseases has resulted in an older mean age in world population with a welldocumented consequent higher incidence of femoral neck fractures 1 . Likewise, life expectancy in HIV-positive patients has also increased significantly, due to successful medical management with Highly Active Antiretroviral Therapy (HAART) 2 . Whilst HAART therapy is effective in treating HIV infection it also plays an important role in suppressing osteoclastogenesis, inhibiting osteoblast differentiation and causing a significant bone mass index (BMI) reduction 3,4 . In addition, HIV infection is more common in patients with methadone/opioid addiction and Hepatitis C virus (HCV), both conditions adversely affecting bone quality 5 .
Many clinical studies have been published documenting the clinical outcomes of orthopaedic surgeries in HIV-positive patients often with controversial results. Some authors suggest that HIV-positive patients have higher rates of wound infection and non-union after internal fixation than HIV-negative patients 6,7 . Other studies have suggested that HIV infection does not correlate with a higher rate of postoperative infection and fracture non-union [8][9][10] .
The purpose of this study was to determine specifically whether intracapsular femoral neck fractures in HIV-positive patients are more prone to short-term post-operative complications than similar fractures occurring in HIV-

Femoral Neck Fractures in HIV-Positive Patients: Analysis of 10 Years Short-Term Post-operative Complications
negative patients and consequently best addressed in a multispecialist hospital with a dedicated infectious diseases unit. classifies co-morbid conditions predicting mortality risk with a score ranging from 1 to 6 for 19 pathological conditions (including HIV-positivity). The CCI is an easily applicable method for the pre-operative assessment of comorbidities even in patients undergoing orthopaedic surgery 11 . In our matching process, the HIV-positivity score (max 6 points) in CCI index was not included to achieve a homogeneous distribution of comorbidities between the two groups. In HIV-positive group, patients were assessed for: viral load, CD4 cells count and the use of HAART within three months prior to surgery. A viral load less than 50 copies/ml was considered undetectable and CD4 count lower than 200 cells/l as a severe immunodeficiency 12 . In both groups, length of stay, percentage of patients operated on within 48 hours of fracture, surgical time, 3-month postoperative Harris Hip Score and presence of short-term complications was assessed. These data have been routinely collected during the ordinary three months rehabilitation follow-up and orthopaedic visit, as institute protocol. Shortterm complications (within three months of index surgery) were divided into surgical and medical groups according to Carpintero et al 13 . We considered post-operative anaemia, defined as patients requiring a post-operative blood transfusion, and urinary tract infections (UTIs), defined as urine culture colony counts >100000 colony-forming units per millilitre (CFU/mL), as medical complications.

MATERIALS AND METHODS
Haemoglobin value <8g/dl was used as a decision threshold in all patients undergoing red blood cell transfusion. Surgical complications included post-operative mortality within three months of index surgery, any revision surgery, hip pain (Numeric Rating Scale value: ranging from 0 to 10), limping (positive Trendelenburg sign) and limb length discrepancy (more than 1.5cm). All surgical wound problems including aseptic dehiscence, hypoesthesia and superficial or deep infections were also considered surgical complications.
Statistical analysis was performed using the Odds Ratio with a 95% confidence interval for systemic and local postoperative complications immediately after surgery and at three months. Statistical analyses were performed using MedCalc for Windows, version 15.0 [MedCalc Software, Ostend, Belgium]. The paired t test and chi-squared test were performed for comparisons and the significance level was taken as P<0.05 for all values.

RESULTS
FNF in the HIV-positive group occurred in a younger population (mean 57 years) compared to the control group (mean 63 years); however this value did not have a statistical significance (P-Value=0.13). In both groups, there were 17 (68%) B-type proximal femoral fractures and 8 (32%) Atype fractures according to AO classification and 20 (82%) patients in both the groups were treated within 48 hours of the fracture occurrence (Table I).
In group A, the mean CD4+ count at the time of surgery was 536 (STD +246) with an undetectable viremia in 18 (72%) patients (mean<37 copies/ml) and 14 (56%) patients, despite different antiretroviral protocols, were already on HAART pre-operatively while three (12%) started HIV antiretroviral therapy in the perioperative period. Only two cases (8%) of high-energy trauma were seen in the HIV-positive group compared to eight (32%) cases in the control group, showing a statistical significant difference (P-Value = 0.035).
The mean length of stay was 11.6 days (STD +8.8) for patients in Group A and 10.30 days (STD +6.12) for those in Group B. In both the groups all hemiarthroplasty and total

Total rate of complications HIV+ (Group A) % (n) HIV-(Group B) % (n)
ODD RATIO IC 95% P-Value for peritrochanteric nail. There were no statistically significant differences in surgical time for the different surgical procedures except for hip sliding screw procedure with a significant longer surgical time in Group A (p<0.01) ( Table II).
The rate of surgical complications was the same in the two groups with no statistical differences (Table III). Mortality within three post-operative months occurred in three patients; of these two patients were HIV-negative and one HIV-positive. In each case the cause was secondary to preexisting co-morbidities unrelated to the femoral fracture (p=0.55). Three patients (12%) in Group A and one patient (4%) in Group B underwent revision surgery because of implant related problems (p=0.30).
At three months post-operative according to Carpintero classification there were no statistical significant differences in post-operative complication except for both superficial surgical site infections and UTIs.  (Table II). No statistical difference (p=0.08) was found in the occurrence of post-operative anaemia despite a higher number of patients requiring blood transfusion in Group A (12) compared to Group B (six). There was a significant increase in the number of HIVpositive patients developing post-operative urinary tract infection (seven, 28%) compared to HIV-negative patients (one, 4%) (p=0.021) (Table III). We consequently assessed the immunological status of these seven HIV-positive patients who had developed urinary tract infection. One patient was HIV treatment naive with a viremia >20000 and a CD4 + count of less than 200/mcl, four patients had a T-Helper lymphocyte count <350/mcl with an undetectable viral load and the one had a CD4 + <500/mcl and a viral load >50.  17 . In our study, despite no statistical significance between the two groups in term of age, FNF occurred in a younger population (mean 57 years) compared to the control group (mean 63 years) in accordance with the epidemiological data on fractures occurrence in HIV-positive patients reported in the literature 18,19 . Likewise we observed a higher statistical significant incidence of low energy trauma in HIV-positive population and we hypothesise a poorer bone quality as a possible explanation for these two findings 5 . In our study 56% of the patients in HIV-positive group were already on HAART and further 12% started HIV antiretroviral therapy during the perioperative period. However, because both a nothomogeneous antiretroviral therapy protocol in term of doses, length of assumptions, and the relative small sample size, we could not perform any statistical analysis for significant correlation among HAART therapy, trauma mechanism and fracture occurrence.

DISCUSSION
In accordance with literature 8-10 , we did not detect any statistically significant difference in the total rate of both surgical and medical complications between HIV-positive and the HIV-negative patients. In the HIV-positive group, one patient underwent two revision surgeries because of implant breakage and a subsequent infection at the surgical site. This patient was poorly adherent to the anti-viral therapy, with both the CD4 count and viremia not adequately controlled. In another two cases requiring revision surgery, one secondary to high energy trauma and the other implant intolerance, we found no reasonable correlation between the re-interventions and HIV status.
We noted a significantly longer duration surgical procedure for Group A patients specifically when fixation was undertaken using sliding hip screws. Even if several variables such as fracture configuration and surgeon expertise can occur in influencing surgery time, in our study all the orthopaedic consultants involved in surgery had a similar surgical expertise following a standardised protocol in term of surgical technique indications. This ensured greater caution by the surgeons to avoid intra-operative exposure to HIV infection in a relatively wider and bloodier surgical exposure.
We observed a significantly higher incidence of postoperative urinary tract infections in HIV-positive patients and hypothesise that this may be due to either a state of immune deficiency or a lack of control of the underlying pathologies [20][21][22][23][24] . We specifically assessed the immunological status of these seven HIV-positive patients with a urinary tract infection and we could not detect any correlation between patient immunological status and higher rates of urinary tract infection.
In the present study we registered a 12% superficial surgical site infection rate in HIV-positive group compared to none in the control group and despite a statistical no significant difference (P-Value=0.07) this could show in Group A trend towards a higher surgical site infection risk even considering significant longer surgical time in selected surgical procedures [22][23][24] . One patient with surgical site infection was in HAART at surgery times and two patients were started HAART during recovery. Ma et al 24 stated that analyses of CD4, ESR, and PCT could help in predicting the incidence of surgical site infection in HIV-positive patients but according to our results it still remains to be proven whether poor adherence to anti-viral therapy is one of the modifiable risk factors for surgical site infection in HIV-positive patients undergoing surgery for femoral fractures . In our analysis, and in accordance to Baburam et al 23 , no statistically significant difference at three months was seen in postoperative pain, Harris hip scores, limb length discrepancy and wound healing between the two groups and even the surgical site infection observed in the positive group did not cause any adverse effects on the three months post-operative outcome.
Limitations of our study include a retrospective analysis with a relatively small sample size and short-term follow-up. However, the authors faced difficulties in recruiting adequate number of HIV-positive patients because of common poor compliance with both the therapies and the follow-up arrangements in several patients. To overcome these difficulties in the matching process the authors modified the Charlson Comorbidity Index omitting the fixed six-point score for HIV-positivity. Likewise the present study is the only one in the literature, performed in a single centre by a single homogeneous surgical team, specifically addressing early outcome of femoral neck fractures in HIV-positive patient matched to a HIV-negative control group.

CONCLUSIONS
There was no statistically significant increase in early complications for femoral neck fracture fixation in HIVpositive compared to HIV-negative patients without the necessity to address these patients in dedicated centres. Only one HIV-positive patient with a poor HAART compliance reported a bad outcome. However, patients with poor adherence to antiretroviral therapy and uncontrolled parameters including viremia, CD4 counts and T-helper lymphocytes counts, could be more likely to face early postoperative complications and to support this concept it is recommended in the future similar larger multicentric study be conducted considering the objective difficulties both in enrolling and matching these patients.