Aird, J; (2012) Human Immunodeficiency Virus and open fractures. Is wound or fracture healing affected in surgically stabilised open fractures? A prospective study. Doctoral thesis , UCL (University College London).

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Abstract

Background: 33 million people worldwide are infected with HIV, a complex disease that affects many of the processes involved in wound and fracture healing. There is little evidence available to guide acute management of open fractures in these patients and fears of acute and delayed sepsis often inhibit the use of surgical fixation, which may be the most effective way of achieving union. This study addresses the hypothesis that the presence of either HIV or advanced HIV (CD4 count <=350) leads to an increased risk of complications in patients with open fractures treated with surgical stabilization. South Africa has one of the highest rates of both HIV and high energy trauma in the world, so was deemed an appropriate place for the study of this interaction. Methods: This prospective observational study compared surgical fixation of open fractures in HIV positive and negative patients. 133 patients with 135 open fractures fulfilled the inclusion criteria. 86 fractures were in HIV negative and 33 in HIV positive patients. The remaining 16 patients refused HIV tests. 12 HIV positive patients had advanced disease (CD4 <=350), 14 had early disease (CD4 >350), 7 refused CD4 count testing. This cohort was three times larger (number of HIV positive patients) than any similar previously published study. There was no randomised allocation; the treatment of these patients was based on locally developed protocols and was dependent on; fracture type, location and the grade of wound. Patients were followed up either till union had been achieved or for 6 months in tibia/femur fractures, and 3 months in other fractures. The primary outcome was acute wound infection, secondary outcomes tested were fracture union and pin site sepsis. The analysis of the binary nominal data was done using the Chi squared test. In cases where the expected value was less than 5, then the Fisher’s exact test was used. In the assessment of multiple potential risk factors, binary logistic regression was used. Results: Analysis of background characteristics showed that HIV positive and negative populations were broadly similar with regard to demographics, injury type/location and grade of wound. In the analysis of the primary outcome, the risk of wound infection was marginally higher in patients without HIV (22%) as compared to patients with HIV (15%). This difference was small and did not reach statistical significance (n=135, Risk Ratio 0.7, p value 0.40). However, as hypothesized, the infection risk was higher in patients with advanced HIV (26%), compared to patients with early HIV (5%). The numbers, however, were small and this did not reach statistical significance (n=33, Risk Ratio=4.8, P value= 0.12). Sub group analyses, conceived prior to the study, provided strong evidence that patients with Gustilo Anderson grade 1 injuries had a higher risk of wound infection in patients with advanced HIV than controls (HIV negative and early HIV) (n=46, Risk Ratio=6.3, P value =0.02). Of note, departmental guidelines meant that patients with grade 1 injury were not prioritised for theatre and had, on average, a delay of 3.5 days to surgery. The average delay was similar in both HIV positive and negative groups. Analysis of the secondary outcome, nonunion, provided strong evidence that the risk of nonunion was higher in HIV positive than HIV negative patients (n=115, Risk Ratio=4.1, P value=0.04). Interestingly, the patients with advanced HIV had a slightly lower nonunion risk (13%) than patients with early HIV (20%). However the numbers were small and the difference was not statistically significant (n=33, Risk Ratio=0.8, P value=1). The incidence of nonunion was not correlated with the presence of wound infection. The risk of mild pin site sepsis in fractures treated with external fixation was similar in both HIV positive (60%) and negative (67%) patients (n=31, Risk Ratio=0.9, P value=1). An increased risk of severe pin site sepsis was noted in patients with advanced HIV (50%), compared to controls (25%). Although the difference is large, the numbers are small and the difference was not statistically significant (n=28, Risk Ratio=2, P value= 0.31). It would require 160 patients to prove a difference of this size. Conclusions: Data from this study appears to dispute the conclusion of previous studies that suggest that all patients with HIV are at higher risk of wound infection, and therefore internal fixation should be considered with caution. In this study it was only the patients with advanced HIV that showed a small increase in the risk of wound infection. Based on this study the author suggests that early HIV should not be a contraindication to either internal or external fixation in open fractures, due to concerns of wound infection. However, advanced HIV should continue to be considered a relative contraindication to internal fixation, until further data becomes available. Since this finding applied equally to grade 1 (Gustilo Anderson) injuries, the data suggests that any theatre delays in patients with advanced HIV may be detrimental to outcomes. This is contrary to published data that suggests that grade 1 injuries do not need to be prioritised. The data provides strong evidence that HIV leads to an increased risk of non unions. Interestingly, the risk of non union is less in patients with advanced HIV. This may fit with recently published laboratory studies suggesting that the absence of lymphocytes is beneficial to bone healing. Based on this evidence the author suggests that in patients with HIV treatment strategies should be aimed at achieving union, rather than on potentially unfounded concerns of preventing infection. In patients treated with external fixation, the data provides weak evidence of an increased risk of severe pin site sepsis in advanced HIV. This observation may be due to an increased susceptibility to infection, or to problems with bone healing in these patients. Based on this evidence, and the evidence that patients with HIV may be at increased risk of non union, the author suggests that HIV positive patients being treated with external fixators, should be considered for treatment strategies that will prolong the life of the pin bone interface. These may include additional pins, wires and/or the use of hydroxyapatite coated half pins.

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