HIP
Total hip replacement in HIV-positive patients
S. M. Graham, N. Lubega, N. Mkandawire, W. J. Harrison From Beit CURE International Hospital, Blantyre, Malawi
We report the short-term follow-up, functional outcome and incidence of early and late infection after total hip replacement (THR) in a group of HIV-positive patients who do not suffer from haemophilia or have a history of intravenous drug use. A total of 29 patients underwent 43 THRs, with a mean follow-up of three years and six months (five months to eight years and two months). There were ten women and 19 men, with a mean age of 47 years and seven months (21 years to 59 years and five months). No early (< 6 weeks) or late (> 6 weeks) complications occurred following their THR. The mean pre-operative Harris hip score (HHS) was 27 (6 to 56) and the mean post-operative HHS was 86 (73 to 91), giving a mean improvement of 59 points (p = < 0.05, Student’s t-test). No revision procedures had been undertaken in any of the patients, and none had any symptoms consistent with aseptic loosening. This study demonstrates that it is safe to perform THR in HIV-positive patients, with good short-term functional outcomes and no apparent increase in the risk of early infection. Cite this article: Bone Joint J 2014; 96-B:462–6.
S. M. Graham, MBChB, MRCS, MSc (Res), Specialist Registrar Orthopaedics and Trauma W. J. Harrison, MA(Oxon), FRCS (Tr & Orth), Consultant Orthopaedic Surgeon The Countess Of Chester Hospital, Health Park, Chester, Cheshire, UK. N. Lubega, MBChB, MMed (Ortho), FCS (ESSA), Consultant Orthopaedic Surgeon Beit CURE International Hospital, Blantyre, Malawi. N. Mkandawire, BMBS, FRCS, MCh(ORTH), FCS(ECSA), Consultant Orthopaedic Surgeon. Professor of Orthopaedics College Of Medicine University of Malawi, The Department of Surgery, Blantyre Malawi and Beit CURE International Hospital. Blantyre, Malawi. Correspondence should be sent to Mr S. M. Graham; e-mail: simonmatthewgraham@doctors .org.uk ©2014 The British Editorial Society of Bone & Joint Surgery doi:10.1302/0301-620X.96B4. 33213 $2.00 Bone Joint J 2014;96-B:462–6. Received 17 September 2013; Accepted after revision 21 January 2014
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The introduction of highly active antiretroviral therapy (HAART) in 19971 has altered the course and nature of patients infected by the human immunodeficiency virus (HIV). This has resulted in significant reductions in HIVrelated infection, morbidity and mortality,1-3 and has coincided with an increase in the number of joint replacement operations.4 However, HIV and HAART are independent risk factors for osteonecrosis of the femoral head.5,6 It has also been reported that osteoporosis can occur in patients on HAART, and the risk of hip fracture is increased.7,8 Consequently, HIV-positive patients in both high- and low-income countries are now regularly considered for arthroplasty.4,9 HIV-positive patients suffer progressively deteriorating immunity as their CD4-lymphocyte count falls, and are prone to opportunistic infections.1 In the past HIV has been considered an independent risk factor for infection, raising questions about the safety of performing arthroplasty on HIV-positive patients.10 Previous studies have focused on total joint replacement (TJR) in HIV-positive patients with haemophilia10-16 and intravenous drug use (IVDU).17-19 However, these conditions are independent risk factors for developing infection and complications following TJR.12,17,20 The long-term complication rates and functional outcome of TJR in HIV-positive patients
without haemophilia or IVDU are conflicting and with small patient numbers. This study reports the short-term follow-up, functional outcome and incidence of early and late infection in a group of HIV-positive patients without haemophilia or a history of IVDU, undergoing total hip replacement (THR) in a low-income country.
Patients and Methods All patients in Malawi who were HIV positive and had undergone THR were identified from the Malawian National Joint Registry (MNJR). The MNJR was established in 2005, with ethical approval from the Research and Ethics Committee of the College of Medicine of Malawi. All patients who have ever undergone THR or total knee replacement (TKR) in Malawi have been included, and to date there are 207 THRs and 115 TKRs entered into the registry. From this database we identified 48 THRs in 33 HIV-positive patients (19 men, ten women) who had a mean age of 47 years (21 to 59.5). This included, 14 patients (18 hips) from our original cohort study, reporting incidence of infection at 6-week follow up.4 All of the patients were aware of their HIV status pre-operatively and had been taking HAART for a mean period of six years (1 to 11 years) pre-operatively. All patients were assessed by a single senior research nurse one week before surgery. This THE BONE & JOINT JOURNAL
TOTAL HIP REPLACEMENT IN HIV-POSITIVE PATIENTS
included calculating the Harris hip score (HHS)21 and obtaining informed consent from the patient for both the procedure and inclusion in the registry. After counselling and consent, HIV testing was carried out in all patients and CD4 levels were determined. A total of six different surgeons at four different hospitals performed the operations. None of the hospital operating theatres had a laminar-flow system. The majority of patients (25) had THR performed for symptomatic osteonecrosis (37 hips), at a mean follow-up of three years and six months (five months to eight years and two months). Other indications included: osteoarthritis (three THRs); a post-tuberculosis (TB) infected hip (three THRs); previous Perthes’ disease (one THR); and failed conservative management of a fractured neck of femur (two THRs). A Charnley prosthesis (DePuy Orthopaedics Inc, Warsaw, Indiana) with either a flanged or a round-backed femoral stem and a standard long posterior wall or Ogee acetabular component (DePuy) were used in 45 THRs, and Stanmore implants with modular stems and 28 mm cobalt–chrome heads (Biomet Inc, Warsaw, Indiana) were used in three THRs. All the implants were secured using Smartset GHV cement with gentamicin (DePuy), and the patients received either a single dose of intravenous antibiotic at the start of surgery (40 THRs) or intravenous antibiotic at the start of surgery plus an additional 24-hour prophylactic course postoperatively (eight THRs). The antibiotic used was cefuroxime, or gentamicin for patients with a penicillin allergy. After the operation a senior research nurse reviewed all patients at six weeks, three and six months, and then annually. The same research nurse carried out all follow-ups apart from the final follow-up, which was performed by the first author (SMG). The patients were assessed for pain, post-operative complications and function using the HHS. Patient’s surgical wounds/scars were inspected and assessed using the ASEPSIS wound-scoring system,22 which assigns a score out of 70 based on the appearance of the wound as well as additional treatments required. For the purposes of this study a score > 10 was considered an infection, which is a low threshold for defining wound infection. An anteroposterior (AP) pelvis and lateral hip radiograph was made at each follow-up appointment. At final follow-up radiographs were reviewed by the first author (SMG), who was not involved in the surgery. Acetabular and femoral components were assessed for position, fixation and stability and the presence and progress of radiolucent lines.23,24 All HIV-positive patients had their CD4 count rechecked annually. Thromboembolus-deterrent (TED) graduated compression stockings were used along with low-dose aspirin for a period of six weeks after operation. All patients were mobilised on the first post-operative day. Malawi has a national policy (established in 2005) of using oral co-trimoxazole 960 mg (trimethoprim-sulfamethoxazole) daily as a prophylactic antibiotic in all HIVpositive patients. No information on compliance with this national policy was available for this study.25 VOL. 96-B, No. 4, APRIL 2014
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Statistical analysis. The parametric data were analysed using the Student’s t-test. A p-value < 0.05 was considered significant.
Results Of the 33 HIV-positive patients, four (five THRs) were lost to final follow-up and so were excluded from the analysis. All four of these patients were seen at six weeks and had no early complications related to their THRs. However, none of the four attended for further follow-up. Two of these patients, one of whom had undergone bilateral THRs, were reported to have died 12 months post-operatively. Unconfirmed reports from the relatives suggested that one patient died of tuberculosis approximately 12 months after his procedure, with no reported issues with his bilateral THRs. The relatives of the second patient reported that he may have died with a late infection in his THR, approximately 12 months post-operatively. However, as the patient lived in a remote village and was not seen before death, the presence of post-operative hip sepsis could not be confirmed. The patient had disseminated acquired immunodeficiency syndrome (AIDS) at the time of death. Therefore, a total of 29 patients (19 men, 10 women; 43 hips) were included in the final analysis, of whom 14 patients underwent bilateral primary THRs. These results are summarised in Table I. The mean duration of follow-up for these patients was 3.5 years (5 to 8.2). The mean age of these patients at the time of surgery was 47 years and seven months (21 to 59.5) at which time their mean body mass index (BMI) was 25.5 g/m2. There were no early (< 6 weeks) or late (> 6 weeks) complications, such as dislocation, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or superficial or deep wound infection, following the THRs. Mortality at six weeks post-operatively was zero. The mean pre-operative HHS was 27 (6 to 56) which increased to a mean post-operative HHS of 86 (73 to 91), giving a mean improvement of 59 points (p = < 0.05; Student’s t-test). All but one patient were taking HAART at the time of final follow-up. Patients had a mean pre-operative CD4 count of 489 cells/mm3 (183 to 1017) and a mean current CD4 count of 473 cells/mm3 (232 to 964). One patient had recently stopped their HAART medication, owing to side effects. No revision procedures were undertaken in any of the patients and no patients had any symptoms consistent with aseptic loosening, such as pain, dislocation or alteration in their level of post-operative mobility. Radiographs were available for all patients at final follow-up and radiolucent lines were observed in two hips in a patient who underwent bilateral THRs (hips 3 and 5), in Gruen Zone 1; these were not progressive.23 No osteolysis was observed around any of the femoral or acetabular components. No radiolucent line was observed on the acetabular side in Charnley and DeLee zones.24 Additionally,
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S. M. GRAHAM, N. LUBEGA, N. MKANDAWIRE, W. J. HARRISON
Table I. Summary of all HIV-positive patients having undergone total hip replacement (THR) in Malawi (HHS, Harris hip score) Gender (M/F)
Duration of follow-up
Side
Prosthesis
Early post-op complication
Late post-op complications Pre-op HHS
Latest HHS
1
M
Osteonecrosis
2
M
Osteonecrosis
42 yrs 2 mths
6 yrs 10 mths
Left
Stanmore
Nil
Nil
28
81
394
471
42 yrs 5 mths
6 yrs 9 mths
Right
Stanmore
Nil
Nil
30
81
394
471
3
M
Osteonecrosis
4
M
Osteonecrosis
51 yrs 2 mths
8 yrs 2 mths
Right
Stanmore
Nil
Nil
54
91
487
388
45 yrs 9 mths
7 yrs 9 mths
Right
Charnley
Nil
Nil
15
91
1017
5
M
Osteonecrosis
576
51 yrs 8 mths
7 yrs 8 mths
Left
Charnley
Nil
Nil
28
87
487
388
6
M
7
F
Fracture
39 yrs 10 mths
2 yrs 2 mths
Right
Charnley
Nil
Nil
14
87
300
468
Osteonecrosis
49 yrs 4 mths
6 yrs 9 mths
Left
Charnley
Nil
Nil
15
72
507
8
M
232
Osteonecrosis
42 yrs 8 mths
6 yrs 2 mths
Right
Charnley
Nil
Nil
42
91
773
9
M
964
Osteonecrosis
47 yrs 11 mths
5 yrs 7 mths
Left
Charnley
Nil
Nil
14
87
183
576
10
M
Osteonecrosis
53 yrs 8 mths
5 yrs 2 mths
Left
Charnley
Nil
Nil
36
91
512
496
11
F
Osteoarthritis
36 yrs 9 mths
5 yrs 3 mths
Left
Charnley
Nil
Nil
25
87
347
452
Diagnosis
Age at time surgery
Latest CD4 Pre-op CD4 (cells/mm3) (cells/mm3)
THR
12
M
Osteonecrosis
54 yrs 9 mths
5 yrs 3 mths
Right
Charnley
Nil
Nil
8
74
193
280
13
F
Previous Perthes
49 yrs 3 mths
5 yrs 3 mths
Left
Charnley
Nil
Nil
28
91
441
206
14
F
Osteonecrosis
53 yrs 3 mths
5 yrs 2 mths
Right
Charnley
Nil
Nil
20
77
285
468
15
F
Osteonecrosis
40 yrs 11 mths
4 yrs 7 mths
Right
Charnley
Nil
Nil
24
88
468
668
16
M
Osteonecrosis
21 yrs 0 mths
4 yrs 4 mths
Right
Charnley
Nil
Nil
20
88
550
389
17
F
Osteoarthritis
37 yrs 9 mths
4 yrs 3 mths
Right
Charnley
Nil
Nil
26
88
477
452
18
M
Osteonecrosis
42 yrs 10 mths
4 yrs 3 mths
Right
Charnley
Nil
Nil
22
88
224
667
19
M
Osteonecrosis
50 yrs 0 mths
3 yrs 6 mths
Right
Charnley
Nil
Nil
44
88
345
609
20
M
Osteonecrosis
49 yrs 2 mths
3 yrs 5 mths
Left
Charnley
Nil
Nil
15
91
484
503
21
M
Osteonecrosis
56 yrs 7 mths
4 yrs 3 mths
Right
Charnley
Nil
Nil
34
91
241
600
22
M
Previous TB hip
41 yrs 11 mths
2 yrs 7 mths
Left
Charnley
Nil
Nil
52
87
567
589
23
M
Osteonecrosis
47 yrs 1 mths
2 yrs 7 mths
left
Charnley
Nil
Nil
6
82
780
543
24
M
Osteonecrosis
57 yrs 8 mths
3 yrs 5 mths
Left
Charnley
Nil
Nil
56
91
876
600
25
M
Osteonecrosis
50 yrs 1 mth
2 yrs 6 mths
Right
Charnley
Nil
Nil
15
91
484
503
26
F
Osteonecrosis
50 yrs 11 mths
2 yrs 4 mths
Right
Charnley
Nil
Nil
25
87
539
626
27
M
Osteonecrosis
33 yrs 0 mths
2 yrs 2 mths
Left
Charnley
Nil
Nil
56
89
242
456
28
M
Osteonecrosis
47 yrs 6 mths
2 yrs 2 mths
Right
Charnley
Nil
Nil
6
78
672
543
29
M
Osteonecrosis
53 yrs 11 mths
2 yrs 0 mths
Left
Charnley
Nil
Nil
43
77
512
446
30
F
Osteonecrosis
53 yrs 6 mths
2 yrs 0 mths
Right
Charnley
Nil
Nil
28
91
613
509
31
F
Osteonecrosis
53 yrs 6 mths
1 yrs 10 mths
Right
Charnley
Nil
Nil
25
91
613
512
32
M
Osteonecrosis
24 yrs 4 mths
1 yrs 11 mths
Left
Charnley
Nil
Nil
25
88
550
389
33
F
Fracture
53 yrs 10 mths
1 yrs 8 mths
Left
Charnley
Nil
Nil
41
91
630
509
34
M
Osteonecrosis
54 yrs 3 mths
2 yrs 5 mths
Right
Charnley
Nil
Nil
40
87
434
360
35
M
Osteonecrosis
50 yrs 3 mths
1 yrs 5 mths
Right
Charnley
Nil
Nil
29
87
335
520
36
M
Osteonecrosis
54 yrs 6 mths
1 yrs 2 mths
Left
Charnley
Nil
Nil
35
91
457
360
37
F
Osteonecrosis
54 yrs 2 mths
1 yrs 2 mths
Left
Charnley
Nil
Nil
12
88
613
512
38
F
Osteonecrosis
57 yrs 0 mths
1 yrs 0 mths
Left
Charnley
Nil
Nil
30
91
632
468
39
F
Osteonecrosis
45 yrs 4 mths
1 yrs 1 mths
Right
Charnley
Nil
Nil
25
74
413
345
40
F
Osteonecrosis
58 yrs 9 mths
1 yrs 1 mths
Left
Charnley
Nil
Nil
12
91
600
305
41
M
Osteonecrosis
46 yrs 2 mths
1 yrs 0 mths
Left
Charnley
Nil
Nil
37
91
296
281
42
F
Osteonecrosis
46 yrs 2 mths
5 mths
Left
Charnley
Nil
Nil
12
74
458
345
43
F
Osteonecrosis
59 yrs 5 mths
5 mths
Right
Charnley
Nil
Nil
22
73
600
305
no patients showed signs of infection in their surgical scars using the ASEPSIS wound scoring system.22
Discussion This study demonstrates good short-term results for 43 THRs performed in 29 HIV-positive patients. This is the largest study to date reporting outcomes and infection rates in HIV-positive patients without haemophilia or IVDU. Additionally, it is the first study to publish post-operative functional outcomes and potential causes of revision other than infection, including dislocation and aseptic loosening. The majority of reports to date have focused on TJR in HIV-positive patients with haemophilia. Several studies have demonstrated high a incidence of late deep sepsis in HIV-positive patients with haemophilia following TJR surgery,10,14-16 although Habermann et al13 and Powell et al11 concluded that TJR in patients with HIV and haemophilia was safe with regard to the post-operative infection rate and no difference was found in functional outcome compared to an HIV-negative population.
In a mixed patient group of HIV-positive patients undergoing arthroplasty, Lehman et al17 reported infections in 27% with haemophilia (4/15) and 50% (2/4) who were IVDU. None of the patients in the subgroup who were only HIV positive developed deep infection (0/4). In other mixed patient groups low rates of infection have been reported following arthroplasty in those who were HIV positive. However, in all the studies reported there were few patients without a history of haemophilia or IVDU.18,19 Patients with IVDU and/or haemophilia have a higher risk of infection than HIV-negative patients undergoing joint replacement surgery.10,17,18 This is because patients with haemophilia receive regular injections of Factor VIII, which may be a source of bacterial infection.12,20 They are also prone to bleeding around the joint, which may predispose to infection, whereas bacteraemias are common in IVDU.26 We have previously reported no difference in early infection (< 6 weeks) in 14 patients (18 hips) who were HIV positive but without haemophilia, compared to a cohort group of HIV-negative patients.4 In a recent retrospective THE BONE & JOINT JOURNAL
TOTAL HIP REPLACEMENT IN HIV-POSITIVE PATIENTS
review Lin et al27 found an increase in deep infection in 20 HIV-positive patients compared to HIV-negative patients (9.2% vs 2.2%; p < 0.102) who underwent THR or TKR at a single institute in the United States. All but one of these patients was taking HAART at the time of surgery. However, although none of the patients were active intravenous drug users, seven (31.8%) had a previous history of IVDU. Additionally, eight of their patients suffered from significant liver disease, which has been shown to be an independent risk factor for periprosthetic joint infection.28 Using the Nationwide Inpatient Sample (NIS), Lin et al9 also reported the outcome of 8229 HIV-positive patients admitted for primary THR and THR in the United States between 2000 and 2008. They found no difference in total complications, compared to 5 681 024 admissions of patients who were HIV negative (8.3% compared to 7.8%; p = 0.52).9 However, this study only looked at the complications patients experienced during the admission and did not report all early or late complications or functional outcomes. In addition, this was a mixed patient group including patients with a history of haemophilia and IVDU. In a similar patient group to ours, Brijlall29 found no incidence of infection at a mean of 62 months’ follow-up, despite three of the 14 patients having a CD4 count < 200 cells/mm3. They gave all HIV-positive patients undergoing arthroplasty an extended period of treatment with rifampicin.29 In our study, patients received a standard regimen of antibiotics at the induction of surgery and/or for 24 hours post-operatively. Based on our findings of no THR infections to date, we do not recommend the extended use of antibiotics in this cohort of patients. One of the main limitations of our study is the relatively small number of patients and the short follow-up. A further limitation is the fact that four patients were lost to follow-up. One of these was reported to have disseminated AIDS at the time of his death. This patient had a pre-operative CD4 count of 322 cells/mm3 and died approximately 12 months after the operation. This raises the problem of developing AIDS after a THR, leading to late infection.27 Our institute aims to identify all HIV-positive patients prior to surgery, and subsequently check their CD4 count. If this is < 200 cells/mm3 then HAART is started and surgery is delayed until the CD4 count has increased above 200 cells/mm3. Globally, at the end of 2011 between 31.4 million and 35.9 million people were living with HIV,30 although the burden of the epidemic continues to vary considerably between countries and regions.30 Since the introduction of HAART, the number of people dying globally from AIDSrelated causes has declined by 24% over the last eight years, with a larger decline in sub-Saharan Africa (32%) from 2005 to 2011.30 This reduction in the number of deaths and the concomitant increase in life expectancy for those infected with HIV indicates that there is likely to be an increase in the number of such patients presenting for arthroplasty surgery.
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Our study demonstrates that it is safe to perform THR in HIV-positive patients in the short term. The long-term outcome, however, remains unknown. The authors would like to thank Joint Action for their financial help in funding the registry. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by S. Hughes and first proof edited by G. Scott.
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22. Wilson AP, Treasure T, Sturridge MF, Grüneberg RN. A scoring method (ASEPSIS) for postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet 1986;1:311–313. 23. Gruen TA, McNeice GM, Amstutz HC. "Modes of failure" of cemented stem-type femoral components: a radiographic analysis of loosening. Clin Orthop Relat Res 1979;141:17–27. 24. DeLee JG, Charnley J. Radiological demarcation of cemented sockets in total hip replacement. Clin Orthop Relat Res 1976;121:20–32. 25. Hutchinson E, Parkhurst J, Phiri S, et al. National policy development for cotrimoxazole prophylaxis in Malawi, Uganda and Zambia: the relationship between Context, Evidence and Links. Heal Res Policy Syst 2011;(Suppl):S6.
26. Murphy EL, DeVita D, Liu H, et al. Risk factors for skin and soft-tissue abscesses among injection drug users: a case-control study. Clin Infect Dis 2001;33:35–40. 27. Lin CA, Takemoto S, Kandemir U, Kuo AC. Mid-term outcomes in HIV-positive patients after primary total hip or knee arthroplasty. J Arthroplasty 2013;29:277–282. 28. Bozic KJ, Lau E, Kurtz S, Ong K, Berry DJ. Patient-related risk factors for postoperative mortality and periprosthetic joint infection in medicare patients undergoing TKA. Clin Orthop Relat Res 2012;470:130–137. 29. Brijlall S. Arthroplasty in HIV-infected patients: a 5 year follow-up. J Bone Joint Surg [Br] 2008;90-B(Supp):473. 30. No authors listed. UNAIDS Report on the global AIDS epidemic, 2012. Joint United Nations Programme on HIV/AIDS (UNAIDS). http://www.unaids.org/globalreport/ Global_report.htm (date last accessed 28 January 2014).
THE BONE & JOINT JOURNAL
Total hip replacement in HIV-positive patients
S. M. Graham, N. Lubega, N. Mkandawire, W. J. Harrison From Beit CURE International Hospital, Blantyre, Malawi
We report the short-term follow-up, functional outcome and incidence of early and late infection after total hip replacement (THR) in a group of HIV-positive patients who do not suffer from haemophilia or have a history of intravenous drug use. A total of 29 patients underwent 43 THRs, with a mean follow-up of three years and six months (five months to eight years and two months). There were ten women and 19 men, with a mean age of 47 years and seven months (21 years to 59 years and five months). No early (< 6 weeks) or late (> 6 weeks) complications occurred following their THR. The mean pre-operative Harris hip score (HHS) was 27 (6 to 56) and the mean post-operative HHS was 86 (73 to 91), giving a mean improvement of 59 points (p = < 0.05, Student’s t-test). No revision procedures had been undertaken in any of the patients, and none had any symptoms consistent with aseptic loosening. This study demonstrates that it is safe to perform THR in HIV-positive patients, with good short-term functional outcomes and no apparent increase in the risk of early infection. Cite this article: Bone Joint J 2014; 96-B:462–6.
S. M. Graham, MBChB, MRCS, MSc (Res), Specialist Registrar Orthopaedics and Trauma W. J. Harrison, MA(Oxon), FRCS (Tr & Orth), Consultant Orthopaedic Surgeon The Countess Of Chester Hospital, Health Park, Chester, Cheshire, UK. N. Lubega, MBChB, MMed (Ortho), FCS (ESSA), Consultant Orthopaedic Surgeon Beit CURE International Hospital, Blantyre, Malawi. N. Mkandawire, BMBS, FRCS, MCh(ORTH), FCS(ECSA), Consultant Orthopaedic Surgeon. Professor of Orthopaedics College Of Medicine University of Malawi, The Department of Surgery, Blantyre Malawi and Beit CURE International Hospital. Blantyre, Malawi. Correspondence should be sent to Mr S. M. Graham; e-mail: simonmatthewgraham@doctors .org.uk ©2014 The British Editorial Society of Bone & Joint Surgery doi:10.1302/0301-620X.96B4. 33213 $2.00 Bone Joint J 2014;96-B:462–6. Received 17 September 2013; Accepted after revision 21 January 2014
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The introduction of highly active antiretroviral therapy (HAART) in 19971 has altered the course and nature of patients infected by the human immunodeficiency virus (HIV). This has resulted in significant reductions in HIVrelated infection, morbidity and mortality,1-3 and has coincided with an increase in the number of joint replacement operations.4 However, HIV and HAART are independent risk factors for osteonecrosis of the femoral head.5,6 It has also been reported that osteoporosis can occur in patients on HAART, and the risk of hip fracture is increased.7,8 Consequently, HIV-positive patients in both high- and low-income countries are now regularly considered for arthroplasty.4,9 HIV-positive patients suffer progressively deteriorating immunity as their CD4-lymphocyte count falls, and are prone to opportunistic infections.1 In the past HIV has been considered an independent risk factor for infection, raising questions about the safety of performing arthroplasty on HIV-positive patients.10 Previous studies have focused on total joint replacement (TJR) in HIV-positive patients with haemophilia10-16 and intravenous drug use (IVDU).17-19 However, these conditions are independent risk factors for developing infection and complications following TJR.12,17,20 The long-term complication rates and functional outcome of TJR in HIV-positive patients
without haemophilia or IVDU are conflicting and with small patient numbers. This study reports the short-term follow-up, functional outcome and incidence of early and late infection in a group of HIV-positive patients without haemophilia or a history of IVDU, undergoing total hip replacement (THR) in a low-income country.
Patients and Methods All patients in Malawi who were HIV positive and had undergone THR were identified from the Malawian National Joint Registry (MNJR). The MNJR was established in 2005, with ethical approval from the Research and Ethics Committee of the College of Medicine of Malawi. All patients who have ever undergone THR or total knee replacement (TKR) in Malawi have been included, and to date there are 207 THRs and 115 TKRs entered into the registry. From this database we identified 48 THRs in 33 HIV-positive patients (19 men, ten women) who had a mean age of 47 years (21 to 59.5). This included, 14 patients (18 hips) from our original cohort study, reporting incidence of infection at 6-week follow up.4 All of the patients were aware of their HIV status pre-operatively and had been taking HAART for a mean period of six years (1 to 11 years) pre-operatively. All patients were assessed by a single senior research nurse one week before surgery. This THE BONE & JOINT JOURNAL
TOTAL HIP REPLACEMENT IN HIV-POSITIVE PATIENTS
included calculating the Harris hip score (HHS)21 and obtaining informed consent from the patient for both the procedure and inclusion in the registry. After counselling and consent, HIV testing was carried out in all patients and CD4 levels were determined. A total of six different surgeons at four different hospitals performed the operations. None of the hospital operating theatres had a laminar-flow system. The majority of patients (25) had THR performed for symptomatic osteonecrosis (37 hips), at a mean follow-up of three years and six months (five months to eight years and two months). Other indications included: osteoarthritis (three THRs); a post-tuberculosis (TB) infected hip (three THRs); previous Perthes’ disease (one THR); and failed conservative management of a fractured neck of femur (two THRs). A Charnley prosthesis (DePuy Orthopaedics Inc, Warsaw, Indiana) with either a flanged or a round-backed femoral stem and a standard long posterior wall or Ogee acetabular component (DePuy) were used in 45 THRs, and Stanmore implants with modular stems and 28 mm cobalt–chrome heads (Biomet Inc, Warsaw, Indiana) were used in three THRs. All the implants were secured using Smartset GHV cement with gentamicin (DePuy), and the patients received either a single dose of intravenous antibiotic at the start of surgery (40 THRs) or intravenous antibiotic at the start of surgery plus an additional 24-hour prophylactic course postoperatively (eight THRs). The antibiotic used was cefuroxime, or gentamicin for patients with a penicillin allergy. After the operation a senior research nurse reviewed all patients at six weeks, three and six months, and then annually. The same research nurse carried out all follow-ups apart from the final follow-up, which was performed by the first author (SMG). The patients were assessed for pain, post-operative complications and function using the HHS. Patient’s surgical wounds/scars were inspected and assessed using the ASEPSIS wound-scoring system,22 which assigns a score out of 70 based on the appearance of the wound as well as additional treatments required. For the purposes of this study a score > 10 was considered an infection, which is a low threshold for defining wound infection. An anteroposterior (AP) pelvis and lateral hip radiograph was made at each follow-up appointment. At final follow-up radiographs were reviewed by the first author (SMG), who was not involved in the surgery. Acetabular and femoral components were assessed for position, fixation and stability and the presence and progress of radiolucent lines.23,24 All HIV-positive patients had their CD4 count rechecked annually. Thromboembolus-deterrent (TED) graduated compression stockings were used along with low-dose aspirin for a period of six weeks after operation. All patients were mobilised on the first post-operative day. Malawi has a national policy (established in 2005) of using oral co-trimoxazole 960 mg (trimethoprim-sulfamethoxazole) daily as a prophylactic antibiotic in all HIVpositive patients. No information on compliance with this national policy was available for this study.25 VOL. 96-B, No. 4, APRIL 2014
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Statistical analysis. The parametric data were analysed using the Student’s t-test. A p-value < 0.05 was considered significant.
Results Of the 33 HIV-positive patients, four (five THRs) were lost to final follow-up and so were excluded from the analysis. All four of these patients were seen at six weeks and had no early complications related to their THRs. However, none of the four attended for further follow-up. Two of these patients, one of whom had undergone bilateral THRs, were reported to have died 12 months post-operatively. Unconfirmed reports from the relatives suggested that one patient died of tuberculosis approximately 12 months after his procedure, with no reported issues with his bilateral THRs. The relatives of the second patient reported that he may have died with a late infection in his THR, approximately 12 months post-operatively. However, as the patient lived in a remote village and was not seen before death, the presence of post-operative hip sepsis could not be confirmed. The patient had disseminated acquired immunodeficiency syndrome (AIDS) at the time of death. Therefore, a total of 29 patients (19 men, 10 women; 43 hips) were included in the final analysis, of whom 14 patients underwent bilateral primary THRs. These results are summarised in Table I. The mean duration of follow-up for these patients was 3.5 years (5 to 8.2). The mean age of these patients at the time of surgery was 47 years and seven months (21 to 59.5) at which time their mean body mass index (BMI) was 25.5 g/m2. There were no early (< 6 weeks) or late (> 6 weeks) complications, such as dislocation, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or superficial or deep wound infection, following the THRs. Mortality at six weeks post-operatively was zero. The mean pre-operative HHS was 27 (6 to 56) which increased to a mean post-operative HHS of 86 (73 to 91), giving a mean improvement of 59 points (p = < 0.05; Student’s t-test). All but one patient were taking HAART at the time of final follow-up. Patients had a mean pre-operative CD4 count of 489 cells/mm3 (183 to 1017) and a mean current CD4 count of 473 cells/mm3 (232 to 964). One patient had recently stopped their HAART medication, owing to side effects. No revision procedures were undertaken in any of the patients and no patients had any symptoms consistent with aseptic loosening, such as pain, dislocation or alteration in their level of post-operative mobility. Radiographs were available for all patients at final follow-up and radiolucent lines were observed in two hips in a patient who underwent bilateral THRs (hips 3 and 5), in Gruen Zone 1; these were not progressive.23 No osteolysis was observed around any of the femoral or acetabular components. No radiolucent line was observed on the acetabular side in Charnley and DeLee zones.24 Additionally,
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S. M. GRAHAM, N. LUBEGA, N. MKANDAWIRE, W. J. HARRISON
Table I. Summary of all HIV-positive patients having undergone total hip replacement (THR) in Malawi (HHS, Harris hip score) Gender (M/F)
Duration of follow-up
Side
Prosthesis
Early post-op complication
Late post-op complications Pre-op HHS
Latest HHS
1
M
Osteonecrosis
2
M
Osteonecrosis
42 yrs 2 mths
6 yrs 10 mths
Left
Stanmore
Nil
Nil
28
81
394
471
42 yrs 5 mths
6 yrs 9 mths
Right
Stanmore
Nil
Nil
30
81
394
471
3
M
Osteonecrosis
4
M
Osteonecrosis
51 yrs 2 mths
8 yrs 2 mths
Right
Stanmore
Nil
Nil
54
91
487
388
45 yrs 9 mths
7 yrs 9 mths
Right
Charnley
Nil
Nil
15
91
1017
5
M
Osteonecrosis
576
51 yrs 8 mths
7 yrs 8 mths
Left
Charnley
Nil
Nil
28
87
487
388
6
M
7
F
Fracture
39 yrs 10 mths
2 yrs 2 mths
Right
Charnley
Nil
Nil
14
87
300
468
Osteonecrosis
49 yrs 4 mths
6 yrs 9 mths
Left
Charnley
Nil
Nil
15
72
507
8
M
232
Osteonecrosis
42 yrs 8 mths
6 yrs 2 mths
Right
Charnley
Nil
Nil
42
91
773
9
M
964
Osteonecrosis
47 yrs 11 mths
5 yrs 7 mths
Left
Charnley
Nil
Nil
14
87
183
576
10
M
Osteonecrosis
53 yrs 8 mths
5 yrs 2 mths
Left
Charnley
Nil
Nil
36
91
512
496
11
F
Osteoarthritis
36 yrs 9 mths
5 yrs 3 mths
Left
Charnley
Nil
Nil
25
87
347
452
Diagnosis
Age at time surgery
Latest CD4 Pre-op CD4 (cells/mm3) (cells/mm3)
THR
12
M
Osteonecrosis
54 yrs 9 mths
5 yrs 3 mths
Right
Charnley
Nil
Nil
8
74
193
280
13
F
Previous Perthes
49 yrs 3 mths
5 yrs 3 mths
Left
Charnley
Nil
Nil
28
91
441
206
14
F
Osteonecrosis
53 yrs 3 mths
5 yrs 2 mths
Right
Charnley
Nil
Nil
20
77
285
468
15
F
Osteonecrosis
40 yrs 11 mths
4 yrs 7 mths
Right
Charnley
Nil
Nil
24
88
468
668
16
M
Osteonecrosis
21 yrs 0 mths
4 yrs 4 mths
Right
Charnley
Nil
Nil
20
88
550
389
17
F
Osteoarthritis
37 yrs 9 mths
4 yrs 3 mths
Right
Charnley
Nil
Nil
26
88
477
452
18
M
Osteonecrosis
42 yrs 10 mths
4 yrs 3 mths
Right
Charnley
Nil
Nil
22
88
224
667
19
M
Osteonecrosis
50 yrs 0 mths
3 yrs 6 mths
Right
Charnley
Nil
Nil
44
88
345
609
20
M
Osteonecrosis
49 yrs 2 mths
3 yrs 5 mths
Left
Charnley
Nil
Nil
15
91
484
503
21
M
Osteonecrosis
56 yrs 7 mths
4 yrs 3 mths
Right
Charnley
Nil
Nil
34
91
241
600
22
M
Previous TB hip
41 yrs 11 mths
2 yrs 7 mths
Left
Charnley
Nil
Nil
52
87
567
589
23
M
Osteonecrosis
47 yrs 1 mths
2 yrs 7 mths
left
Charnley
Nil
Nil
6
82
780
543
24
M
Osteonecrosis
57 yrs 8 mths
3 yrs 5 mths
Left
Charnley
Nil
Nil
56
91
876
600
25
M
Osteonecrosis
50 yrs 1 mth
2 yrs 6 mths
Right
Charnley
Nil
Nil
15
91
484
503
26
F
Osteonecrosis
50 yrs 11 mths
2 yrs 4 mths
Right
Charnley
Nil
Nil
25
87
539
626
27
M
Osteonecrosis
33 yrs 0 mths
2 yrs 2 mths
Left
Charnley
Nil
Nil
56
89
242
456
28
M
Osteonecrosis
47 yrs 6 mths
2 yrs 2 mths
Right
Charnley
Nil
Nil
6
78
672
543
29
M
Osteonecrosis
53 yrs 11 mths
2 yrs 0 mths
Left
Charnley
Nil
Nil
43
77
512
446
30
F
Osteonecrosis
53 yrs 6 mths
2 yrs 0 mths
Right
Charnley
Nil
Nil
28
91
613
509
31
F
Osteonecrosis
53 yrs 6 mths
1 yrs 10 mths
Right
Charnley
Nil
Nil
25
91
613
512
32
M
Osteonecrosis
24 yrs 4 mths
1 yrs 11 mths
Left
Charnley
Nil
Nil
25
88
550
389
33
F
Fracture
53 yrs 10 mths
1 yrs 8 mths
Left
Charnley
Nil
Nil
41
91
630
509
34
M
Osteonecrosis
54 yrs 3 mths
2 yrs 5 mths
Right
Charnley
Nil
Nil
40
87
434
360
35
M
Osteonecrosis
50 yrs 3 mths
1 yrs 5 mths
Right
Charnley
Nil
Nil
29
87
335
520
36
M
Osteonecrosis
54 yrs 6 mths
1 yrs 2 mths
Left
Charnley
Nil
Nil
35
91
457
360
37
F
Osteonecrosis
54 yrs 2 mths
1 yrs 2 mths
Left
Charnley
Nil
Nil
12
88
613
512
38
F
Osteonecrosis
57 yrs 0 mths
1 yrs 0 mths
Left
Charnley
Nil
Nil
30
91
632
468
39
F
Osteonecrosis
45 yrs 4 mths
1 yrs 1 mths
Right
Charnley
Nil
Nil
25
74
413
345
40
F
Osteonecrosis
58 yrs 9 mths
1 yrs 1 mths
Left
Charnley
Nil
Nil
12
91
600
305
41
M
Osteonecrosis
46 yrs 2 mths
1 yrs 0 mths
Left
Charnley
Nil
Nil
37
91
296
281
42
F
Osteonecrosis
46 yrs 2 mths
5 mths
Left
Charnley
Nil
Nil
12
74
458
345
43
F
Osteonecrosis
59 yrs 5 mths
5 mths
Right
Charnley
Nil
Nil
22
73
600
305
no patients showed signs of infection in their surgical scars using the ASEPSIS wound scoring system.22
Discussion This study demonstrates good short-term results for 43 THRs performed in 29 HIV-positive patients. This is the largest study to date reporting outcomes and infection rates in HIV-positive patients without haemophilia or IVDU. Additionally, it is the first study to publish post-operative functional outcomes and potential causes of revision other than infection, including dislocation and aseptic loosening. The majority of reports to date have focused on TJR in HIV-positive patients with haemophilia. Several studies have demonstrated high a incidence of late deep sepsis in HIV-positive patients with haemophilia following TJR surgery,10,14-16 although Habermann et al13 and Powell et al11 concluded that TJR in patients with HIV and haemophilia was safe with regard to the post-operative infection rate and no difference was found in functional outcome compared to an HIV-negative population.
In a mixed patient group of HIV-positive patients undergoing arthroplasty, Lehman et al17 reported infections in 27% with haemophilia (4/15) and 50% (2/4) who were IVDU. None of the patients in the subgroup who were only HIV positive developed deep infection (0/4). In other mixed patient groups low rates of infection have been reported following arthroplasty in those who were HIV positive. However, in all the studies reported there were few patients without a history of haemophilia or IVDU.18,19 Patients with IVDU and/or haemophilia have a higher risk of infection than HIV-negative patients undergoing joint replacement surgery.10,17,18 This is because patients with haemophilia receive regular injections of Factor VIII, which may be a source of bacterial infection.12,20 They are also prone to bleeding around the joint, which may predispose to infection, whereas bacteraemias are common in IVDU.26 We have previously reported no difference in early infection (< 6 weeks) in 14 patients (18 hips) who were HIV positive but without haemophilia, compared to a cohort group of HIV-negative patients.4 In a recent retrospective THE BONE & JOINT JOURNAL
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review Lin et al27 found an increase in deep infection in 20 HIV-positive patients compared to HIV-negative patients (9.2% vs 2.2%; p < 0.102) who underwent THR or TKR at a single institute in the United States. All but one of these patients was taking HAART at the time of surgery. However, although none of the patients were active intravenous drug users, seven (31.8%) had a previous history of IVDU. Additionally, eight of their patients suffered from significant liver disease, which has been shown to be an independent risk factor for periprosthetic joint infection.28 Using the Nationwide Inpatient Sample (NIS), Lin et al9 also reported the outcome of 8229 HIV-positive patients admitted for primary THR and THR in the United States between 2000 and 2008. They found no difference in total complications, compared to 5 681 024 admissions of patients who were HIV negative (8.3% compared to 7.8%; p = 0.52).9 However, this study only looked at the complications patients experienced during the admission and did not report all early or late complications or functional outcomes. In addition, this was a mixed patient group including patients with a history of haemophilia and IVDU. In a similar patient group to ours, Brijlall29 found no incidence of infection at a mean of 62 months’ follow-up, despite three of the 14 patients having a CD4 count < 200 cells/mm3. They gave all HIV-positive patients undergoing arthroplasty an extended period of treatment with rifampicin.29 In our study, patients received a standard regimen of antibiotics at the induction of surgery and/or for 24 hours post-operatively. Based on our findings of no THR infections to date, we do not recommend the extended use of antibiotics in this cohort of patients. One of the main limitations of our study is the relatively small number of patients and the short follow-up. A further limitation is the fact that four patients were lost to follow-up. One of these was reported to have disseminated AIDS at the time of his death. This patient had a pre-operative CD4 count of 322 cells/mm3 and died approximately 12 months after the operation. This raises the problem of developing AIDS after a THR, leading to late infection.27 Our institute aims to identify all HIV-positive patients prior to surgery, and subsequently check their CD4 count. If this is < 200 cells/mm3 then HAART is started and surgery is delayed until the CD4 count has increased above 200 cells/mm3. Globally, at the end of 2011 between 31.4 million and 35.9 million people were living with HIV,30 although the burden of the epidemic continues to vary considerably between countries and regions.30 Since the introduction of HAART, the number of people dying globally from AIDSrelated causes has declined by 24% over the last eight years, with a larger decline in sub-Saharan Africa (32%) from 2005 to 2011.30 This reduction in the number of deaths and the concomitant increase in life expectancy for those infected with HIV indicates that there is likely to be an increase in the number of such patients presenting for arthroplasty surgery.
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Our study demonstrates that it is safe to perform THR in HIV-positive patients in the short term. The long-term outcome, however, remains unknown. The authors would like to thank Joint Action for their financial help in funding the registry. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. This article was primary edited by S. Hughes and first proof edited by G. Scott.
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