➢ With the advent of highly active antiretroviral therapy (HAART), total joint arthroplasty has become a safe and effective procedure for patients infected with the human immunodeficiency virus (HIV).
➢ A correlation between a low CD4+ count (<200 cells/mm3) and major postoperative complications such as deep joint infection has been postulated, although high-level studies are not available in the literature.
➢ As most studies have not demonstrated an increase in the incidence of deep-vein thrombosis in patients with HIV/AIDS (acquired immunodeficiency syndrome), our recommendation is to use the standard prophylaxis that is followed by the operating surgeon.
Advances in orthopaedic implants and techniques have allowed for improved clinical outcomes and longer implant survival, especially following total joint arthroplasty (TJA)1,2. Medical advances in recent years have led to reduced rates of morbidity and mortality among patients with many chronic conditions, including the human immunodeficiency virus (HIV) (Fig. 1).
The Centers for Disease Control and Prevention (CDC) has estimated that roughly 1.2 million people in the United States who are ≥13 years of age have an HIV infection. The incidence of HIV has been reported to be about 50,000 new infections per year3. In 2011, 24% of persons with HIV were ≥50 years of age, an increase of 17% since 20014. It has been estimated that, by 2015, more than half of all HIV-infected patients in the United States will be >50 years of age5 (Fig. 1).
As patients with HIV are living longer, they are more prone to develop chronic conditions, such as degenerative joint diseases in the hips and knees, in a similar fashion to other aging individuals without HIV6. In addition, patients with HIV have a 100-fold increased risk of developing osteonecrosis of the femoral head compared with the general population7.
In light of these epidemiological data, patients with HIV are presenting more frequently than ever before to the orthopaedic surgeon for consideration of lower-extremity TJA. Thus, the specific considerations related to TJA in this patient subgroup mandate the attention of orthopaedic surgeons and collaborating providers who care for this potentially challenging population.
Natural Course of HIV/AIDS
Infection with HIV leads to a progressive decline in immunological function, resulting in the development of opportunistic infections, malignant disease, and death. After HIV acquisition, patients undergo a so-called acute or seroconversion phase followed by chronic HIV infection. Patients with chronic HIV infection can be clinically classified into 3 different stages: an asymptomatic phase, a symptomatic phase, and, if left untreated, acquired immunodeficiency syndrome (AIDS).
During the acute phase, the virus integrates into the DNA of the infected cell and rapidly replicates; infected cells then carry the virus to CD4+ T cells and widely disseminate to the blood and lymphoid tissue8. As a result, plasma HIV RNA is very high and CD4+ cell counts drop transiently until an appropriate CD8+ T-cell response and anti-HIV antibodies are developed9,10. A proportion of patients remain asymptomatic during this phase, but others may present with fever, sore throat, influenza-like illness, lymphadenopathy, headache, and rash (Fig. 2).
After acute HIV infection, chronically infected patients may remain in a period of clinical latency and may be asymptomatic for years. During this stage, viral replication is ongoing and the viral load is at a relatively steady state, but, if the infection is untreated, the CD4+ count will continue to gradually decline11. The progressive deterioration of the immune system eventually will lead to symptomatic disease or the development of AIDS, defined by a CD4+ cell count of <200 cells/mm3 or by the presence of AIDS-defining illness irrespective of the CD4+ cell count12. Some of the most common AIDS-defining illnesses include opportunistic infections such as esophageal candidiasis, Pneumocystis jiroveci pneumonia, disseminated mycobacterial and Histoplasma infection, and malignant diseases such as Kaposi sarcoma and high-grade lymphomas13.
Once the CD4+ count drops below 50 cells/mm3, the mean survival is 12 to 18 months in the absence of antiretroviral therapy (ART)14. Highly active antiretroviral therapy (HAART) reduces HIV transmission, restores immune function, reduces HIV-related morbidity and mortality, and improves survival13. The life expectancy of patients with HIV receiving optimum ART now might approach that of patients without HIV15.
HIV-Associated Non-AIDS Conditions
Untreated HIV infection is also associated with the development of non-AIDS-associated disease, such as cardiovascular disease, kidney disease, liver disease, neurological complications, and malignant disease. Even with higher CD4+ cell counts, HIV infection is associated with higher rates of age-related comorbidities16. Chronic inflammation, immune activation, and immunosenescence associated with HIV infection are some of the proposed mechanisms of this phenomenon17.
Cardiovascular disease has emerged as an important cause of death among HIV-infected patients18,19. The specific mechanisms and extent of how the HIV infection itself, the use of HAART, and traditional cardiovascular risk factors contribute to the increased risk of cardiovascular disease in these patients remain unknown. Even when adjusted for age, sex, race, hypertension, diabetes mellitus, and cholesterol, HIV infection has been associated with a substantially higher prevalence of coronary artery disease19.
Studies have suggested that higher CD4+ cell counts and lower HIV RNA levels are associated with lower rates of myocardial infarction, suggesting that the initiation of HAART also could be beneficial for reducing the cardiovascular risk20,21. Hypertension, dyslipidemia, and other cardiovascular risk factors such as smoking also have been reported to be considerably higher in patients with HIV than in the general population19. The use of some antiretroviral drugs, such as protease inhibitors, also has been linked to the development of insulin resistance and other metabolic abnormalities22.
HIV-infected patients also have an increased incidence of a variety of cancers and precancerous lesions. In the era before the use of ART, Kaposi sarcoma, non-Hodgkin lymphoma, and invasive cervical cancer were the most predominant malignant diseases among HIV-infected individuals. The widespread use of ART has changed the spectrum of neoplasias in this population. Non-AIDS-defining cancers now account for an increasing proportion of death among HIV-infected patients23.
Bone Disorders in HIV-Infected Patients
Osteonecrosis of the hip also has been associated with HIV infection24. A cross-sectional study demonstrated that the prevalence of osteonecrosis of the hip was 4.4% in HIV-infected patients, compared with 0% in asymptomatic controls25. The etiological basis for this increased prevalence is thought to be multifactorial. In addition to known agents such as corticosteroids and alcohol, HIV has been associated with some vasculitides, which cause subacute swelling and disruption of the vascular endothelium, leading to necrosis of bone26-28. Finally, HAART has been independently associated with osteonecrosis, although this relationship is controversial and is not clearly understood29. Some have suggested that many of the side effects of ART, such as hyperlipidemia, pancreatitis, hyperuricemia, and osteomyelitis may be responsible for this association29.
Intravenous drug use and HIV infection are both independent risk factors for native septic joint infections, which can alter the joint surfaces, often necessitating a subsequent TJA for painless use of that joint30,31. In summary, a multitude of causes have led to a growing need for TJA in patients with HIV infection and warrant the attention of health-care providers (Table I).
Total Joint Arthroplasty in Patients with HIV
We searched MEDLINE for articles that discussed TJA in HIV-infected patients with use of the following keywords: “HIV,” “total joint,” “total hip,” and “total knee.” We included articles that discussed outcomes of elective arthroplasty in HIV-infected patients. We excluded articles in which the data from patients with HIV could not be isolated from the data for a larger group. In addition, we reviewed the bibliography of included articles to ensure that we included the most relevant articles.
There has been recent interest in performing TJA for patients with HIV given the increase in demand, along with a focus on identifying potential complications, patient stratification, and perioperative measures to improve outcomes. Articles on TJA in patients with HIV are discussed below. A summary of these articles can be found in Table II.
Initial reports on these patients often described high rates of complications in the postoperative period. Parvizi et al. described their experience with TJA in 15 patients (21 joints; 13 knees and 8 hips) in 200332. Thirteen of the 15 patients received HAART at some point during the course of the study, but only 3 patients were receiving the medications at the time of the arthroplasty. The authors encountered a high rate of complications, including 6 deep joint infections (29%), 4 instances of aseptic loosening (19%), and 3 knee hematomas (14%). A total of 13 repeat operations were performed to address the various complications. The average CD4+ count was 239 cells/mm3 for the patients with joint infection, compared with 523 cells/mm3 in the study population as a whole.
Similarly, in 2001, Lehman et al. reported a deep infection rate of 14.3% (4 of 28 joints) in HIV-positive patients and 40% (2 of 5 joints) in HIV-positive patients who were also current intravenous drug users33. CD4+ counts and use of HAART were not disclosed.
Importantly, it should be noted that patient populations that were initially studied were not beneficiaries of HAART as the treatment was introduced in 1997, after a majority of the operations in the above studies took place. More recent studies, however, have demonstrated improved outcomes following TJA in HIV-infected patients. These findings may be attributed to our improved understanding of the disease, the inception of HAART treatment (which helped to maintain CD4+ levels), and a multidisciplinary approach that centered on close monitoring of these patients by the infectious-disease community34-37. Lin et al. queried the Nationwide Inpatient Sample to identify patients who underwent primary TJA between 2000 and 2008 to identify comorbidities and perioperative complications in HIV-positive patients34. They found that HIV-infected patients who underwent TJA were more likely to be younger, to be male, and to have a history of intravenous drug abuse, alcoholism, and osteonecrosis. The authors identified a higher rate of wound infection in patients with HIV undergoing total hip arthroplasty (0.6% compared with 0.3%; p = 0.02). However, when the authors evaluated the overall rate of complications in the group of patients who underwent surgery between 2000 and 2008, no significant differences were identified in either the hip or knee replacement groups when HIV-positive and HIV-negative patients were compared. Unfortunately, long-term outcomes were not reported in that study.
Graham et al., in 2014, reviewed the Malawi (southeast Africa) database for HIV-positive patients who underwent total hip arthroplasty35. The authors identified 29 patients who underwent 43 hip replacement operations, were HIV-positive, and had no history of intravenous drug abuse or hemophilia. All patients had been receiving HAART for an average of 6 years, and the average CD4+ count was 489 cells/mm3 preoperatively. The authors reported no early (<6 weeks) or late (>6 weeks) complications such as dislocation, deep-vein thrombosis (DVT), pulmonary embolism (PE), or superficial or deep wound infection. In addition, they reported substantial improvement in the average Harris hip score, from 27 preoperatively to 86 postoperatively (p < 0.05)35,38.
Tornero et al., in 2012, compared 13 HIV-positive patients (18 hips) with 27 HIV-negative patients (36 hips) who had undergone total hip arthroplasty for the treatment of osteonecrosis of the femoral head between 2001 and 2010 in Barcelona, Spain36. For the HIV-positive group, the viral load was <50 copies/mL in all but 1 patient and the mean CD4+ count was 434 cells/mm3. There were no significant differences between the 2 groups in terms of operative time (109 compared with 106 minutes; p = 0.66), duration of hospitalization (9.4 compared with 7.8 days; p = 0.16), blood loss (3 compared with 2.6 g hemoglobin/dL; p = 0.56), or functional results based on the Merle d’Aubigné scale39. Similarly, short and long-term outcomes were not significantly different between the 2 groups.
Lin et al., in a retrospective review, compared HIV-positive and HIV-negative patients who had undergone TJA at their institution between 2003 and 201040. The authors found no significant differences between the groups in terms of the rate of deep infection (9.1% for HIV-positive patients, compared with 2.2% for HIV-negative patients; p = 0.102) or the rate of revision for all causes (9.1% for HIV-positive patients, compared with 5.4% for HIV-negative patients; p = 0.357). The 2 patients who needed revision surgery for the treatment of deep infection at the site of the implant had CD4+ counts of 1,147 and 563 cells/mm3 prior to the revision procedure, compared with 32 and 18 cells/mm3, respectively, after the revision procedure. The authors suggested that perhaps the trending of the CD4+ count may be a better predictor of successful outcome. A declining yet normal CD4+ count may indicate a worsening immune status, whereas a stable yet low-normal CD4+ count may indicate a stable immune system.
Although specific recommendations for serial CD4+ cell counts prior to the procedure were not given in the study by Lin et al.40, regular cell counts by the infectious-disease specialist may be beneficial for helping to better characterize a patient’s risk profile for complications. Postoperatively, the CD4+ cell counts should be followed and perhaps reviewed at regular follow-up visits with the orthopaedic surgeon, given that there have been some suggestions that complications may be associated with declining counts because of either worsening of the HIV disease process or perhaps diminished adherence to HAART40. Similarly, viral loads in the perioperative period may lend insight into complication rates. Although high-level data correlating HIV viral loads with complication rates are not available in the arthroplasty literature to our knowledge, Horberg et al., in a study of patients undergoing surgical procedures (including both orthopaedic and non-orthopaedic procedures), found that HIV viral loads of <500 copies/mL were associated with minimal complications whereas HIV viral loads of >30,000 copies/mL were associated with an increased risk of complications41. More importantly, there is a strong need for prospective studies that will specifically examine the correlation between longer-term surgical complications and markers of severity of the HIV infection, such as CD4+ cell counts and viral loads.
Naziri et al., in what we believe to be the largest such study to date, used data from the Nationwide Inpatient Sample to compare HIV-positive and HIV-negative patients who had undergone TJA from 1998 to 2010 in the United States42. The authors identified 9,275 patients with HIV and roughly 2.7 million patients without HIV who had undergone a total hip arthroplasty. They found that HIV-positive patients had an increased rate of major complications (2.9% compared with 2.7%; p = 0.014), an increased rate of minor complications (5.2% compared with 4.8%; p = 0.001), and an increased length of hospital stay (4.31 compared with 3.83 days; p = 0.001). Although the differences between HIV-positive and HIV-negative patients were significant, the authors of that study were not against performing TJA for patients with HIV who otherwise met reasonable surgical indications, as they thought that the statistical differences that they identified were not clinically significant. The authors did not report the CD4+ counts or HAART status.
The advent of HAART has allowed HIV-infected patients to live longer than ever before. Unfortunately, this patient population is subject to an increased risk of osteonecrosis and degenerative changes compared with the HIV-negative population; osteonecrosis is a common complication in HIV-positive patients that can require TJA at later stages of disease. Studies have shown that the use of ART has allowed CD4+ counts to remain at a relatively normal level, which seems to be associated with better outcomes5. A correlation between a low CD4+ count (<200 cells/mm3) and major postoperative complications such as deep joint infection also has been postulated40. Declining CD4+ counts after TJA also may expose patients to a risk of subsequent infection, even after a successful index procedure40. Although this inference is yet to be supported by high-level evidence, the studies that exist today point in that direction36,40,41. On the basis of the indirect evidence present in the current literature, a CD4+ count of >400 cells/mm3 may be used as the lower limit of acceptable before proceeding with an elective arthroplasty. Similarly, viral loads of <50 copies/mL are ideal for patients undergoing such surgery41.
On the basis of the available studies in the literature and the conclusions that can be drawn from them, it is our recommendation that ongoing CD4+ and HIV viral load monitoring, as well as patient adherence to HAART medications, should become part of the routine management strategy for patients in this at-risk population who undergo any orthopaedic procedure. CD4+ cell counts and viral loads should be routinely assessed before the operation to ensure that they remain stable after the operation. Postoperatively, the patient should be monitored in the intermediate and longer term for potential CD4+ count decline or HIV viral load rise that may indicate lack of adherence to the HAART regimen and that also may be a harbinger for potential TJA-related complications. Additional prospective investigation is needed to better define the exact relationship between the rate of decline in the CD4+ count and susceptibility to complications such as periprosthetic joint infection.
Given the variety of medical comorbidities that plague the HIV population, a medical clearance with special focus on the cardiovascular system (hypertension, hyperlipidemia, organic cardiac disease) and endocrine system (diabetes mellitus) should be obtained. Similarly, a thorough social history should be obtained to screen for current intravenous drug use and urine toxicology testing should be performed to screen for evidence of drug abuse. Evidence of illicit drug use should be a strong contraindication for TJA given its implications for future infections and complications.
Perioperatively, given that most studies have not demonstrated an increase in the incidence of DVT in patients with HIV/AIDS, our recommendation is to use the standard prophylaxis that is followed by the operating surgeon.
Fortunately, the recent literature supports the use of TJA for patients with HIV, despite the elevated risk of some perioperative complications in such patients. Ideally, this higher-risk population should be comprehensively evaluated preoperatively by a multidisciplinary team of specialists with an understanding of the individual risk factors for each patient. If performed safely, TJA can lead to similar functional outcomes in patients with HIV as in control populations and therefore is a viable solution for improving quality of life. The lessons learned from performing TJA in the HIV-positive population can likely be extrapolated to all other areas of orthopaedic surgery in order to educate surgeons and to improve patient safety.
Finally, attention must be directed to the safety of the surgeon and operating-room personnel who care for these patients. Identifying that a patient has HIV during the routine time-out process prior to the onset of surgery may help all personnel to be vigilant throughout the duration of the operation. A recent Cochrane review indicated that double-gloving lowers the risk of intraoperative fluid exposure secondary to a needle-stick or sharps injury43. Although no evidence exists, careful handling of sharps in the operating room with use of a plastic kidney-shaped basin to pass instruments may prove beneficial.
Investigation performed at Brown University, Providence, Rhode Island
Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had other relationships or activities that could be perceived to influence, or have the potential to influence, what was written in this work.
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