1) Modern antiretroviral treatment has increased life expectancy for HIV-positive patients, resulting in more presenting for elective and emergency orthopaedic surgery. 2) HIV-positive patients can experience various musculoskeletal manifestations including bone disorders, joint diseases, myopathies, and neoplasms. Common conditions include osteomyelitis, osteonecrosis, septic arthritis, and Kaposi sarcoma. 3) Outcomes for procedures like joint replacements and fracture treatments in HIV-positive patients have been found to be comparable to HIV-negative patients when considering infection and complication rates, with some increased risk for certain patient subgroups or procedures. Overall management requires consideration of individual factors like CD4 count and viral load

1. CURRENT CONCEPTS
REVIEW- HIV and
ORTHOPAEDICS
Dr. Libin Thomas Manathara
A Journal Club presentation at
Amala Institute of Medical Sciences, Thrissur

2. Introduction
• A larger number of HIV-positive patients may present for elective and
emergency surgery as modern antiretroviral treatment has increased
life expectancy and quality of life
• A young person with promptly recognized and treated HIV infection
should now have a life expectancy very similar to that of age-
matched, uninfected individuals

3. Topics
• Musculoskeletal Manifestations
• Outcomes in Orthopaedic Surgery

4. Musculoskeletal Manifestations
• Bone Disorders
• Osteomyelitis
• Osteonecrosis
• Joint Disease
• Septic Arthritis
• Other arthropathies
• Myopathies
• Infectious Pyomyositis
• Primary and/or Noninfectious Myositis
• Neoplasms
• Kaposi Sarcoma
• Non-Hodgkin Lymphoma

5. Bone disorders- Osteomyelitis
• 13% of cases of tuberculosis are associated with HIV
• The spine is the most common site of involvement
• Because of the relative lack of proteolytic enzymes, tuberculosis has a tendency to spare the
intervertebral disc, spreading in a subligamentous fashion in the anterior soft tissues, and
resulting in partially calcified “cold abscesses” that show little evidence of active inflammation
• In HIV-positive patients, there is a trend toward
• larger epidural abscesses
• less vertebral body collapse
• subsequent kyphosis
compared with endemic tuberculous spondylitis
• Among nontuberculous osteomyelitis, Staphylococcus represents the most common
cause in adults with HIV
• Other causes of osteomyelitis in HIV-infected patients include secondary syphilis and
bacillary angiomatosis caused by Bartonella henselae

6. Bone disorders- Osteonecrosis
• Osteonecrosis may be directly mediated by the HIV virus or may be secondary to
embolic phenomena because of antiphospholipid antibody formation, protein S
deficiency, and hypergammaglobulinemia
• Magnetic resonance imaging (MRI) has a sensitivity of 99% and is the imaging
modality of choice for diagnosis and staging
• There is no effective treatment to arrest, delay, or reverse the progression of
subchondral collapse and bone destruction, and surgery is often required

7. Joint disease- Septic Arthritis
• Arthropathy commonly arises from both pyogenic and atypical organisms
• Older literature had suggested that opportunistic infections accounted for a
majority of the cases of septic arthritis in HIV patients; however, more
recently, authors have maintained that Staphylococcus aureus remains the
most common pathogen in septic arthritis regardless of HIV status
• A high index of suspicion of opportunistic organisms in septic arthritis is
required when patients present with a CD4 count of <200/mm
• The Phemister triad, consisting of
• peripheral erosions
• juxtaarticular osteopenia
• gradual joint-space loss,
has been classically associated with mycobacterial arthropathy

8. Joint disease- Other arthropathies
• Primary HIV arthropathy is a transient (duration of <6 weeks), non erosive,
oligoarthritis preferentially affecting the lower extremities
• Seronegative spondyloarthropathies such as psoriatic arthritis and reactive
arthritis are 40 to 200 times more common in HIV-infected patients- here disease
course is frequently more debilitating in the setting of HIV than in non infected
patients

9. Myopathies- Infectious Pyomyositis
• Bacterial myositis (pyomyositis) is one of the more common late complications
of HIV to affect the musculoskeletal system
• The most frequently implicated organism is S. aureus
• Pyomyositis is very often an indicator of late-stage with CD4 counts typically
of <200 cells/mm
• There are 3 stages of pyomyositis that describe increasing disease severity:
invasive, suppurative, and late
• The serum creatinine kinase level, as opposed to the erythrocyte
sedimentation rate (ESR), is generally not elevated, in contradistinction to
polymyositis and rhabdomyolys
• Early recognition and aggressive management with parenteral antibiotics and
surgical drainage are mainstays of treatment

10. Myopathies- Primary and/or Noninfectious
Myositis
• Primary HIV infection can result in nonbacterial myositis and rhabdomyolysis
• Patients typically present with proximal muscle weakness that is relatively symmetric
• This entity should be a diagnosis of exclusion after a meticulous search for infectious
etiologies, including fungal, atypical mycobacterial, and other unusual organisms, has
been conducted
• MRI may aid in the identification of an optimal target from which to obtain tissue for
culture and biopsy
• Histologic examination shows extensive perivascular and interstitial lymphocytic
infiltration, necrosis, and phagocytosis of degenerated muscle tissue
• Seroconversion may present with influenza-like clinical features including myalgia, which
can be associated with MRI findings identical to those of polymyositis
• In fact, bilateral proximal muscle weakness and elevated serum creatinine kinase
presenting in high-risk individuals may justify screening for HIV

11. Neoplasms- Kaposi Sarcoma
• Kaposi sarcoma is an angioproliferative neoplasm, associated with
human herpesvirus 8, that is likely of lymphatic origin; typically involves
the skin, mucosa, and lymphatics; and, once the CD4 count decreases to
<200cells/mm3, appears as a late complication
• Kaposi sarcoma only rarely involves the musculoskeletal system, and
usually does so secondary to contiguous extension from mucocutaneous
involvement; however, there are case reports of metastatic
dissemination
• Most osseous lesions are osteolytic and destructive, although sclerotic
and expansile lesions are occasionally seen
• Treatment consists of chemotherapy and radiation

12. Neoplasms- Non-Hodgkin Lymphoma
• Non-Hodgkin lymphoma risk in HIV-positive patients is approximately 60 times
that in the general population
• Patients may present with painful limb swelling, pathological fracture and B-type
constitutional symptoms
• However, Santos et al. showed that, in AIDS patients with fevers of unknown
origin, bone marrow biopsy rarely resulted in the diagnosis of non-Hodgkin
lymphoma
• Skeletal involvement can be observed in up to 20% to 30% of patients and lesions
are typically osteolytic and commonly associated with a soft-tissue mass
• Because of the rapid tumor growth rate, periosteal reaction is frequently absent
• Anthracycline-based chemotherapy and radiation therapy (30to 40 Gy) should
follow as adjuvant treatment for consolidation and durable complete remission
• The 5-year overall survival is 5% to 10%

13. Outcomes in Orthopaedic Surgery
• Joint Replacements (Total Knee and Total Hip Arthroplasty)
• Hip Arthroplasty
• Knee Arthroplasty
• Orthopaedic Trauma
• Early Infection Rates
• Bone Union
• Late Infection
• Polytrauma

14. Hip Arthroplasty
• Lin et al demonstrated that HIV-positive patients are more likely than
HIV-negative patients to develop acute renal failure, a wound
infection and undergo postoperative irrigation and debridement
• However, HIV-positive patients were less likely to have a myocardial
infarction, and the overall complication rates were similar between
individuals with and without HIV infection
• Naziri et al found that HIV-positive patients compared with patients
who did not have HIV had an increased risk of major and minor
perioperative complications

15. Knee Arthroplasty
• Boylan et al found that people with HIV who had a total knee
arthroplasty had an increased risk of perioperative wound infections
and a longer length of stay but no increased adjusted risk of overall
complications

16. Cofactors
• Hemophilia: The deep infection rate is increased in HIV-positive patients with
hemophilia who have a revision
• CD4 counts: Patients with CD4 counts of <200 cells/mm3 had a tenfold increased
risk of infection
• Intravenous drug users: Patients who are intravenous drug users have an
increased deep infection rate and risk of total hip replacement failure
• cART: Treatment with cART may offer little or no overall difference in infection
rates, postoperative complications, clinical outcomes, or implant failure, on the
basis of the findings of nonrandomized controlled trials

17. Orthopaedic Trauma
• Low bone mineral density (BMD) and decreased bone mass affect HIV-infected
patients independently of age and sex
• HIV can generate the release of inflammatory cytokines that may promote
osteolysis and bone resorption
• Moreover, high concentrations of HIV RNA increases osteoclast presence in bone
• Particular concerns in treating fractures in HIV-positive patients include early and
late wound infection rates, bone union, and polytrauma

18. Early Infection Rates
• Older literature has suggested that HIV-positive patients with internal fixation of fractures had an
increased risk of infection but the use of cART has changed these findings
• Harrison et al used the ASEPSIS scoring system (Additional treatment, the presence of Serous
discharge, Erythema, Purulent exudate, and Separation of the deep tissues, the Isolation of
bacteria, and the duration of inpatient Stay) to assess wounds and found an infection rate of only
a 3.5% among HIV-positive patients which was comparable with that in the HIV negative group
(5%)
• When open fractures are involved, an increase in the infection rates can be expected
• Bates et al. found a slightly higher infection rates for open or contaminated fractures in HIV-
positive patients
• There is still controversy in this area
• External fixators are widely used for treating open fractures, but an increased pin-track infection
rate within HIV-positive patients has not been confirmed

19. Bone Union
• There are a number of issues that complicate the study of the effect of the HIV
status on the outcome of fracture-healing
• The unraveling of the effect of HIV infection from those of immune reconstitution
after cART, drug side effects, cachexia, and secondary infections demands
rigorous study designs, and for these reasons there is still controversy on this
topic
• It is well recognized that fracture-healing is initiated by an inflammatory response
to bone injury
• Although HIV infection is immunosuppressive, there are increased serum levels of
TNF-a, which in noninfected individuals would contribute to the formation of
callus and bone repair; however, an increased baseline level could lead to
desensitization, preventing or decelerating the healing process

20. Bone Union
• Harrison et al. found an increase in the incidence of nonunion of externally
stabilized tibial fractures in HIV-positive patients compared with HIV-negative
patients, although the difference was not significant
• The same authors, in a later prospective study of open tibial fractures did not find
any difference between patients with and without HIV with respect to fracture
union at 6 months
• As we can see, there is no correlation between clinical results and the theoretical
hypothesis mentioned above, i.e., that increased baseline levels of TNF-a could
lead to desensitization, preventing or decelerating the healing process; however,
this could be related to confounding bias when designing the studies and
warrants further investigation

21. Late Infection
• There is a theoretical risk of late infection around implants in patients
with HIV; however, this has not been proven in the clinical setting
• At this point, there is no indication to routinely remove implants after
fracture union

22. Polytrauma
• There is no difference in the mortality rate after polytrauma for HIV-positive
patients compared with HIV-negative patients
• But HIV-positive patients carry a higher risk of pulmonary, renal, and infectious or
septic complications
• Also, no difference has been found with respect to the length of stay in the
intensive care unit
• However, HIV-positive patients have a substantially longer hospital stay, probably
because of the complications that they develop
• The rates of early and late infection around implants in HIV-positive patients are
comparable with those in the HIV negative population HIV-infected individuals
have been shown to have a twofold to tenfold increased risk of venous
thrombosis, which has to be taken into account when treating this population

23. Overview
• Advances in cART in recent years have transformed HIV infection into a
chronic disease when treatment is available, increasing a patient’s life
expectancy and the chances that an orthopaedic surgeon will treat
patients within this population
• These patients can be affected by musculoskeletal conditions and
neoplasms that are usually not seen in immunocompetent individuals

24. Overview
• Furthermore, as life expectancy increases, HIV-positive patients are
more susceptible to age-related pathology such as osteoarthritis that
may require surgical intervention
• Since the advent of cART, total joint arthroplasty has been shown to
be a safe procedure; however, perioperative infection remains a small
risk in patients with uncontrolled viral loads or CD4 counts of <400
cells/mm3

25. Overview
• With regard to trauma surgery, the rates of early and late infection
around implants, as well as union rates, are comparable with those in
the HIV-negative population; however, there is an increased risk of
pulmonary, renal, and infectious or septic complications in the
polytrauma setting
• Factors such as CD4 count, nutritional status, cART, viral load count,
and other comorbidities (hemophilia, intravenous drug use, etc.)
should be considered when treating these patients in order to
optimize their outcomes

26. Overview
• Even though there are several studies dealing with this topic, we
should be aware of the limitations within this field such as the lack of
randomized trials involving HIV-infected patients and the missing data
related to CD4 count, viral load, nutritional status, and renal condition
in the perioperative period within some of these studies
• Future studies should take into account these limitations and should
record the details with regard to these factors since the use of cART is
now a more common treatment

27. Thank You