HIV and the Musculoskeletal System

Why it matters. Musculoskeletal complications affect 20-40% of people with HIV, and the subject is tested regularly. With effective antiretroviral therapy, HIV-positive patients are living longer and presenting for elective and trauma orthopaedic surgery in increasing numbers, so the surgeon needs the spectrum of HIV-associated musculoskeletal pathology, the altered infection risk, the perioperative implications of HIV and ART, and the management of an occupational exposure.

Who and where. Approximately 39 million people are living with HIV worldwide. Sub-Saharan Africa carries the highest burden, and its musculoskeletal disease is dominated by infection and trauma. In high-income settings the cohort is ageing, and degenerative disease and elective surgery are increasing.

The scale of the risk. Septic arthritis is 10-15 times more common than in the general population. Osteonecrosis prevalence is put at up to 1-4%, higher than age-matched controls; Miller's MRI survey of asymptomatic HIV-infected adults (evidence base) found femoral-head lesions in 4.4%, against none of the matched controls. Fragility fracture incidence is 30-70% higher on ART, and surgical site infection rates are higher when the CD4 count is under 200 cells/uL or the patient is viraemic at surgery.

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Five overlapping mechanisms. HIV reaches the skeleton by more than one route, and several usually act together: a direct viral effect on immune cells and bone turnover, opportunistic infection from immunosuppression, ART toxicity, immune reconstitution inflammatory syndrome (IRIS), and a chronic systemic inflammation that persists even on suppressive ART.

Direct viral effect on bone. The HIV proteins Tat and gp120 activate the RANKL pathway (RANKL/RANK/OPG), which promotes osteoclast differentiation and bone resorption while osteoblast function falls. The result is osteopenia, osteoporosis and fragility fracture, and the persistent cytokine elevation of chronic inflammation (TNF-alpha, IL-6) drives ongoing bone loss on top of it.

Immunosuppression. CD4 depletion opens the door to opportunistic infection: septic arthritis, osteomyelitis and spinal tuberculosis. A CD4 count under 200 cells/uL is the major risk threshold.

ART toxicity. Tenofovir disoproxil fumarate (TDF) causes proximal renal tubular toxicity with phosphate wasting, which lowers bone mineral density further. Protease inhibitors alter vitamin D metabolism and lipid profiles, and the dyslipidaemia contributes to AVN through vascular mechanisms. Between them, ART toxicity is linked to AVN, fragility fractures and tendon rupture.

Immune reconstitution inflammatory syndrome. Rapid immune recovery after ART is started in a patient with an existing opportunistic infection produces a paradoxical inflammatory reaction: new or worsening arthritis, tenosynovitis or osteomyelitis within weeks of starting ART. It occurs while the CD4 count is rising and the viral load falling, which is what separates it from treatment failure. Management is to continue ART, treat the underlying infection, and consider NSAIDs or a short course of corticosteroids for the inflammation.

Chronic systemic inflammation. Persistent immune activation, even on suppressive ART, drives rheumatologic-type disease: HIV-associated arthropathy, reactive arthritis and vasculitis.

ArthropathySeptic ArthritisAvascular Necrosis

Four patterns. HIV-associated arthropathy is a diagnosis of exclusion, made once infection has been ruled out by aspiration. The four patterns:

HIV-associated arthralgia

Features

Migratory arthralgia, no joint destruction, self-limiting

CD4 Context

Any CD4 level, often at seroconversion

Treatment

NSAIDs, rest; resolves in weeks

Reactive arthritis-like pattern

Features

Asymmetric oligoarthritis, enthesitis, dactylitis

CD4 Context

Often early HIV, higher CD4

Treatment

NSAIDs, sulphasalazine; ART may help

Psoriatic arthritis-like pattern

Features

Distal joint involvement, nail changes, psoriasis

CD4 Context

Variable CD4

Treatment

NSAIDs, methotrexate (caution), biologics if refractory

Painful articular syndrome

Features

Severe acute joint pain hours to days, no swelling

CD4 Context

Advanced HIV (low CD4)

Treatment

NSAIDs; self-limiting but distressing

Pattern	Features	CD4 Context	Treatment
HIV-associated arthralgia	Migratory arthralgia, no joint destruction, self-limiting	Any CD4 level, often at seroconversion	NSAIDs, rest; resolves in weeks
Reactive arthritis-like pattern	Asymmetric oligoarthritis, enthesitis, dactylitis	Often early HIV, higher CD4	NSAIDs, sulphasalazine; ART may help
Psoriatic arthritis-like pattern	Distal joint involvement, nail changes, psoriasis	Variable CD4	NSAIDs, methotrexate (caution), biologics if refractory
Painful articular syndrome	Severe acute joint pain hours to days, no swelling	Advanced HIV (low CD4)	NSAIDs; self-limiting but distressing

The organism follows the CD4 count. Staphylococcus aureus is the most common organism at every CD4 level, as in the general population, and the knee is the joint it most often affects. Below 200 cells/uL Salmonella and Mycobacterium tuberculosis become real possibilities; below 50 atypical mycobacteria and fungi (Candida, Cryptococcus, Aspergillus) join the list, and disseminated MAC suggests very advanced HIV. Neisseria gonorrhoeae is common in young sexually active patients at any CD4 count.

Staphylococcus aureus

CD4 Context

Any CD4 level

Joint Pattern

Monoarthritis, knee most common

Key Notes

Most common organism in HIV as in general population

Neisseria gonorrhoeae

CD4 Context

Any CD4 level

Joint Pattern

Migratory polyarthralgia plus tenosynovitis

Key Notes

Common in young sexually active patients

Salmonella species

CD4 Context

CD4 less than 200

Joint Pattern

Septic arthritis or osteomyelitis; bacteraemia common

Key Notes

Recurrent salmonella infection is AIDS-defining

Mycobacterium tuberculosis

CD4 Context

CD4 less than 200 (often less than 100)

Joint Pattern

Spine (TB spondylitis), hip, knee; indolent onset

Key Notes

High in endemic regions; AFB culture and PCR on aspirate

Atypical mycobacteria (MAC)

CD4 Context

CD4 less than 50

Joint Pattern

Indolent osteomyelitis or septic arthritis

Key Notes

Disseminated MAC suggests very advanced HIV

Candida and fungal organisms

CD4 Context

CD4 less than 50

Joint Pattern

Large joint, indolent; seed from disseminated disease

Key Notes

Consider in IV drug users with advanced HIV

Organism	CD4 Context	Joint Pattern	Key Notes
Staphylococcus aureus	Any CD4 level	Monoarthritis, knee most common	Most common organism in HIV as in general population
Neisseria gonorrhoeae	Any CD4 level	Migratory polyarthralgia plus tenosynovitis	Common in young sexually active patients
Salmonella species	CD4 less than 200	Septic arthritis or osteomyelitis; bacteraemia common	Recurrent salmonella infection is AIDS-defining
Mycobacterium tuberculosis	CD4 less than 200 (often less than 100)	Spine (TB spondylitis), hip, knee; indolent onset	High in endemic regions; AFB culture and PCR on aspirate
Atypical mycobacteria (MAC)	CD4 less than 50	Indolent osteomyelitis or septic arthritis	Disseminated MAC suggests very advanced HIV
Candida and fungal organisms	CD4 less than 50	Large joint, indolent; seed from disseminated disease	Consider in IV drug users with advanced HIV

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Who gets it. HIV itself and protease inhibitor-based ART are both implicated, and corticosteroids, alcohol and smoking add to the risk. Protease inhibitor-based ART is an independent risk factor, and the risk increases with PI duration; the Miller MRI survey in the evidence base did not implicate protease inhibitors. Combined risk factors make multifocal disease more likely.

HIV infection itself

Mechanism

Direct endothelial damage, procoagulant state, raised intraosseous pressure

Common Sites

Femoral head (60-80%), humeral head, femoral condyles

Presentation

Insidious groin pain, worse with weight-bearing

Protease inhibitor-based ART

Mechanism

Dyslipidaemia, lipid-induced vascular occlusion, impaired fibrinolysis

Common Sites

Same sites; risk increases with PI duration

Presentation

Similar to non-HIV AVN but at younger age

Corticosteroid use

Mechanism

Increased intraosseous pressure, fat cell hypertrophy, osteocyte death

Common Sites

Multifocal AVN more likely with combined risk factors

Presentation

Rapid onset after high-dose or prolonged steroids

Alcohol and smoking

Mechanism

Additional hepatotoxicity and vascular injury

Common Sites

Compounding risk in HIV patients

Presentation

Counsel on smoking cessation and alcohol reduction

Risk Factor	Mechanism	Common Sites	Presentation
HIV infection itself	Direct endothelial damage, procoagulant state, raised intraosseous pressure	Femoral head (60-80%), humeral head, femoral condyles	Insidious groin pain, worse with weight-bearing
Protease inhibitor-based ART	Dyslipidaemia, lipid-induced vascular occlusion, impaired fibrinolysis	Same sites; risk increases with PI duration	Similar to non-HIV AVN but at younger age
Corticosteroid use	Increased intraosseous pressure, fat cell hypertrophy, osteocyte death	Multifocal AVN more likely with combined risk factors	Rapid onset after high-dose or prolonged steroids
Alcohol and smoking	Additional hepatotoxicity and vascular injury	Compounding risk in HIV patients	Counsel on smoking cessation and alcohol reduction

How it presents. Insidious groin pain, worse with weight-bearing, at a younger age than AVN in the general population, and multifocal in up to 40% of cases. The femoral head (60-80%) is the commonest site; the humeral head, femoral condyles and tibial plateau follow. A young patient with bilateral hip pain and multifocal osteonecrosis who has never used corticosteroids and does not have sickle cell disease should prompt HIV testing.

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Pyomyositis. A swollen joint is not the only soft-tissue infection in HIV; bacterial pyomyositis is a classic and frequently missed manifestation. It is a primary bacterial infection of skeletal muscle, not contiguous spread from bone or skin, and HIV is the dominant risk factor in both tropical ("tropical pyomyositis") and temperate settings. Staphylococcus aureus causes roughly 90% of cases. It favours the large muscles of the lower limb and pelvis (quadriceps, gluteals, iliopsoas) and is multifocal in up to a quarter of HIV cases.

Three clinical stages. Knowing them prevents the classic miss:

• Stage 1, invasive or diffuse. Crampy deep muscle pain with woody induration and low-grade fever. Pus has not yet formed and the overlying skin looks normal, so it is repeatedly mistaken for a strain, a DVT or cellulitis
• Stage 2, suppurative (around 2 to 3 weeks). A frank intramuscular abscess with fluctuance and systemic upset. Most patients present here
• Stage 3, late or septic. Bacteraemia, metastatic abscesses and septic shock

Investigation and management. MRI is the best test, showing muscle oedema and then a rim-enhancing collection; ultrasound guides aspiration. Inflammatory markers are raised, but creatine kinase is often normal or only mildly elevated, a clue that distinguishes it from a primary myositis. Anti-staphylococcal antibiotics (empirical MRSA cover per local prevalence) treat the early invasive stage; once an abscess has formed it needs drainage, image-guided or open, and in advanced HIV the pus goes for AFB and fungal culture too. A deep muscle with woody induration and normal overlying skin in an HIV patient should trigger immediate suspicion.

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Non-infective myopathy. The muscle can also fail without infection, and telling the causes apart is a recognised discriminator:

• HIV-associated polymyositis. Symmetrical proximal weakness and myalgia with a markedly raised creatine kinase, often more than ten times normal. It can appear at any stage, including seroconversion; biopsy shows an inflammatory infiltrate. Treat with corticosteroids or IVIG alongside ART optimisation
• Zidovudine (AZT) mitochondrial myopathy. Chronic zidovudine inhibits mitochondrial DNA polymerase gamma, producing ragged red fibres on biopsy, proximal weakness, myalgia, a raised creatine kinase and a raised serum lactate. The cardinal discriminator is that it improves after stopping or switching zidovudine: the temporal link to the drug and the recovery on withdrawal separate it from HIV polymyositis
• HIV-associated wasting / sarcopenia. Unintentional loss of more than 10% of body weight with muscle depletion is an AIDS-defining process and compounds perioperative and fracture-healing risk

The statin trap. Ritonavir- or cobicistat-boosted protease inhibitors inhibit CYP3A4 and sharply raise the levels of CYP3A4-metabolised statins (simvastatin, lovastatin), precipitating myositis and even rhabdomyolysis. Use pravastatin, rosuvastatin or low-dose atorvastatin instead, and consider a drug interaction whenever an HIV patient on a boosted regimen develops new muscle pain or weakness. New muscle inflammation soon after starting ART, while the CD4 count is rising and the viral load falling, may be IRIS rather than a primary myopathy.

History. Start with the HIV: duration of diagnosis, current ART regimen, CD4 count and viral load, then the CD4 trajectory, opportunistic infection history and any AIDS-defining illness that stratify the risk. Ask specifically about the ART agents with musculoskeletal side effects, tenofovir for bone density and protease inhibitors for AVN and dyslipidaemia. The musculoskeletal history covers the pattern of joint pain, swelling, duration, fever, weight loss and night pain; the exposure history covers needlestick injury, occupation and travel to TB-endemic areas.

Examination. Look first for the markers of advanced HIV: cachexia, Kaposi lesions and oral candidiasis. Then examine the joint for effusion, range of motion, tenderness, erythema and warmth. Three patterns to recognise:

• Septic joint. Painful, hot, swollen, restricted range, fever and systemic signs
• Hip AVN. Loss of internal rotation is the earliest sign; FABER positive; groin pain on flexion and internal rotation
• Spinal TB. Gibbus deformity, spinous process tenderness, neurological deficit

Baseline bloods. They establish immune status, nutritional bone health and the inflammatory markers that will be used for monitoring:

• Routine: FBC, CRP, ESR, LFTs, renal function, calcium, phosphate, ALP, vitamin D
• HIV-specific: CD4 count (current and nadir), HIV viral load, current ART regimen
• Serology: rheumatoid factor and anti-CCP if the pattern is inflammatory; hepatitis B and C

The joint. Aspirate any swollen joint, as above. Plain AP and lateral radiographs of the affected joint show osteopenia, erosions and the late signs of AVN (crescent sign, collapse), but they are normal in early AVN and in early infection. Ultrasound detects an effusion, guides aspiration and assesses synovitis and tenosynovitis.

MRI. The gold standard for avascular necrosis, osteomyelitis and spinal TB (disc destruction, paraspinal collection). In AVN the characteristic finding is a serpiginous low-signal line on T1-weighted images surrounding a high-signal area, the double-line sign on T2. MRI detects AVN before any radiographic change, so it is requested at once when AVN is suspected in a high-risk patient with hip pain: by the time sclerosis or a crescent sign shows on the radiograph the disease is already Ficat II, and subchondral collapse is Ficat III.

CT and nuclear medicine. CT assesses bone destruction in chronic osteomyelitis and guides surgical planning for spinal TB. A bone scan is used when multifocal AVN is suspected, as whole-body screening for asymptomatic sites.

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Bone health. DEXA is targeted, not a blanket rule: any patient with a fragility fracture, all post-menopausal women with HIV and all HIV-infected men aged 50 and over (the McComsey recommendations), plus anyone on tenofovir-DF with biochemical evidence of phosphate wasting. FRAX incorporates HIV as a secondary cause of osteoporosis. The biochemistry is 25-OH vitamin D, PTH, calcium and phosphate, the phosphate screening for tenofovir-induced renal phosphate wasting. Repeat DEXA every 2-3 years in patients on tenofovir, with a low baseline BMD, or with an abnormal result or ongoing risk.

Three domains. Operating on an HIV-positive patient means addressing immune status (CD4 count and viral load), ART continuation, and the interactions between ART and anaesthetic agents, antibiotics and analgesics. HIV medicine, anaesthetics and pharmacy are involved. CD4 count and viral load guide the risk, not HIV status alone, and the viral load is always checked alongside the CD4 count:

ART is continued without interruption. Interruption causes viral rebound within days, risks drug resistance and can trigger IRIS on restarting. The regimen is checked before surgery for interactions with the planned anaesthetic and analgesic drugs; protease inhibitors interact with CYP450 and may alter analgesic metabolism, so the anaesthetist is warned. The only exception is a specific drug interaction (ritonavir-boosted regimens with certain sedatives, for example), which is handled by physician-guided temporary substitution rather than cessation.

• Nil by mouth: ART is taken with a sip of water on the morning of surgery, coordinated with the anaesthetist
• Post-operatively: resume as soon as the patient can take oral medication

Wound healing. Optimise nutrition (albumin, zinc, vitamin C and D; consider dietitian referral), use meticulous technique, and delayed primary closure in contaminated cases. Antibiotic prophylaxis is standard, with extended cover considered if the CD4 count is under 200. Hepatitis B and C co-infection is common, so check LFTs and coagulation pre-operatively. Smoking cessation is critical, because smoking compounds the HIV-related and surgical risks to wound healing.

Why the orthopaedic theatre. Orthopaedic surgeons have one of the highest occupational exposure rates among surgical specialties: K-wires, pins, drill bits, sharp instruments and power tools in a bloody field. All theatre staff must know the PEP protocol, where the starter pack is stored and who to call. PEP is not delayed until occupational health opens; it is started in the emergency department if the starter pack is available, and it is started on the exposure risk, not on the source patient's known status, since a patient may be HIV-positive and undiagnosed.

Immediately.

• Wash the wound: irrigate thoroughly with water or saline and encourage gentle bleeding. Do not squeeze it, apply antiseptics or cauterise
• Report to occupational health, the theatre manager and a senior colleague at once
• Assess the risk: depth of injury, device type (a hollow-bore needle is highest risk), visible blood and the source patient's viral load
• Identify the source patient and test for HIV, hepatitis B and hepatitis C, with consent

Starting PEP. Efficacy is time-dependent: starting within 1 hour gives the highest protection, it declines rapidly after 24 hours, and PEP is never started after 72 hours. The regimen is three drugs, tenofovir/emtricitabine (TDF/FTC or TAF/FTC) plus dolutegravir or bictegravir, for 28 days of continuous treatment. Baseline bloods are an HIV test of the exposed person, hepatitis B and C serology, LFTs and renal function. Counsel on side effects (nausea, fatigue, myalgia), the importance of adherence and the follow-up schedule.

Follow-up.

• Week 6: fourth-generation HIV antibody test; assess adherence and manage side effects
• Week 12: repeat HIV test; hepatitis C RNA if the source was HCV-positive
• Week 24: final HIV antibody test to confirm negative status
• Complete the incident report, occupational health follow-up and psychological support

Closed fractures. In well-controlled HIV (CD4 over 350 with an undetectable viral load on ART) fracture healing and union rates are comparable to the general population, so standard fixation techniques, standard weight-bearing protocols and standard implants apply; no implant is superior in HIV. Problems arise in advanced, uncontrolled HIV with malnutrition and immunosuppression, where weight-bearing is advanced with caution. Peri-articular fractures use standard approaches, with an eye to the AVN risk at already-compromised sites.

Open fractures. Debridement is prompt and urgent, but the six-hour rule is not supported (PMID 34058873): timing follows open-fracture standards, with extended antibiotics and staged management. The infection risk that is documented declares itself late, as the table shows, so the follow-up intensity is held for a year, not a month. In uncontrolled HIV, early aggressive debridement, extended antibiotic cover and careful soft-tissue management remain essential.

Bone health on ART. TDF is associated with 1-3% BMD loss per year through renal phosphate wasting. Check 25-OH vitamin D and supplement to over 30 ng/mL, ensure a calcium intake of 1000-1200 mg/day, and encourage weight-bearing exercise. If BMD loss is significant, consider switching TDF to TAF, checking phosphate and renal function first, since TDF tubulopathy (up to Fanconi syndrome) is the mechanism to exclude. The case below runs the whole sequence: a diffusely osteoporotic pelvis, bilateral femoral-neck stress fractures on CT and MRI, and the DXA that quantified the fragility.

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The one that matters most. Joint destruction from undiagnosed septic arthritis. HIV patients have a higher baseline prevalence of arthralgia and inflammatory arthritis, so there is a real risk of attributing a hot swollen joint to HIV-associated arthropathy when it is actually septic. The consequences are rapid chondral destruction, osteomyelitis and permanent functional loss.

What decides the outcome. The best prognosis belongs to well-controlled HIV (CD4 over 350, suppressed viral load), early presentation, prompt treatment of infection, good nutritional status and ART adherence. The poor-prognosis features are advanced HIV (CD4 under 200), viraemia at surgery, delayed diagnosis of septic arthritis, malnutrition, atypical organisms (TB, fungal) and open fractures. A CD4 count of 200 cells/uL is the single most important perioperative decision point: above it, outcomes approach those of non-HIV patients; below it, complication rates rise significantly.