Disease and disease-related disability from non-AIDS co-morbidities

There is clear evidence that the burden of HIV-associated non-AIDS co-morbidities has been increasing steadily in people with HIV infection, with an increasing prevalence of CVD, CKD, osteoporosis, cancer and type 2 diabetes mellitus. [4, 38]

Bone disease

The primary objectives of bone health programmes in healthy adults are to prevent bone loss occurring prematurely and decrease fracture risk later in life. In addition to traditional risk factors, people with HIV infection are at increased risk of bone disease attributable to HIV-associated immune activation and exposure to antiretroviral drugs. [36] Those people on effective ART have lower bone mineral density (BMD) than those not on ART. They also experience more fractures than age and sex-matched people in the general population.[28, 39]  Loss of height is a clue that subclinical vertebral fractures have occurred, necessitating further investigation with radiography and dual energy X-ray absorptiometry (DXA) scans.  Bone disease in people with HIV infection is characterised by a high rate of bone turnover evidenced by elevated markers of bone formation and resorption. [40] Risk of fragility fracture can be assessed by using the Fracture Risk Assessment Tool (FRAX®) further informed by DXA scan to determine bone mineral density. [36, 41]

The classical risk factors for osteoporosis to consider in people with HIV infection include older age, female gender, hypogonadism, family history of hip fracture, low body mass index (BMI) (≤ 19 kg/m2 ), vitamin D deficiency, smoking, physical inactivity, history of low trauma fracture, alcohol excess (> 3 units/day), glucocorticoid exposure (minimum prednisone 5 mg/day or equivalent for > 3 months). [42] Causes of secondary osteoporosis to consider include hyperparathyroidism, vitamin D deficiency, hyperthyroidism, malabsorption, hypogonadism or amenorrhoea, diabetes mellitus, and chronic liver disease. [42]

It is well known that initiation of ART is associated with increased bone turnover and loss of BMD over the first 1-2 years of ART which tends to stabilise thereafter [36]. For example, the START BMD substudy showed a greater decline in BMD in the immediate ART group compared with the deferred ART group.[43]  ART regimens containing TDF, boosted PIs, or both have been associated with significantly greater loss of BMD than regimens containing other NRTIs and integrase strand inhibitors (INSTIs). [28, 42, 44-47] Additional loss and gains in BMD have been observed with switch to, and away from, TDF-containing ART regimens, respectively. [42] However, the clinical relevance for fracture risk is unknown. [42] Abacavir, NRTI-sparing regimens, and tenofovir alafenamide (TAF) may be considered alternatives to the use of TDF in older people with HIV infection at risk of osteopenia or osteoporosis. [28] The benefit of a switch from TDF to abacavir should be balanced with the potential increased risk of cardiovascular disease. [28]

Expert recommendations currently advise screening for low BMD by DXA scan in men aged ≥50 years and postmenopausal women, patients with a history of fragility fractures, those on chronic glucocorticoid treatment or with a high risk of falls. [28, 36] The risk of falls can be assessed using the Fall Risk Assessment Tool (FRAT) -  The frequency of subsequent DXA scans is determined by the result of the initial screen: if the T-score is normal at both the hip and spine, repeat screening is recommended in 5 years, if the T-score is between -2 and -2.5 (advanced osteopenia) the DXA should be repeated in 1-2 years [36]

Treatment of osteoporosis in older people with HIV infection is generally similar to that in the general population and is addressed in the section on Osteoporosis

There is evidence that anti-resorptive agents are safe and effective in increasing BMD in people with HIV infection and reducing fracture risk. [39, 48, 49] The safety and efficacy of denosumab (RANK Ligand inhibitor) has not been established in HIV infection to date. While switching ART to replace TDF and/or PIs has been shown to increase BMD, 2 infusions of zoledronic acid 12 months apart demonstrated that treating low BMD with zoledronic acid was superior to switching from TDF, with a trend to fewer fractures (in a randomised controlled trial, the ZEST study). [39, 50]

For current recommendations regarding calcium and vitamin D supplementation and their clinical relevance to bone health, please go to the section on Bone Disease.

Supervised exercise programs for people with advanced osteoporosis can help avoid fractures, prevent falls, and reduce declines in quality of life. Programs for older adults focus on weight bearing exercise, posture and balance, gait and co-ordination, with hip and trunk stabilization.

Key recommendations

  1. People with HIV infection are at increased risk of osteopenia and osteoporosis, and fragility fractures compared with the general population. Risk of fragility fracture should be assessed using the Fracture Risk Assessment Tool (FRAX®) in all people with HIV infection aged 40 years and over, and further informed by DXA scan to determine bone mineral density.
  2. Expert opinion recommends the measurement of bone mineral density using DEXA scanning in men over 50 years, post-menopausal women, patients with a history of fragility fractures, those on chronic glucocorticoid treatment or with a high risk of falls. Frequency of subsequent screening is dictated by results of the initial DXA scan
  3. Regularly screen people with HIV infection for traditional and secondary risk factors for osteoporosis, regardless of age, and institute appropriate management (eg. smoking cessation, increased physical activity).
  4. Treatment of osteoporosis with zoledronic acid is more effective in increasing bone mineral density and the effect more durable compared with switching ART
  5. The ART regimen in people with potential (i.e. high FRAX score) or confirmed osteoporosis should be reviewed and a switch from TDF or boosted PIs to an alternate ART regimen should be considered. Abacavir, NRTI-sparing regimens, and TAF are potential alternatives to TDF.
  6. Measure and record height every 2 years in those over the age of 50 years
  7. Supervised exercise programs focusing on balance, co-ordination and weight bearing should be encouraged