HIV infection and antiretroviral therapy are associated with increased risk of cartilage damage in the knee associated with osteoarthritis, according to the results of a small US study published in BMC Musculoskeletal Disorders. The case-controlled study showed a higher prevalence of several key markers of knee cartilage damage at baseline and greater deterioration over eight years of follow-up.
“Our results suggest that treated HIV infection is associated with compositional changes of the cartilage matrix and increased knee joint inflammation, but findings appear not to have a significant impact on structural knee degeneration,” comment the authors.
Despite the small study size (ten people with HIV and 20 matched controls) the study had a rigorous methodology and hints that ageing HIV-positive people may well have an increased risk of arthritis.
As well as ageing, metabolic problems such as high lipids, hypertension, body fat disturbances and diabetes can all increase the risk of osteoarthritis. Thanks to improvements in treatment and care, many people with HIV now have an excellent life expectancy, but the inflammation caused by untreated HIV and the side-effects of some antiretroviral drugs can increase the long-term risk of metabolic problems.
Dr Yao Liu and colleagues from the US Osteoarthritis Initiative therefore wanted to see if people taking antiretroviral therapy (ART) were more likely than matched controls to have knee cartilage degeneration and structural knee changes over eight years of follow-up.
At baseline and during follow-up, cartilage health and knee structure were assessed using an intensive battery of tests including MRI imaging and measures of cartilage structure, composition and texture.
The people with HIV and controls were closely matched for age, sex, race and BMI. Approximately a third were female and the mean age was 52 years.
All the people with HIV had been on HIV therapy for at least 12 months.
Baseline analysis showed that the HIV-positive people had a higher prevalence of several markers of cartilage damage, including fat pad abnormalities and higher knee effusion (accumulation of fluid around the knee, a marker of inflammation) scores, when compared to the controls. However, these individuals were less likely to have a type of bone cyst associated with osteoarthritis.
Over the eight years of follow-up, the ART group showed a significantly greater decline in markers of cartilage texture and composition and also more severe knee effusion. However, as at baseline, bone cysts were less severe in people with HIV than the controls.
The investigators believe their findings show “a more heterogeneous and disordered cartilage matrix composition” in ART-treated people, adding that “cartilage damage is the hallmark of knee osteoarthritis, and cartilage matrix degeneration is an essential event that determines the irreversible progression of knee OA [osteoarthritis].”
A possible cause for the cartilage degeneration seen in the ART-treated people is HIV-associated loss of skeletal muscle mass around the knee, leading to changes in the biomechanics of the knee and cartilage damage. Alternatively, the damage and inflammation could be due to a combination of HIV-related inflammation, treatment side-effects and metabolic disorders.
The investigators were puzzled by their finding that the HIV group had lower bone cyst scores than the controls and comment: “Given the complex effects of HIV and ART on bone resorption and bone formation, additional mechanisms may be involved reducing the development of subchondral cysts.”
The investigators acknowledge that their study had a number of limitations, especially the small sample size and call for further research to validate their findings.
“Our study showed a more heterogeneous and disordered cartilage matrix composition in PLWH [people living with HIV] on ART, suggesting that treated ART infection may accelerate the degeneration of the knee cartilage matrix,” conclude the authors. “In addition, compared with the HIV-negative group, PLWH had significantly more severe knee joint effusion over 8 years.”
The clinical significance of these findings will need to be confirmed by larger studies. However, the analysis does underline the importance of assessing bone health and arthritis risk as part of the routine care of ageing people with HIV.
Liu Y et al. Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative. BMC Musculoskeletal Disorders, 20:190. https://doi.org/10.1186/s12891-019-2573-5