Associations Between Antiretroviral Treatment and Avascular Bone Necrosis: The Swiss HIV Cohort Study

Abstract

BackgroundHIV-infected individuals have an increased risk of avascular bone necrosis (AVN). Antiretroviral therapy (ART) and particularly protease inhibitors (PI) have been implicated as a risk factor. We aimed to study the associations of ART with the occurrence of AVN among Swiss HIV Cohort Study participants (SHCS).MethodsWe used incidence density sampling to perform a case control study within the Swiss HIV Cohort Study (SHCS) comparing prospectively collected AVN cases and controls by conditional logistic regression analysis. To evaluate the effect of ART, multivariable models were adjusted for HIV transmission risk group, age, alcohol consumption, use of corticosteroids, CD4 nadir, maximum viral load, and pancreatitis.ResultsWe compared 74 AVN cases and 145 controls. Associations with AVN were shown for heterosexual HIV acquisition (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1–10), alcohol consumption (OR, 2.7; 95% CI, 1.3–5.7), and hyperlipidemia (OR, 3.6; 95% CI, 1.4–9.6). After adding ART substances to the multivariable base model, there was evidence of an association for treatment with tenofovir (TDF) >1 year (OR, 4.4; 95% CI, 1.4–14) with AVN. Neither exposure to specific frequently prescribed ART combinations or ART drug classes nor cumulative ART exposure showed any associations with AVN.ConclusionsIn the HIV-infected population, a combination of risk factors such as heterosexual HIV acquisition, moderate to severe alcohol intake, and hyperlipidemia seem to contribute to AVN. ART does not seem to be a relevant risk factor for AVN. The association of prolonged TDF exposure with AVN needs to be confirmed.

Complications of combination intranasal corticosteroids and anti-retroviral therapy

“…30 Ritonavir has been found to displace drugs metabolised by CYP3A, leading to increased bioavailability and potentiation of the adverse effect of systemically available corticosteroids. 5,30 Although it is important to note that ritonavir use alone has been associated with avascular necrosis of bone, 31 patients demonstrating multiple features of hypercortisolism, as observed in this patient with Cushing's syndrome and avascular necrosis of the shoulder while on ritonavir and a corticosteroid, should prompt consideration for an interaction between the medications.…”

Osteonecrosis of the Femoral Head

“… 40 One recent study revealed a strong association between high-activity antiretroviral therapy and development of osteonecrosis, although the authors caution that the association does not imply a pathologic role. 40 Other studies have found no association between osteonecrosis and antiretroviral therapy (ART), citing instead association with alcohol, hyperlipidemia, 41 or low nadir CD4 counts, 42 although the mechanism is not well understood.…”

Does Diabetes Mellitus Increase the Risk of Avascular Osteonecrosis? A Systematic Review and Meta-Analysis

“…AVN may be caused by trauma, such as fracture, particularly displaced fractures [ 18 ], or it can be non-traumatic. The pathogenesis of non-traumatic osteonecrosis is unclear, but there are several established risk factors such as corticosteroid treatment, alcohol abuse, rheumatic diseases, bone-marrow transplantation, or antiretroviral treatment [ 15 , 19 , 20 , 21 , 22 , 23 ]. Diabetes mellitus (DM), which causes disease of both large vessels (macroangiopathy) and small vessels (microangiopathy) [ 24 ], can also increase the risk of avascular osteonecrosis [ 25 , 26 , 27 ].…”