CROI 2016 : Single Dose Zoledronic Acid Prevents Antiretroviral-Induced Bone Loss : Proof of concept study

HIV infection is an independent risk factor for osteoporosis. Initiation of ART induces additional 1-6% loss in bone mineral density (BMD). ART-associated bone loss occurs early and happens with most of ART agents.

Zoledronic acid is a biphosphonate drug licensed for the treatment of bone-related cancers alongside chemotherapy and for the treatment of osteoporosis in men and women at increased risk of fracture. It is administered as an infusion once a year. The drug slows down the loss of calcium from the bones, reducing the risk of fractures.

Reduced bone mineral density is common in people living with HIV, and as previously noted, modest bone mineral loss is a common occurrence during the first year of antiretroviral therapy. Investigators from Emory University School of Medicine, Atlanta, designed a study to investigate whether a single infusion of zoledronic acid could limit bone mineral loss during the first year of antiretroviral therapy.

This was a single-centre, randomised, double-blind, placebo controlled phase 2 study. Patients starting HIV therapy for the first time with no history of bone loss were eligible for inclusion. All participants received an antiretroviral regime of atazanavir with tenofovir/emtricitabine. Patients were randomised to receive a single 5mg infusion of zoledronic acid or placebo. The study lasted 48 weeks with assessment of bone turnover and bone mineral density at baseline and weeks 12, 24 and 48.

Therapy with zoledronic acid was associated with a 74% reduction in bone loss by week 12. The benefits persisted through to week 24 and 48 (65% and 56% reduction, respectively, relative to placebo).

By week 12, patients in the treatment arm had an 8% increase in lumbar spine bone mineral density relative to placebo, the difference increasing to 11% at weeks 24 and 48. At week 48, lumbar spine bone mineral density had increased by 2% in patients treated with zoledronic acid; this compared to a 4% decrease among patients who received the placebo. Lumbar spine T- and Z-scores were significantly higher among patients who received zoledronic acid versus placebo at all follow-up points (all p < 0.05). Similar trends were also observed at the hip and femoral neck.

Zoledronic acid was well tolerated with no major adverse events reported. Rates of viral suppression and CD4 cell increase were similar between the treatment and placebo arms.

The investigators conclude that a single infusion of zoledronic acid at the time HIV therapy was started prevented antiretroviral-induced bone resorption and bone loss at key fracture-prone body sites. The benefits of therapy were present at week 12 and persisted through 48-weeks of follow-up. The researchers suggest that zoledronic acid could be used as a prophylaxis against bone mineral loss during the first year of antiretroviral treatment and call for a multicentre randomised trial to confirm their findings.

Take home message: Single dose of zoledronic acid infusion may be an effective preventative measure of BMD loss in HIV