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ART and CV/Bone Health
How New Data From IAS 2017 May Inform Use of ART in Patients With Cardiovascular or Bone Comorbidities

Released: September 11, 2017

Expiration: September 10, 2018

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In this HIV case series, we highlight common patient case scenarios and the critical decision making that goes into selecting optimal patient management strategies. This commentary focuses on the case of a patient with elevated cardiovascular disease (CVD) risk who is currently virologically suppressed on a boosted PI–based regimen and how data from the 2017 International AIDS Society (IAS) meeting might inform future ART choices for this type of patient. Meeting data surrounding ART and bone health are also discussed.

Case Details
A 53-year-old man has been virologically suppressed on darunavir/ritonavir plus emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF )for 5 years. He had no resistance mutations prior to initiating his current ART regimen and has never experienced virologic failure. The patient has several CVD risk factors and now has a Framingham risk score of 15% at 10 years. He has difficulty controlling his lipid levels even with lipid-lowering agents. As boosted PI–based ART can have a negative effect on lipids, you are considering switching this patient to a more lipid-friendly regimen in an effort to reduce his CVD risk.

Switching ART to Reduce CVD Risk
In the NEAT 022 study, virologically suppressed patients with high CVD risk (older than 50 years of age and/or Framingham risk score > 10% at 10 years) were randomized to either continue a regimen of a boosted PI plus 2 NRTIs or switch to dolutegravir (DTG) plus 2 NRTIs (N = 415). The 48-week data for this study were presented at the 2017 IAS meeting and demonstrated similar preserved virologic suppression for both regimens, with > 93% of patients remaining suppressed overall. Dramatic improvements in lipid parameters (including total cholesterol, non-HDL and LDL cholesterol, triglycerides, and total cholesterol-to-HDL ratio) were observed for those patients switching to DTG-based ART; the only parameter that did not show improvement was HDL cholesterol, which remained largely unchanged with either continuation or switching. Although not completely unexpected, these data confirm that switching a patient receiving boosted PI–based ART to a DTG-based regimen can improve lipid parameters and possibly reduce CVD risk.

ART and Bone Health
In terms of HIV and bone health, we know that HIV-infected patients have an increased risk of low bone mineral density (BMD) and fracture. Treatment with TDF has been associated with decreased BMD compared with treatment with tenofovir alafenamide (TAF) or with abacavir-containing regimens. However, data regarding the risk of fracture in patients receiving TDF are conflicting, and there is some controversy over how best to manage the loss of BMD in patients who are treated with this agent.

The ANRS presented results from a case-control study that evaluated the risk of fracture in HIV-infected patients who received ARVs from 2000 to 2010 (n = 254 cases; n = 376 controls). They focused on patients who had low energy fractures (fractures occurring after traumatic events of low intensity) and found no evidence of an increased risk of fracture in participants receiving TDF or PIs using several different multivariable models. So, although it is clear that there is a loss of BMD associated with certain ARVs, it is less clear that this loss necessarily leads to an increased fracture risk.

However, some patients clearly have serious BMD loss that may place them into the category of having osteoporosis. Two studies presented at IAS 2017 examined potential strategies to alleviate BMD loss for patients receiving TDF-based regimens. In the ZEST study, patients with low BMD who were virologically suppressed on TDF-based ART (N = 87) were randomized to either switch to non-TDF–based ART or to continue on TDF-based ART and also receive zoledronic acid, a bisphosphonate used to treat osteoporosis. Patients also received calcium supplementation, and those in the zoledronic acid arm received vitamin D. The study showed that there was a significantly greater increase in BMD at the lumbar spine, femoral neck, and hip for patients randomized to continue TDF-based ART and add zoledronic acid, as compared with those who switched to non-TDF–based ART. This study suggests that even though BMD can be improved by switching to non-TDF–based ART, this may not be sufficient for those patients who have serious BMD loss; as with other patients who have severe osteopenia or osteoporosis, bisphosphonate therapy may be required.

Data were also presented on the BMD effect of switching from TDF-based ART to a 2-drug regimen of DTG plus rilpivirine (RPV) in a subanalysis of the SWORD 1 and 2 studies. It was previously reported in the main analysis of these studies that switching to DTG plus RPV was noninferior to remaining on baseline triple-therapy ART in virologically suppressed patients. The substudy presented at IAS 2017 assessed BMD in patients who had been receiving a TDF-containing triple ART regimen at baseline (N = 102). As noted in other studies, switching from a TDF-based to a non-TDF–containing regimen (DTG plus RPV) resulted in significant increases in BMD at the hip and lumbar spine. These data should to be considered in the context of the ZEST study where, again, the magnitude of increase in BMD is dramatically enhanced by the use of a bisphosphonate. Which strategy for managing patients with low BMD makes most sense really depends on the severity of bone loss in the individual patient.

Your Thoughts
Would you switch from a suppressive boosted PI–based ART regimen in a patient at high risk for CVD? How do you manage bone loss in patients receiving ART? Please share your experiences and insights by joining the conversation in the comments box below.

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