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  IAS 2017: Conference on HIV Pathogenesis
Treatment and Prevention
Paris, France
July 23-26 2017
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PIs Plus Tenofovir Not Tied to Fracture in French Case-Control Study
  9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris
Mark Mascolini
Use of protease inhibitors (PIs) with tenofovir disoproxil fumarate (TDF) was not linked to higher odds of fracture in a 630-person case-control study in France [1]. Cumulative use of atazanavir plus TDF did confer higher odds of fracture.
Research shows a higher fracture risk in people with HIV than in the general population. By lowering bone mineral density, certain antiretrovirals--notably TDF and PIs--may contribute to fractures with HIV. But the impact of individual antiretrovirals on fracture risk has proved difficult to sort out. French investigators aimed to address that issue in a case-control study involving people in the French Hospital Database on HIV (FHDH-ANRS CO4). Specifically, they wanted to assess the potential impact of each antiretroviral on risk of low-energy fracture at possible osteoporotic sites.
The analysis focused on people yet to begin antiretroviral therapy when they entered the FHDH. Cases had a first prospectively reported low-energy osteoporotic fracture between January 2000 and December 2010. Control patients without fractures were matched to cases by sex, age, HIV diagnosis period, and clinical center. The researchers used conditional logistic regression to assess fracture risk according to cumulative duration of individual antiretrovirals (model 1) and whether or not a person ever took the antiretroviral (model 2). The researchers did not report results for certain antiretrovirals infrequently used by participants in the study period (darunavir, tipranavir, enfuvirtide, raltegravir, and maraviroc).
The FHDH team matched 254 fracture cases to 376 no-fracture controls. Median age of both groups was 49, about two thirds were men, and about two thirds got diagnosed with HIV before 1997. Median CD4 counts in cases and controls were 436 and 451 and nadir CD4 counts 172 and 196. Median viral load lay below 50 copies in both groups. A higher proportion of cases than controls drank more than 2 glasses of alcohol daily (24% versus 13.3%, P = 0.002), a higher proportion had taken systemic glucocorticoids (9.8% versus 3.7%, P = 0.011), and a higher proportion had known osteoporosis (10.2% versus 2.1%, P = 0.002).
Ever using TDF with any PI was not independently associated with higher odds of fracture. Cumulative exposure to TDF and only one PI, atazanavir, was linked to higher odds of fracture (adjusted odds ratio [aOR] 1.43, 95% confidence interval [CI] 1.01 to 2.02). Adjusted analysis found no association between ever using any nucleoside and fracture, while nevirapine use was linked to higher fracture odds (aOR 1.73, 95% CI 1.01 to 2.95). Adjusted analysis linked cumulative use of zidovudine to higher fracture odds, while cumulative use of lamivudine lowered fracture odds (aOR 0.83, 95% CI 0.73 to 0.95).
The researchers concluded "there was no evidence of excess risk of fracture following exposure to tenofovir or to PIs." For PIs, they proposed, that finding is not unexpected because PIs are linked to low bone mineral density only at the spine, and that association may be an artefact linked to increased visceral fat. The FHDH team noted that research does tie tenofovir to low bone mineral density, but little work addresses the impact of tenofovir treatment over many years. They stressed that most published studies do not see an increased fracture risk with tenofovir or PIs. The investigators suggested their tenofovir finding "is an important result in the debate about TAF [tenofovir alafenamide] and generic tenofovir [TDF]."
IAS: Impact of exposure to each antiretroviral treatment (ARV) on the risk of fracture in HIV-infected individuals - (07/27/17)
1. Costagliola D, Potard V. Lang S, et al. Impact of exposure to each antiretroviral treatment (ARV) on the risk of fracture in HIV-1-infected individuals: an analysis from FHDH ANRS CO4 9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris. Abstract WEAB0103.