Fracture Risk Predictor Declines Nearly Twice as Quickly in HIV-infected Women Vs Men

In a recent poster presented at the 9th International AIDS Society Conference on HIV Science, bone density at the hip (femoral neck), a significant predictor of fracture risk, declined nearly twice as quickly in HIV-infected women compared with HIV-infected men and sex was independently associated with lower hip bone mineral density (BMD) in adjusted models.¹

HIV-infected men (N=1759) and women (N=839) on long-term antiretroviral therapy (ART) in the Modena Metabolic Clinic underwent dual-electron X-ray absorptiometry (DXA) scans every 6 to 12 months for up to 10 years. To determine factors associated with BMD, mixed methods regression models were created for women and men in combined and stratified models. Models included the following variables: age, body mass index, duration of integrase strand transfer inhibitors (INSTI) use, duration of tenofovir disoproxil fumarate (TDF) use, physical activity, hypogonadism or post-menopause, AIDS wasting, viral load (≤50 copies/mL), vitamin D insufficiency, and hepatitis C virus (HCV) coinfection. CD4 nadir (<200 cells/µL), CD4 total and percent, smoking, diabetes, and duration of protease inhibitor use were considered in univariate models but were not significant.

Both women and men contributed ≥2 DXA scans. The majority were age ≤50 (82%) and 49% had HIV-1 RNA <50 copies/mL at baseline. Of the patients, 15% post-menopausal women and 7% men with hypogonadism. HCV coinfection was present in 30% and 27% of women and men, respectively.

Significant adjusted average annual declines in hip and spine BMD in women and men were observed; women (hip: –.008, L-spine –.012 g/cm²/year) and men (hip: –.004; L-spine: –.007 g/cm2/year; P <.0001 for all). Moreover, female sex was associated with lower hip but not spine BMD (P <.0001) in combined mixed effect models. Models stratified by sex yielded similar results except that physical activity (in women) and HCV coinfection (in men) were no longer significant.

In an interview with Endocrinology Advisor, lead presenter Kristine M. Erlandson, MD, assistant professor in the division of infectious diseases at the University of Colorado in Aurora noted that the “results highlight BMD loss among women, independent of menopause, and that these effects require future consideration with ART selection, particularly when prioritizing switch from TDF to tenofovir alafenamide and when using pre-exposure prophylactic therapy.”

Dr Erlandson went on to note that there are several findings that can potentially have an impact on clinical care and should be emphasized.  She emphasized the following 3 points:

1. Age-associated changes in BMD were most pronounced following age 45, even after adjusting for post-menopausal or hypogonadal state, supporting the current HIV guidelines to screen for BMD starting at age 50.²

2. A protective effect of INSTI therapy (almost entirely raltegravir use in this cohort) was apparent in both men and women, and has been demonstrated in multiple prior studies with raltegravir initiation or switch^3-5 and in limited data with other INSTIs.^6-8

3. The effect of HCV on BMD was similar to that of 5 additional years of aging, and was most significant in women, as reported in prior studies.^9,10 The impact of direct-acting HCV therapies on BMD after eradication of HCV are currently not known, but may prove to be a simple and effective (albeit costly) treatment intervention to preserve BMD with aging, particularly in HIV/HCV coinfected women.¹¹ 

“Importantly, low BMD is one of several risk factors for fracture: the interventions likely to have the greatest impact in this aging population are those that both attenuate BMD losses and minimize fracture risk through reduced falls,” concluded Dr Erlandson.

References

1. Erlandson K, Lake J, Sim M, et al. Bone mineral density at the hip declines twice as quickly among HIV-infected women than men. Presented at: IAS 2017; June 23-26, 2017; Paris, France; Poster WEPEB0506.
2. McComsey GA, Tebas P, Shane E, et al. Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis. 2010;51:937-946.
3. Brown TT, Moser C, Currier JS, et al. Changes in bone mineral density after initiation of antiretroviral treatment with tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. J Infect Dis. 2015;212:1241-1249.
4. Bernardino JI, Mocroft A, Mallon PW, et al; NEAT001/ANRS143 Study Group. Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial. Lancet HIV. 2015;2:e464-e473.
5. Curran A, Martinez E, Saumoy M, et al. Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy. AIDS. 2012;26:475-481.
6. Negredo E, Estrada V, Domingo P, et al. Switching from a ritonavir-boosted PI to dolutegravir as an alternative strategy in virologically suppressed HIV-infected individuals. J Antimicrob Chemother. 2017;72:844-849.
7. Tebas P, Kumar P, Hicks C, et al. Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks. AIDS. 2015;29:2459-2464.
8. Trottier B, Lake JE, Logue K, et al. Dolutegravir/abacavir/lamivudine versus current ART in virally suppressed patients (STRIIVING): a 48-week, randomized, non-inferiority, open-label, Phase IIIb study [published online April 12, 2017]. Antivir Ther. doi:10.3851/IMP3166
9. Lawson-Ayayi S, Cazanave C, Kpozehouen A, et al; Groupe Epidémiologie Clinique du SIDA en Aquitaine (GECSA). Chronic viral hepatitis is associated with low bone mineral density in HIV-infected patients, ANRS CO 3 Aquitaine Cohort. J Acquir Immune Defic Syndr. 2013;62:430-435.
10. Lo Re V 3rd, Guaraldi G, Leonard MB, et al. Viral hepatitis is associated with reduced bone mineral density in HIV-infected women but not men. AIDS. 2009;23:2191-2198.
11. Yin MT, Brown TT. HIV and bone complications: understudied populations and new management strategies. Current HIV/AIDS Rep. 2016;13:349-358.

This article originally appeared on Endocrinology Advisor