Effects of Antiretroviral Therapy with Tenofovir and Other Antiretroviral Drugs on the Inflammatory State and Bone Remodeling on Newly Diagnosed HIV-Patients at Basal and 3 Months after Starting Treatment

Aranzazu Mediero¹, Francisco Miguel Conesa-Buendia², Patricia Llamas³, Patricia Atencio⁴, Ramon Perez-Tanoira⁴, Alfonso Cabello⁵, Laura Prieto-Perez⁴, Beatriz Alvarez⁴, Manuel Fernandez-Guerrero⁴, Raquel Largo⁶, Gabriel Herrero-Beaumont⁶ and Miguel Gorgolas⁷, ¹Joint and Bone Research Unit, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain, ²Bone and Joint Research Unit, IIS-Fundacion Jimenez Diaz- UAM, Madrid, Spain, ³Bone and Joint Research Unit, IIS-Fundacion Jimenez Díaz-UAM, Madrid, Spain, ⁴Internal Medicine Department, IIS-Fundacion Jimenez Diaz, MADRID, Spain, ⁵Internal MEdicine Department, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain, ⁶Bone and Joint Research Unit, Fundación Jiménez Díaz University Hospital & Health Research Institute, Madrid, Spain, ⁷Internal Medicine Department, IIS-Fundacion Jimenez Diaz-UAM, Madrid, Spain

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Adenosine receptors, Disease susceptibility, osteoporosis and viruses

Session Information

Date: Sunday, October 21, 2018

Title: 3S104 ACR Abstract: Infection-Related Rheumatic Disease (946–951)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose:

Bone alterations have been observed in the course of HIV infection, with a notable decreases in bone mineral density (BMD) and fractures due to fragility. Anti-retroviral drugs may have a direct or indirect effect on bone cells, via alterations in RANK/RANKL, cytokines profile, mitochondrial function and changes in phosphate/Vitamin D metabolism. The aim of this study was to evaluate the deleterious effects in bone metabolism and systemic inflammation, produced by Tenofovir vs. other HIV treatment in naïve patients.

Methods: A cohort of 114 HIV-naïve patients were included in the study. Patients were separated by treatment: 1) Tenofovir Disoproxil Fumarate (TDF) (n=23), 2) Tenofovir Alafenamide (TAF) (n=22), 3) Abacavir/Dolutegravir/Lamivudin combo (ADL) (n=39), 4) Protease Inhibitors (PI) (n=12), and 5) patients who changed treatment during the study (n=18). Epidemiological, immunological, and metabolic parameters, as well as BMD were evaluated. Bone markers, proinflammatory and anti-inflammatory cytokines were analyzed in serum at basal and 3 months post-treatment by MILLIPLEX® MAP Luminex® Technology. The diagnosis of osteopenia/osteoporosis was made according to the WHO criteria.

Results: The mean age was 34.7 years (range 19-50 years). 91% was on CDC stage A. The median CD4 was 481 cell/µL (IQR=339.5), 10% had CD4 under 200 cell/µl, and 42% had CD4/CD8 under 0.4. 71% (71/143 p) had low Vitamin D levels, 4% low BMI (<18.5). Osteopenia (op) or osteoporosis (OP) was found in 53% and 11% respectively. In the serum we found differences at molecular level among different treatments (Tables 1 and 2). We observed that both TDF and TAF presented an osteoclastic profile but not the other treatments. All treatments reduce proinflammatory cytokines 3 months after treatment but no differences among treatments were found.

	BONE MARKERS (pg/ml)
	OPN		OPG		RANKL		DKK1		SOST
Treatment	*Basal*	*3 m*	*Basal*	*3 m*	*Basal*	*3 m*	*Basal*	*3 m*	*Basal*	*3 m*
TDF (n=23)	11811±10179	13441±9716	239.2±133.7	156.9±107.1	77.33±50.6	98.18±60.60	536.47±377.9	378.28±284.7	1916±1126	1677±1147
TAF (n=22)	12110±6251	14832±7098	236.8±127.7	173.2±78.57	123.9±131.7	96.18±139	436.3±284.5	324.2±198.7	1428±893.9	1081±538.1
ADL (n=39)	14632±8955	14835±10371	282.2±177.3	249.3±256.5	89.89±100.2	51.60±50.19	622.7±562.4	427±366.9	2108±1509	1967±1656
PI (n=12)	16725±5928	16342±7284	216.9±67.57	256.7±132.6	87.73±103.9	85.44±113.5	421.4±140.6	403.1±169.6	1166±614.7	1618±603
Change of treatment (n=18)	17080±7111	17014±6026	262.1±121.5	211.3±81.14	67.8±108.1	16.09±26.86	489.8±227.3	354.5±165.2	1336±443.4	1115±440.4

CYTOKINES (pg/ml)

IL2

INFg

IL4

IL10

IL1-b

TNFa

Treatment

Basal

3 m

Basal

3 m

Basal

3 m

Basal

3 m

Basal

3 m

Basal

TDF (n=23)

2.3±1.9

2.24±1.62

32±44

27.80±373.14

48.47±50.21

37.34±29.03

28.10±30.04

27±29.4

1±1.1

1.14±1.12

3.42±3

3.41±2.61

TAF (n=22)

1.53±0.76

1.9±1.1

5.71±3.46

6.77±3.83

31.44±16.34

33.48±15.78

11.36±11.47

13.83±10.32

0.54±0.37

0.62±0.35

1.73±1.08

2.39±1.48

ADL (n=39)

2.5±2

2.1±1.4

35.6±59.2

19.83±30.63

51.13±51.67

38.73±28.96

32.95±40.49

19.20±17.96

1.24±1.44

0.91±0.78

4.42±5.44

3.15±2.32

PI (n=12)

2.11±0.73

1.94±1

5.5±2.6

5.69±2.56

41.71±24.26

42.97±23.06

17.46±9.69

15.58±13.31

0.59±0.27

0.72±0.42

2.46±1.5

2.3±1.2

Change of treatment (n=18)

1.91±0.78

2.14±0.93

7±3

7.5±3.5

38.34±13.77

43.89±15.24

18.94±13.48

19.74±0.30

0.67±0.31

0.73±0.35

2.45±1.16

2.5±1.2

Conclusion: HIV-naïve patients under 50 years have a high prevalence of osteopenia/osteoporosis, and patients treated with Tenofovir had greater bone deterioration than other patients.

Disclosure: A. Mediero, CP15/00053 PI16/0991, 2, 9; F. M. Conesa-Buendia, None; P. Llamas, None; P. Atencio, None; R. Perez-Tanoira, None; A. Cabello, None; L. Prieto-Perez, None; B. Alvarez, None; M. Fernandez-Guerrero, None; R. Largo, None; G. Herrero-Beaumont, None; M. Gorgolas, None.

To cite this abstract in AMA style:

Mediero A, Conesa-Buendia FM, Llamas P, Atencio P, Perez-Tanoira R, Cabello A, Prieto-Perez L, Alvarez B, Fernandez-Guerrero M, Largo R, Herrero-Beaumont G, Gorgolas M. Effects of Antiretroviral Therapy with Tenofovir and Other Antiretroviral Drugs on the Inflammatory State and Bone Remodeling on Newly Diagnosed HIV-Patients at Basal and 3 Months after Starting Treatment [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/effects-of-antiretroviral-therapy-with-tenofovir-and-other-antiretroviral-drugs-on-the-inflammatory-state-and-bone-remodeling-on-newly-diagnosed-hiv-patients-at-basal-and-3-months-after-starting-treat/. Accessed .

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