Bone Safety of Dolutegravir-Containing Regimens in People Living with HIV: Results from a Real-World Cohort

Figures & data

Table 1 Baseline Characteristics of the 160 Patients Enrolled in the Study

Variables
Sex (n, %)
Female	42	26.3%
Male	118	73.8%
Age, years (mean, SD)	49.9	11.2
BMI, Kg/m^2 (mean, SD)	24.0	4.2
BMI, Kg/m^2 (n, %)
<25.0	105	65.6%
≥25	55	34.4%
Risk factor for HIV acquisition (n, %)
Sexual route	119	74.4%
Intravenous drug use	20	12.5%
Other	21	13.1%
HCV Ab Positive (n, %)	24	15.0%
Ethnicity (n, %)
Caucasians	146	91.2%
Other	14	8.8%
CDC stage (n, %)
A	87	54.4%
B	38	23.8%
C	35	21.9%
Naive (n, %)	37	23.1%
HIV-RNA Undetectable (n, %) (exp.pts)	104	84.6%
CD4 cells/mL (median, IQR)	531	346–786
CD8 cells/mL (median, IQR)	795	606–1098
CD4/CD8 (median, IQR)	0.67	0.41–0.96
Previous regimen including (n, %)
Protease inhibitors	48	30.0%
Non nucleoside reverse transcriptase inhibitors	51	31.9%
Years of ART (median, IQR)	9.7	4.0–18.0
Current regimen including DTG (n, %)
Triple	125	78.1%
3TC/ABC/DTG	105	65.6%
TDF/FTC/DTG	20	12.5%
Dual	28	17.5%
Other combinations	7	4.4%
Previous diagnosis of osteopenia/osteoporosis (n, %)	25	15.6%
New diagnosis of osteopenia/osteoporosis (n, %), n=135	62	45.9%
Vitamin D supplementation (n, %)	52	32.5%
Femoral neck mg/cm^3 (mean, SD)	822	166
Lumbar spine mg/cm^3 (mean, SD)	935	167

Abbreviations: SD, standard deviation; IQR, interquartile range; BMI, body mass index; HCV, hepatitis C virus; CDC, center for disease control and prevention; 3TC, lamivudine; ABC, abacavir; DTG, dolutegravir; TDF, tenofovir disoproxil fumarate; FTC, emtricitabine.

Table 2 Baseline Bone Mineral Density (BMD) According to Selected Characteristics in 160 Subjects with DXA at Femoral Neck and/or Lumbar Spine

Baseline Characteristics	FN BMD (mg/cm^3) Mean ± SD	p-value*	LS BMD (mg/cm^3) Mean ± SD	p-value*
Age <50 years	861 ± 175	0.02	950 ± 170	0.30
Age ≥50 years	793 ± 154		923 ± 164
Men	840 ± 173	0.048	956 ± 170	0.007
Women	776 ± 139		875 ± 140
BMI<25.0	782 ± 160	0.0002	921 ± 186	0.14
BMI≥25.0	891 ± 155		963 ± 117
Experienced	821 ± 159	0.92	923 ± 156	0.10
Naive	825 ± 196		974 ± 194

Note: *Analysis of variance.

Abbreviations: BMD, bone mineral density; FN, femoral neck; SD, standard deviation; LS, lumbar spine; BMI, body mass index.

Figure 1 Femoral neck and lumbar spine bone mineral density at baseline and last observation.

Table 3 Bone Mineral Density (BMD) Change from Baseline in 133 Subjects with Follow-Up DXA at Femoral Neck (n=112) and/or Lumbar Spine (n=128)

Baseline Characteristics	BMD Change from Baseline Mean (95% CI)
	FN				LS
	mg/cm^3	P^#	%	P^#	mg/cm^3	P^#	%	P^#
Age <50 years	−6.2 (−25.5, 13.1)	0.10	−0.6 (−3.1, 1.9)	0.08	19.0 (1.7, 36.6)*	0.40	2.2 (0.2, 4.2)*	0.38
Age ≥50 years	17.8 (−2.4, 37.9)		2.9 (0.0, 5.7)		9.0 (−6.6, 24.5)		1.1 (−0.6, 2.8)
Men	8.1 (−9.1, 25.3)	0.97	1.4 (−1.0, 3.8)	0.99	12.2 (−0.3, 24.7)	0.79	1.4 (0.1, 2.8)*	0.75
Women	7.5 (−19.0, 34.0)		1.5 (−2.1, 5.0)		15.6 (−11.3, 42.5)		1.9 (−1.3, 5.1)
BMI<25.0 kg/m^2	3.7 (−17.2, 24.5)	0.46	1.0 (−1.9, 4.0)	0.61	−2.2 (−16.4, 12.0)	0.0008	−0.1 (−1.7, 1.5)	0.002
BMI≥25.0 kg/m^2	14.5 (−2.8, 31.9)		2.1 (−0.2, 4.4)		37.1 (17.2, 55.0)*		4.1 (2.1, 6.1)*
Experienced	10.0 (−6.8, 26.8)	0.55	1.7 (−0.6, 4.1)	0.55	16.9 (4.7, 29.2)*	0.21	2.0 (0.6, 3.4)*	0.16
Naive	−1.0 (−23.9, 21.9)		0.2 (−2.7, 3.1)		−1.1 (−31.4, 29.3)		−0.2 (−3.5, 3.0)
TDF in previous regimen^§	−11.2 (−36.4, 11.9)	0.02	−1.4 (−4.5, 1.6)	0.01	12.9 (−5.2, 31.0)	0.53	1.6 (−0.4, 1.6)	0.56
No TDF in previous regimen^§	28.2 (6.0, 50.4)*		4.4 (1.1, 7.8)*		20.7 (3.5, 37.9)*		2.4 (0.4, 4.4)*
PI in previous regimen^§	−2.5 (−35.0, 30.0)	0.24	0.0 (−4.3, 4.2)	0.23	25.1 (0.0, 50.1)*	0.28	3.2 (0.4, 6.1)*	0.16
No PI in previous regimen^§	18.1 (−0.5, 36.8)		2.9 (0.1, 5.6)*		11.6 (−0.9, 24.1)		1.2 (−0.2, 1.6)
Normal BMD at baseline	−1.7 (−24.0, 20.6)	0.22	−0.3 (−2.9, 2.4)	0.12	4.4 (−10.0, 18.8)	0.16	0.4 (−1.0, 1.8)	0.10
Reduced BMD at baseline	16.0 (−2.6, 34.6)		2.9 (0.0, 5.7)*		20.6 (3.1, 38.1)*		2.5 (0.5, 4.6)
Vitamin D supplement	−4.0 (−27.0, 19.0)	0.19	0.6 (−3.0, 4.2)	0.51	26.8 (7.7, 45.9)*	0.09	3.4 (1.0, 5.7)*	0.04
No Vitamin D supplement	15.3 (−3.0, 33.7)		2.0 (−0.4, 4.3)		6.0 (−8.4, 20.3)		0.6 (−0.9, 6.1)
3TC/ABC/DTG	5.2 (−9.6, 20.0)	0.48	1.2 (−1.1, 2.4)	0.57	19.1 (7.8, 30.5)*	0.20	2.1 (0.8, 3.4)*	0.24
TDF/FTC/DTG	1.8 (−78.6, 72.2)		0.4 (−8.5, 9.3)		−12.4 (−70.5, 45.7)		−1.0 (−7.0, 4.9)
Dual therapy	11.8 (−29.4, 53.0)		1.9 (−3.0, 6.7)		17.2 (−23.2, 57.5)		2.4 (−2.3, 7.0)
Other Therapies	66.0 (−18.2, 150.2)		8.5 (−2.2, 19.2)		−18.3 (−52.9, 16.3)		−2.0 (−5.6, 1.6)
Never smokers	−4.7 (−29.5, 4.1)	0.73	−0.3 (−3.5, 2.9)	0.68	19.7 (2.9–36.6)*	0.06	2.1 (0.4, 3.9)*	0.06
Former smokers	4.0 (−72.6, 70.6)		0.9 (−6.8, 8.6)		23.0 (−11.6, 57.6)		3.1 (−1.5, 7.7)
Current smokers	11.0 (−16.1. 38.1)		2.1 (−2.8, 7.1)		−9.5 (−28.7, 9.8)		−0.9 (−3.1, 1.2)

Notes: ^#Comparison between groups, analysis of variance; *p<0.05 for change from baseline, paired t-test; ^§limited to experienced patients.

Abbreviations: BMD, bone mineral density; CI, confidence interval; FN, femoral neck; LS, lumbar spine; BMI, body mass index; TDF, tenofovir disoproxil fumarate; PI, protease inhibitors; 3TC, lamivudine; ABC, abacavir; DTG, dolutegravir; FTC, emtricitabine; smoking status was only reported in 88 patients.