Paper # 94LB
Effects of FTC/TDF on Bone Mineral Density in Seronegative Men from 4 Continents: DEXA Results of the Global iPrEx Study
Kathleen Mulligan*1, D Glidden1, P Gonzales2, M-E Ramirez-Cardich3, A Liu1,4, S Namwongprom5, P Chodacki6, L Mendonηa7, V McMahan8, R Grant1,8, and iPrEx Study Team
1Univ of California, San Francisco, US; 2Investigaciones Medicas en Salud, Lima, Peru; 3Assn Civil Impacta Salud y Ed, Lima, Peru; 4San Francisco Dept of Publ Hlth, CA, US; 5Chiang Mai Univ, Thailand; 6Desmond Tutu HIV Fndn, Cape Town, South Africa; 7Federal Univ of Rio de Janeiro, Brazil; and 8Gladstone Inst of Virology and Immunology, San Francisco, CA, US
Background: Oral emtricitabine/tenofovir (FTC/TDF)
pre-exposure prophylaxis (PrEP) decreases HIV acquisition among men who have
sex with men (MSM). Initiation of TDF has been associated with decreases in
bone mineral density in HIV+ people. HIV infection itself, host
response to HIV, and other antiretroviral drugs may also contribute to bone
loss in HIV populations. The effect of the combination of FTC/TDF
on bone mineral density in the absence of HIV infection is not known.
Methods: DEXA scans of the hip and spine were
performed at baseline and 24-week intervals in a substudy of iPrEx, an
international randomized, double-blind, placebo-controlled trial of FTC/TDF
PrEP in MSM. Data are reported as the mean (SE) difference of change since
enrollment in the FTC/TDF vs placebo groups; p values were based on a
linear mixed model.
Results: We enrolled 503 participants (247
randomized to FTC/TDF and 256 to placebo) in this optional substudy (Peru n = 221, Thailand n = 95, US n = 71, South Africa n = 61, Brazil n = 55) with variable periods
of followup. Mean body mass index was 23.5 (0.2) kg/m2; 18% were
Caucasian, 13% black, 20% Asian, 49% mixed race; 52% were of Hispanic or
Latino; 48% of subjects were age 18 to 24 years and likely still accruing bone
mass. At baseline, 36% had low bone mineral density (Z-score <1) in the
spine and 18% in the hip. There were no differences between randomization
groups in baseline bone mineral density or percentage with low bone mineral
density. Percentage changes in bone mineral density at weeks 24 (n = 418), 48
(n = 268), and 72 (n = 126) are shown below. Bone mineral density tended to
increase in the placebo arm and decrease in the FTC/TDF arm, resulting in
modest (0.7 to 1.0%) but statistically significant differences between the
groups by week 24. There were no differences between the groups in bone
fractures (p = 0.56) or the incidence of low bone mineral density using
WHO or International Society for Clinical Densitometry criteria.
Mean (SE) percent change in bone mineral density from
enrollment
|
|
FTC/TDF
|
Placebo
|
Difference (95%CI)
|
p value
|
|
Total hip
|
|
|
|
|
|
week 24
|
0.31 (0.13)
|
+0.34 (0.13)
|
0.65 (1.03 to 0.28)
|
0.001
|
|
week 48
|
0.05 (0.22)
|
+0.90 (0.22)
|
0.95 (1.56 to 0.35)
|
0.002
|
|
week 72
|
+0.27 (0.28)
|
+0.49 (0.28)
|
0.22 (1.00 to 0.56)
|
0.581
|
|
Spine
|
|
|
|
|
|
week 24
|
0.66 (0.20)
|
+0.29 (0.20)
|
0.95 (1.51 to 0.39)
|
0.001
|
|
week 48
|
0.41 (0.24)
|
+0.13 (0.24)
|
0.54 (1.20 to 0.12)
|
0.106
|
|
week 72
|
0.97 (0.32)
|
0.10 (0.32)
|
0.87 (1.75 to 0.01)
|
0.052
|
Conclusions: In this large, diverse group of HIV
MSM, there were small but significant decreases in bone mineral density in
those randomized to FTC/TDF relative to placebo, suggesting an effect of
FTC/TDF on bone mass in the absence of HIV infection.
|
