 |
|
|
| |
Bone Loss in HIV-Negatives in PrEP Study: 'a surprising percent of HIV-neg MSM had low bone mineral density before starting TDF, drug use associated with bone mineral density loss - vitamin D/calcium supplementation was protective'; in some HIV+ persons low BMD likely predated HIV-infection....in summary Kathy Mulligan said "it is not known whether there will be any long-term clinically important effects of PrEP with TDF/3TC (Truvada) on bone health"
|
| |
| |
Jules Levin
CROI 2011 March 2 Boston
Popper use & amphetamine use was associated with low BMD at baseline in TDF PrEP study, use of calcium & vitamin D supplements were protective against having low BMD. Starting TDF led to small declines in BMD in first 12-15 months at femoral neck after starting but there were no further declines during 2 year followup, about a 1.1% decline, 0.8% decline in hip. In spine there appeared to be a small nonsignificant decline in first year which actually improved back to baseline at the 24 months timepoint. When looking at a greater than 3% decline in BMD at 24 months timepoint individuals receiving TDF exhibited significantly greater loss of 3% with 14% of persons on TDF experiencing BMD of 3% or more at the hip vs 3% on placebo (p=0.02), at the femoral neck 36% receiving TDF experienced 3% or more BMD loss vs 20% receiving placebo (p=0.02), but at the spine there was no difference between the 2 arms with17% of those on TDF experiencing this loss vs 15% on placebo. When looking at a 5% decline there were no differences between the arms. In the 2nd study reported by Kathy Mulligan of young men, mostly under 25, receiving TDF/FTC PrEP, the baseline z-scores at hip and spine were less than zero thus they had low bone mineral density before the study and again in young men who have yet to reach there bone mass meaning bone mass was still building in these young men at this age and Mulligan commented it was surprising they had low BMD as she expected a z-score of zero since they were healthy young men. After starting TDF/FTC there was a decline in BMD by week 24 after this time the numbers of patients were too small to evaluate at this time. The difference between those getting placebo & drug were about 0.7-0.9% in spine & hip BMD. When looking at 2% or greater BMD loss there was no difference between the TDF/FTC & placebo groups but when looking at persons who experienced a greater than 5% loss in the spine at any time point there was a slightly significant difference with for those receiving TDF/FTC there was a greater percent experiencing a 5% or more loss from baseline (p=0.47).
http://app2.capitalreach.com/esp1204/servlet/tc?c=10164&cn=retro&s=20445&&dp=player.jsp&e=13726&mediaType=podiumVideo (at 00.33:16)
Albert Liu*1,2, E Vittinghoff2, R Irby2, K Mulligan2, D Sellmeyer3, K Mayer4, M Thompson5, R Gvetadze6, L Grohskopf7, and S Buchbinder1,2. 1San Francisco Dept of Publ Hlth, CA, US; 2Univ of California, San Francisco, US; 3Johns Hopkins Univ Sch of Med, Baltimore, MD, US; 4Fenway Hlth, Boston, MA, US; 5AIDS Res Consortium of Atlanta, GA, US; 6Northrop Grumman, Atlanta, GA, US; and 7CDC, Atlanta, GA, US
Background: Several pre exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir disoproxil fumarate (TDF) in HIV- individuals for HIV prevention. Little is known about the effect of daily TDF on bone mineral density (BMD) in this population.
Methods: From 2005 to 2007, 200 HIV- men who have sex with men (MSM) enrolled in San Francisco in a double-blind, randomized trial evaluating the safety of daily oral TDF vs placebo. Half began the study drug after a 9-month delay to evaluate changes in risk behavior with pill use. Longitudinal DEXA bone densitometry was performed in 184 men at baseline, 9 or 12 months, and 24 months. Linear mixed models were used to assess effects of TDF on percentage change in BMD. A secondary workup including thyroid-stimulating hormone, testosterone, urine calcium/creatinine, 25-OH vitamin D, and parathyroid hormone, was performed in men with low BMD (Z score ≤2.0 at the total spine, total hip, or femoral neck) or a ≥5% decrease from baseline.
Results:
Median age was 40 years; 77% were white, 7% Latino or Hispanic, 5% African American, and 5% Asian or Pacific Islander.
Body mass index (BMI) was slightly higher in the TDF group at baseline; otherwise there were no significant differences between groups.
In the intention-to-treat analysis, there was a 1.1% net decrease in mean BMD in the TDF vs pre-treatment or placebo group at the femoral neck (95% CI 0.4 to 1.9%, p = 0.004) and a 0.8% net decline at the total hip (95%CI 0.3 to 1.3%, p = 0.003); at the L2 to L4 spine, there was a non to significant trend towards an adverse effect (0.7% decline, 95%CI -0.1 to 1.5%, p = 0.11).
Results were similar after adjustment for baseline BMD, BMI, race, age, and baseline creatinine clearance.
Declines in BMD in the TDF group were most prominent during the first 12 to 15 months of treatment.
Overall, 13% vs 6% participants experienced ≥5% loss of BMD at the femoral neck in the TDF vs placebo groups (p = 0.13). Evaluations performed in 27 men revealed 2 with vitamin D deficiency and 2 with hypogonadism.
In all, 10 participants reported fractures during follow-up: 6 in the TDF group and 4 in the placebo group (p = 0.75); all were trauma-related and assessed as not related to study drug.
Conclusions: TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck in HIV- men participating in a PrEP trial. Larger studies with longer follow-up are needed to determine the trajectory of these BMD changes and any association with clinical fractures.
------------------------
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 Mendonca7, 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 follow-up. 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
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.
|
| |
|
|
|
|
|
