Bone Mineral Density in a Cohort of Young Adult Women using Depoprovera and Tenofovir, Kampala, Uganda

Transcription

1 Bone Mineral Density in a Cohort of Young Adult Women using Depoprovera and Tenofovir, Kampala, Uganda Flavia Matovu Kiweewa, Noah Kiwanuka, Delia Scholes, Esther Isingel, Mary Glenn Fowler, Clemensia Nakabiito, Monica L. Nolan, Philippa Musoke, John M. Pettifor, Todd Brown, Mags Beksinska 19th International Workshop on Adverse Drug Reactions and Co-Morbidities in HIV, 24 October 2017

2 BONE: CARE Study BONE: Contraception and Anti-Retroviral Effects Study

3 Introduction Sub-Saharan Africa bears greatest burden of the HIV epidemic (70% of 38 million infections) Women account for 57% of HIV infections & are more likely to acquire HIV at an earlier age Roll out of HAART in resource limited settings (RLS) has resulted in increased survival Newer treatment options like tenofovir disoproxil fumarate (TDF) promise even further increases in survival HIV-infected individuals experience accelerated bone mineral density (BMD) loss, higher rates of osteopenia and osteoporosis, and subsequent fractures, compared to HIVuninfected individuals Longer term effects of TDF on bone are concerning

4 Introduction Rapid acceleration of bone turnover with ART-initiation; bone resorption outstrips bone formation reduced BMD Among HIV-infected women, Depot medroxyprogesterone (DMPA) induces hypoestrogenemia bone resorption outstrips bone formation reduced BMD TDF & DMPA are independently associated with reduced BMD yet frequently used together in many RLS Co-administration of TDF and DMPA may potentiate each other s effect increased burden of early osteoporosis and fragility fractures BONE: CARE Study is the first longitudinal assessment of the combined effect of DMPA use and TDF initiation on BMD among women

5 Objectives To use the baseline data in the BONE CARE study to: compare BMD in untreated HIV-infected young women to non-infected women determine the independent effect of DMPA on BMD

6 Methods Study based at MU-JHU Research Collaboration, Kampala Women recruited from 11 HIV clinics & general health care facilities Classified into 4 groups based on their combination of HIV status, intention to start ART with TDF, and DMPA use Study population Women ages years Current DMPA users Non-hormonal users HIV infected HIV infected Group D Group A TDF/ ART Group B No ART Group C TDF/ ART HIV uninfected

7 Inclusion criteria Groups A, B, C & D able & willing to provide written informed consent aged18 to 35 years having a documented HIV test result Group A (HIV+, DMPA+, TDF ART) Group B (HIV +DMPA+, No ART) Group C (HIV+, DMPA-, TDF ART) Group D (HIV-, DMPA-) Using DMPA (new & prevalent users) Eligible but naïve to ART at screening (CD4 500) CD4 100 Using DMPA (new & prevalent users) Ineligible for ART per local guidelines CD4 650 Using non-hormonal contraception (intra-uterine device, tubal ligation) Eligible but naïve for ART at screening (CD4 500) No h/o use of hormonal contraception in last 2yrs CD4 100 No h/o use of hormonal contraception in last 2yrs No h/o use of PEP in last 6 months

8 Methods All HIV-infected women were ART-naïve at baseline Baseline BMD assessments of lumbar spine (LS), total hip (TH) and femoral neck (FN) were done using dual energy x-ray absorptiometry Inter-tech variation assessed prior to study start Z-scores were derived from the National Health and Nutrition Examination Survey (NHANES) white female reference s Multivariable linear regression was used to assess the independent effects of HIV-infection status on BMD and BMD Z-scores, adjusting for age, BMI, history of breastfeeding, parity, and DMPA use

9 Results

10 Accrual began March 2015 Completed October Screened 7 Screened Out (not Pregnant) 10 identified as Pregnant at Screening Group A 158 Enrolled Group B 192 Enrolled Group C 108 Enrolled Group D 50 Enrolled Total Enrollment =

11 Table 1: Participant Baseline Characteristics Characteristic (Median / %) Total (N=508) Group A (n=158) Group B (n=192) Group C (n=108 ) Group D (n=50) Age (years) 26.0 (23, 29) 26.0 (23, 29) 26.5 (23,29) 26.0 (23, 31) 22.5(20, 26) <0.001 Education ( 286 (56.3) 83 (52.5) 92 (47.9) 68 (63.0) 43 (84.3) <0.001 secondary) Married 270 (53.1) 84 (53.2) 106 ( 55.2) 53 (49.1) 27 (54.0) Ever pregnant 432 ( 84.4) 145 (91.8) 178 (92.2) 89 (81.7) 20 (38.5) <0.001 Parity 2 (1,3) 2 (1,4) 2 (1,3) 2 (1,3) 0 (0,1) <0.001 Ever used DMPA 337 (65.8) 127 (80.3) 155 (80.3) 47(43.1) 8 (15.4) <0.001 Current DMPA use 212 (60.6) 88 ( 55.7) 124 (64.6) N/A N/A Duration of DMPA Use (months) Breastfeeding Duration (mths) CD4 cell count (cells/ul) (398, 858) BMI (Kg/m 2 ) 24.0 (21.5, 27.2) 22.5 (6, 47) 24 (9, 48) 18 (6, 36) N/A N/A (21.9) 32.8 (24.2) (20.7) (21.0) 27.4 (18.8) (294,581) 24.3 (21.8,27.0) 856 (755, 1025) 24.6 (21.5,28.0) 442 (302,625) 23.8 (21.4, 26.7) N/A < (21.2, 24.0) 0.002

12 Table 2: Baseline BMD Z-Scores *Z-Score Total (N=508) Group A (n=158) Group B (n=192) Group C (n=108 ) Group D (n=50) Lumbar Spine Median (IQR) -1 (-1.5, -0.3 ) -1.1(-1.6,-0.3) -1.1 (-1.6,-0.4) -0.8 (-1.3, -0.1) -0.6 (-1.3, 0.0) SD 240 (47.24) 81 (51.27) 98 (51.31) 43 (39.82) 18 (35.29) Neck Femur Median (IQR) 0.1 (-0.6,0.9) 0 (-0.7, 0.7) 0 (-0.7, 0.8) 0.4 (-0.4, 1) 0.2 (-0.1, 1.2) SD 62 (12.2) 23 (14.56) 23 (12.04) 14 (12.97) 2 (3.92) Total Hip Median (IQR) 0.1 (-0.5,0.8) 0 (-0.6, 0.5) 0 (-0.5, 0.7) 0.4 (-0.3, 1.1) 0.4 (-0.2, 1.1) SD 52 (10.23) 17 (10.76) 16 (8.38) 17 (15.74) 2 (3.92) *Z scores were derived from NHANES white female reference s

13 Table 3: Differences in BMD Z-scores by HIV Status Body site Lumbar spine Total hip Femur neck Crude Z-score mean difference (95% CI) *Adjusted mean Z- score difference (95% CI) (-0.576, 0.004) (-0.861, 0.012) (-0.589,-0.463) (-0.713, ) (-0.588, 0.011) (-0.061, 0.269) *Adjusted for age, BMI, ever breastfeeding, parity, ever use of DMPA

14 Table 4: Differences in BMD by HIV Status Body site Lumbar spine Total hip Femur neck Crude BMD mean difference g/cm 2 (95% CI) *Adjusted BMD mean difference g/cm 2 (95% CI) (-0.073, ) (-0.067, 0.004) (-0.081, ) (-0.075, ) (-0.079, 0.011) (-0.062, 0.008) *Adjusted for age, BMI, ever breastfeeding, parity, ever use of DMPA

15 Table 5: Differences in BMD Z-scores by DMPA Status Body site Lumbar spine Total hip Femur neck Crude BMD Z-score mean difference (95% CI) *Adjusted BMD z- score mean difference (95% CI) (-0.447, ) (-0.808,-0.175) (-0.045, ) (-0.735,-0.159) (-0.057, ) (-0.976,-0.348) <0.001 *Adjusted for age, BMI, ever breastfeeding, parity

16 Table 6: Differences in BMD by DMPA Status Body site Lumbar spine Total hip Femur neck Crude BMD mean difference g/cm 2 (95% CI) *Adjusted BMD mean difference g/cm 2 (95% CI) (-0.046, -.005) ( ) (-0.045, 0.002) (-0.068, ) < (-0.057, ) (0.833, 0.919) <0.001 *Adjusted for age, BMI, ever breastfeeding, parity

17 Conclusion Lower BMD among untreated HIV-infected compared to HIV-uninfected women Statistically significant differences observed at the hip DMPA use was associated with significantly lower BMD at all sites Follow-up data from this cohort will determine whether ART-initiation with TDF is impacted by DMPA use

18 Acknowledgements The Research participants BONE CARE Study team MU-JHU Research Collaboration NIH The BONE CARE Study is supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R01AI The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.