Weekly Alendronate Safe and Effective at Increasing Bone Mineral Density in HIV-Infected Persons on Antiretroviral Therapy Slideset on: McComsey GA, Kendall MA, Tebas P, et al. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007;21: This program is supported by educational grants from Jointly sponsored by Postgraduate Institute for Medicine and Clinical Care Options, LLC

clinicaloptions.com/hiv Alendronate Safe and Effective at Increasing BMD in HIV-Infected Persons Background  HIV-infected individuals commonly develop decreased BMD  Bisphosphonates (eg, alendronate) standard of care for treating osteoporosis in HIV-uninfected men and postmenopausal women –Safety and efficacy of agents not well established in HIV- infected individuals  Current study compared efficacy and safety of alendronate plus calcium/vitamin D vs calcium/vitamin D alone for improving BMD in HIV-infected patients with osteopenia or osteoporosis on stable antiretroviral therapy McComsey GA, et al. AIDS. 2007;21:

clinicaloptions.com/hiv Alendronate Safe and Effective at Increasing BMD in HIV-Infected Persons Summary of Study Design McComsey GA, et al. AIDS. 2007;21: HIV-infected patients on stable ART, with HIV-1 RNA ≤ 5000 copies/mL, CD4+ cell count ≥ 100 cells/mm 3, and lumbar spine BMD t- score ≤ -1.5 (N = 82) Alendronate 70 mg once weekly + Calcium/Vitamin D supplement* (n = 42) Placebo + Calcium/Vitamin D supplement* (n = 40) Week 48 Stratified by CD4+ cell count cells/mm 3 vs > 200 cells/mm 3 *Calcium/vitamin D supplement consisted of a coformulated tablet containing calcium carbonate 500 mg and vitamin D 200 IU, administered twice daily.  Patients instructed to take all study medication in morning under fasting conditions and to remain upright for  30 minutes after ingestion

clinicaloptions.com/hiv Alendronate Safe and Effective at Increasing BMD in HIV-Infected Persons Main Findings McComsey GA, et al. AIDS. 2007;21: Change in BMD From Baseline to Week 48, % Alendronate, Vitamin D, and Calcium (n = 39) Placebo, Vitamin D, and Calcium (n = 37) Difference Between Groups, % (95% CI) P Value Lumbar spine3.38*1.10*2.29 ( ).03 Total hip3.95*1.31*2.64 ( ).004 Trochanter4.52*NS3.80 ( ).007 Femoral neck2.21*1.24NG.35 *P <.05 compared with baseline value.  Patients receiving alendronate vs placebo, each combined with vitamin D and calcium, demonstrated significantly greater increases in BMD –Differences in BMD at lumbar spine, total hip, and trochanter; not at femoral neck –Treatment outcomes did not differ according to sex or menopausal status  Patients receiving vitamin D and calcium alone demonstrated significant increases in BMD at certain sites compared with baseline values

clinicaloptions.com/hiv Alendronate Safe and Effective at Increasing BMD in HIV-Infected Persons Main Findings (cont’d) CharacteristicRRT Initiation During Pre-HAART Era RRT Initiation During HAART Era P Value Median age, yrs (IQR)36 (33-41)42 (37-48)<.001 Median current CD4+ cell count, cells/mm 3 (IQR) 303 (64-460)162 (50-311).03 Median nadir CD4+ cell count, cells/mm 3 (IQR) 212 (64-335)99 (19-193).002 AIDS, % McComsey GA, et al. AIDS. 2007;21:  Among HIV-seronegative blacks, RRT only initiated among HCV-seropositive (vs HCV- seronegative) individuals: 2.2% (22/1021) vs 0% (0/160) (P =.07)  Incidence of RRT initiation increased over time for HIV-seropositive individuals  AIDS status only variable independently associated with RRT initiation by multivariate analysis; adjusted incidence rate ratio: 2.7 (95% CI: )  Factors associated with more advanced disease significantly more common among HIV-infected patients who initiated RRT in HAART vs pre-HAART era

clinicaloptions.com/hiv Alendronate Safe and Effective at Increasing BMD in HIV-Infected Persons Main Findings (cont’d) McComsey GA, et al. AIDS. 2007;21: Outcome and VariableChange From BL to Week 48, % (95% CI)P Value Change in lumbar spine BMD  Alendronate treatment2.457 ( to ).02  Black race ( to ).003 Change in total hip BMD  Alendronate treatment2.613 ( to ).003  Male ( to ).003 Change in femoral neck BMD  Baseline weight (per 10 kg) ( to ).03  Current smoker2.326 ( to ).03 Change in trochanter BMD  Alendronate treatment3.343 ( to ).01  DEXA t-score (  -2 vs > -2) ( to ).04  Male ( to ).005 Change in CTx  Alendronate treatment ( to )<.001  NNRTI use0.141 ( to ).05  Current smoker0.144 ( to ).04

clinicaloptions.com/hiv Alendronate Safe and Effective at Increasing BMD in HIV-Infected Persons Other Outcomes Adverse Events  Grade 2 Occurring in > 5% of Patients in Either Arm, n (%) Alendronate (n = 42) Placebo (n = 40) Any29 (69)23 (58) Serious (  grade 3) 8 (19)14 (35) Hepatic system15 (36)12 (30) Abnormal chemistry6 (14)7 (18) General body6 (14)7 (18) Metabolic5 (12)4 (10) Neurologic2 (5)4 (10) Gastrointestinal2 (5)4 (10) Cardiovascular1 (2)4 (10) Pancreatic3 (7)3 (8) Respiratory2 (5)3 (8) McComsey GA, et al. AIDS. 2007;21:

clinicaloptions.com/hiv Alendronate Safe and Effective at Increasing BMD in HIV-Infected Persons Summary of Key Conclusions  Alendronate plus calcium and vitamin D supplementation produced significantly greater increases in BMD compared with calcium and vitamin D supplementation alone in HIV- infected individuals on stable antiretroviral therapy –BMD increases observed at lumbar spine, total hip, and trochanter, but not at femoral neck  Alendronate well tolerated with no evidence of major adverse events McComsey GA, et al. AIDS. 2007;21: