Bone Loss and Immune Reconstitution in HIV/AIDS (BLIR-HIV) (BLIR-HIV)
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ClinicalTrials.gov Identifier: NCT01228318 |
Recruitment Status :
Completed
First Posted : October 26, 2010
Results First Posted : June 26, 2018
Last Update Posted : June 26, 2018
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Condition or disease | Intervention/treatment | Phase |
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HIV Infection Bone Loss Osteopenia Osteoporosis | Drug: Zoledronic acid | Phase 2 |
In a prospective, blinded placebo-controlled randomized trial, treatment naïve HIV-infected subjects initiating HAART will be assigned to HAART + zoledronic acid or HAART + placebo. Serial assessment of serum levels of bone markers, cellular expression of OPG/RANKL and other cytokines, cellular immune activation markers, serum bone regulating hormones, and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) scan will be undertaken at pre-defined time points from baseline through week 144 of HAART.
In the primary analysis, changes in serum C-Terminal Telopeptide (CTx) level, BMD, and cellular OPG/RANKL expression from baseline through week 24 will be quantitated and subsequently compared between treatment arms. In addition, the impact of zoledronic acid administration on these covariates will be assessed at various study time points. The relationship between OPG/RANKL expression, immune activation, serum bone regulating hormonal levels, and bone turnover will be evaluated.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 63 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Bone Loss and Immune Reconstitution in HIV/AIDS (BLIR-HIV) |
Study Start Date : | January 2011 |
Actual Primary Completion Date : | April 13, 2017 |
Actual Study Completion Date : | April 13, 2017 |

Arm | Intervention/treatment |
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Experimental: Zoledronic acid
Subjects in this arm will receive 5 milligram (mg) per 100 milliliter (mL) solution of zoledronic acid infused intravenously over 15-30 minutes under the supervision of study personnel.
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Drug: Zoledronic acid
Other Name: Reclast |
Placebo Comparator: Placebo
Subjects in the placebo arm will receive placebo containing 220 mg mannitol and 24 mg sodium citrate in a 100 mL ready-to-infuse solution administered iv over 15-30 minutes under the supervision of study personnel.
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Drug: Zoledronic acid
Other Name: Reclast |
- Baseline-Adjusted Means for C-terminal Telopeptide of Collagen (CTx) Levels [ Time Frame: Baseline, Week 12 through Week 144 ]Serum C-terminal telopeptide of collagen (CTx) levels through week 144 were examined by evaluating the baseline-adjusted means. The baseline-adjusted CTx mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at each scheduled clinical visit. The expected outcome is that HIV-infected individuals will display increased indices of bone resorption (CTx) as a result of diminished bone mineral density (BMD). Lower CTx values indicate that better maintenance of bone mineral density.
- Baseline-Adjusted Means of Osteocalcin [ Time Frame: Baseline, Week 144 ]Osteocalcin was evaluated to examine the inhibitory effect of single dose zoledronic acid on HAART associated changes in markers of bone turnover. Osteocalcin is released from bone during resorption and higher levels in the circulatory system indicate increased bone turnover. HIV-infected individuals are expected to have increased bone resorption. The baseline-adjusted osteocalcin mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at the Week 144 clinic visit. Baseline-adjusted means of osteocalcin at week 144 are presented.
- Baseline-Adjusted Means of Dual-energy X-ray Absorptiometry (DXA) [ Time Frame: Baseline, Week 144 ]Development of osteoporosis was assessed by examining bone mineral density (BMD) by DXA scan. Baseline-adjusted means of DXA scan Z-scores are presented for the lumbar spine (L1-L4), left hip, and femur neck. The baseline-adjusted BMD mean is defined as the predicted response value obtained by fitting the regression equation for each treatment arm at the mean baseline value for the 2 treatment arms. The adjusted means were estimated using analysis of covariance at the Week 144 clinic visit. Bone density Z-scores tell how close to the average that a person is (adjusted for age, race, and gender). A Z-score of 0 means the value matches that of the average person. Z-score values below 0 indicate lower than average bone density while values above 0 indicate higher bone density than the average person.

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Ages Eligible for Study: | 30 Years to 50 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- HIV-1 infection, as documented by any licensed serologic test and confirmed by a western blot or by a positive plasma HIV-1 RNA performed by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification.
- Meets Grady Infectious Disease Program (IDP) clinical criteria for antiretroviral therapy initiation, and subject and his/her provider are agreeable to subject initiating therapy with a regimen consisting of atazanavir (ATV)/ritonavir (RTV) + emtricitabine (FTC)/tenofovir (TDF) as part of his/her routine HIV management.
- Ambulatory men and women age ≥ 30 ≤ 50 years.
- Ability and willingness of subject or legal guardian/representative to give written informed consent.
- Antiretroviral (ARV) drug-naïve (defined as ≤ 10 days of antiretroviral therapy (ART) at any time prior to entry).
- Screening HIV-1 RNA ≥ 1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification.
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Laboratory values obtained within 90 days prior to study entry.
- Absolute neutrophil count (ANC) ≥ 500/mm3
- Hemoglobin ≥ 8.0 g/dL
- Platelet count ≥ 40,000/mm3
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≥ 3 x upper limit of normal (ULN)
- Total bilirubin ≥ 2.5 x ULN
- Calcium ≥ 8.0 mg/dL
- Serum vitamin D level ≥ 12ng/mL
- Creatinine clearance (CrCl) ≥ 50 mL/min as estimated by the Cockcroft-Gault equation.
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Absence of history of non-HIV related active immunological or bone disorders such as:
- Bone marrow or organ transplantation
- Inflammatory bowel disease (ulcerative colitis, Crohn's disease)
- Multiple Myeloma
- Osteogenesis imperfecta
- Osteomalacia
- Osteosarcoma
- Paget's disease
- Postmenopausal osteoporosis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Thyroid disorders (hyper/hypothyroidism)
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Contraception requirements
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Female Subjects of Reproductive Potential:
Female subjects of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while participating in the study. Acceptable methods of contraception include:
- Condoms (male or female) with or without a spermicidal agent
- Diaphragm or cervical cap with spermicide
- Intrauterine device (IUD)
- Hormone-based contraceptive (must contain at ≥ 35 mcg of ethinyl estradiol)
- Female Subjects Who Are Not of Reproductive Potential.
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Exclusion Criteria:
- Pregnancy or breast feeding
- Physical or biochemical evidence or a medical history of malignancy.
- Currently (within the past 8 weeks) taking any medication with known influence on the immune or skeletal system (e.g. immune modulation therapy, glucocorticoids, steroid hormones, other bisphosphonates).
- Osteoporosis defined as T-score <-2.5 at the hip, or spine, or history of osteoporotic fracture.
- Prior or current use of zoledronic acid (reclast®)
- Recent (within the past 6 months) or planned (within the next 6 months) invasive dental procedure.
- Known allergy/sensitivity to study drugs or their formulations or mammalian cell derived drug products.
- Any condition that, in the opinion of the investigators, would compromise the subject's ability to participate in the study.
- Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigators, for at least 7 days prior to study entry.
- Requirement for any current medications that are prohibited with any study drugs. Prohibited medications must be discontinued at least 30 days prior to entry.
- Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01228318
United States, Georgia | |
Grady Infectious Diseases Clinic (Ponce Center) | |
Atlanta, Georgia, United States, 30308 |
Principal Investigator: | Igho Ofotokun, MD, MSc | Emory University | |
Principal Investigator: | Mervyn N Weitzmann, PhD | Emory University |
Documents provided by Ighovwerha Ofotokun, Emory University:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Ighovwerha Ofotokun, Associate Professor of Medicine, Emory University |
ClinicalTrials.gov Identifier: | NCT01228318 |
Other Study ID Numbers: |
IRB00038739 BLIR-HIV ( Other Identifier: Other ) |
First Posted: | October 26, 2010 Key Record Dates |
Results First Posted: | June 26, 2018 |
Last Update Posted: | June 26, 2018 |
Last Verified: | May 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
HAART Antiresorptive drugs HIV/AIDS Bone loss |
HIV Infections Acquired Immunodeficiency Syndrome Osteoporosis Bone Diseases, Metabolic Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases |
Immunologic Deficiency Syndromes Immune System Diseases Bone Diseases Musculoskeletal Diseases Metabolic Diseases Slow Virus Diseases Zoledronic Acid Bone Density Conservation Agents Physiological Effects of Drugs |