Effect of HIV Infection and Highly Active Antiretroviral Treatment (HAART) on Bone Homeostasis

NCT01020045 | Completed

• 2 other identifiers: IRB00027210R01AR059364-01
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Advances in HAART have been a huge success story in the management of HIV infection. However, serious metabolic complications including osteoporosis and bone fractures are increasingly been seen with HAART, and the responsible mechanisms remain poorly elucidated. The skeleton continually regenerates through homeostatic bone remodeling. Osteoclasts the cells responsible for bone resorption form under the influence of the key osteoclastogenic cytokine Receptor- Activator of NF-KB (RANKL). The osteoclastogenic and pro-resorptive activities of RANKL are moderated by its physiological decoy receptor osteoprotegerin (OPG). Increase in the ratio of RANKL to OPG accelerates the rate of osteoclastic bone resorption leading to osteoporosis. The investigators' preliminary studies have now demonstrated that in an animal model of HIV/AIDS, the HIV-1 Transgenic rat, the development of osteoporosis is recapitulated as observed in human patients. Furthermore, the investigators found that B cell expression of OPG is significantly downregulated, concurrent with a significant upregulation in production of RANKL.

Conditions

HIV Infection; Osteopenia; Osteoporosis

Keywords

HIV; Osteopenia; Osteoporosis

Outcome Measures

Primary Outcomes (1)

• To correlate serum and B cell and T cell OPG and/or RANKL production in treatment-naïve HIV-infected patients, with indices of bone turnover and structure and with viral load.

  During entry visit

Study Arms (2)

HIV-seropositive, HIV seronegative

No intervention - biologic samples were collected from both HIV positive and HIV negative subjects

Treatment naive subjects

HIV-seropositive subjects naive to antiretroviral therapy. HIV-seronegative subjects otherwise healthy.

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Healthy (HIV sero-negative) volunteers and otherwise healthy antiretroviral treatment naïve HIV-1 sero-positive patients, age \>18 years.

You may qualify if:

• Healthy (sero-negative) volunteers and otherwise healthy treatment naïve HIV-1 sero-positive patient.
• Age \>30\<50 years and segregated into age and gender ranges as described above in section 3.2 (15 subjects per stratification based on Power Test).
• Ability and willingness of subject or legal guardian/representative to give written informed consent.
• Antiretroviral naivety.
• No CD4 T-cell counts requirement.
• Absence 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 imperfect
• Osteomalacia
• Osteosarcoma
• Paget's disease
• Postmenopausal osteoporosis
• Rheumatoid arthritis

You may not qualify if:

• 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, bisphosphonates).
• The patient is not fully ambulatory.
• Pregnancy or breast feeding.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Grady Infectious Diseases Program Clinic

Atlanta, Georgia, 30308, United States

Location

Related Publications (1)

• Titanji K, Vunnava A, Sheth AN, Delille C, Lennox JL, Sanford SE, Foster A, Knezevic A, Easley KA, Weitzmann MN, Ofotokun I. Dysregulated B cell expression of RANKL and OPG correlates with loss of bone mineral density in HIV infection. PLoS Pathog. 2014 Nov 13;10(10):e1004497. doi: 10.1371/journal.ppat.1004497. eCollection 2014 Oct.

  PMID: 25393853 RESULT

Related Links

• Dysregulated B Cell Expression of RANKL and OPG Correlates with Loss of Bone Mineral Density in HIV Infection

MeSH Terms

Conditions

HIV Infections; Bone Diseases, Metabolic; Osteoporosis

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Ighovwerha Ofotokun, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 24, 2009
• First Posted: November 25, 2009
• Study Start: October 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: October 1, 2015
• Last Updated: October 19, 2015

Record last verified: 2015-10

Locations

US (1)