Low Baseline CD4+Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation

• Published in: Clinical infectious diseases Vol. 57; no. 10; pp. 1483 - 1488
• Main Authors: Grant, Philip M., Kitch, Douglas, McComsey, Grace A., Dube, Michael P., Haubrich, Richard, Huang, Jeannie, Riddler, Sharon, Tebas, Pablo, Zolopa, Andrew R., Collier, Ann C., Brown, Todd T.
• Format: Journal Article
• Language: English
• Published: Oxford OXFORD UNIVERSITY PRESS 15.11.2013; Oxford University Press
• Subjects: Absorptiometry, Photon; Adult; AIDS; Analysis of Variance; Anti-HIV Agents - administration & dosage; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretrovirals; Antiviral agents; Arts; Biological and medical sciences; Body mass index; Bone density; Bone Density - drug effects; Bones; CD4 Lymphocyte Count; Disease risks; Female; Hepatitis C virus; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - pathology; HIV Infections - virology; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Investigative techniques, diagnostic techniques (general aspects); Lentivirus; Linear Models; Male; Medical sciences; Middle Aged; Osteoarticular system. Muscles; Osteoporosis; Pharmacology. Drug treatments; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Regression analysis; Risk Factors; RNA; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Infection; Immunopathology; Antiretroviral agent; Chemotherapy; Treatment; Viral disease; Antiviral; AIDS; Bone mineral density; Immune deficiency; HIV infections; drug therapy/virology; anti-HIV agents; administration and dosage; bone density
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/cit538

Background. Bone mineral density (BMD) decreases 2%–6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss. Methods. We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4 + and 16-week CD4 + change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)– or tenofovir-containing regimen on 96-week total BMD change. Results. The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4 + cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4 + <50 cells/μL lost significantly more BMD compared to those with CD4 + ≥500 cells/μL. A greater relative, but not absolute, 16-week increase in CD4 + count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4 + count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline. Conclusions. Low pretreatment CD4 + count, but not greater CD4 + count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4 + counts may reduce the burden of osteoporosis and fragility fractures.