Low baseline CD4+ count is associated with greater bone mineral density loss after antiretroviral therapy initiation.
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.
Division of Infectious Diseases, Department of Medicine, Stanford University, Palo Alto, California.
Philip M
PM
Grant
Douglas
D
Kitch
Grace A
GA
McComsey
Michael P
MP
Dube
Richard
R
Haubrich
Jeannie
J
Huang
Sharon
S
Riddler
Pablo
P
Tebas
Andrew R
AR
Zolopa
Ann C
AC
Collier
Todd T
TT
Brown
D015502:Absorptiometry, Photon; D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D015519:Bone Density / Q000187:drug effects*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019562:Viral Load
D019380:Anti-HIV Agents
HIV infections; administration and dosage; anti-HIV agents; bone density; drug therapy/virology