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.