Background:  Osteopenia is very frequent among HIV-infected individuals. Both HIV infection and its treatment play a role in its development. However, longitudinal data of the effects of initiating ART on bone mineral content are very limited. The goals of this study were to measure bone mineral content among ART-naïve individuals, to evaluate the longitudinal effects of the initiation of ART on bone, and to study the relationships of bone changes with other metabolic parameters.

Methods:  In A5005s, the metabolic substudy of AIDS Clinical Trials Group (ACTG) 384, whole-body DEXA scans were performed at entry and every 16 weeks thereafter in 157 subjects. Participants were randomized to receive nelfinavir (NFV), efavirenz (EFV), or both drugs combined with open-label zidovudine (AZT) and lamivudine (3TC) or didanosine (ddI) and stavudine (4dT) (NRTI groups). Percentage change in total bone mineral content was the primary outcome variable.

Results:  After the initiation of ART, there was a small but statistically significant decrease in total bone mineral content at 16 weeks (median:  –0.44%, IQR –1.96 to 1.07%, p = 0.02). Total bone mineral content continued to decrease. At 48 weeks, the decrease was 1.02% (IQR –3.63 to 1.24%, p <0.01), while at 96 weeks, the decrease was 2.25% (IQR –4.75 to 0.35%, p <0.01). Even though the decline in total bone mineral content in the EFV group was slightly less using a mixed models analysis limited to participants remaining on original treatment, the difference between the NFV and EFV groups was not statistically significant (p = 0.08), nor was the effect of nucleoside reverse transcriptase inhibitor (NRTI) assignment (p = 0.60). Higher baseline CD4 cell count was associated with a slower decline in total bone mineral content after ART initiation (p = 0.002). Baseline total bone mineral content correlated weakly with HDL cholesterol (R = –0.24, p <0.01) and percentage of free testosterone (R = 0.26, p <0.01). CD4 and HIV RNA levels were not associated with baseline total bone mineral content. Correlations between changes in total bone mineral content and other metabolic parameters were generally not significant.

Conclusions:  The initiation of ART was associated with a modest but statistically significant bone loss that was independent of the regimen used in our study. The amount of bone loss after ART initiation was greater in individuals with lower baseline CD4. These findings suggest that the treatment effect of ART on bone was not a direct toxic effect, but might be mediated through the antiviral or immunological changes associated with the initiation of ART.