Protease Inhibitor Regimens Associated with Greater Decrease in Bone Mineral Density than NNRTI Regimens in Treatment-naive HIV Patients

HIV positive individuals taking combination antiretroviral therapy (ART) commonly develop reduced bone mineral density (BMD), a metabolic disorder. This high prevalence of osteopenia and the more severe osteoporosis has been linked to various factors including HIV infection itself, aging of this population, lower body weight, and smoking. Although some studies suggest that reduced BMD is associated with use of protease inhibitors (PIs), others have not confirmed these findings.

The aim of the current study, published in the April 27, 2009 issue of AIDS, was to evaluate the change in BMD at specific sites in treatment-naive patients who started ART in a substudy of the French ANRS 121 trial.

A total of 71 participants were randomly assigned (2: 1: 1) to 3 treatment strategy arms: a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus a ritonavir-boosted PI (n = 36), a boosted PI plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) (n = 19), or a NNRTI plus 2 NRTIs (n = 16). In the arms with NRTIs, 86% received zidovudine (AZT; Retrovir) plus lamivudine (3TC; Epivir).

About three-quarters of the participants (77%) were men and 69% were white. At study entry, the median age was 40 years, 58% were smokers, the mean body mass index (BMI) was 23 kg/m2, and the mean CD4 cell count was 219 cells/mm3.

The investigators assessed hip and lumbar spine standardized BMD at baseline and at week 48 using dual X-ray absorptiometry evaluated by a central reading laboratory.

Results

• At baseline, 31% of study participants had osteopenia and 3% had osteoporosis.
• At week 48, the mean change in BMD was -4.1 +/- 3.9% at the lumbar spine and -2.8 +/- 4.7% at hip (both P < 0.001).
• The decrease in BMD at the lumbar spine was significantly worse in the boosted PI plus NNRTI arm (-4.4 +/- 3.4%) and the boosted PI plus NRTIs arm (-5.8 +/- 4.5%) compared with the NNRTI plus NRTIs arm (-1.5 +/- 2.9%) (P = 0.007 and P = 0.001, respectively).

This study showed a significant reduction in BMD at the hip and lumbar spine sites after 1 year of treatment, regardless of which antiretroviral regimens were used.

"The decrease at lumbar spine after 1 year of [ART] was of a similar magnitude to the yearly decrease observed in women after menopause," stated the authors.

In addition, they wrote, "Moreover, at the lumbar spine, the decrease was significantly greater when patients received a [ritonavir-boosted PI]-containing regimen, whereas no difference was evidenced at [the] hip."

Finally, they recommended, "BMD at specific sites should be monitored during lifelong antiretroviral therapy."

4/14/09

Reference

C Duvivier, S Kolta, L Assoumou, and others (ANRS 121 Hippocampe Study Group). Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS 27(7): 817-824. April 27, 2009.