AIDS 2010: Majority of HIV Positive People on Antiretroviral Therapy May Have Reduced Bone Density

About half of people with HIV taking antiretroviral therapy (ART) in a Spanish study had low bone mineral density, and another quarter had more severe bone loss, researchers reported at the XVIII International AIDS Conference (AIDS 2010) last month in Vienna. This study found that bone loss was associated with use of tenofovir and protease inhibitors, a finding also supported by results of the ACTG 5142 trial in the U.S.

A considerable body of research has shown that people with HIV have a higher risk of bone problems compared with the general population -- including reduced bone mineral density (osteopenia) and the more advanced bone loss of osteoporosis -- but it has not yet been established whether this is due to HIV infection itself, resulting inflammation, antiretroviral therapy, or some combination of these and other factors.

Anna Bonjoch from University Hospital German Trias in Barcelona and colleagues aimed to determine the prevalence of, and factors associated with, low bone mineral density in HIV positive people.

This retrospective analysis included 671 participants. Most (72%) were men and the median age was 43 years. Almost all of whom were on ART, with an average duration of about 7 years; about half were taking protease inhibitors and about half were on tenofovir (Viread, also in the Truvada and Atripla coformulations).

All participants received at least 1 dual energy X-ray absorptiometry (DEXA) scan and were included in the cross-sectional analysis. The investigators also looked at longitudinal changes over time in a subset of 391 patients who had at least 2 DEXAs during a median 2.5 years of follow-up.

Results

• 48% of study participants were diagnosed with osteopenia.
• 25% were found to have more severe osteoporosis.
• In the longitudinal group, 49% had osteopenia and 22% had osteoporosis according to their first DEXA scan, rising to 53% and 27%, respectively, by the end of follow-up.
• About 16% progressed from osteopenia to osteoporosis during follow-up.
• In the cross-sectional analysis, factors significantly associated with bone loss included:
  • Male sex: -0.6955 (P = 0.0019);
  • Older age: -0.044 (P < 0.001);
  • Low body mass index (BMI): 0.0962 (P = 0.0037);
  • High viral load: -0.079 (P = 0.033).
• In the longitudinal follow-up analysis, sex, age, and body weight remained significant, but antiretroviral drugs were also significant predictors:
  • Longer duration of protease inhibitor use: odds ratio (OR) 1.18 (P < 0.0001);
  • Longer duration on tenofovir: OR 1.08 (P < 0.0019);
  • Current use of a protease inhibitor at the time of DEXA: OR 0.61 (P < 0.0001).

These results, the researchers concluded, "showed a high prevalence of osteopenia and osteoporosis," associated with being male, low BMI, use of protease inhibitors, and duration of protease inhibitors and tenofovir.

"These results demonstrate the high frequency of these abnormalities and the need for an early detection and prevention of them," they added.

In a second AIDS 2010 presentation, Richard Haubrichdescribed changes in bone mineral density among people taking 3 types of antiretroviral regimen. In the open-label ACTG study 5142, a total of 753 treatment-naive participants were randomly allocated in equal numbers to receive the following regimens:

• Protease inhibitor-based: lopinavir/ritonavir (Kaletra) plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs);
• NNRTI-based: efavirenz (Sustiva, also in the Atripla pill) plus 2 NRTIs;
• NRTI-sparing: lopinavir/ritonavir plus efavirenz.

For people assigned to the first 2 regimens, NRTIs were selected prior to randomization and included zidovudine (AZT; Retrovir), stavudine (d4T; Zerit), or tenofovir, all with lamivudine (3TC; Epivir).

About 80% of participants were men, the median age was 38 years, about one-third were white, and the median CD4 count was low, at 190 cells/mm3.

Whole body DEXA was used to assess total body bone mineral density at baseline (687 patients had baseline measurements available), 48 weeks, and 96 weeks.

Results

• In each study arm, significant declines in bone density were observed at week 48 and persisted to week 96.
• With regard to NRTI choice, participants taking tenofovir experienced significantly more bone loss than those taking zidovudine or stavudine, which were similar to each other (-2.82%, -1.18%, and -1.17%, respectively, at 48 weeks; -3.00%, -1.75%, and -2.02% at 96 weeks; P < 0.001).
• Patients taking lopinavir/ritonavir plus NRTIs had a trend toward more bone loss at week 48 compared with those taking efavirenz plus NRTIs, but the difference did not reach statistical significance (-0.5%; P = 0.08).
• Looking at complete combinations, people taking lopinavir/ritonavir plus tenofovir/lamivudine experienced significantly greater bone loss at week 48 than those on the NRTI-sparing regimen (-3.1% vs -1.9%, respectively; P = 0.004).
• Those taking efavirenz plus either zidovudine/lamivudine (+1.1%) or stavudine/lamivudine (-0.9%), however, had smaller decreases in bone density at week 48 compared with the NRTI-sparing combination (P < 0.03 for both).
• Bone changes between week 48 and week 96 were statistically similar for all regimens.

"ART therapy was associated with reductions in bone mineral density, especially in the first year after initiation," the researchers concluded.

"Among the NRTI-containing arms, NRTI selection, especially use of [tenofovir], had a greater effect on bone mineral density change with a non-significant trend for greater declines in the [lopinavir/ritonavir] arm," they continued. "The long-term clinical significance of these bone mineral density changes remains to be determined."

Finally, as previously reported, Veterans Administration researchers presented a study showing that HIV/HCV coinfected people are more likely to sustain fractures due to bone loss than individuals with either virus alone. In this study, however, use of ART had a protective effect.

Investigator affiliations:

THPDB104: Lluita contra la SIDA Foundation, University Hospital Germans Trias, Badalona, Spain; Statistics and Operations Research, Technical University of Catalunya, Barcelona, Spain; Lluita contra la SIDA Foundation, Germans Trias University Hospital and IrsiCaixa Foundation, Badalona, Spain.

WEAB0304: University of California at San Diego, San Diego, CA; Harvard School of Public Health, Boston, MA; University of Pittsburgh, Pittsburgh, PA.

8/3/10

References

A Bonjoch, M Figueras, J Puig, and others. Prevalence and associated factors of low bone mineral density in a large cohort of HIV infected patients. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. AbstractTHPDB104.

J Huang, M Hughes, S Riddler, and others. Effects of randomized regimen and nucleoside reverse transcriptase inhibitor (NRTI) selection on 96 week bone mineral density (BMD): results from ACTG 5142. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract WEAB0304.