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The Body Covers: The 1st International AIDS Society Conference on HIV Pathogenesis and Treatment
Toxicities of HAART
July 10, 2001 To view a video of this presentation, click here
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Dr. Tebas concentrated on problems of low bone mass -- osteopenia and osteoporosis. Another problem, aseptic necrosis, seems to have separate etiology and epidemiology. Dr. Tebas reminded us that bone is a dynamic tissue. Up to 10% of bone turns over every year in normal hosts. Bone density scans, usually done by DEXA, have shown an increased prevalence of low bone density in HIV-infected persons. Initial studies, including those by Tebas, suggested that low-bone density was associated with the use of protease-containing HAART. However, association is not the same as saying it is the cause. In fact, other studies have shown a modest increase in osteopenia in HIV-infected persons who were not treated with protease inhibitors. Moreover, bone mineral density varies, and in a cross-sectional study, a predicted proportion of normal people will have low bone mineral density. Nonetheless, cross-sectional studies show that HIV-positive patients on protease inhibitor-containing HAART have about twice the risk of osteopenia as HIV-positive people who are not on treatment, and those not on treatment have a higher risk than people who are HIV-negative. However, Dr. Tebas warned that cross-sectional studies can never answer the question of whether protease inhibitors cause osteopenia. He went on to describe detailed studies of vitamin D, calcium excretion and bone biopsy. These studies are in their early phases, but suggest that there is increased turnover. Preliminary, limited data shows there may be an association between fat redistribution and bone loss, and between increased lactate and bone loss. The reasons for bone loss remain unclear. Low testosterone levels do not explain it. There is a potential interaction between vitamin D hydroxylating enzymes and protease inhibitors, but this may be only an in vitro phenomenon. Other in vitro studies have looked at the effect of protease inhibitors on osteoblasts and osteoclasts in vitro. Many challenges remain. One problem is the lack of data in women, who are at increased baseline risk of osteopenia. As Dr. Tebas suggested, quoting Plutarch: "Time is the wisest counselor." We will need to wait for good science and longitudinal studies to understand this new problem.
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