We continue to study antiretroviral therapy and its potential complications. We demonstrated that phenotypic susceptibility was an important predictor of virologic response in a trial of abacavir, efavirenz and amprenavir in patients who had failed to respond optimally to a protease-inhibitor regimen. A better response to treatment was associated with baseline factors: lower viral load, fewer mutations associated with efavirenz resistance, absence of phenotypic resistance to abacavir and/or efavirenz and susceptibility to a larger number of drugs. We have begun a protocol designed to take a detailed look at the relationship between phenotype and treatment outcome. In addition, we demonstrated that concomitant efavirenz results in suboptimal amprenavir concentrations, and then that the use of a second protease inhibitor prevents the decrease in amprenavir concentration and results in high drug levels that suggest that once-daily dosing is feasible. Finally, we showed that an over-the-counter herbal product, St. John's wort, lowers blood levels of indinavir and thus could contribute to the treatment failure; we are investigating the effect of garlic supplements on protease inhibitor levels. We have shown that lipodystrophy is characterized by increased visceral fat; that it is not caused by dysregulation of the hypothalamic-pituitary-adrenal axis; and that loss of facial fat measured by MRI scan correlates with the duration of therapy. We have demonstrated that osteonecrosis of the hip is surprisingly common, and that it is associated withuse of systemic corticosteroids, lipid-lowering agents, testosterone or body-building equipment or the presence of anticardiolipin antibodies. We continue our efforts to improve access to clinical trials by local minority populations through a close relationship with a local clinic for the medically under-served.We continue to follow patients with idiopathic CD4 lymphocytopenia (ICL) in order to the learn its natural history, and we have begun to explore interleukin-7 in ICL.
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