We continue to study antiretroviral therapy and its potential complications in people infected with HIV. In a trial of abacavir, efavirenz and amprenavir in patients who had failed to respond optimally to a protease-inhibitor regimen, response to treatment was associated with baseline factors: viral load, HIV drug resistance mutations and drug susceptibility (phenotype). From another study, we have shown that the relative inhibitory quotient, a measure of the relationship between an individual patient's drug levels and the drug susceptibility of the HIV infecting that patient, is a significant predictor of outcome for salvage therapy with amprenavir. We have begun a clinical trial designed to evaluate the relationship between phenotype and treatment outcome. We have extended our investigations of the effects of herbal products on anti-retroviral agent pharmacokinetics to show that St. John's wort lowers blood levels of indinavir; milk thistle does not affect indinavir concentrations; and garlic supplements can depress concentrations of saquinavir. We have demonstrated that osteonecrosis of the hip is surprisingly common, outlined some risk factors for its development, and we are now characterizing its incidence and natural history . 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 to investigate possible pathogenic mechanisms; through collaborations, we have studied cell surface markers and IL7 levels in these patients. We have begun two studies of adefovir for hepatitis B in patients with HIV infection who have high levels of hepatitis B virus in the blood despite at least one year of lamivudine (one portion also enrolls those who are HIV negative); subjects can have stable or decompensated liver disease.
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