We continue to study antiretroviral therapy and its potential complications in people infected with HIV, and we have begun clinical trials of hepatitis B therapies. We reported further data on indinavir-associated urinary tract toxicity. 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). Acquired mutations are being reported. 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 are conducting a trial of the relationship between resistance mutations and viral load suppression. We have a study that looks at sequence variation in untreated patients. 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, we have outlined some risk factors for its development, and we are now characterizing its incidence and natural history . We have on-going studies of the safety and efficacy of adefovir for the treatment of hepatitis B in HIV-infected patients, and we will use samples from these trials to examine the natural history and immune response to hepatitis B in this population. We have begun studies of the role of P-glycoprotein (PGP) in the pharmacokinetics of drugs, first by investigating whether ritonavir will affect concentrations of digoxin through inhibition of renal PGP, and secondly by investigating whether differences in the concentrations of indinavir and saquinavir and in PGP expression correlate with PGP genotype. 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.
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