Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality, but the management of HIV-infected patients has become increasingly complex. We continue to address aspects of the following questions: when to discontinue medications to prevent opportunistic infections; how to dose anti-retroviral drugs; how to design salvage therapies for those patients who fail to respond to anti-retroviral therapy with sustained maximal viral load suppression; what is the mechanism for and clinical importance of the HIV-associated lipodystrophy syndrome; and what happens to viral load and other measures after the discontinuation of successful anti-retroviral therapy. We continue work on a database designed to capture clinical and laboratory data for the dual purposes of rapid access to data for patient care and research use. We continue our efforts to improve access to clinical trials by local minority populations through an outreach that includes a close relationship with a local clinic for the medically under-served.In drug-naive patients, we demonstrated that HIV can be detected in spinal fluid for at least two months after the initiation of a 4-drug regimen. HIV antigens were shown to persist in lymph nodes despite the rapid anti-viral effect of the regimen; however, improvements in lymph node architecture were observed, suggesting partial reconstitution of immune function.In patients who had undetectable levels of plasma viremia during combination antiretroviral therapy for more than 1 year, we have shown that discontinuation of therapy results in prompt viral relapse. In a group of patients with inactive CMV retinitis, we demonstrated the safety of discontinuing anti-CMV maintenance therapy after HAART- induced increases in CD4 cell counts were observed. Immune recovery vitritis occurred in this setting, possibly as a result of enhanced immune responses against CMV antigens. Our observations contributed to the 1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus, now available for public comment, that are likely to have a significant impact on the approach to opportunistic infections.Patients with antiretroviral therapy-associated lipodystrophy were also studied. We showed that lipodystrophy is not caused by dysregulation of the hypothalamic-pituitary-adrenal axis. We also found that loss of facial fat measured by MRI scan correlated with the duration of therapy, and that avascular necrosis of the hip is occurring with an unexpectedly high frequency in patients receiving HAART.Finally, in a population requiring salvage therapy, we found that a combination of abacavir, amprenavir, and efavirenz was safe, although the occurrence of rash was fairly common. Responses to this regimen could be predicted by several baseline charactersitics. Important drug-drug interactions with this regimen were also demonstrated and alternative dosing regimens were delineated - HIV-1; antiretroviral therapy; opportunistic infection; human; cytomegalovirus; minority health; clinical trial; lipodystrophy - Human Subjects
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