Clinical Correlates: Immune Reconstitution Advanced HIV

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Abstract

Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality; however the management of HIV-infected patients has become increasingly complex. We are conducting studies that: characterize the immune recovery in persons with advanced HIV infection, including studies of discontinuation of prophylaxis against opportunistic infections; evaluate the management of antiretoviral therapy in individuals with advanced infection; and determine the HIV replication kinetics after interruption of successful anti-retroviral therapy. 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+ T cell counts were observed. Immune recovery vitritis occurred in this setting, possibly as a result of enhanced immune responses from HAART. We continue to monitor these patients for the durability of the enhanced immune response and associated problems. Our observations contributed to the 1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. In addition, mathematical modeling of HIV viral load kinetics in a group of HIV-infected persons who were naive to therapy and were subsequently treated suggests that HIV continues to disseminate in spite of apparent control of HIV in the plasma. A metanalysis of persons receiving potent antiretroviral therapy suggested that it is possible to predict the long term response of antiretroviral therapy based on the response to the level of HIV in the plasma. In persons who discontinued antiretroviral therapy after having had a prolonged period of effective suppression, HIV viral levels in the plasma returned to levels approximating their baseline levels, suggesting that even prolonged antiretroviral therapy will not lead to long-term durable benefits without continued therapy. We continue to develop 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 local clinics for the medically underserved.