Although highly active antiretroviral therapy (HAART) has been successful in suppressing plasma HIV RNA levels in infected patients, it has not resulted in eradication of virus. It is now clear that virus replication persists despite undetectable plasma viremia in individuals receiving HAART. In this regard, withdrawing HAART, even after prolonged periods of virus suppression, leads to an almost universal rapid rebound of plasma viremia. It is also now clear that prolonged, continuous HAART carries a risk of significant toxicity and side effects. These recent observations may argue for a different approach to HAART with the goals of: 1) durable suppression of virus replication, without an attempt at eradication, and; 2) minimization of toxicity and side effects and improvement in patient life-style. Therefore, we propose to study the virologic and immunologic effects of intermittent versus continuous HAART in HIV-infected individuals as a possible means to achieve these goals. Our primary interest is to determine if 30-70% less HAART than is required for continuous therapy, administered in a cyclic, intermittent fashion, can effectively maintain suppression of HIV replication and CD4+ T cell counts to levels equivalent to continuous treatment. These studies include a randomized, controlled trial of long cycle intermittent HAART (1 month off drugs followed by 2 months on HAART for 22months) and several pilot studies of short cycle intermittent HAART (e.g. 7 days off HAART followed by 7 days on HAART for up to 2 4 months). The reduction in medication needs will reduce cost and may slow or prevent the onset of toxicity while enhancing adherence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000862-01
Application #
6414584
Study Section
Immunological Sciences Study Section (IMS)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Chang, Larry W; Alamo, Stella; Guma, Samuel et al. (2009) Two-year virologic outcomes of an alternative AIDS care model: evaluation of a peer health worker and nurse-staffed community-based program in Uganda. J Acquir Immune Defic Syndr 50:276-82
Lutalo, Tom; Gray, Ronald H; Wawer, Maria et al. (2007) Survival of HIV-infected treatment-naive individuals with documented dates of seroconversion in Rakai, Uganda. AIDS 21 Suppl 6:S15-9
Colebunders, Robert; Moses, Kamya R; Laurence, John et al. (2006) A new model to monitor the virological efficacy of antiretroviral treatment in resource-poor countries. Lancet Infect Dis 6:53-9
Dybul, Mark; Nies-Kraske, Elizabeth; Dewar, Robin et al. (2004) A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection. J Infect Dis 189:1974-82
Dybul, Mark; Daucher, Marybeth; Jensen, Mark A et al. (2003) Genetic characterization of rebounding human immunodeficiency virus type 1 in plasma during multiple interruptions of highly active antiretroviral therapy. J Virol 77:3229-37
Dybul, Mark; Nies-Kraske, Elizabeth; Daucher, Marybeth et al. (2003) Long-cycle structured intermittent versus continuous highly active antiretroviral therapy for the treatment of chronic infection with human immunodeficiency virus: effects on drug toxicity and on immunologic and virologic parameters. J Infect Dis 188:388-96
Dybul, Mark (2002) Structured Treatment Interruption: Approaches and Risks. Curr Infect Dis Rep 4:175-180
Dybul, M; Chun, T W; Yoder, C et al. (2001) Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: effects on virologic, immunologic, and toxicity parameters. Proc Natl Acad Sci U S A 98:15161-6