Five-Drug Anti-HIV Treatment Followed by Treatment Interruption in Patients Who Have Recently Been Infected With HIV

Condition(s) targeted: HIV Infections

Intervention: Ritonavir (Drug); Abacavir sulfate (Drug); Amprenavir (Drug); Lamivudine (Drug); Stavudine (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Paul Volberding, MD, Study Chair, Affiliation: San Francisco Veterans Medical Center
Elizabeth Connick, MD, Study Chair, Affiliation: Infectious Disease Division, University of Colorado Health Sciences Center

This study will determine what effect taking a combination of five anti-HIV drugs during the early stage of HIV infection, then temporarily stopping them once or twice, may have on the amount of HIV virus in the blood (viral load). The study will also evaluate the safety and effectiveness of this anti-HIV drug combination.

Official title: A Phase II Trial to Evaluate the Safety and Efficacy of Induction Treatment With Lamivudine Plus Stavudine Plus Abacavir Plus Amprenavir/Ritonavir Followed by Supervised Treatment Interruption in Subjects With Acute HIV Infection or Recent Seroconversion

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Detailed description: Acute, primary HIV infection represents a potentially unique opportunity to eradicate the infection. Although plasma viral load rises rapidly, the dominant infecting virus is relatively uniform genetically, and infection may not be fully established in all tissue sites until some time after exposure. Current antiretroviral therapy is able to reduce plasma viral load to unmeasurable levels in established infection. However, there are many questions that remain about the treatment of primary HIV infection. While it is assumed that aggressive antiretroviral regimens are required, it is not known how long they must be continued. It is hoped that after an interval of aggressive therapy, the number of agents could be safely reduced. This study evaluates if viral suppression can be sustained after study therapy is withdrawn.

Participants in this study will receive lamivudine (3TC), stavudine (d4T), abacavir (ABC), amprenavir (APV), and ritonavir (RTV) for at least 52 weeks. During this induction phase, participants will be followed through regular study visits every 4 or 8 weeks. If the participant's viral load and CD4 counts are within study parameters at the end of 52 weeks, the participant will discontinue all antiretroviral medications simultaneously. Participants in the treatment interruption phase will be followed weekly initially, every 2 weeks for 8 weeks, and then every 4 or 8 weeks. Treatment may be restarted if necessary during this phase based on viral load and CD4 counts. If treatment is restarted, the participant will receive 3TC, d4T, APV, and RTV but not ABC. During this reinduction phase, participants will be followed every 4 or 8 weeks.

Depending on viral load and CD4 counts, participants may be eligible for a second treatment interruption phase following the reinduction phase. Participants will once again stop all antiretroviral medications simultaneously and will have the same monitoring as in the first treatment interruption phase. Following this second treatment interruption, participants will be restarted on 3TC, d4T, APV, and RTV and will be evaluated at Weeks 4, 8, 16, and 24, at which time participants go off study.

The length of study participation for individual participants will vary. The length of each phase will be highly dependent on the participant's laboratory parameters. In general, participants will be enrolled in the study for 3 to 4 years. Participants may also enroll in immunology, compartment, pharmacology, and medication compliance substudies.

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Acute HIV infection (recently infected with HIV or recent seroconversion)

- Karnofsky status of 80 or greater within 14 days prior to study entry

- Acceptable methods of contraception

- Able and willing to give written informed consent

Exclusion Criteria:

- Previously received anti-HIV drugs

- Hepatitis within 30 days prior to study entry

- Pancreatitis within 120 days prior to study entry

- Radiation or chemotherapy within 30 days prior to study entry

- Certain medications within 14 days prior to study entry

- Experimental or investigational therapy within 30 days prior to study entry

- Illness (non-HIV infection, cancer, etc.) at the time of study entry

- Pregnant or breastfeeding

Univ of Puerto Rico, San Juan 009365067, Puerto Rico

Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States

San Francisco Gen Hosp, San Francisco, California 941102859, United States

UCLA CARE Ctr, Los Angeles, California 90095, United States

Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States

Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States

Univ of Miami School of Medicine, Miami, Florida 331361013, United States

Univ of Hawaii, Honolulu, Hawaii 96816, United States

Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States

Washington Univ (St. Louis), St. Louis, Missouri 63108-2138, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Mount Sinai Med Ctr, New York, New York 10029, United States

Cornell Univ Med Ctr, New York, New York 10021, United States

Beth Israel Med Ctr, New York, New York 10003, United States

Columbia Presbyterian Med Ctr, New York, New York 10032, United States

Chelsea Ctr, New York, New York 10021, United States

St Mary's Hosp (Univ of Rochester/Infectious Diseases), Rochester, New York 14642, United States

Community Health Network Inc, Rochester, New York 14642, United States

Univ of North Carolina, Chapel Hill, North Carolina 27514, United States

Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States

Presbyterian Med Ctr- Univ of PA, Norristown, Pennsylvania 19401, United States

Miriam Hosp / Brown Univ, Providence, Rhode Island 02906, United States

Click here for more information about stavudine.

Click here for more information about lamivudine.

Click here for more information about ritonavir.

Click here for more information about abacavir sulfate.

Click here for more information about amprenavir.

Haga clic aquí para ver información sobre este ensayo clínico en español.

Related publications:

Ait-Khaled M, Rakik A, Griffin P, Cutrell A, Fischl MA, Clumeck N, Greenberg SB, Rubio R, Peters BS, Pulido F, Gould J, Pearce G, Spreen W, Tisdale M, Lafon S; CNA3003 International Study Team. Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. Antivir Ther. 2002 Mar;7(1):43-51.

Garcia F, Plana M, Mestre G, Arnedo M, Gil C, Miro JM, Cruceta A, Pumarola T, Gallart T, Gatell JM. Immunological and virological factors at baseline may predict response to structured therapy interruption in early stage chronic HIV-1 infection. AIDS. 2002 Sep 6;16(13):1761-5.

Garcia F, Plana M, Ortiz GM, Bonhoeffer S, Soriano A, Vidal C, Cruceta A, Arnedo M, Gil C, Pantaleo G, Pumarola T, Gallart T, Nixon DF, Miro JM, Gatell JM. The virological and immunological consequences of structured treatment interruptions in chronic HIV-1 infection. AIDS. 2001 Jun 15;15(9):F29-40.

Mira JA, Macias J, Nogales C, Fernandez-Rivera J, Garcia-Garcia JA, Ramos A, Pineda JA. Transient rebounds of low-level viraemia among HIV-infected patients under HAART are not associated with virological or immunological failure. Antivir Ther. 2002 Dec;7(4):251-6.

Tilling R, Kinloch S, Goh LE, Cooper D, Perrin L, Lampe F, Zaunders J, Hoen B, Tsoukas C, Andersson J, Janossy G; Quest Study Group. Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection. AIDS. 2002 Mar 8;16(4):589-96.

Starting date: March 1997
Last updated: September 28, 2007