Clinical Trials


Effects on the Immune System of Anti-HIV Drugs in Patients Recently Infected With HIV

This study has been completed
National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID) Identifier

First received: November 2, 1999
Last updated: March 1, 2011
Last Verified: January 2005
History of Changes


The purpose of this study is to find out whether these powerful combinations of anti-HIV drugs are safe and effective for use in patients in the early stages of HIV infection and to find out how patients' immune systems react to HIV and anti-HIV drugs.

Doctors generally treat patients in the early stages of HIV infection with the same anti-HIV drugs taken by patients who have had HIV for a long time. These drugs lower the level of HIV in the blood. However, doctors do not know whether patients who take anti-HIV drugs in the early stages of HIV infection actually live longer or have fewer AIDS-related diseases. This study will help doctors answer these questions. In the main study, doctors will look at how 2 different anti-HIV drug combinations affect the immune system. In the 2 substudies, doctors will look at how the body reacts to the hepatitis B vaccine and the tetanus vaccine. These substudies may help doctors learn how HIV-infected patients respond to new infections.

Condition Intervention
HIV Infections

Biological : Tetanus Toxoid Vaccine
Drug : Indinavir sulfate
Drug : Lamivudine/Zidovudine
Drug : Ritonavir
Drug : Abacavir sulfate
Drug : Amprenavir
Drug : Efavirenz
Biological : Hepatitis B Vaccine (Recombinant)
Drug : Lamivudine
Drug : Zidovudine

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Study of the Effects of Combination Antiretroviral Therapy in Acute HIV-1 Infection With an Emphasis on Immunological Responses

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Enrollment: 288
Study Start Date: October 1999
Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)

Detailed Description:

Current treatment guidelines recommend combination ART for acute primary HIV-1 infection. However, it is not known whether ART given during acute infection delays progression to AIDS or improves survival rates. Preliminary studies suggest ART given early in HIV infection not only reduces viral load but also restricts CD4+ cell loss, delays the development of opportunistic infections, and preserves T-helper cells and naive T cells. The immunologic basis of these protective effects has not been characterized thoroughly. This protocol assesses ART's effects on immune responses in early HIV infection through a variety of cellular, humoral, and virologic assays, including 2 substudies. The substudies focus on antibody responses to neoantigen immunization (hepatitis B and tetanus). Primary endpoint analysis occurs at Week 72, but patients may be followed for long-term outcomes.
In the main study, patients with HIV-1 infection of less than 120 days are given the option of taking a potent ART combination of abacavir (ABC), efavirenz (EFV), indinavir (IDV), and lamivudine (3TC) for 96 weeks. [AS PER AMENDMENT 9/15/00: Patients choose either Regimen 1: ABC, 3TC, IDV, and ritonavir (RTV) or Regimen 2: ABC, 3TC, and EFV.] Patients who decline treatment provide a concurrent, non-randomized comparison group. These patients may choose to be considered for study treatment at any time or to start antiretrovirals provided through another source. [AS PER AMENDMENT 9/15/00: If a patient who initially does not start therapy subsequently starts antiretroviral therapy provided by the study (within the 120-day limit), the visit schedule is re-set.] During the treatment period, all patients undergo regular physical exams and blood tests to characterize T cells, viral resistance, antibody responses, and other markers. Patients presenting within 30 days of HIV-1 infection undergo leukapheresis (where available) prior to starting ART. At Month 12, these patients and all untreated patients undergo leukapheresis to assess the proportion of latently infected CD4+ T cells. In addition, all patients in the main study and patients in 2 comparison groups (Cohorts A and B) participate in 1 of 2 substudies of antibody responses to neoantigen. Volunteers are recruited to 2 cohorts to serve as controls. Cohort A volunteers have established HIV-1 infection. Cohort B volunteers are HIV-1 seronegative but at high risk for HIV. In the first substudy, hepatitis B-seronegative patients from the main study and from Cohorts A and B receive hepatitis B vaccine at Weeks 40, 44, and 64 and undergo humoral and cellular response assessments at Week 68. In the second substudy, patients from the main study and from Cohorts A and B who did not qualify for the hepatitis B vaccination undergo intramuscular vaccination with tetanus toxoid at Week 64 and immune responses are assessed at Week 68. Volunteers in Cohorts A and B receive no anti-HIV medication as part of these substudies.



Ages Eligible for Study: 16 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: Yes  


Inclusion Criteria
Patients may be eligible for the main study if they:

  • Became infected with HIV within the last 120 days.
  • Are at least age 16 and have written consent of a parent or guardian if under 18.
  • Are willing to practice abstinence or use barrier methods of birth control, such as condoms.
  • Are available for at least 72 weeks.
  • Patients may be eligible for 1 of the 2 substudies if they:
  • Are at least age 16 and have written consent of a parent or guardian if under 18.
  • Have had HIV infection for more than 1 year and have a CD4 cell count greater than 500 cells/mm3, or do not have HIV infection but are at risk of getting HIV because of their lifestyle, such as sexual activity or injection drug use.
  • Have never had hepatitis B infection or a hepatitis B vaccine and they are available for 28 weeks (hepatitis B vaccine substudy only).
  • Have not received a tetanus shot in the past 5 years, have never had an allergic reaction to a tetanus shot, and are available for 8 weeks (tetanus shot substudy only).

  • Exclusion Criteria
    Patients will not be eligible for the main study if they:
  • Have taken anti-HIV drugs for more than 7 days for the treatment of HIV. However, anti-HIV drugs taken to help prevent HIV are acceptable.
  • Have certain types of cancer.
  • Are receiving an experimental treatment.
  • Are pregnant or breast-feeding.
  • Are allergic to study drugs.
  • Have taken certain medications that may interfere with the study.
  • Patients will not be eligible for 1 of the 2 substudies if they:
  • Are receiving an experimental treatment.
  • Are pregnant or breast-feeding.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00001119


United States, California
San Francisco Dept of Hlth / AIDS Office
San Francisco, California, United States, 94102
United States, Illinois
Univ of Illinois Chicago / Howard Brown Hlth Ctr
Chicago, Illinois, United States, 60612
United States, Massachusetts
Fenway Community Health Ctr / HIVNET
Boston, Massachusetts, United States, 02115
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Bronx-Lebanon Hosp Ctr
Bronx, New York, United States, 10453
New York Univ Med Ctr
New York, New York, United States, 10016
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Rhode Island
Mem Hosp of Rhode Island
Pawtucket, Rhode Island, United States, 02860
United States, Washington
Seattle HIVNET
Seattle, Washington, United States, 98104
Univ of Washington
Seattle, Washington, United States, 98104
Fred Hutchinson Cancer Research Ctr
Seattle, Washington, United States, 98109
Saint Vincent's Hosp Med Centre
Darlinghurst, Australia

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)


Study Chair: Lawrence Corey
More Information

More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00001119   History of Changes  
Other Study ID Numbers: AIEDRP AI-02-001  
Study First Received: November 2, 1999  
Last Updated: March 1, 2011  

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

Immunity, Cellular
Drug Therapy, Combination
HIV Protease Inhibitors
Antibody Formation
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
Tetanus Toxoid
Case-Control Studies
Hepatitis B Surface Antigens
Acute Infection

Additional relevant MeSH terms:
Lamivudine, zidovudine drug combination
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