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