Trial Information

A Study of the Effects of Combination Antiretroviral Therapy in Acute HIV-1 Infection With an Emphasis on Immunological Responses

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.