• The QuadriVar Study: d4T/ddI/SaquinavirSGC/Nelfinavir/Hydroxyurea/IL-2 in Primary HIV-1 Infection -- Preliminary Results
  Poster 807
  Authored by A. Lafeuillade, E. Counillon, P. Deljiudice, S. Marlier, A. Rieu, G. Hittinger, S. Chadapaud, A. Pottier, C. Poggi, M. Chouraqui

The conventional treatment of primary HIV infection continues to be challenged by the possibility that we may be able to preserve anti-HIV CD4-specific activity by approaching the treatment of primary HIV infection with more than HAART. Previous studies by Dr. Fauci and Dr. Chun described the establishment of a pool of latently-infected, resting CD4+ T-cells during HIV infection. In addition, residual HIV RNA is found in plasma even after the successful uses of HAART, as described by Dr. Dornadula (JAMA 999:282.1627-32).

The QuadriVar Study is an elegant, ongoing French study by Lafeuillade, et. al. aimed to evaluate the effects of adding hydroxyurea (HU) and IL-2 to HAART at primary HIV infection. The addition of IL-2 to HAART has been found to be partially beneficial in work also done by Dr. Chun (Nature Med, 1999; 5:651-5).

Fifteen naive patients diagnosed with primary HIV-1 infection were started on HAART (d4t/ddI/SaquinavirSGC/Nelfinavir). HU 500 BID was started after three months. Two cycles of IL-2 (six MUI/day x six days) were given after 15 months. Data collected at baseline and at different intervals included: plasma HIV RNA (Amplicor), flow cytometry, proviral DNA levels, sequencing of RT and Pr gene mutations, coculture of CD4 T cells, evaluation of anti-HIV specific cellular activity, and evaluation of reservoir and sanctuaries of HIV (CSF, genital fluid and lymph node biopsy).

At baseline, seven subjects had no mutations identified in HIV sequencing, and seven had only one mutation in either the RT or Pr gene. Only one patient had multiple mutations and did not achieve viral suppression after initiation of HAART. All other patients had persistent non-detected HIV RNA in blood, CSF and genital secretions. CD4+ t-cells increased during the initial five months, but then remained stable (close to baseline levels). CD8 T-cells also decreased from baseline, even before HU was added. But the most striking finding in this study was that the HIV RNA in lymph node biopsies (LNMC), and cocultures of isolated blood CD4+ T-cells in enhanced conditions, were positive in all four patients that had already reached 12 months in the study, and in one patient, after 24 months.

This study is still ongoing and the results presented in this poster are very preliminary. We certainly have not heard the end of the story. It's going to be very interesting to follow the progression of these patients as they go into the next phase, which will involve the use of structured treatment interruption (STI) after two years, restarting HAART when viral load are above 30,000 and interrupting therapy again once viral loads remain undetectable for three months.

This is one of many studies that continue the search for immunotherapy's (and perhaps treatment interruption's) place in the treatment of HIV infection.