Third International Congress Drug Therapy in HIV Infection 3-7 November 1996 Glasgow, UK

THREE AND 4-DRUG COMBINATIONS AT DIFFERENT STAGES OF HIV-1 INFECTION: INSIGHTS INTO VIRAL DYNAMICS AND IMMUNE RECONSTITUTION

A. Lafeuillade*, C. Poggi*, G. Kaplanski**, C. Tamalet**, N. Profizi*, C. Farnarier**, S. Kaplanski**, O. Costes*


Int Cong Drug Therapy HIV 1996 Nov 3-7;3:Abstract No. OP1.2
AIDS 1996, Vol. 10 (Suppl. 2);S9

BACKGROUND: To target HIV-1 replication in blood but also in lymphoid reservoirs, combinations of 3 or more drugs seem necessary.

METHODS: 11 patients with primary HIV-1 infection and 45 patients with chronic disease naïve of prior antiretroviral therapy have received a combination of ZDV/ddI/3TC. Furthermore, 16 additional cases currently receive ZDV/ddI/3TC/Saquinavir as first line therapy. In 15 patients the evolution of viral load and CD4. T cells was also investigated in lymph nodes obtained by biopsy.

RESULTS: Down regulation of HIV-1 RNA was demonstrated in plasma in each trial and levels became undetectable in more than 90% of cases. The drop in plasma HIV-1 RNA followed a two-compartment model with an initial rapid phase and then a slower clearance rate representing the "burn out" of lymphoid tissues. Patients with primary infection that achieved plasma RNA levels < 20 copies/ml (with a sensitized procedure) and a major reduction of HIV replication in lymph nodes showed a progressive decrease in Western blot positivity after 9 months of therapy. In one case, gp160 was only positive with a shadow in the p25 band after 1 year. Very low levels of HIV-1 RNA were found by PCR in lymph nodes of patients treated with the 4-drug combination after 3-6 months. This regimen also produced decreased productions of TNF-α and IL-1β and increased production of INF-γ. The number of CD4/CD2 cells in lymph nodes showed a major expansion after therapy that was related to an increased proliferation (Ki67+) of memory (CD45RO) cells in these tissues.

CONCLUSIONS: Such pilot studies are designed to determine the best therapeutic regimens. However, they also allow to investigate more precisely the pathophysiologic mechanisms of the disease.

Presenting author:

1996-11-03
OP1.2

Originally published in AIDS Volume 10, Supplement 2 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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