Will killing the last HIV1 particle cure AIDS patients? II: Second Part. Decrease of viral load and of T-suppressor cells, and increase of the cytotoxic cells, without effect on CD4, after the use of 10 virostatics applied in 3 or 4 drug combinations of different sequences. The time for CD4 immunotherapy?

Abstract

We reported in the first part of this editorial and in an article AIDS therapy with five HIV1 virostatics applied in two then three, or initially three, or initially four agent combinations, given in 3 week sequences differing from each other due to drug rotation, the contrast between: a) the decrease of viral load, possible below the detectable level, b) the absence of effect on the helper CD4+, the CD8+ C57- cytotoxics and the CD8+ C57+ suppressor cells. We proposed a thesis according to which the HIV1-AIDS complex might have another pathogenic component other than HIV1, ie, a microchimerism graft-versus host reaction (GvH) or an autologous GvH-like reaction. Shifting from five to 10 virostatics owing to the availability of lamivudine or 3TC, stavudine or d4T and three HIV1 protease inhibitors, saquinavir, ritonavir and indinavir, applied according to the same modality, we have enhanced the reduction of viral load, and significantly decreased the CD8+ C57+ suppressor cell counts, and increased those of the CD8+ C57- cytotoxic cells. This result which indirectly shows the role of HIV1 in the increase of suppressor CD8+ cells, hence in the late loss of immune memory and of opportunistic infections, reinforces the thesis of a role, in AIDS pathogenesis, of a latent GvH reaction activated by HIV1 primo-infection, and its evolution from the hyperplastic phase to the hypoplastic one, which, inducing severe immune suppression, is responsible for HIV1 active infection relapse after the so-called latent phase. Hence the proposition we make, of an indication of CD4 modulation with non specific immunotherapy by bestatin, of which we showed the effect in another population of HIV1-AIDS complex patients. Its effect can be potentiated by tuftsin. When the suppressor cell number goes up over that of the cytotoxic one after the HIV1 active infection relapse, interferon gamma could be added, which, by amplifying the CD28 pathway on CD8+ cytotoxics, while suppressor cells lack CD28, which might reestablish a ratio of suppressor over cytotoxic cells nearer to normal. It remains that the role of the five secondarily included agents in the decrease of suppressor cells will only be attributed with certainty and entirely to their virostatic effect, if it is shown that none of them exerts a selective anti-suppressor cell action.