Combinations of four virostatics applied in rotational sequences induce anexponential VL regression curve, the first part of which is rapidly decreasing to a PCR-undetectable level, while the last part is insensitive to themodel. Indications for virostatic and immunotherapeutic reinforcements?

Between 1992 and 1995, we have had five virostatics available: zidovudine ( AZT), didanosine (ddI), zalcitabine (ddC) (as retrotranscriptase nucleosidi c antagonists, RTNA), acriflavine (ACF), and hydroxy-methyl-ellipticine (HE L), as respectively a DNA synthesis and structure antagonist, and a topoiso merase II inhibitor. Between 1995 and now, we have had ten virostatics the same, plus lamivudine (3TC), stavudine (d4T) as RTNA, and indinavir (IDV), ritonavir (RTV) and saquinavir (SQV) as protease inhibitors. We first conducted a phase I-like study concerning the ratios of the drug n umbers in combinations over the numbers available. The optimal model for th e study was that of four virostatics selected out of the ten. The four viro static combinations were applied in short (3 week) sequences, differing eac h others by drug rotation. The patients were, before treatment, nine at the phase of AIDS, one at the A3 stage. They presented a very rapid decrease of viral load (VL) which bec ame undetectable at PCR, being first below 200 RNA copies/ml, then below 20 . We call this condition 'minimum residual disease' as HIV, persistence is revealed by virus rebounds, reversible, and probably induced by cofactors. The frequency of the latter selection is due to the very frequent teach 3 w eeks) VL evaluations. The last part of the VL exponential curve which the minimum residual diseas e represents, is almost horizontal and quasi insensitive to the powerful vi rostatic model described above, though no resistance has appeared at the co mbination or sequence levels. Thus we propose to add phases of: a) reinforc ements by virostatics, adding two more ones to the four of the model; and b ) treatment complement by active immunotherapy phases: the most adapted imm unomodulator is the combination of the peptidic cytokine, tuftsine, and of its antipeptidase, bestatine If they are not available, another interleukin e, able to help restoring the AIDS disturbed immunologic system, interleuki n 2, could be tried, as it has induced beneficial effects at very small dos es by subcutaneous injections. (C) 1999 Elsevier, Paris.