Abstract :
Daily journals in France recently published a declaration of eight AIDS-assistance associations stating because of already established resistance of most of types of HIV, to the so called “tritherapies”, 8,000 subjects in France will soon be “in condition of treatment failure”. This tritherapeutic “flat note” is a double flat, for relative and absolute reasons: a) relative indeed was the case of well-known results: the tritherapies initially performed better than bitherapies, which had done better than monotherapies; b) absolute is their failure, which induce, as the other types, toxicity, resistance and relapses. Toxicity and resistance are due to the fact that, as the T1/2 of the virus is very short, virostatics must be applied continuously. But in AIDS groups tritherapies are applied not only in a continuous fashion, but in an identical form and for an undefined time, the process which is used in experimental cancer chemotherapy to induce resistant cell lines. Applying them in sequences of 3 weeks (a duration chosen with the knowledge that resistance may occur in about 12 weeks), we have shown in AIDS not only an absence of toxicity, but also an absence of resistance in patients treated with four drugs affecting four different targets. There is indeed another point to underline: AIDS group tritherapies are comprised of three drugs, but whatever the choices of these drugs they affect only two targets: retrotranscriptase and HIV1-protease. We had obtained in the best murine model of HIV1-infection (Friendʹs virus infection) eradication with a combination of three drugs, AZT, acriflavine (ACF) and the ellipticine analogue methyl-hydroxy-ellipticine (MHE); (the two last were discovered to be rather more efficient that AZT in our virostatic screening). This combination affects three virus targets (AZT, retrotranscriptase; MHE, topoisomerase 2; and ACF, integrated and proviral DNA).
The next article will show that sequential drug combinations of three virostatics chosen from ten drugs available, affecting four targets, are more efficient in HIV1-AIDS than three drug combinations affecting three targets because they were chosen from a pool of only five drugs. It will, however, be shown that the same type of sequential combinations with four drug rotations chosen among the ten available ones affecting four targets rapidly reduced, and for years maintained, the viral load at undetectable levels. This level has been < 200 RNA copies/mL during the trial, and is, at the end of the study, < 20 RNA copies/mL.
