Download PDF by Erik De Clercq (auth.), Erik D. A. De Clercq, Anne-Mieke I.: Combination Therapy of AIDS

By Erik De Clercq (auth.), Erik D. A. De Clercq, Anne-Mieke I. Vandamme (eds.)

HIV an infection has been a better problem to present medication than the other viral ailment ofmodem occasions. HIV results in a continual an infection and the virus has a huge genetic flexibility less than selective strain. in the course of its copy­ tive cycle in sufferers, HIV accumulates mutations at one of these excessive expense that the selective strain inflicted at the immune approach, or generated by way of antiviral medications quickly triggers the looks of get away mutants. at present to be had medicinal drugs, whilst used singly, should not able to suppressing virus replication in sufferers to this kind of point that the iteration of mutations, from which a version proof against immune assault or antiviral medications should be chosen, is avoided. this is often the most this is why mixture remedy, often of 3 medicines, has turn into the normal process for the therapy ofAIDS. it really is noticeable that virus eradication won't quite simply be conceivable, in order that medicines need to be taken for a chronic time or perhaps lifelong which will hold the viral load as little as attainable. no matter if the at the moment used drug combos may be capable of keep an eye on virus replication in a selected sufferer for the sort of seasoned­ longed time period is determined by many elements, so much of that are addressed within the varied chapters of this booklet. the purpose of antiviral drug mixture remedy for AIDS is finally to revive complete functionality of the immune system.

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AIDS Clinical Trials Group. N Engl J Med; 334: 1011-1017 29 Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D, Richman DD, Valentine FT, Jonas L, Meibohm A et al. (1997) Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 337: 734-739 30 Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, Kingsley LA, Todd JA, Saah AJ, Detels R et aI. (1997) Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-I infection.

Anti-HIV agents to be used in drug combination regimens 19 that a rational choice of the optimal combination will be hard, if not impossible. It also follows that the optimal drug combination could not be generalized but should be individualized. From an overview of the anti-HIV drug combinations that have been the subject of several clinical studies (Fig. 19), it appears that the highest success rates, in terms of achieving undetectable HIY loads in the highest percentage of patients, have been achieved with the combination of stavudine (d4T) + larnivudine (3TC) + efavirenz (EFV) and the combination of tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) [65, 66].

These heavy regimens have sometimes been initiated after drug holidays aiming to release the selection pressure induced by HAART letting the wild-type HIV replace the mutant strains. Favourable effects have been suggested in a 52 weeks trial including patients with very low CD4 cells levels (27/IlL) [64]. A perspective of the history of HAART 33 Unfortunately this was not confirmed in less advanced patients probably because drug holidays induce severe immune loss that are more harmful in less immunosuppressed patients.

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