Loss of zidovudine related mutations in the reverse transscriptase gene of HIV after switching therapy.
The standard treatment for HIV infected patients is the highly active antiretroviral therapy. Due to resistance developments treatment failure can be found in some patients. In our study two different strategies are compared, which may reduce resistance mutations. Six patients (group A and B) have been monitored for about six years. Group A patients had a switch in their AZT-containing treatment to non AZT-containing regimens. In group B patients AZT-containing regimens' were interrupted by drug holidays. Early mono- and dual-therapies containing zidovudine (AZT) have been applied in all patients with poor long-term improvements. Due to the rapid development of escape mutants viral rebound was observed soon after treatment initiation. Genotypic assays were developed to asses AZT-resistance mutations. The longer AZT had been applied the more mutations had developed. These mutations disappeared when patients were taking "drug-holidays" and drug selection pressure was missing. Besides, it was demonstrated in two patients that these AZT-mutations could disappear, if in combination therapies AZT was replaced by other antiretroviral drugs. This study shows that not only by drug-holidays but also by switches in therapy mutations can disappear, which is especially important for patients with low CD 4 cell counts and high viral load levels.
Falkensammer
B
B
Department of Hygiene and Social Medicine and Ludwig Bolzmann-Institute for AIDS Research, Leopold-Franzens-University of Innsbruck, Faculty of Medicine, Austria. Barbara.Falkensammer@uibk.ac.at
El Attal
R
R
Müllauer
B
B
Sarcletti
M
M
Parson
W
W
Dierich
M P
MP
Stoiber
H
H
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase