Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy

Objective: To study the kinetics of HIV-1 RNA and drug-induced mutations af ter cessation of anti retroviral therapy (ART). Design and methods: Successive plasma samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations associated with drug resistance by s equencing of the pol gene. Results: After cessation of ART the phase of undetectable virus (< 50 copie s/ml), ranging from 6 to more than 29 days, was followed by a rapid viral i ncrease, which slowed down before a plateau corresponding to pre-treatment levels or higher was reached in most cases (14/19 patients). In one patient virus was still undetectable at 4 weeks. Also, a significantly larger numb er of primary protease inhibitor (PI)-associated mutations reverted to wild -type, as compared with secondary PI-, and primary reverse transcriptase in hibitor (RTI)-associated mutations. During the rapid viral increase no muta tions disappeared, which instead happened during the slower viral increase preceding the viral plateau level. Conclusion: After discontinuation of ART large individual Variations were f ound for the time period until HIV-1 became detectable in plasma, possibly due to differences in the HIV-1 specific immunity. The more rapid loss of p rimary PI mutations suggests that they might cause a more impaired viral fi tness than primary RTI mutations. However, the persistence of drug mutation s during the initial viral load increase indicates that mutated strains may still replicate efficiently (C) 2001 Lippincott Williams & Wilkins.