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 after cessation of antiretroviral therapy (ART).


METHODS
Successive plasma samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations associated with drug resistance by sequencing of the pol gene.


RESULTS
After cessation of ART the phase of undetectable virus (< 50 copies/ml), ranging from 6 to more than 29 days, was followed by a rapid viral increase, 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 number of primary protease inhibitor (PI)-associated mutations reverted to wild-type, as compared with secondary PI-, and primary reverse transcriptase inhibitor (RTI)-associated mutations. During the rapid viral increase no mutations disappeared, which instead happened during the slower viral increase preceding the viral plateau level.


CONCLUSIONS
After discontinuation of ART large individual variations were found 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 primary PI mutations suggests that they might cause a more impaired viral fitness than primary RTI mutations. However, the persistence of drug mutations during the initial viral load increase indicates that mutated strains may still replicate efficiently.
Birk
M
M
Division of Clinical Virology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Svedhem
V
V
Sönnerborg
A
A
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000187:drug effects* / Q000235:genetics; D017423:Sequence Analysis, RNA; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral