Transient relapses ("blips") of plasma HIV RNA levels during HAART are associated with drug resistance.
BACKGROUND
In a large number of patients on HAART who achieved plasma HIV RNA levels below the limit of detection (50 copies/ml), transient relapses of HIV RNA levels ("blips") are observed.


OBJECTIVE
To determine whether relapses of plasma HIV RNA during HAART are associated with development of drug resistance.


METHODS
Plasma samples from 15 patients with a transient viral load relapse during HAART were studied. All regimens contained lamivudine (3TC). We used an ultrasensitive sequence approach to analyze the presence of drug resistance mutations during the relapse.


RESULTS
The median plasma HIV RNA load of the relapse was 76 copies/ml (range 50-1239). In 11 of 15 cases, a genotype of HIV could be obtained. Mutations in the RT and protease gene conferring resistance to one or more drugs were observed in 8 of 11 patients, 6 of whom had the M184V substitution. During a median follow-up of 27 months after the relapse, plasma HIV RNA levels remained undetectable in 13 of 15 patients.


CONCLUSIONS
Plasma HIV RNA blips during HAART can be associated with selection of drug-resistant HIV. This indicates that viral replication may occur during HAART, probably caused by a temporary decrease in active drug concentrations. A blip containing only wild-type virus is not necessarily caused by viral replication. In this situation the raise of HIV RNA could also originate from release of wild-type viruses, caused by activation of the latent virus reservoir. Independent of the mechanism, blips did not preclude successful inhibition of viral replication during 2-year follow-up in the majority of these cases.
Cohen Stuart
J W
JW
Department of Virology, Eijkman-Winkler Institute, University Medical Center, Utrecht, The Netherlands.
Wensing
A M
AM
Kovacs
C
C
Righart
M
M
de Jong
D
D
Kaye
S
S
Schuurman
R
R
Visser
C J
CJ
Boucher
C A
CA
D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D006678:HIV / Q000235:genetics / Q000302:isolation & purification*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D009154:Mutation; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine