Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure.
OBJECTIVE
To analyse the immunological and virological effects of treatment interruptions in HIV-1-infected patients with treatment failure and multidrug-resistant virus.


METHODS
Drug susceptibility was assessed using Antivirogram and genotypic analysis was based on population and clonal sequencing for 48 patients who had interrupted treatment (> or = 2 months).


RESULTS
Treatment interruption resulted in viral load increases (mean 0.7 log 10 copies/ ml; P = 0.0001) and CD4 cell count decreases (mean 89 x 10(6) cells/l; P = 0.0001). A complete shift to wild-type virus at the phenotypic, genotypic and clonal level was observed in 28/45 patients. These patients differed from those that did not show a shift to wild type in baseline CD4 cell counts (192 versus 59 x 10(6) cells/l; P= 0.007) and in the relationship between baseline viral load and CD4 cell count (no correlation versus a significant negative correlation; P= 0.008). Response to re-initiation of treatment fell with increasing viral load [relative hazard (RH) 0.33; P= 0.001] and with increasing total number of drugs with reduced susceptibility (RH 0.51; P = 0.0003); it improved with the number of new drugs received (RH 2.12; P = 0.0002) and a shift to wild type (RH 5.22, P = 0.006).


CONCLUSIONS
Changes in surrogate markers suggest that treatment provided benefit in spite of virological failure and resistant virus. Although patients with a shift to wildtype virus responded better in the short term to treatment re-initiation, the long-term effects are not known and the risk of immune deterioration needs to be carefully considered.
Miller
V
V
Klinikum der Johann Wolfgang Goethe-Universität, Zentrum der Inneren Medizin, Frankfurt, Germany.
Sabin
C
C
Hertogs
K
K
Bloor
S
S
Martinez-Picado
J
J
D'Aquila
R
R
Larder
B
B
Lutz
T
T
Gute
P
P
Weidmann
E
E
Rabenau
H
H
Phillips
A
A
Staszewski
S
S
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy; D017211:Treatment Failure; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors