Shift in HIV resistance genotype after treatment interruption and short-term antiviral effect following a new salvage regimen.
OBJECTIVE
To investigate the changes in genotypic drug-resistance pattern, plasma HIV RNA and CD4 cell count after treatment interruption and assess the short-term antiviral effect of a new salvage regimen.


METHODS
Prospective study of 38 patients with multiple failing regimens who had completely stopped all medication for 3 months before a three to five-drug regimen was reintroduced according to clinical guidelines.


METHODS
Patients were tested for HIV resistance before and after treatment interruption by population-based sequencing and clonal analysis of selected patients.


RESULTS
Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 0.4 log10 and a median decrease in CD4 cell count of 43 x 10(6)/l. Sixty-one per cent of patients had a shift from the drug-resistant genotype to a predominantly wild-type genotype. The patients significantly likely to show genotype reversion were those in Centers for Disease Control groups A or B, who had been exposed to few drugs, had a low plasma HIV RNA, or a high CD4 cell count. The only independent factor predicting genotype reversion was the clinical stage. The median change in plasma HIV RNA at month 3 after treatment reintroduction was -2.3 log10 copies/ml in patients who had genotype reversion compared with -0.6 log10 copies/ml in patients without genotype reversion (P = 0.004).


CONCLUSIONS
Suspending treatment for 3 months after multiple failures could be a suitable strategy for optimizing salvage therapy provided it is instituted early, before the HIV disease becomes too advanced.
Izopet
J
J
Laboratoire de Virologie, Hôpital Purpan, CHU Toulouse, France. izopet@cict.fr
Massip
P
P
Souyris
C
C
Sandres
K
K
Puissant
B
B
Obadia
M
M
Pasquier
C
C
Bonnet
E
E
Marchou
B
B
Puel
J
J
D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004352:Drug Resistance, Microbial / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016879:Salvage Therapy / Q000379:methods*; D017386:Sequence Homology, Amino Acid
D019380:Anti-HIV Agents; D012367:RNA, Viral