Evolution of HIV-1 genotype in plasma RNA and peripheral blood mononuclear cells proviral DNA after interruption and resumption of antiretroviral therapy.
BACKGROUND
Structured antiretroviral therapy interruption (TI) is discouraged because of poorer AIDS and non-AIDS-related outcomes, but is often inevitable in clinical practice. Certain strategies could reduce the emergence of resistance mutations related to TI.


METHODS
A total of 106 HIV-1-infected patients on stable HAART with undetectable plasma viral load were randomized to therapy continuation (n=50) or CD4(+) T-cell-guided TI (n=56). Staggered interruption involved stopping non-nucleoside reverse transcriptase inhibitors (NNRTIs) 7 days before the nucleoside backbone. Genotypic resistance testing (GRT) was performed on proviral DNA from peripheral blood mononuclear cells (PBMCs) at baseline and before each TI, and on plasma RNA after each TI.


RESULTS
At baseline, GRT on PBMCs detected mutations in nine patients and only two major mutations were identified. GRT on plasma samples performed after TIs showed nucleoside reverse transcriptase inhibitors (NRTI), NNRTI and protease inhibitor major resistance associated mutations in 10/56, 3/46 and 1/8 patients receiving these drugs, respectively. Only in two patients had the same mutations been observed in GRT on PBMCs at baseline. Three patients presented virological failure after resumption of therapy, all receiving NNRTIs. In one of them, resistance mutations detected at failure had been also observed previously in GRT on plasma after TI.


CONCLUSIONS
Staggered interruption of NNRTIs 7 days before the nucleoside backbone does not avoid resistance emergence completely, but does not necessarily lead to virological failure after treatment resumption. Plasma HIV-1 RNA genotype after the interruption and the patient's treatment history seem to be more useful than baseline proviral DNA genotype to assess the risk of virological failure after restarting therapy.
HIV Unit, Infectious Diseases Department, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. aimaz@bellvitgehospital.cat
Arkaitz
A
Imaz
Montserrat
M
Olmo
Maria
M
Peñaranda
Félix
F
Gutiérrez
Joan
J
Romeu
Maria
M
Larrousse
Pere
P
Domingo
José A
JA
Oteo
Jordi
J
Niubó
Jordi
J
Curto
Concepción
C
Vilallonga
Mar
M
Masiá
José
J
López-Aldeguer
José A
JA
Iribarren
Daniel
D
Podzamczer
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors