Virological response to HIV-1 nucleoside/nucleotide reverse transcriptase inhibitors-based, tenofovir DF-including regimens in the ANRS Aquitaine Cohort.
BACKGROUND
HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTI)-only based, comprising tenofovir DF(TDF) have been shown to lead to high rates of virological failures (VF), mainly in patients on first-line combination therapy. We wished to investigate the virological response to these regimens in a large cohort of antiretroviral (ARV)-treated patients.


METHODS
Patients followed-up in the Aquitaine Cohort in 2001-2003 and who had received NRTI-based, TDF-including regimens for at least 3 months were included. The VF was defined as: (i) a decrease in plasma HIV-1 RNA <0.5 log(10)copies/ml between M0 and M3; or (ii) a plasma HIV-1 RNA >50 copies/ml at M3 in patients with plasma HIV-1 RNA <50 copies/ml at M0. The baseline RT genotype was determined in a subgroup of patients.


RESULTS
Within 121 patients (95% ARV-experienced) who received either lamivudine (3TC)/didanosine (DDI)/TDF (n=48), or abacavir (ABC)/3TC/TDF (n=14), or 3TC/zidovudine (ZDV)/TDF (n=27), or 3TC/ZDV/ABC/TDF (n=20), or DDI/ABC/TDF (n=12), the ABC/3TC/TDF and DDI/ABC/TDF combinations were associated with the highest frequencies of VF. In contrast the use of ZDV was related to a better virological response. The baseline RT genotype was also predictive of the virological outcome.


CONCLUSIONS
NRTI-based, TDF-including therapies can lead to high rates of VF both in ARV-naïve and in ARV-experienced patients. Our data strongly suggest the interest of associating ZDV and TDF in these regimens.
INSERM U593, Université Victor Segalen, Bordeaux, France.
Eric
E
Balestre
Michel
M
Dupon
Sophie
S
Capdepont
Rodolphe
R
Thiébaut
Sébastien
S
Boucher
Hervé
H
Fleury
François
F
Dabis
Bernard
B
Masquelier
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015331:Cohort Studies; D016049:Didanosine / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005602:France; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006785:Hospitals, University; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013045:Species Specificity; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
D000225:Adenine; D016049:Didanosine; D015224:Dideoxynucleosides; D054303:HIV Reverse Transcriptase; D019259:Lamivudine; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir