Mutations in HIV-1 reverse transcriptase potentially associated with hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors: effect on response to efavirenz-based therapy in an urban observational cohort.
BACKGROUND
Hypersusceptibility to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was described in association with reverse-transcriptase (RT) mutations conferring resistance to nucleoside reverse-transcriptase inhibitors (NRTIs). We evaluated the effect of RT mutations associated with hypersusceptibility to NNRTIs on the response to efavirenz-based therapy.


METHODS
We analyzed an observational database of patients for whom highly active antiretroviral therapy failed and who received genotypic resistance testing-guided therapy, either efavirenz or protease inhibitor (PI) based. Study end points were achievement of virus load <80 copies/mL, achievement of virus load <80 copies/mL without rebound to >500 copies/mL, and changes in CD4 cell counts.


RESULTS
The baseline RT mutations M41L, M184V, L210W, and T215Y and the M41L/T215Y and M41L/T215Y/M184V combinations were associated with virological suppression for efavirenz-treated patients, whereas, for PI-treated patients, only the M184V mutation was associated with virological suppression, and the L210W mutation showed a negative correlation; no correlation was found between any mutation and virological response without rebound.


CONCLUSIONS
The M41L, M184V, L210W, and T215Y mutations were associated with a better, although transient, virological outcome in patients treated with efavirenz-based regimens.
Tozzi
Valerio
V
National Institute for Infectious Diseases Lazzaro Spallanzani, Rome, Italy. tozzi@inmi.it.
Zaccarelli
Mauro
M
Narciso
Pasquale
P
Trotta
Maria Paola
MP
Ceccherini-Silberstein
Francesca
F
De Longis
Patrizio
P
D'Offizi
Giampiero
G
Forbici
Federica
F
D'Arrigo
Roberta
R
Boumis
Evangelo
E
Bellagamba
Rita
R
Bonfigli
Sandro
S
Carvelli
Chiarina
C
Antinori
Andrea
A
Perno
Carlo Federico
CF
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D009154:Mutation; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014505:Urban Population; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz