Prevalence of pre-existing resistance-associated mutations to rilpivirine, emtricitabine and tenofovir in antiretroviral-naive patients infected with B and non-B subtype HIV-1 viruses.
OBJECTIVE
The prevalence of rilpivirine, emtricitabine and tenofovir resistance-associated mutations (RAMs), described in vitro and in vivo, was determined in antiretroviral-naive patients.


METHODS
From 2008 to 2011, 1729 treatment-naive patients were tested for resistance by bulk sequencing. We studied the primary rilpivirine RAMs (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, H221Y, F227C and M230I/L) and other potential rilpivirine-associated mutations (V90I, L100I, K101T, E138S, V179D/I, Y188L, V189I, G190A/E/S and M230V). We also studied the M184V/I and K65R mutations for emtricitabine and tenofovir, respectively.


RESULTS
Among 1729 sequences, half of patients had B-subtype viruses and the other half non-B (with 26.7% CRF02, n=461). Primary rilpivirine RAMs were infrequent (4.6%, n=79) and the most prevalent were E138A (3%, n=52), E138K, (0.3%, n=5), H221Y (0.3%, n=5), E138G (0.2%, n=4) and Y181C (0.2%, n=4). The frequency of the primary rilpivirine RAMs was similar between B and non-B subtypes. The other potential rilpivirine-associated mutations that were most prevalent were V179I (8.4%, n=145), V90I (3.8%, n=65) and V189I (2.3%, n=40). The common V179I, V189I and V90I polymorphisms have not been associated with virological failure in Phase 3 clinical studies. By the ANRS algorithm, 4.9% (n=84) of samples were resistant to rilpivirine, 3.7% (n=32) of B-subtype viruses versus 6% (n=52) of non-B-subtype viruses (P=0.02, χ(2) test). The prevalence of K65R and M184I/V was 0.06% (1/1729) and 1% (18/1729), respectively. The prevalence of K103N was 2% (35/1729).


CONCLUSIONS
The prevalence of rilpivirine, emtricitabine and tenofovir resistance mutations was very low in antiretroviral-naive patients. The prevalence of resistance to rilpivirine (4.9%, n=84) was not statistically different from the prevalence of efavirenz and nevirapine resistance in our population.
APHP, Hôpital Pitié-Salpêtrière, Laboratoire de Virologie, UPMC Univ Paris 06, INSERM U 943, Paris, France. sidonie.lambert@psl.aphp.fr
S
S
Lambert-Niclot
C
C
Charpentier
A
A
Storto
D B
DB
Fofana
C
C
Soulié
S
S
Fourati
B
B
Visseaux
M
M
Wirden
L
L
Morand-Joubert
B
B
Masquelier
P
P
Flandre
V
V
Calvez
D
D
Descamps
A-G
AG
Marcelin
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D023241:Antiretroviral Therapy, Highly Active; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics*; D000068679:Emtricitabine; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology*; D015995:Prevalence; D011743:Pyrimidines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068696:Rilpivirine; D000068698:Tenofovir
D009570:Nitriles; D063065:Organophosphonates; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D000068698:Tenofovir; D000068696:Rilpivirine; D000068679:Emtricitabine; D000225:Adenine
NNRTIs; non-nucleoside reverse transcriptase inhibitors; primary resistance