Resistance mutations in HIV-infected patients experiencing early failure with nelfinavir-containing triple combinations.
BACKGROUND
The purpose of our study was to assess the presence of nelfinavir (NFV)-associated resistance mutations at the time of early virological failure in subjects receiving NFV as part of a first protease inhibitor (PI)-based triple regimen.


METHODS
Subjects failing their first PI-based NFV-containing triple regimen were identified in six Spanish hospitals. HIV genotyping was carried out in plasma samples collected at the time of the first viral rebound.


RESULTS
Upon initiation of NFV-based therapy, 19 of the 30 subjects (63%) were naïve; 11 (37%) had been exposed to nucleoside analogues. Median HIV-RNA at the time of viral rebound was 4, 180 copies/ml. PCR-amplified products were obtained in 22 subjects (73%). These products were sequenced and primary PI resistance mutations were recognized in 6 patients (27%). All six individuals harbored the D30N mutation, and none presented the L90M mutation. Other PI resistance mutations were present in 5 subjects (at codons 36, 63, 71, 77, 82 and/or 88). Secondary PI resistance mutations were present in another 9 subjects. By contrast, mutations conferring resistance to reverse transcriptase inhibitors were present in 50% of the patients, and the M184V substitution was the most frequently seen.


CONCLUSIONS
Nearly 75% of patients failing their first PI-based triple regimen containing NFV do not harbor PI resistance mutations. The D30N substitution, rather than L90M, is the most frequently recognized, which does not challenge the efficacy of further rescue interventions with other PIs. This observation supports the use of nelfinavir as first protease inhibitor.
Núńez
Marina
M
Service of Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain.
de Mendoza
Carmen
C
Valer
Luisa
L
Casas
Esperanza
E
López-Calvo
Soledad
S
Castro
Angeles
A
Rosón
Beatriz
B
Podzamczer
Daniel
D
Rubio
Amalia
A
Berenguer
Juan
J
Soriano
Vincent
V
D000328:Adult; D004351:Drug Resistance; D005260:Female; D005814:Genes, Viral; D005838:Genotype; D006678:HIV / Q000235:genetics*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019888:Nelfinavir / Q000627:therapeutic use*
D017320:HIV Protease Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D019888:Nelfinavir