Prevalence of HIV protease mutations on failure of nelfinavir-containing HAART: a retrospective analysis of four clinical studies and two observational cohorts.
BACKGROUND
Both D30N and L90M in HIV-1 protease are primary resistance mutations that emerge under nelfinavir drug pressure. Although D30N confers little or no cross-resistance to other protease inhibitors (PIs) and has been shown to allow effective substitution of a second PI, L90M with secondary mutations is involved in broad cross-resistance to the class. Although L90M has been observed rarely to date under nelfinavir selection, data on the relative incidence of these two mutations on failure of first-line nelfinavir HAART are sparse.


METHODS
We performed a systematic review of HIV-1 protease genotypes from four clinical trials and two observational cohorts in which PI-naive patients failed to achieve or sustain full virological suppression on a nelfinavir-based first HAART regime.


RESULTS
Wild-type protease was observed in 61.9% of 189 isolates and secondary PI mutations were observed in only <3%. D30N and L90M (+/- secondary mutations) occurred in 30.7% and 4.8%, respectively. Only one sample displayed both mutations (0.5%).


CONCLUSIONS
Almost 95% of failures on first-line nelfinavir-based triple-drug HAART occur without PI mutations or with D30N as the primary protease change. L90M occurs in only 5% of cases. These results are of significance for determining the feasibility of initiating a second PI after first-line nelfinavir failure.
Clotet
Bonaventura
B
Retrovirology Laboratory IrsiCaixa Foundation, Barcelona, Spain.
Ruiz
Lidia
L
Martinez-Picado
Javier
J
Negredo
Eugènia
E
Hill
Andrew
A
Popescu
Matei
M
D002986:Clinical Trials as Topic; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics; D016679:Genome, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D019888:Nelfinavir / Q000627:therapeutic use*; D012189:Retrospective Studies; D017211:Treatment Failure
D017320:HIV Protease Inhibitors; D016333:HIV Protease; D019888:Nelfinavir