Prevalence of HIV Protease Mutations on Failure of Nelfinavir-Containing HAART: A Retrospective Analysis of Four Clinical Studies and Two Observational Cohorts

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Abstract
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. 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. 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%). 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.

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