New patterns of HIV-1 resistance during HAART.

HIV-1 resistance and subsequent virologic failure occur in a substantial proportion of HIV-infected patients receiving HAART regimens. In the present article, we summarize new data on resistance to current and forthcoming antiretroviral drugs which will help in the interpretation of the results of resistance tests and the individualization of therapy. Nucleoside analog mutations (NAMs) (M41L, D67N, K70R, L210W, T215Y/F and K219Q/E) are associated with reduced susceptibility to most nucleoside analogs and the nucleotide tenofovir. This recently approved drug has shown a reduced virologic response in the presence of three or more NAMs, including M41L or L210W, as well as in the presence of T69 insertions. Hypersusceptibility (IC50 < 0.5) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) has recently been described in association with increased resistance to nucleoside analogs, and it seems to enhance the immunologic and virologic reponses in patients receiving efavirenz-containing regimens. New protease inhibitors (PIs) have a lower cross-resistance profile, although more clinical data are needed to establish appropriate PI sequencing to promote sustained virologic success. Cross-resistance between amprenavir (APV) and lopinavir (LPV/r) in the presence of only four APV-related mutations has been described, suggesting that phenotypic tests should be applied before prescribing LPV/r to APV-experienced patients. Resistance to the new entry inhibitor class compound T-20 (enfuvirtide) has also been detected.