Cross-validated stepwise regression for identification of novel non-nucleoside reverse transcriptase inhibitor resistance associated mutations.

Background: Linear regression models are used to quantitatively predict drug resistance, the phenotype, from the HIV-1 viral genotype. As new antiretroviral drugs become available, new resistance pathways emerge and the number of resistance associated mutations continues to increase. To accurately identify which drug options are left, the main goal of the modeling has been to maximize predictivity and not interpretability.

Residual activity of two HIV antiretroviral regimens prescribed without virological monitoring.

Virological residual activity (VRA) denotes the degree of HIV RNA suppression achieved by antiretroviral therapy in the presence of resistant virus. This concept is particularly important in resource-limited settings, where rapid switching after detection of virological failure may not be feasible. Using data from the NORA trial, we estimated VRA for two regimens-zidovudine-lamivudine-abacavir (ZDV-3TC-ABC) and zidovudine-lamivudine-nevirapine (ZDV-3TC-NVP)-and related this to the phenotypic drug sensitivity of the component drugs in the two regimens.

HIV-1 drug-resistance patterns among patients on failing treatment in a large number of European countries.

Background: Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy.

Methods: The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries.

HIV-1 resistance testing influences treatment decision-making.

Objective: To investigates how the use of HIV-1 resistance tests influences physician decision-making.

Methods: Ten experienced reference physicians from the Brazilian Network for Drug Resistance each received ten patients' case histories. The selected patients had experienced at least two virological failures.

The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations.

We measured the effects of non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutations K101E+G190S, on replication fitness and EFV-resistance of HIV(NL4-3). K101E+G190S reduced fitness in the absence of EFV and increased EFV resistance, compared to either single mutant. Unexpectedly, K101E+G190S also replicated more efficiently in the presence of EFV than in its absence.