RESUMO
Since the free therapy program was started by the Thai government, the number of patients infected by HIV-1 with access to antiretroviral drugs has increased. The selection of effective interpretation algorithms for antiretroviral drug resistance has become even more important for clinical management. In this retrospective study, the level of agreement was evaluated in 721 antiretroviral-therapy failing HIV-1 subjects. Regarding genetic diversity, about 89% was recognized as non-B variants (CRF01_AE). The level of complete concordant interpretation score in all seven algorithms was recognized in non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) (67%), but not in nucleoside reverse transcriptase inhibitors (NRTIs) (52%). Over 10% of the major discordance score with TRUGENE was revealed in didanosine (Agence Nationale de Recherches sur le SIDA[ANRS]; Detroit Medical Centre [DMC]), abacavir (ANRS; Centre Hospitalier de Luxembourg [CHL]), and also with delavirdine, indinavir and amprenavir (Grupo de Aconselhamento Virológico [GAV]). A good to excellent agreement range of kappa scores was detected for most antiretroviral drugs. However, poor agreement with the TRUGENE system (k<0.40) was seen in the ANRS system with didanosine, abacavir and lopinavir; GAV system in indinavir and amprenavir; and DMC system in ritonavir. These might be an option for resource limited countries when selecting the use of a low cost or free algorithm interpretation, which has excellent agreement as the U.S. Food and Drug Administration (FDA)-approved TRUGENE commercial system.
Assuntos
Algoritmos , Farmacorresistência Viral/genética , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/farmacologia , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Protease de HIV/genética , Inibidores da Protease de HIV , Transcriptase Reversa do HIV/genética , HIV-1/classificação , HIV-1/enzimologia , HIV-1/genética , Humanos , Testes de Sensibilidade Microbiana , Inibidores da Transcriptase Reversa , Tailândia/epidemiologiaRESUMO
Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its ligand CCL2 results in activation of the cascade consisting of phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat homology protein, FROUNT, directly bound activated CCR2 and formed clusters at the cell front during chemotaxis. Overexpression of FROUNT amplified the chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense strategy substantially diminished signaling via CCR2. In a mouse peritonitis model, suppression of endogenous FROUNT markedly prevented macrophage infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium protrusion cascade and could be a therapeutic target in chronic inflammatory immune diseases associated with macrophage infiltration.