Chemokine receptors expression on T cells and response to HAART among chronic HIV-1-infected subjects.

Chemokines receptors are used by HIV-1 for entry into CD4(+) T cells. The beta-chemokines are capable of inhibiting HIV replication. This study determined the CCR5 and CXCR4 expression on T cells in HIV-1-infected patients treated with HAART. The successfully treated group (plasma viral load <400 copies/mL), when compared with the failure group (plasma viral load >400 copies/mL), had higher median CD4(+) T cells count (583 and 245 cells/mm(3); respectively, p< 0.0001). The failure patients had higher numbers and intensity of CCR5 and CXCR4-expressing T cells. Successfully treated patients were able to normalize the co-receptors expression-over on T cells. The viremic group showed higher CCR5 expression on CD4(+) T cells and lower number of cells; CCR5 expression was normalized in the aviremic group; the naïve group showed lower CCR5 expression and higher numbers of CD4 T cells; all groups showed normal CXCR4 expression compared to healthy controls. These findings may have clinical implications, since down-regulation of these co-receptors could be an adjuvant strategy for anti-HIV treatment.

Drug resistance among chronic HIV-1-infected patients naïve for use of anti-retroviral therapy in Sao Paulo city.

Primary infection with drug-resistant HIV appears to be increasing in the regions where HAART is widely available, which may reduce efficacy of first-line antiretroviral therapy. To determine prevalence of antiretroviral drug-resistant mutations in newly diagnosed subjects in a clinical setting where HAART has been widely used since 1997. One hundred and thirty-six HIV-1-infected adult patients were diagnosed with HIV infection between January 2000 and December 2006 in the HIV out-clinic at the HC/FMUSP, Sao Paulo city. These antiretroviral naïve patients were mainly referred from the blood bank, situated in the same building or elsewhere in the city. The samples were genotyped to provide HIV protease and reverse transcriptase sequence data. Major antiretroviral drug resistance mutations were classified according to Shafer et al. [Shafer, R.W., Rhee, S.Y., Pillay, D., et al., 2007. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance. AIDS 21, 215-223]. Thirteen cases had no DNA amplification, and 123 patients were successfully analyzed, with a mean age of 37 years and 89 (72%) were males. Antiretroviral drug resistance mutations were detected in 8/123 patients (6.5%), all eight were heterosexuals and HIV asymptomatic, the mean of the CD4 cells count was 323 cells/mm(3), and the RNA plasma viral load was 4.7 log(10)/mL. We found NRTI (n=2, 1.6%), NNRTI-resistant (n=2, 1.6%) mutations, and one cases with PI mutation (0.8%). Three cases (2.4%) showed mutations for NRTI, NNRTI or PI, simultaneously. Eighty-two percent were HIV-1 B subtype, and HIV-1 F (6.5%), HIV-1 C (5.7%) and recombinant viruses (5.8%) were observed. In an unselected cohort, primary drug resistance was seen in 6.5% of the naïve for drug ART use. These results indicate that HIV drug resistance testing should be a practical approach in monitoring first-line ART. In addition, HIV-1 C seems to be emerging in Sao Paulo city.