Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy

In order to assess the human immunodeficiency virus type 1 (HIV-1) drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV) therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance genotyping was performed using ViroSeqTM Genotyping System (Celera Diagnostic-Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences (protease and reverse transcriptase-RT regions) was as follows: subtype B (91.2 percent), subtype F (4.9 percent), and B/F viral recombinant forms (3.3 percent). The subtype C was identified in two patients (0.4 percent) and the recombinant CRF_02/AG virus was found infecting one patient (0.2 percent). The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.

Co-Infection by HTLV-I/II is Associated With Increased Viral Load in PBMC of HIV-1 Infected Patients in Bahia, Brazil.

To evaluate the viral load in peripheral blood mononucler cells (PBMC) of patients infected by HIV-1 we performed 96 quantitative cultures in 74 patients infected by HIV-1, using the co-culture method. The viral load was expressed in tissue culture infectious doses (TCID), and the results were analyzed according to gender, age and clinical stage of patients, duration of previous antiretroviral therapy, detectable p24 antigenemia, CD4(+)/CD8(+) cell counts, co-infection by HTLV-I/II and viral subtype. We detected a statistically significant association between co-infection by HTLV-I/II and viral load higher than >50 TCID (p=0.003). We also found a significant association between co-infection by HTLV-I/II and p24 antigenemia (p=0.028). CD4(+) cell counts were significantly higher for patients presenting negative cultures, but there was no detectable association between lower CD4(+) cell counts and higher TCID. The majority of patients were infected by subtype B virus. The observation in this study that co-infection with HTLV-I/II was significantly associated with higher viral load raises the possibility that these agents act as co-factors of AIDS progression, in doubly-infected patients.