Prevalencia de resistencia primaria en pacientes con infección reciente por VIH-1 en Chile / Prevalence of primary antiretroviral resistance among HIV infected patients in Chile

Background: The main cause of virological failure during AIDS treatment is the resistance to antiretroviral medications (ARV). Aim: To search for mutations associated with ARV resistance in recently HIV-1 infected patients naïve to treatment, in Chile. Material and Methods: Patients over 18 years old with HIV-1 infection, naïve to antiretroviral drugs before the study were included. Patients with CD4 cell counts less than 200 cells/mm³, viral load below 2.000 copies/mL or any condition indicative of advanced AIDS were excluded. Criteria for diagnosis of recent infection (< 18 months) were a previous negative test for HIV antibodies or a history of an acute retroviral syndrome in the past 18 months. Resistance to drugs was analyzed using the TRUGENEtm HIV-1 assay from Bayer and the OpenGene DNA sequencing system. Results: Ninety nine percent of patients had at least one mutation, 27 percent had 4 or more mutations, but high level resistance to ARV was found only in 2.7 percent of cases. Point mutations for non nucleoside reverse transcriptase inhibitors (NNRTI) were detected in 4.1 percent of cases (K103N in 1 patient, V179D in 2 patients), for nucleoside reverse transcriptase inhibitors (NRTI) in 8.1 percent of cases (T215S in 1 patient, V118I in 4 patients, M41L in 1 patient) and for protease inhibitors (PI) in 1.3 percent of cases. All mutations detected in the protease gene were secondary. Of these, the most common were L63P/T (38 patients), L10I/V (27 patients) and V77I (26 patients). Resistance to two or more antiretroviral classes was not detected. Conclusions: This study supports that, by now, primary resistance has a low prevalence in Chile. Therefore, a genotyping test before starting antiretroviral therapy is not necessary.

Resistencia a la terapia antirretroviral en pacientes infectados con el virus VIH-1 en Chile 2002-2005 / Resistance to anti-retroviral therapy in Chilean patients with HIV-1 from 2002 to 2005

Background: Resistance limits the effectiveness of anti-retroviral therapy. In Chile, there is free access to highly active anti-retroviral therapy since 2001, but there is no information about the frequency of mutations associated to drug resistance. Aim: To determine the most common mutations associated to anti-retroviral drug resistance in Chile. Materials and Methods: Retrospective study of 710 genotype analysis coming from 568 patients aged 22 to 70 years (85 percent males) with virological failure. The analysis was performed using a commercially available sequencing kit (Trugene HIV-1 genotypic assay from Bayer S.A). Results: Mean CD4+ cell count and viral load were 154 cells/fil and 228784 RNA copies/ml, respectively. The frequency of resistance to nucleoside RT inhibitors (NRTI), non nucleoside RT inhibitors (NNRTI) and protease inhibitors (PI) was 71 percent, 62 percent and 22 percent, respectively. The most common mutations found were T215Y (46 percent), L10F (44 percent), Ml84V (3896), K103N (35 percent) and M41L (32 percent). Fifty five percent of mutations corresponded to the TAM (thymidine analogue mutations) group. Multiresistance was 47 percent to NNRTI, 7 percent to NRTI, 4 percent to PI and 0.7 percent to all groups. During the four years of the study, there was a significant increase in NNRTI resistance. Conclusions: These data provides important information about the epidemiology of drug resistance mutations and should help to design newHAARTstrategies.

Resistencia primaria a terapia antirretroviral en pacientes con infección por VIH/SIDA en Chile / Primary resistance to antiretroviral therapy in patients with HIV/AIDS in Chile

Background: Resistance to antiretroviral therapy is a determining factor for therapeutic failure in HIV/AIDS. The prevalence of primary resistance (i.e. in those patients that have not received treatment) varies in different parts of the world. Aim: To study the prevalence of primary resistance to antiretroviral drugs in patients living in Northern Santiago. Patients and methods: Viral load, lymphocyte subpopulations by flow cytometry and genotypic resistance testing were assessed in blood samples from 60 HIV-1 infected patients (mean age 37 years, 54 male). Results: Mean CD4 cell count and viral load was 200 cells/ml and 142,840 RNA copies/ml respectively. Ten mutations were identified: V179D, L10I/V, M361, L63P, A71T/V, Y115F, V118I and K20R. None of these mutations is associated to a high degree of resistance to reverse transcriptase inhibitors, nucleoside analogs (NRTI), non nucleoside analogs (NNRTI) or viral protease inhibitors. Conclusions: This is a first approach to study antiretroviral resistance in Chilean patients. This study must be amplified, since the prevalence of resistance may experience changes with time.