RESUMO
In this viewpoint we would like to describe our results in terms of resistance pattern in Chilean patients with virological failure (VF) on raltegravir (RAL)-containing-regimens and highlight the need for the concomitant availability of genotypic resistance testing to integrase strand transfer inhibitors (INSTIs) introduction in antiretroviral regimens, particularly in countries in South America. Indeed we found in our study the presence of two or more primary mutations in some of the participants which is associated with cross-resistance to all INSTIs. By using timely genotyping, we could optimally manage these patients, early after detection of VF.
RESUMO
BACKGROUND: HIV in Chile has a notification rate of 0.01%. Coreceptor antagonists are a family of antiretroviral drugs that are used with the prior knowledge of patients HIV-1 tropism. Viral RNA-based tropism detection requires a plasma viral load ≥1000 copies/mL, while proviral DNA-based detection can be performed regardless of plasma viral load. This test is useful in patients with low or undetectable viral loads and would benefit with a proper therapy. The aim of this study was to determine the correlation between HIV RNA and proviral genotypic DNA tropism tests. FINDINGS: Forty three Chilean patients were examined using population-based V3 sequencing, and a geno2pheno false-positive rate (FPR) cutoff values of 5, 5.75, 10 and 20%. With cutoff 5.75% a concordance of 88.4% in tropism prediction was found after a simultaneous comparison between HIV tropism assessment by RNA and DNA. In total, five discrepancies (11.6%) were found, 3 patients were RNA-R5/DNA-X4 and two were RNA-X4/DNA-R5. Proviral DNA enabled the prediction of tropism in patients with a low or undetectable viral load. For cutoff 5 and 5.75% genotypic testing using proviral DNA showed a similar sensitivity for X4 as RNA. We found that the highest sensitivity for detecting the X4 strain occurred with proviral DNA and cutoff of 10 and 20%. Viral loads were higher among X4 strain carriers than among R5 strain carriers (p < 0.05). CONCLUSIONS: A high degree of concordance was found between tropism testing with RNA and testing with proviral DNA. Our results suggest that proviral DNA-based genotypic tropism testing is a useful option for patients with low or undetectable viral load who require a different therapy.
Assuntos
DNA Viral/genética , Técnicas de Genotipagem/métodos , Infecções por HIV/virologia , HIV-1/fisiologia , RNA Viral/genética , Tropismo Viral , Virologia/métodos , Adolescente , Adulto , Idoso , Chile , Feminino , Genótipo , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
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 anti-retroviral drugs before the study were included. Patients with CD4 cell counts less than 200 cells/mm3, viral load below 2000 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 TRUGENE HIV-1 assay from Bayer and the OpenGene DNA sequencing system. RESULTS: Ninety nine percent of patients had at least one mutation, 27% had 4 or more mutations, but high level resistance to ARV was found only in 2.7% of cases. Point mutations for non nucleoside reverse transcriptase inhibitors (NNRTI) were detected in 4.1% of cases (K103N in 1 patient, V179D in 2 patients), for nucleoside reverse transcriptase inhibitors (NRTI) in 8.1% of cases (T215S in 1 patient, V118I in 4 patients, M41L in 1 patient) and for protease inhibitors (PI) in 1.3% 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.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Mutação/genética , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Chile , Feminino , Infecções por HIV/virologia , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Adulto JovemRESUMO
Background: In countries with universal access to antiretroviral therapy a progressive increase in the number of patients that are infected with resistant virus, is observed. Aim To detect the presence of primary resistance to antiretroviral drugs among patients with a recent diagnosis of HIV infection. Material and methods: Twenty five male patients aged 25 to 45 years, with a diagnosis of a recent HIV infection, done between 2004 and 2005, were studied. Genotypic resistance to antiretroviral drugs was studied using the Genetic Resistance Test TRUGENE® from Bayer. Results: Resistance mutations were detected in 10 patients. All had an university title or had university studies. All lived in northeastern Santiago and had risky sexual behaviors while traveling abroad. Seven mutations were detected in reverse transcriptase. Of these, three were associated to a high resistance level and four, to an intermediate or low resistance, were also detected. Conclusions: A high frequency of genotypic resistance was detected in this group of Chilean patients recently infected with HIV. A higher socioeconomic status and lifestyle could have influenced these results.
Assuntos
Adulto , Humanos , Masculino , Pessoa de Meia-Idade , HIV , Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/virologia , Mutação/genética , HIV , Fármacos Anti-HIV/uso terapêutico , Chile , Genótipo , Infecções por HIV/tratamento farmacológico , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , Carga ViralRESUMO
BACKGROUND: In countries with universal access to antiretroviral therapy a progressive increase in the number of patients that are infected with resistant virus, is observed. AIM: To detect the presence of primary resistance to antiretroviral drugs among patients with a recent diagnosis of HIV infection. MATERIAL AND METHODS: Twenty-five male patients aged 25 to 45 years, with a diagnosis of a recent HIV infection, done between 2004 and 2005, were studied. Genotypic resistance to antiretroviral drugs was studied using the Genetic Resistance Test TRUGENE from Bayer. RESULTS: Resistance mutations were detected in 10 patients. All had an university title or had university studies. All lived in northeastern Santiago and had risky sexual behaviors while traveling abroad. Seven mutations were detected in reverse transcriptase. Of these, three were associated to a high resistance level and four, to an intermediate or low resistance, were also detected. CONCLUSIONS: A high frequency of genotypic resistance was detected in this group of Chilean patients recently infected with HIV. A higher socioeconomic status and lifestyle could have influenced these results.
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV/efeitos dos fármacos , Mutação/genética , Adulto , Fármacos Anti-HIV/uso terapêutico , Chile , Genótipo , HIV/genética , Infecções por HIV/tratamento farmacológico , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Carga ViralRESUMO
BACKGROUND: Highly active antiretroviral therapy (HAART) in HIV/AIDS infection induces an important reduction of the viral load (VL) and an immune system reconstitution. CD4+ T lymphocyte count is the immunological measurement commonly used for the follow up of HIV/AIDS patients. AIM: To study prospectively the restoration of the innate immune system in patients with HIV/AIDS infection during their first year on HAART. PATIENTS AND METHODS: 25 naive HIV/AIDS patients, from San José Hospital and University of Chile Clinical Hospital, Santiago, Chile, were studied between years 2002-2003. Every 4 months after HAART initiation, CD3+, CD4+, CD8+ T lymphocytes and CD16/56+ natural killer (NK) cells were quantified by flow cytometry. NK cell cytotoxicity was measured using radioactive chrome liberation (Cr51). Tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in peripheral blood mononuclear cells and viral load was determined using Amplicor HIV-1 from Roche Diagnostics Systems. RESULTS: Thirteen of the 25 patients continued in the study. They were all males, average age 35 years old (23-50). At baseline average CD4+ count was 146 cells/microL (31-362) and average viral load was 82.000 copies/mL (4.000-290.000). A raise in CD3+, CD4+, CD8+, and CD16/56 cells was noted at months 9-12 of therapy. Viral load became undetectable in the same period. NK cell function was decreased at the beginning of the therapy (1-4 months), reaching its highest values at months 9-12. There was no significant change in IL-10. TNF-alpha increased in six patients during the study. CONCLUSIONS: In this group of patients, innate immunity was restored during HAART. These results should be confirmed in studies with a longer follow up period and also measuring cytokines such as MIP-1a, MIP-1ss and RANTES.
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Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/imunologia , Imunidade Inata , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Contagem de Linfócito CD4 , Seguimentos , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Interleucina-10/sangue , Células Matadoras Naturais/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Carga ViralRESUMO
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.
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Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1 , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Chile/epidemiologia , Feminino , Genótipo , Transcriptase Reversa do HIV/genética , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
BACKGROUND: Esophageal candidiasis is associated with conditions that cause an immune depression. It is a defining disease for AIDS, is observed in poorly controlled diabetics, in patients with renal or hepatic failure, in patients with cancer and in subjects using medications causing immunosuppression or broad spectrum antimicrobials. AIM: To report the features of 10 immunocompetent patients with esophageal candidiasis. PATIENTS AND METHODS: Six males and four females aged between 48 and 82 years, without conditions associated with immunosuppression, in whom an esophageal candidiasis was found on an upper gastrointestinal endoscopy. Delayed skin hypersensitivity to eight antigens, lymphocyte subpopulations, yeast phagocytosis and neutrophil chemotaxis were measured. RESULTS: Six patients had a low CD4 lymphocyte count and seven had a low CD8 count. Seven patients were anergic on skin hypersensitivity challenge. Yeast phagocytosis was abnormal in one patient and neutrophil chemotaxis was abnormal in two. Humoral immunity was normal in all subjects. All patients were treated with oral fluconazole in doses of 150 mg/day for 14 days, with complete resolution of candidiasis in all. CONCLUSIONS: Patients with esophageal candidiasis, have frequent alterations of cellular immunity, that must be diagnosed and treated.
Assuntos
Candidíase/imunologia , Doenças do Esôfago/imunologia , Imunocompetência/imunologia , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/imunologia , Candidíase/complicações , Doenças do Esôfago/microbiologia , Feminino , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
En los últimos años, la participación del sistema inmune innato en el desarrollo de la pre-eclampsia ha sido el objetivo de numerosos estudios. Sin embargo, el rol de las células agresoras naturales (NK) en esta patología no ha sido totalmente aclarado. Las células NK, componentes del sistema inmune innato, poseen actividad citotóxica espontánea, y secretan citoquinas tales como interferón gamma (INF-y ) y Factor de Necrosis Tumoral alfa (TNF-alfa). En el presente estudio hemos analizado la actividad funcional y el inmunofenotipo de células NK obtenidas desde sangre periférica de pacientes con pre-eclampsia, mujeres sanas embarazadas y mujeres sanas no embarazadas. Se cuantificó la actividad cititóxica usando el ensayo de liberación de51cromo. La producción de citoquinas en respuesta a activadores policlonales y el inmunofenotipo (CD3-CD16+CD56+) fueron determinados por citometría de flujo. Estos parámetros no evidenciaron diferencias significativas entre los grupos estudiados; sin embargo, en las pacientes con pre-eclampsia se observa una tendencia hacia una menor citotoxicidad y menor producción de TNF-alfa en células NK estimulada sin vitro, y una proporción aumentada del subtipo celular NK CD56-CD16+ en sangre periférica en relación con los otros dos grupos estudiados.
NK cells functionality during pregnancy. During the last few years, the role of innate immune system in development of pre-eclampsia has been the focus of a number of studies. However, the role of natural killer (NK) cells in pregnancy and pre-eclampsia has not been totally clarified. NK cells, an important component of innate immune system, normally exhibit spontaneus cytolytic activity and secrete cytokines such as interferon gamma (IFN-y) and tumor necrosis factor alpha (TNF-alpha). In current paper, we studied functional activity and immunophenotype of peripheral blood NKcells obtained from patients with pre-eclampsia, healthy pregnant women and non-pregnant healthy women. For this purpose, we quantified cytolytic activity using 51chromium release assay. We determined cytokine production in response to polyclonal activators and cells immunophenotype (CD3-CD16+CD56+) by flow cytometry. We found no significant differences in these parameters among the three groups studied, however, in patients with pre-eclampsia, there is a tendency to a decreased cytotoxic activity and less production of TNF-alpha by NK cells in vitro as well as an increased proportion of the NK subset CD56-CD16+, in peripheral blood.