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Medisan ; 25(6)2021. ilus
Article in Spanish | LILACS, CUMED | ID: biblio-1356477


El SARS-CoV-2, agente causal de la actual pandemia de la COVID-19, va sufriendo mutaciones como consecuencia de su ciclo evolutivo, lo que ha originado diferentes variantes genéticas, que han sido agrupadas en dos categorías: preocupante (alfa o británica, beta o sudafricana, gamma o brasileña y delta o india) y de interés (lamdba, mu, épsilon, eta, iota, kappa, zeta, theta); estas conllevan implicaciones clínicas en la transmisibilidad, virulencia y resistencia del SARS-CoV-2 a la inmunidad natural y adquirida, lo que representa un serio desafío para los servicios de salud en todo el mundo. En este artículo se describen dichas variantes genéticas, con énfasis en su probable impacto clínico, y además se plantea la posibilidad de que aparezcan otras, como fenómeno natural en la evolución de los virus.

The SARS-CoV-2, causal agent of the COVID-19 current pandemic, is suffering mutations as a consequence of its evolutive cycle, what has originated different genetic variants that have been grouped in two categories: worrying (alpha or British, beta or South African, gamma or Brazilian and delta or Indian) and of interest (lamdba, mu, epsilon, eta, iota, kappa, zed, theta); these categories bear clinical implications in the transmissibility, virulence and resistance from SARS-CoV-2 to the natural and acquired immunity, what represents a serious challenge in health services worldwide. These genetic variants are described in this work, with emphasis in its probable clinical impact, and the possibility that other variants could appear is also explained, as natural phenomenon in the evolution of viruses.

Coronavirus , SARS-CoV-2/genetics , COVID-19 , Drug Resistance, Viral , Mutation
Article in English | WPRIM | ID: wpr-880560


Covid-19 pandemic has caused hundreds of thousands deaths and millions of infections and continued spreading violently. Although researchers are racing to find or develop effective drugs or vaccines, no drugs from modern medical system have been proven effective and the high mutant rates of the virus may lead it resistant to whatever drugs or vaccines developed following modern drug development procedure. Current evidence has demonstrated impressive healing effects of several Chinese medicines (CMs) for Covid-19, which urges us to reflect on the role of CM in the era of modern medicine. Undoubtedly, CM could be promising resources for developing drug candidates for the treatment of Covid-19 in a way similar to the development of artemisinin. But the theory that builds CM, like the emphasis of driving away exogenous pathogen (virus, etc.) by restoring self-healing capacity rather than killing the pathogen directly from the inside and the 'black-box' mode of diagnosing and treating patients, is as important, yet often ignored, an treasure as CM herbs and should be incorporated into modern medicine for future advancement and innovation of medical science.

Antiviral Agents/therapeutic use , COVID-19/therapy , Disease Outbreaks , Drug Development/standards , Drug Resistance, Viral/genetics , Drug Therapy, Combination , Drugs, Chinese Herbal/therapeutic use , Humans , Medicine, Chinese Traditional/trends , Mutation Rate , Pandemics , Phytotherapy/methods , SARS-CoV-2/physiology
Prensa méd. argent ; 105(3): 99-105, may 2019. tab
Article in Spanish | LILACS, BINACIS | ID: biblio-1025198


Introducción: El tratamiento antirretroviral de alta eficacia (TARGA) ha desplazado a las infecciones oportunistas como principal causa de hospitalización en infectados por el HIV. Sin embargo, algunos autores hallaron que las causas de internación por HIV en Buenos Aires no cambiaron a pesar del acceso universal al TARGA desde 1996. Pacientes y Métodos. Para confirmar estos resultados revisamos todos los ingresos hospitalarios ocurridos durante tres años en un hospital general de la ciudad de Buenos Aires. Resultados: 57 pacientes (34 hombres) tuvieron 79 hospitalizaciones: 43 ingresaron sólo una vez y los 14 restantes tuvieron dos o más ingresos hasta totalizar 36 internaciones. La edad fue de 44.46 ± 11.55 años (promedio ± desvío estándard), 43 pacientes (75.45%) se sabían HIV + y 28 de ellos (65.12%) recibían TARGA al ingreso, 31 hospitalizaciones (39.24%) fueron causadas por enfermedades marcadoras de SIDA; 35 (44.30%) por infecciones no marcadoras de SIDA (INMS) y 13 (13.46%) por enfermedades no infecciosas. Tuberculosis fue el diagnóstico más frecuente (11 casos, 13.92%), seguida por meningitis a Cryptococcus neoformans en 9 (11.39%) y toxoplasmosis cerebral en 6 (7.59%). Entre las INMS, la neumonía fue la principal causa de hospitalización (13 pacientes, 16.46%). Discusión: Estos resultados confirman resultados previos comunicando que las causas de hospitalización en infectados por el HIV no cambiaron en respuesta al TARGA en Buenos Aires, lo que puede estar reflejando problemas de detección o adherencia, o puede estar relacionado con resistencia viral, razones sociales o cualquier combinación de estos factores (AU)

Introduction. High Active Antiretroviral Treatment (HAART) displaced opportunistic infections as the main cause of hospitalization in HIV infected patients. However, some authors found that causes for hospitalization in HiV infected patients did not changed at Buenos Aires although this country offers universal access to HAART since 1996. Patients and Methods. We analyzed all the HIV related admissions recorded during three years at a general hospital. Results. 57 patients (34 men) were hospitalized 79 times. 43 out of them were hospitalized only one time. The reaining 14 were hospitalized 36 times. Age was 44.46 ± 11.55 years (mean ± standard deviation). 43 patients (75.45%) had a previous diagnosis of HIV infection. 28 of them (65.12%) received HAART. 31 hospitalizations (39.24%) were caused by AIDS defining events. 35 (44.30%) related to non-AIDS-defining infections diseases (NADID), and 13 (13.46%) to non-infections diseases. Tuberculosis was the prevalent illness (11 cases, 13.92%), followed by cryptoccal meningitis in 9 (11.39%) and cerebral toxoplasmosis in 6 (7.59%). Among NADID, pneumonia was the main cause of admission (13 patientes, 16,46%). Discussion: These results confirm previous reports showing that causes of HIV related hospitalization remain unchanged in spite of HAART at Buenos Aires, which may be reflecting problems of detection and adherence, or may be related to local viral resistance, social reasons, or any combination of these factors (AU)

Humans , Adult , Middle Aged , Communicable Diseases/diagnosis , Statistical Analysis , Retrospective Studies , HIV/immunology , Antiretroviral Therapy, Highly Active/statistics & numerical data , Drug Resistance, Viral/immunology , Noncommunicable Diseases , Inpatients/statistics & numerical data
Braz. j. infect. dis ; 22(6): 477-486, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-984016


ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.

Humans , Female , Middle Aged , Antiviral Agents/pharmacology , Virus Replication/drug effects , Hepatitis B virus/drug effects , Lamivudine/pharmacology , Cytidine/analogs & derivatives , DNA, Viral/chemistry , Microbial Sensitivity Tests , Cell Line , Hepatitis B virus/isolation & purification , Hepatitis B virus/physiology , Hepatocytes/virology , Drug Resistance, Viral/drug effects , Mutation
Braz. j. infect. dis ; 22(4): 294-304, July-Aug. 2018. tab, graf
Article in English | LILACS | ID: biblio-974222


ABSTRACT Background Hepatitis B virus (HBV) infection is a major public health problem in Brazil. HBV endemicity is usually moderate to low according to geographic regions, and high prevalence of this virus has been reported in people of some specific Brazilian counties, including those with a strong influence of Italian colonization in southern Brazil. Analysis of HBV diversity and identification of the main risk factors to HBV infection are necessary to understand hepatitis B epidemiology in these high prevalence regions in southern Brazil. Objective To investigate epidemiological characteristics and HBV genotypes and subgenotypes circulating in a specific city with high HBV prevalence. Methods A cross-sectional study was performed with 102 HBV chronically infected individuals, recruited in reference outpatient clinics for viral hepatitis in a city of high HBV prevalence (Bento Gonçalves) in Rio Grande do Sul state, Brazil between July and December 2010. Socio-demographic, clinical and behavior-related variables were collected in a structured questionnaire. HBV serological markers (HBsAg, anti-HBc), viral load, genotypes/subgenotypes and drug resistance were evaluated and comparatively analyzed among all patients. Results The HBV infected subjects had a mean age of 44.9 (±12.2) years, with 86 patients (84.3%) reporting to have a family history of HBV infection, 51 (50.0%) to share personal objects, and were predominantly of Italian descendants (61; 64.9%). There was a predominance of genotype D (49/54; 90.7%), but genotype A was also detected (5/54; 9.3%). Subgenotypes D1 (1; 4.7%), D2 (3; 14.3%), and D3 (17; 81.0%) were identified. LAM-resistant mutation (rtM204I) and ADV-resistant mutations (rtA181V) were detected in only one patient each. Conclusions These results demonstrate a pivotal role of intrafamilial transmission for HBV spreading in this population. Furthermore, there is a high prevalence of HBV genotype D in this region.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Young Adult , Hepatitis B virus/genetics , Hepatitis B, Chronic/epidemiology , Drug Resistance, Viral , Antiviral Agents/therapeutic use , Brazil/epidemiology , Hepatitis B virus/drug effects , Polymerase Chain Reaction , Prevalence , Cross-Sectional Studies , Risk Factors , Viral Load , Hepatitis B, Chronic/virology , Genotype , Hepatitis B Surface Antigens/blood , Mutation
Rev. Soc. Bras. Med. Trop ; 51(2): 141-145, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-897064


Abstract INTRODUCTION: Human cytomegalovirus is one of the causes of opportunist infections in immunocompromised patients, and is triggered by factors such as state of viral latency, weakened immune responses, and development of antiviral resistance to ganciclovir, the only drug offered by the public health system in Brazil to treat the infection. The goal of this study was to identify mutations that may be associated with antiviral resistance in immunocompromised patients. METHODS: Molecular analysis was performed in 82 blood samples and subjected to genomic DNA extraction by a silica-based method. Three sequences of the HCMV UL97 gene, which encodes a phosphotransferase protein required for activation of ganciclovir, were amplified by polymerase chain reaction. Pyrosequencing methods were applied to one external 2096-bp segment DNA and two internal sequences between nucleotides 1087 to 1828 to detect mutations in this gene. RESULTS: Approximately 10% of sequences contained mutations between nucleotides 377 and 594, in conserved regions of the UL97 gene, leading to amino acid changes. Eleven coding mutations were identified, including changes leading to amino acid substitutions, E596K and S604F, which were observed in 100% of samples and are described for the first time in Brazil. In addition, one mutation (A594V) that is associated with ganciclovir resistance was detected in a kidney transplant patient. CONCLUSIONS: Further studies to detect mutations associated with HCMV resistance to antiviral drugs are required to demonstrate the need to increase the variety and availability of drugs used to treat viral infections in the public health care system in Brazil.

Humans , Antiviral Agents/therapeutic use , Phosphotransferases/genetics , Immunocompromised Host , Cytomegalovirus Infections/drug therapy , Cytomegalovirus/enzymology , Drug Resistance, Viral/genetics , Mutation/genetics , Antiviral Agents/pharmacology , Case-Control Studies , Polymerase Chain Reaction , Cross-Sectional Studies , Cytomegalovirus/drug effects , Cytomegalovirus/genetics , Drug Resistance, Viral/drug effects , Genotype
Säo Paulo med. j ; 136(2): 129-135, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-904150


ABSTRACT BACKGROUND: Increasing genetic diversity of HIV-1 and emergence of drug-resistant mutations may reduce the efficacy of antiretroviral therapy and prophylaxis that are used to prevent mother-to-child transmission. The aim of this study was to assess the genetic diversity and prevalence of drug-resistant mutations among HIV-infected pregnant women. DESIGN AND SETTING: Cross-sectional study at an outpatient clinic for infectious diseases within gynecology and obstetrics. METHODS: This study evaluated the dynamics of HIV-1 subtypes and the prevalence of transmitted and acquired drug-resistant mutations among 38 HIV-infected pregnant women (20 previously exposed to antiretroviral therapy and 18 naive), in Ribeirão Preto (SP), Brazil, between 2010 and 2011. Genotyping was performed by means of molecular sequencing of the protease and reverse transcriptase regions of the HIV-1 pol gene. RESULTS: Subtype B was identified in 84.2% of the samples, recombinant forms between B and F in 7.9%, subtype F1 in 5.3% and the recombinant form K/F in 2.6%. No mutation associated with transmitted drug resistance was detected in the samples from the naive pregnant women, whereas mutations associated with acquired drug resistance were found in 35.0% of the pregnant women previously exposed to antiretroviral therapy. CONCLUSION: The results showed that subtype B predominated, while there was low prevalence of sequences with transmitted drug resistance.

Humans , Female , Pregnancy , Pregnancy Complications, Infectious/virology , Genetic Variation , HIV Infections/virology , HIV-1/genetics , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , Mutation/genetics , Phylogeny , Pregnancy Complications, Infectious/drug therapy , Socioeconomic Factors , RNA, Viral/genetics , HIV Infections/drug therapy , Prevalence , Cross-Sectional Studies , HIV-1/drug effects , Genotype
Rev. chil. infectol ; 35(5): 509-517, 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-978065


Resumen Introducción: A nivel mundial, la tasa global de resistencia primaria y secundaria a los anti-retrovirales (ARV) es de 15 y 40%, respectivamente. Se desconoce su prevalencia en Uruguay. Objetivo: Conocer la prevalencia de resistencia a los ARV en niños y adolescentes uruguayos bajo 15 años de edad infectados con VIH que se controlan en el Centro Hospitalario Pereira Rossell entre 2008 y 2016. Objetivos específicos: Cuantificar mutaciones de resistencia primarias y secundarias e identificar variables asociadas a resistencias; describir si el resultado del test de resistencia contribuyó a lograr una carga viral (CV) indetectable. Metodología: Descriptivo observacional, seguimiento longitudinal. Se incluyeron menores de 15 años con test de resistencia entre 1 de enero de 2008 y 15 de diciembre de 2016. Variables maternas y del niño. Resultados: Se incluyeron 56 niños. Tenían test de resistencia previo al inicio TARV 36 niños (64%) y por fallo terapéutico 20 (36%). La resistencia total fue 28,6% (16 niños): cuatro (11,1%) con mutaciones primarias y 12 (60%) secundarias. El test modificó el plan ARV en 15 (26,7%) de los 56 niños. El cambio logró CV indetectable a los seis meses en ocho casos. El cambio de TARV no se asoció con sida o muerte. Discusión: Los estudios de prevalencia son útiles para la toma de decisiones sobre la selección inicial de ARV. La prevalencia de mutaciones primarias fue similar a la publicada, mientras que la secundaria fue mayor.

Background: Primary and secondary antiretroviral (ARV) resistance rates of 15 and 40% respectively have been reported in worldwide. Its prevalence in Uruguay is unknown. Aim: To know the prevalence of ARV resistance in Uruguayan children under 15 years old infected with HIV that are controlled in the Centro Hospitalario Pereira Rossell between 2008 and 2016. Specific objectives: Quantify primary and secondary mutations, to identify variables associated with resistance; to describe if the result of the resistance test contributed to achieve undetectable viral load (VL). Methodos: Observational descriptive, longitudinal follow-up. Only children under 15 years with resistance test done between January first 2008 and December 31th 2016 were included in the study. Maternal and child variables. Results: Fifty six children were included. 36 children (64%) had resistance tests prior to the initiation of ART and the other 20 children (36%) due to therapeutic failure. Total resistance: 28.6% (16 children); 4 (11.1%) children with primary mutations and 12 (60%) secondary mutations. The test result changed the ARV plan in 15 (26.7%) of the 56 children. The change achieved undetectable CV in 8 children at month 6. The ART change was not associated with AIDS or death. Discussion: Prevalence studies are useful in making decisions about initial ARV treatment. The prevalence of primary mutations was similar to that published, while secondary prevalence was higher.

Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , HIV Infections/drug therapy , HIV Infections/virology , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , Mutation/genetics , Uruguay , Prevalence , Longitudinal Studies , Drug Resistance, Viral/drug effects
Braz. j. infect. dis ; 21(4): 396-401, July-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-888887


Abstract Introduction: The widespread use of antiretroviral therapy increased the transmission of antiretroviral resistant HIV strains. Antiretroviral therapy initiation during acute/recent HIV infection limits HIV reservoirs and improves immune response in HIV infected individuals. Transmitted drug resistance may jeopardize the early goals of early antiretroviral treatment among acute/recent HIV infected patients. Methods: Patients with acute/recent HIV infection who underwent resistance test before antiretroviral treatment initiation were included in this analysis. HIV-1 sequences were obtained using an in house protease/reverse transcriptase genotyping assay. Transmitted drug resistance was identified according to the Stanford HIV Database for Transmitted Drug Resistance Mutations, based on WHO 2009 surveillance list, and HIV-1 subtyping according to Rega HIV-1 subtyping tool. Comparison between patients with and without transmitted drug resistance was made using Kruskal-Wallis and Chi-square tests. Results: Forty-three patients were included, 13 with acute HIV infection and 30 with recent HIV infection. The overall transmitted drug resistance prevalence was 16.3% (95% confidence interval [CI]: 8.1-30.0%). The highest prevalence of resistance (11.6%, 95% CI: 8.1-24.5) was against non-nucleoside reverse transcriptase inhibitors, and K103N was the most frequently identified mutation. Conclusions: The high prevalence of nonnucleoside reverse transcriptase inhibitors resistance indicates that efavirenz-based regimen without prior resistance testing is not ideal for acutely/recently HIV-infected individuals in our setting. In this context, the recent proposal of including integrase inhibitors as a first line regimen in Brazil could be an advantage for the treatment of newly HIV infected individuals. However, it also poses a new challenge, since integrase resistance test is not routinely performed for antiretroviral naive individuals. Further studies on transmitted drug resistance among acutely/recently HIV-infected are needed to inform the predictors of transmitted resistance and the antiretroviral therapy outcomes among these population.

Humans , Male , Female , Adult , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , HIV Protease Inhibitors/therapeutic use , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , Brazil , HIV Infections/genetics , HIV Infections/drug therapy , Acute Disease , Genotype , Mutation
Mem. Inst. Oswaldo Cruz ; 112(6): 411-418, June 2017. tab, graf
Article in English | LILACS | ID: biblio-841806


BACKGROUND The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. OBJECTIVE The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. METHODS DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed. FINDINGS Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals. MAIN CONCLUSIONS This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , HIV Infections/genetics , HIV Infections/virology , HIV-1/immunology , Sequence Analysis, DNA , Drug Resistance, Viral/genetics , Brazil/epidemiology , Risk Factors , HIV-1 , Mutation/genetics
Ann. hepatol ; 16(3): 358-365, May.-Jun. 2017. tab, graf
Article in English | LILACS | ID: biblio-887247


ABSTRACT Introduction. Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. Material and methods. A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment. Progression was based on HBV-DNA levels. Rescue therapy with oral antivirals was applied for peg-IFN failure. Disease costs (€, 2014) and utilities were obtained from literature. Results. Compared to natural history, strategy 1 increased QALY (3.98 in HBeAg-positive, 2.16 in -negative cohort). With strategy 2, survival was up to 5.60 (HBeAg-positive) and 3.05 QALY (in HBeAg-negative). The model predicted avoidance of 128 and 86 carcinomas in HBeAg-positive and -negative patients with strategy 1, and up to 181 and 121 in HBeAg-positive and -negative for strategy 2. Total cost increased up to €102,841 (strategy 1) and €105,408 (strategy 2) in HBeAg-positive, and €85,858 and €93,754 in HBeAg-negative. A€1,581/QALY gained ratio was estimated versus the natural history for both strategies. In conclusion, increasing antiviral coverage would be efficient, reducing complications.

Humans , Hepatitis B virus/drug effects , Drug Costs , Hepatitis B, Chronic/economics , Hepatitis B, Chronic/drug therapy , Hepatitis B e Antigens/blood , Computer Simulation , DNA, Viral/blood , Biomarkers/blood , Cost-Benefit Analysis , Models, Economic , Disease Progression , Viral Load , Drug Resistance, Viral , Drug Therapy, Combination
Braz. j. infect. dis ; 21(3): 219-225, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-839208


ABSTRACT Objective: To evaluate the virological outcomes in children and adolescents infected with HIV-1 in Salvador, Bahia according to genotyping results. Methods: We retrospectively evaluated the rates of virological suppression of children and adolescents submitted to HIV-1 genotyping test from January/2008 to December/2012. The participants were followed in the two referral centers for pediatric AIDS care, in Salvador, Brazil. Resistance mutations, drug sensitivity profiles, and viral subtypes were analyzed using the Stanford HIV-1 Drug Resistance Database. Adherence was estimated by drugs withdrawal at pharmacies of the two sites. Results: 101 subjects were included: 35 (34.6%) were drug-naïve, and the remaining 66 were failing ART. In drug-naïve group, 3 (8.6%), presented with NNRTIs resistance mutations, along with polymorphic mutations to PIs in most (82.8%) of them. Among the failing therapy group, we detected a high frequency (89.4%) of resistance mutations to PIs, NRTI (84.8%), and NNRTI (59.1%). Virological suppression after introduction/modification of genotyping-guided ART was achieved only for patients (53.1%) with drug withdrawal over 95%. Main detected HIV-1 subtypes were B (67.3%), F (7.9), C (1.9%), and recombinant forms (22.9%). Conclusions: Despite the use of genotyping tests in guidance of a more effective antiretroviral regimen, poor adherence to ART seems to be the main determinant of low virological suppression rate for children and adolescents, in Salvador, Brazil.

Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , HIV Infections/drug therapy , HIV-1/genetics , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , Medication Adherence , Mutation , HIV Infections/virology , Cross-Sectional Studies , Retrospective Studies , Viral Load/drug effects , Genotype
Chinese Medical Journal ; (24): 914-919, 2017.
Article in English | WPRIM | ID: wpr-266885


<p><b>BACKGROUND</b>Tenofovir disoproxil (TDF) is a promising salvage therapy for patients with chronic hepatitis B (CHB) who failed regimens of other nucleoside analogues (NAs). In this study, we aimed to investigate the clinical efficacy and safety of TDF monotherapy in Chinese CHB patients with genotypic resistance.</p><p><b>METHODS</b>A total of 33 CHB patients who had failed treatment with other NAs and had genotypic resistance were switched to TDF monotherapy for 48 weeks. Patients' demographic data (age, sex, history of hepatitis B virus [HBV] therapy), laboratory testing results (hepatitis B e antigen [HBeAg] status, HBV DNA levels, alanine aminotransferase [ALT] levels, serum creatinine, urinary protein, genotypic assay), clinical symptoms, and liver color ultrasound examinations were collected for evaluation at day 0 (baseline) and the 12th, 24th, 36th, and 48th weeks after initiating treatment. Statistical analyses were carried out using rank sum test or rank correlation.</p><p><b>RESULTS</b>With regard to efficacy, the study found that all patients who switched to TDF monotherapy had undetectable HBV DNA levels after 48 weeks. In addition, patients with lower baseline HBV DNA levels realized earlier virological undetectability (rs = 0.39, P = 0.030). ALT levels were normal in 30 of 33 patients (91%). HBeAg negative conversion occurred in 7 of 25 patients (28%), among whom HBeAg seroconversion (12%) and HBeAg seroclearance (16%) occurred. The time of complete virological response was significantly affected by the number of resistance loci (rs = 0.36, P = 0.040). Concerning safety, the study found that no adverse events were observed during the 48 weeks.</p><p><b>CONCLUSION</b>TDF monotherapy is an effective and safe salvage treatment for CHB patients who are resistant to other NAs.</p>

Adult , Anti-HIV Agents , Therapeutic Uses , DNA, Viral , Genetics , Drug Resistance, Viral , Female , Genotype , Hepatitis B virus , Virulence , Hepatitis B, Chronic , Drug Therapy , Humans , Male , Middle Aged , Prospective Studies , Tenofovir , Therapeutic Uses
Medicina (B.Aires) ; 76(6): 349-354, dic. 2016. tab
Article in Spanish | LILACS | ID: biblio-841608


Se determinó la frecuencia de mutaciones asociadas a resistencia de HIV-1 a antirretrovirales en embarazadas del área metropolitana de Buenos Aires, 2008-2014. Se incluyeron 136 mujeres con carga viral ≥ 500 copias/ml: 77 (56.6%) eran naïve; las otras 59 (43.4%) eran expuestas, ya sea con tratamiento en curso (n: 24) o previo (n: 35). Se realizó análisis de resistencia genotípica basal en plasma de pacientes naïve y con experiencia de tratamiento antirretroviral. Las mutaciones se identificaron según las listas de la Organización Mundial de la Salud y la International Antiviral Society, respectivamente. Se comparó la frecuencia de mutaciones detectadas en los subperíodos 2008-2011 vs. 2012-2014. Un total de 37 (27.2%) mujeres presentaron ≥ 1 mutación asociada a resistencia: 25/94 (26.5%) en 2008-2011 y 12/42 (28.5%) en 2012-2014 (p > 0.05). Entre las naïve, 15 (19.5%) tenían ≥ 1 mutación: 10/49 (20.4%) en el subperíodo 2008-2011 y 5/28 (17.8%) en 2012-2014 (p > 0.05). Las mutaciones encontradas en pacientes naïve estuvieron asociadas a inhibidores no nucleosídicos de la transcriptasa reversa, y, como en estudios anteriores, K103N fue la más frecuente a lo largo de todo el período. Entre las pacientes expuestas, 22/59 (37.3%) presentaron ≥ 1 mutación asociada a resistencia. Este estudio demuestra una alta frecuencia de mutaciones asociadas a resistencia que se mantuvo estable a lo largo del período. Los niveles detectados sugieren una mayor circulación en nuestro medio de cepas de HIV-1 resistentes a antirretrovirales con respecto a los niveles previamente observados en Argentina.

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load ≥ 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina.

Humans , Female , Pregnancy , Adolescent , Adult , Young Adult , Pregnancy Complications, Infectious/drug therapy , HIV Infections/drug therapy , HIV-1/drug effects , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/drug effects , Argentina/epidemiology , Time Factors , HIV Infections/epidemiology , HIV Infections/virology , Age Factors , Gestational Age , HIV-1/genetics , Viral Load , Antiretroviral Therapy, Highly Active/methods , Drug Resistance, Viral/genetics , Genotype , Mutation
Braz. j. infect. dis ; 20(4): 323-329, July-Aug. 2016. tab, graf
Article in English | LILACS | ID: biblio-828125


Abstract Background Development of drug-resistance mutations is the main cause of failure in antiretroviral therapy. In Brazil, there is scarce information on resistance pattern for patients failing antiretroviral therapy. Objectives To define the HIV mutational profile associated with drug resistance in Brazilian patients from 5 large cities, after first, second or further failures to antiretroviral therapy. Methods We reviewed genotyping results of 1520 patients failing therapy in five Brazilian cities. Frequency of mutations, mean number of active drugs, viral susceptibility to each antiretrovirals drug, and regional differences were assessed. Results Mean time of antiretrovirals use was 22.7 ± 41.1 months. Mean pre-genotyping viral load was 4.2 ± 0.8 log (2.1 ± 2.0 after switching antiretrovirals). Mean number of remaining active drugs was 9.4, 9.0, and 7.9 after 1st, 2nd, and 3rd failure, respectively. We detected regional variations in drug susceptibility: while BA and RS showed the highest (∼40%) resistance level to ATV/r, FPV/r and LPV/r, in the remaining cities it was around half of this rate. We detected 90% efavirenz/nevirapine resistance in SP, only 45% in RS, and levels between 25% and 30% in the other cities. Regarding NRTI, we found a similar pattern, with RJ presenting the highest, and CE the lowest susceptibility rates for all NRTI. Zidovudine resistance was detected in only 3% of patients in RJ, against 45–65% in the other cities. RJ and RS showed 3% resistance to tenofovir, while in CE it reached 55%. DRV/r (89–97%) and etravirine (61–85%) were the most active drugs, but again, with a wide variation across cities. Conclusions The resistance mutational profile of Brazilian patients failing antiretroviral therapy is quite variable, depending on the city where patients were tested. This variation likely reflects distinctive choice of antiretrovirals drugs to initiate therapy, adherence to specific drugs, or circulating HIV-1 strains. Overall, etravirine and DRV/r remain as the most active drugs.

Humans , Adult , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Anti-HIV Agents/pharmacology , Drug Resistance, Viral/genetics , Mutation/genetics , Reverse Transcriptase Inhibitors/pharmacology , Viral Load , Antiretroviral Therapy, Highly Active , Genotype
Braz. j. infect. dis ; 20(2): 173-178, Mar.-Apr. 2016. tab
Article in English | LILACS | ID: lil-780801


Abstract Objective There are a lot of disagreements in the studies on hepatitis B virus (HBV) DNA polymerase mutation rate associated with nucleos(t)ide analogues (NAs) in treatment-naive chronic hepatitis B (CHB) patients. This is the first study aimed to investigate the prevalence of spontaneous HBV resistance mutations in Central China. Methods This study included treatment-naive patients with CHB from June 2012 to May 2015 receiving care at the Institute of Liver Disease in Central China. All patients completed a questionnaire covering different aspects, such as family medical history, course of liver disease, medication history, alcohol use, among others. Mutations in HBV DNA polymerase associated with NAs resistance were detected using INNO-LiPA assay. Results 269 patients were infected with HBV genotype B (81.4%), C (17.9%), and both B and C (0.7%). Mutations in HBV DNA polymerase were detected in 24 patients (8.9%) including rtM204I/V (n = 6), rtN236T (n = 5), rtM250V (n = 2), rtL180M (n = 2), rtT184G (n = 1), rtM207I (n = 1), rtS202I (n = 1), rtM204V/I & rtL180M (n = 5), and rtM204I & rtM250V (n = 1). Conclusion Spontaneous HBV resistance mutations in HBV DNA polymerase were found in treatment-naive patients with CHB in Central China. These findings suggest that we should analyze HBV DNA polymerase resistance mutation associated with NAs before giving antiviral therapy such as lamivudine (LAM), adefovir (ADV), and telbivudine (LdT).

Humans , Male , Female , Pregnancy , Adult , Middle Aged , Aged , Young Adult , DNA, Viral/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Drug Resistance, Viral/genetics , DNA-Directed DNA Polymerase/genetics , Mutation/genetics , Antiviral Agents/therapeutic use , China , Hepatitis B virus/drug effects , Prevalence , Prospective Studies , Hepatitis B, Chronic/drug therapy , Genotype
Fortaleza; s.n; 2016. 105 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-971945


A terapia antirretroviraltemporobjetivodiminuiramorbidadeemortalidadedaspessoascomHIV/AIDS,melhorandoaqualidadeeaexpectativadevida. Paradoxalmente, o tratamento irregular pode favorecer a seleçãode variantes resistentes, representandouma das principais causas de falha terapêutica. Tais cepas resistentes podem ser transmitidas a outros indivíduos(resistência transmitida), predispondo àfalha precoce do tratamento inaugural. Ostestesderesistência,principalmenteagenotipagem,permitemadetecçãodemutaçõesdogenomaviral.OobjetivodesteestudofoicaracterizarasmutaçõesderesistênciatransmitidadoHIV-1aosantirretroviraisempacientesrecém-diagnosticadosnoCentro de Testagem e Aconselhamento (CTA) de Fortaleza.Duranteoperíododeoutubrode2013asetembrode2014,foramrecrutadospacientescomtestereagente para oHIVrealizadono CTA. Foram colhidas amostras para realizaçãode quantificação da cargaviral(AbbottRealTime),contagemdelinfócitos CD4+(FACSCaliburBD)egenotipagemHIV-1(TruGeneSiemens).As sequências genéticasforam alinhadas pelo programa MEGA eBioEdit. Ossubtipos do vírus HIV-1 foram determinados e identificados empregando análises no banco de dados do REGA HIV Subtyping Tool. A análisedas mutações de resistência aos antirretrovirais foi realizada utilizando o algoritmo da Universidade de Stanford(HIVdbProgram)e as mutaçõesderesistênciatransmitidaforamidentificadasempregandoaCalibraçãodeResistênciaPopulacional.Foram obtidas amostras biológicas de 108 pacientes, sendo que em 105delas foi possível realizar a reação de sequenciamentoea avaliação quantoàpresençademutaçõesderesistênciaassociadasaos antirretrovirais...

Antiretroviral therapy aims to reduce morbidity and mortality of people with HIV / AIDS, improving the quality and life expectancy. Paradoxically, the irregular treatment may favor the selection of resistant variants, representing a major cause of treatment failure. Such resistant strains can be transmitted to other individuals (transmitted resistance) predisposing to early failure of the inaugural treatment. Resistance tests, particularly genotyping, allow mutation detection in the viral genome. Theaim of this study was to characterize the transmitted resistance HIV-1 mutations to antiretroviral drugs in newly diagnosed patients in the Counseling and Testing Center (CTC) in Fortaleza. During the period October 2013 to September 2014, patients with reagent test for HIV were recruited at CTC. Samples for viral load quantitation (Abbott RealTime), CD4 lymphocytes count (BD FACSCalibur) and HIV-1 genotyping (TRUGENE Siemens), were collected. Genetic sequences were aligned by MEGA and BioEdit program. Thesubtypes of HIV-1 were determined and identified using analysis in REGA HIV subtyping Tool database. The analysis of the antiretroviral resistance mutation was performed using the algorithm of Stanford University (HIVdb Program) and transmitted mutation resistance was identified using the CalibratedPopulationResistance (CPR). Biological samples were obtained from 108 patients, among which in 105 was possible to perform the sequencing reaction and evaluation for the presence of mutations to conferantiretroviral drugresistance...

Humans , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , Mutation , Genetic Variation
Article in English | WPRIM | ID: wpr-46329


BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) exhibits similar antiviral efficacy against treatment-naïve and lamivudine (LAM)-resistant chronic hepatitis B (CHB). However, there are few clinical reports on the antiviral effects of TDF-LAM combination therapy compared to TDF monotherapy in patients with LAM-resistant CHB. METHODS: We investigated the antiviral efficacy of TDF monotherapy vs. TDF-LAM combination therapy in 103 patients with LAM-resistant CHB. RESULTS: The study subjects were treated with TDF alone (n=40) or TDF-LAM combination therapy (n=63) for ≥6 months. The patients had previously been treated with TDF-based rescue therapy for a median of 30.0 months (range, 8-36 months). A virologic response (VR) was achieved in 99 patients (96.1%): 95.0% (38/40) of patients in the TDF monotherapy group and 96.8% (61/63) of patients in the TDF-LAM combination therapy group. The VR rates were not significantly different between the TDF monotherapy and TDF-LAM combination therapy groups (88.9 vs. 87.3% at month 12, and 94.4 vs. 93.7% at month 24, log-rank p=0.652). Univariate and multivariate analyses revealed that none of the pretreatment factors were significantly associated with VR. CONCLUSIONS: TDF monotherapy was as effective as TDF-LAM combination therapy for maintaining viral suppression in the vast majority of patients with LAM-resistant CHB, which suggests that TDF add-on therapy with LAM is unnecessary.

Adult , Aged , Aged, 80 and over , Antiviral Agents/pharmacology , DNA, Viral/blood , Drug Administration Schedule , Drug Resistance, Viral/drug effects , Drug Therapy, Combination , Female , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Kidney Function Tests , Lamivudine/therapeutic use , Liver Function Tests , Male , Middle Aged , Polymerase Chain Reaction , Tenofovir/therapeutic use , Treatment Outcome