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1.
Article in English | WPRIM | ID: wpr-880560

ABSTRACT

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.


Subject(s)
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
2.
Rev. Soc. Bras. Med. Trop ; 51(2): 141-145, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-897064

ABSTRACT

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.


Subject(s)
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
3.
Säo Paulo med. j ; 136(2): 129-135, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-904150

ABSTRACT

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.


Subject(s)
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
4.
Rev. chil. infectol ; 35(5): 509-517, 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-978065

ABSTRACT

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.


Subject(s)
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
5.
Braz. j. infect. dis ; 21(4): 396-401, July-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-888887

ABSTRACT

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.


Subject(s)
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
6.
Mem. Inst. Oswaldo Cruz ; 112(6): 411-418, June 2017. tab, graf
Article in English | LILACS | ID: biblio-841806

ABSTRACT

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.


Subject(s)
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
7.
Braz. j. infect. dis ; 21(3): 219-225, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-839208

ABSTRACT

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.


Subject(s)
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
8.
Medicina (B.Aires) ; 76(6): 349-354, dic. 2016. tab
Article in Spanish | LILACS | ID: biblio-841608

ABSTRACT

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.


Subject(s)
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
9.
Braz. j. infect. dis ; 20(4): 323-329, July-Aug. 2016. tab, graf
Article in English | LILACS | ID: biblio-828125

ABSTRACT

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.


Subject(s)
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
10.
Braz. j. infect. dis ; 20(2): 173-178, Mar.-Apr. 2016. tab
Article in English | LILACS | ID: lil-780801

ABSTRACT

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).


Subject(s)
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
12.
Braz. j. med. biol. res ; 48(9): 777-781, Sept. 2015. ilus
Article in English | LILACS | ID: lil-756404

ABSTRACT

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.


Subject(s)
Humans , Female , Middle Aged , AIDS-Related Opportunistic Infections/genetics , Antiviral Agents/therapeutic use , Cytomegalovirus Retinitis/genetics , Drug Resistance, Viral/genetics , Ganciclovir/therapeutic use , Mutation , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/virology , Cytomegalovirus Retinitis/drug therapy , Disease Progression , DNA, Viral/genetics , Treatment Failure , Viral Load/drug effects
13.
Medicina (B.Aires) ; 75(3): 163-168, June 2015. tab
Article in Spanish | LILACS | ID: lil-757098

ABSTRACT

La vigilancia de resistencia primaria de HIV es fundamental para optimizar el tratamiento antirretroviral (TARV) de la infección. Las mutaciones a vigilar están definidas en una lista de referencia de la Organización Mundial de la Salud (OMS), que no incluye mutaciones para drogas nuevas como la rilpivirina. Revisamos retrospectivamente las historias clínicas de pacientes naive de TARV asistidos en 2011-2013 en un centro privado de derivación de HIV/Sida, pesquisando mutaciones según criterios de OMS y mutaciones específicas de resistencia a rilpivirina. Incluimos 91 pacientes; 71 (78.0%) eran hombres y 46 (50.5%) eran hombres que tenían sexo con hombres; 34 (37.4%) presentaban infección temprana y 60 (65.9%) estaban asintomáticos. Los valores medianos de edad, carga viral y recuento de CD4 fueron 33 años, 62 100 copias/ml y 548 células/μl, respectivamente. Encontramos mutaciones de lista OMS en 11 (12.1%) pacientes, dos de ellos presentaron mutaciones a dos familias de drogas. Siete mutaciones correspondieron a inhibidores no nucleosídicos de la retrotranscriptasa, cuatro a análogos nucleosídicos y dos a inhibidores de la proteasa; las más frecuentes fueron K103N y M41L. No hubo mayor frecuencia de mutaciones en pacientes con infección temprana, ni diferencias según sexo, orientación sexual o recuento de CD4. Tres pacientes (3.3%) presentaron mutaciones asociadas a bajos niveles de resistencia a rilpivirina (E138A, E138G). Los niveles de resistencia primaria observados en este estudio evidencian la importancia de determinar resistencia previo al inicio de TARV en la población asistida en nuestro centro. La prevalencia observada de resistencia primaria a rilpivirina fue baja.


Surveillance of primary drug resistance is critical to optimize antiretroviral therapy (ART) for HIV. Mutations to be monitored are defined in a reference list of the World Health Organization (WHO), which does not include mutations for new drugs, such as rilpivirine. We undertook a retrospective analysis of medical records of ART naive patients treated at a specialized HIV/AIDS center, evaluating the prevalence of WHO mutations and mutations specific for rilpivirine. Ninety-one patients were included during 2011-2013, being male 71 (78.0%), and men who have sex with men 46 (50.5%). The median values for age, viral load, and CD4 counts were 33 years, 62 100 copies/mL, and 548 cells/l, retrospectively; 34 (37.3%) had early infection and 60 (65.9%) were asymptomatic. WHO mutations were found in 11 (12.1%) patients, two of whom presented multiple mutations. Seven mutations corresponded to non-nucleoside reverse transcriptase inhibitors, four to nucleoside analogues, and two to protease inhibitors. The most frequent mutations were K103N and M41L. No differences in mutation frequencies were found when compared by time post-infection, gender, sexual orientation, or CD4 count. Mutations conferring low-level resistance to rilpivirine were found in 3 (3.3%) patients; such mutations were E138A and E138G. The overall moderate primary resistance levels found in this study highlight the value of performing a resistance test before ART initiation in the served population. The observed prevalence of primary resistance to rilpivirine was low.


Subject(s)
Adult , Female , Humans , Male , Anti-HIV Agents , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV-1 , Mutation , HIV-1 , Prevalence , Retrospective Studies , Urban Population , Viral Load
14.
Braz. j. infect. dis ; 19(3): 291-295, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-751886

ABSTRACT

Background: Research has shown that hepatitis B virus (HBV) genotypes are closely linked to the clinical manifestations, treatment, and prognosis of the disease. Objective: To study the association between genotype and drug-resistant HBV mutations in 620 Chinese patients with chronic HBV infection. Methods: HBV DNA levels were determined using real-time quantitative PCR in plasma samples. Microarrays were performed for the simultaneous detection of HBV genotypes (HBV/B, C, and D) and drug-resistance-related hotspot mutations. A portion of the samples analyzed using microarrays was selected randomly and the data were confirmed using direct DNA sequencing. Results: Most samples were genotype C (471/620; 76.0%), followed by genotype B (149/620; 24.0%). Among the 620 patient samples, 17 (2.7%) had nucleotide analogs (NA) resistance-related mutations. Of these, nine and eight patients carried lamivudine (LAM)-/telbivudine (LdT)-resistance mutations (rtL180M, rtM204I/V) and adefovir (ADV)-resistance mutations (rtA181T/V, rtN236T), respectively. No patients had both lamivudine (LAM)- and either ade-fovir (ADV) or entecavir (ETV) resistance mutations. Additionally, out of the 620 patient samples, 64.0% (397/620) were also detected with the precore stop-codon mutation (G1896A) by microarray assay. Conclusion: The results of the current study revealed that the prevalence of nucleotide analogs (NA)-resistance in Chinese hospitalized HBV-positive patients was so low that intensive nucleotide analogs (NA)-resistance testing before nucleotide analog (NA) treatment might not be required. In addition, the present study suggests that chronic HBV patients with genotype C were infected with fitter viruses and had an increased prevalence of nucleotide analogs (NA)-resistance mutations compared to genotype B virus. .


Subject(s)
Adult , Female , Humans , Male , Antiviral Agents/administration & dosage , Drug Resistance, Viral/genetics , Hepatitis B virus/genetics , Hepatitis B, Chronic/virology , Mutation , Asian Continental Ancestry Group , Adenine/administration & dosage , Adenine/analogs & derivatives , DNA, Viral/genetics , Genotype , Guanine/administration & dosage , Guanine/analogs & derivatives , Hepatitis B virus/drug effects , Hepatitis B, Chronic/drug therapy , Lamivudine/administration & dosage , Microarray Analysis , Organophosphonates/administration & dosage , Prognosis , Sequence Analysis, DNA , Thymidine/administration & dosage , Thymidine/analogs & derivatives
15.
Cad. saúde pública ; 31(4): 701-708, 04/2015. tab, graf
Article in Portuguese | LILACS | ID: lil-744862

ABSTRACT

Este estudo teve como objetivo analisar a validade fatorial confirmatória e a fidedignidade de uma escala de medida da autoeficácia para atividade física em idosos. Participaram 118 idosos (78% mulheres), com idade entre 60 a 90 anos. Para avaliar a análise fatorial confirmatória utilizou-se o programa Mplus 6.1. A fidedignidade foi testada pela consistência interna e estabilidade temporal. A escala original foi composta por cinco itens com resposta dicotômica (não/sim), de maneira independente para caminhada e atividade física moderada e vigorosa. O item relacionado à confiança em realizar atividade física quando o mesmo está de férias foi excluído. Foram identificados dois construtos denominados "autoeficácia para caminhada" e "autoeficácia para atividade física moderada e vigorosa", com carga fatorial ≥ 0,50. Houve adequados valores de consistência interna, tanto para caminhada (> 0,70) quanto para atividade física moderada e vigorosa (> 0,80) e de estabilidade temporal para todos os itens. Conclui-se que a escala de autoeficácia para atividade física apresenta validade, consistência interna e fidedignidade adequada para avaliar esse construto em idosos brasileiros.


This study aimed to analyze the confirmatory factor validity and reliability of a self-efficacy scale for physical activity in a sample of 118 elderly (78% women) from 60 to 90 years of age. Mplus 6.1 was used to evaluate the confirmatory factor analysis. Reliability was tested by internal consistency and temporal stability. The original scale consisted of five items with dichotomous answers (yes/no), independently for walking and moderate and vigorous physical activity. The analysis excluded the item related to confidence in performing physical activities when on vacation. Two constructs were identified, called "self-efficacy for walking" and "self-efficacy for moderate and vigorous physical activity", with a factor load ≥ 0.50. Internal consistency was adequate both for walking (> 0.70) and moderate and vigorous physical activity (> 0.80), and temporal stability was adequate for all the items. In conclusion, the self-efficacy scale for physical activity showed adequate validity, reliability, and internal consistency for evaluating this construct in elderly Brazilians.


El presente estudio tuvo como objetivo analizar la validez del análisis factorial confirmatorio y la confianza en la escala de medida de autoeficacia en la actividad física de ancianos. Participaron 118 ancianos (78% mujeres), cuya edad fue de 60 a 90 años. Para evaluar el análisis factorial confirmatorio se utilizó el programa Mplus 6.1. La confianza fue comprobada por la consistencia interna y la estabilidad temporal. La escala original estaba compuesta por cinco ítems con respuesta dicotómica (no/sí), de manera independiente para la actividad física moderada y vigorosa. El ítem relacionado con la confianza para realizar la actividad física cuando el sujeto está de vacaciones fue excluido. Fueron identificados dos constructos denominados "autoeficacia para caminata" y "autoeficacia para actividad física moderada y vigorosa", con carga factorial ≥ 0,50. Hubo adecuados valores de consistencia interna, tanto para la caminata (> 0,70), como para la actividad física moderada y vigorosa (> 0,80), y de estabilidad temporal para todos los ítems. Se concluye que la escala de autoeficacia para actividad física presenta validez, consistencia interna y confianza adecuada para evaluar ese constructo en ancianos brasileños.


Subject(s)
Humans , Anti-HIV Agents/pharmacology , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV-1 , Africa/epidemiology , Anti-HIV Agents/economics , Cost-Benefit Analysis , Genotype , HIV Infections/epidemiology , HIV Infections/virology , HIV-1 , World Health Organization
16.
São Paulo; s.n; 2015. [115] p. tab, graf.
Thesis in Portuguese | LILACS, SES-SP, SESSP-CTDPROD, SES-SP, SESSP-ACVSES, SESSP-TESESESSP, SES-SP | ID: biblio-1083389

ABSTRACT

Crianças e adolescentes em uso de terapia antirretroviral de alta atividade(HAART) caracterizam um grupo especialmente vulnerável no contexto daepidemia pelo HIV-1...O presente estudo tem como objetivo avaliar os genes da protease e transcriptase reversa em crianças e adolescentes vivendo comHIV/aids. Foi realizada uma análise retrospectiva... Entre os pacientes expostos às três classes com mais de uma entrada (n=27), não houve aumento de mutação para essas classes em relação a genotipagemimediatamente anterior. A alta proporção de resistência aos IP em subtipos Fobservada nesse estudo sugere que o uso dos IP deve ser avaliado levandoem consideração o possível impacto na resposta terapêutica. Os dadosdesse estudo demonstram uma taxa intermediária de resistência transmitidae uma elevada proporção de casos com resistência entre os pacientes emfalha, embasa a noção de que esta população representa um segmento derisco para a evolução da doença.


Children and adolescents on highly active antiretroviral therapy (HAART)represents a vulnerable group in the context of the HIV-1 epidemic, due tobiological issues and different socio-behavioral aspects such as those relatedto adherence to HAART... A retrospective analysis was made, in samples collected from naïve patients and patients exposed to antiretrovirals(ART) with virological failure...Among patients exposed to the three ART classes with more than one genotyping test (n=27), mutations prevalence seemed to not increase when we compared with the previous genotyping test, however most of patients samples showed resistance to the main ART available for use. The high proportion of resistance to IP among subtype F suggests thatin these cases, the IP administration should be evaluated considering apossible impact on therapeutic response. Our results showed an intermediaterate of transmitted resistance e a high proportion of resistance amongpatients with virological failure, supporting the fact that this populationrepresents more risk to disease progression.


Subject(s)
Humans , Child , Adolescent , HIV-1 , Adolescent , Child , Drug Resistance, Viral/genetics , Mutation , Antiretroviral Therapy, Highly Active/trends
17.
Article in English | WPRIM | ID: wpr-106137

ABSTRACT

BACKGROUND/AIMS: The efficacy of tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B (CHB) patients following prior treatment failure with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in Asian populations. In this study we investigated the efficacy and safety of TDF rescue therapy in CHB patients after multiple NA treatment failure. METHODS: The study retrospectively analyzed 52 CHB patients who experienced failure with two or more NAs and who were switched to regimens containing TDF. The efficacy and safety assessments included hepatitis B virus (HBV) DNA undetectability, hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT) normalization and changes in serum creatinine and phosphorus levels. RESULTS: The mean HBV DNA level at baseline was 5.4 +/- 1.76 log10 IU/mL. At a median duration of 34.5 months of TDF treatment, the cumulative probabilities of achieving complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12, 24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48 patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly associated with increased CVR rates (p < 0.001). However, CVR rates did not differ between TDF monotherapy or combination therapy with other NAs, and were not affected by mutations associated with resistance to NAs. No significant adverse events were observed. CONCLUSIONS: TDF is an efficient and safe rescue therapy for CHB patients after treatment failure with multiple NAs.


Subject(s)
Adenine/adverse effects , Adult , Aged , Alanine Transaminase/blood , Antiviral Agents/adverse effects , Biomarkers/blood , Creatinine/blood , DNA, Viral/blood , Drug Resistance, Viral/genetics , Drug Substitution , Female , Genotype , Hepatitis B e Antigens/blood , Hepatitis B virus/drug effects , Hepatitis B, Chronic/blood , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Phosphorous Acids/adverse effects , Phosphorus/blood , Retrospective Studies , Time Factors , Treatment Failure , Viral Load , Young Adult
18.
Article in English | WPRIM | ID: wpr-128619

ABSTRACT

BACKGROUND/AIMS: To determine the efficacies of entecavir (ETV) in nucleos(t)ide analogue (NA)-naive chronic hepatitis B (CHB) patients and in those with prior lamivudine (LAM) use who did not develop resistance. METHODS: We retrospectively enrolled 337 patients with CHB who were treated with ETV (0.5 mg daily) for at least 30 months. The study included 270 (80.1%) NA-naive patients and 67 (19.9%) LAM-use patients. Ten of the LAM-use patients were refractory to LAM therapy without developing resistance. RESULTS: Genotypic resistance to ETV developed more frequently in the LAM-use group (13.1%) than in the NA-naive group (2.6%) at 60 months (P=0.009). In subgroup analysis, after excluding the 10 patients who were refractory to LAM therapy, the cumulative probability of ETV resistance did not differ significantly between the two groups (P=0.149). Prior LAM refractoriness and a higher hepatitis B virus DNA level at month 12 were independent predictive factors for the development of ETV resistance. CONCLUSIONS: ETV resistance developed more frequently in LAM-use patients with CHB. However, prior LAM use without refractoriness did not affect the development of ETV resistance. The serum hepatitis B virus DNA level at month 12 was a major predictor for the development of ETV resistance.


Subject(s)
Adolescent , Adult , Aged , Antiviral Agents/therapeutic use , DNA, Viral/blood , Drug Resistance, Viral/genetics , Female , Genotype , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Lamivudine/therapeutic use , Male , Middle Aged , Remission Induction , Retrospective Studies , Young Adult
19.
Gut and Liver ; : 103-108, 2015.
Article in English | WPRIM | ID: wpr-61568

ABSTRACT

BACKGROUND/AIMS: To investigate the association between the baseline profiles and dynamics of hepatitis B virus (HBV) DNA polymerase gene mutations and the long-term virological response of lamivudine (LAM)-adefovir (ADV) combination therapy in patients with LAM-resistant chronic hepatitis B. METHODS: Seventy-five patients who received LAM-ADV combination therapy for more than 12 months were analyzed. Restriction fragment mass polymorphism assays were used to detect and monitor the dynamics of LAM- and ADV-resistant mutations. RESULTS: The median duration of LAM-ADV combination therapy was 26 months (range, 12 to 58 months). The baseline mutation profiles, rtM204I (p=0.992), rtM204I/V (p=0.177), and rtL180M (p=0.051), were not correlated with the cumulative virological response, and the baseline HBV DNA level (p=0.032) was the only independent predictive factor for cumulative virological response. Tests for LAM- and ADV-resistant mutations were performed in 12 suboptimal responders in weeks 48 and 96. The population of rtM204 mutants persisted or increased in 8 of 12 patients, and rtA181T mutants newly emerged as a minor population in four patients until 96 weeks. Nevertheless, the viral loads progressively decreased during rescue therapy, and these dynamics did not correlate with virological response. CONCLUSIONS: The baseline profile and dynamics of LAM-resistant mutations during LAM-ADV combination therapy are not associated with a virological response.


Subject(s)
Adenine/administration & dosage , Adult , Aged , Aged, 80 and over , Antiviral Agents/administration & dosage , DNA-Directed DNA Polymerase/genetics , Drug Resistance, Viral/genetics , Drug Therapy, Combination , Female , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Lamivudine/administration & dosage , Male , Middle Aged , Organophosphonates/administration & dosage , Treatment Outcome , Viral Load/drug effects , Young Adult
20.
Braz. j. infect. dis ; 18(1): 1-7, Jan-Feb/2014. tab
Article in English | LILACS | ID: lil-703060

ABSTRACT

Background: Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil. Methods: Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load <50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression. Results: Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI = 69.7–86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI = 103.4–159.6). In multiple logistic regression analysis, higher baseline viral load (RR = 1.04 per 10,000 copies/mL increase; 95% CI = 1.01–1.09) and higher number of darunavir resistance-associated mutations (RR = 1.23 per each; 95% CI = 0.95–1.48) ...


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Salvage Therapy , Sulfonamides/therapeutic use , Brazil , Drug Resistance, Viral/genetics , Genotype , HIV Infections/immunology , HIV Infections/virology , HIV-1 , Retrospective Studies , Viral Load
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