Resistencia transmitida de VIH-1 en pacientes sin exposición a tratamiento antirretroviral: Guatemala / Transmitted HIV-1 resistance in patients without exposure to antiretroviral treatment: Guatemala / Resistência transmitida ao HIV-1 em pacientes sem exposição ao tratamento antirretroviral: Guatemala

El objetivo del estudio fue describir los niveles de resistencia transmitida de VIH-1 en adultos atendidos en Unidades de Atención Integral de Guatemala. El estudio incluyó registros de 185 pacientes adultos VIH-1 positivo, de reciente diagnóstico sin antecedente de uso de TAR, de noviembre del 2019 a noviembre del 2020. El análisis se realizó en el software DeepChek® v2.0, para la clasificación de la resistencia se siguió el algoritmo de Stanford HIVdb (v9.4 - 07/12/2022). Se encontró 18.4% (IC 95% 13.1 - 24.7%) de resistencia general a alguna familia de ARVs. Se evidenció 15.1% (IC 95% 10.3 - 21.1%) de resistencia individual a la familia de INNTR afectando principalmente a NVP y EFV; 2.2% (IC 95% 0.6 - 5.4%) de resistencia a INTR, mayormente a FTC/3TC; y 2.7% (IC 95% 0.9 - 6.2%) de resistencia intermedia y baja los IP NFV y LPV/r. Tres casos presentaron resistencia múltiple a los INTR + INNTR. Las mutaciones más frecuentemente encontradas fueron K103N (41.2%), M184V/I (8.8%) y M46I (5.9%). La elevada resistencia transmitida del VIH-1 en pacientes atendidos en distintas Unidades de Atención Integral del VIH, demuestra la importancia de analizar periódicamente la tendencia de la resistencia en personas que no han estado expuestas a ARVs, lo cual a su vez es un marcador indirecto de presencia de resistencia adquirida en el país, datos que evidencian la necesidad de acciones e intervenciones prontas y efectivas dado su impacto en la salud pública.

The objective of this study was to describe the levels of transmitted HIV-1 resistance in patients with a recent HIV diagnosis before starting ART, treated in Comprehensive Care Units in Guatemala during the years 2019 and 2020. The study included records of 185 HIV-positive adult patients, recently diagnosed with HIV without a history of ART use. The analysis was carried out in the DeepChek® v2.0 software, the Stanford HIVdb algorithm (v9.4 - 07/12/2022) was followed to classify resistance. 18.4% (95% CI 13.1 - 24.7%) of general resistance to some family of ARVs was found. There was evidence of 15.1% (95% CI 10.3 - 21.1%) of individual resistance to the NNRTI family, mainly affecting NVP and EFV; 2.2% (95% CI 0.6 - 5.4%) resistance to INTR, mostly to FTC/3TC; and 2.7% (95% CI 0.9 - 6.2%) of intermediate and low resistance IP NFV and LPV/r. Three cases presented multiple resistance to NRTIs + NNRTIs. The most frequently found mutations were K103N (41.2%), M184V/I (8.8%) and M46I (5.9%). The high transmitted resistance of HIV-1 in patients treated in different Comprehensive HIV Care Units demonstrates the importance of periodically analyzing the trend of resistance in people who have not been exposed to ARVs, which in turn is an indirect marker. of the presence of acquired resistance in the country, data that demonstrate the need for prompt and effective actions and interventions given its impact on public health.

O objetivo deste estudo foi descrever os níveis de resistência transmitida ao HIV-1 em adultos tratados em Unidades de Cuidados Integrais na Guatemala. O estudo incluiu prontuários de 185 pacientes adultos HIV-1 positivos, recentemente diagnosticados sem histórico de uso de TARV, no período de novembro de 2019 a novembro de 2020. A análise foi realizada no software DeepChek® v2.0, para classificação da resistência, O algoritmo Stanford HIVdb (v9.4 - 07/12/2022) foi seguido. Foi encontrada 18.4% (IC 95% 13.1 - 24.7%) de resistência geral a alguma família de ARVs. Houve evidência de 15.1% (IC 95% 10.3 - 21.1%) de resistência individual à família de NNRTI, afetando principalmente NVP e EFV; 2.2% (IC 95% 0.6 - 5.4%) resistência ao INTR, principalmente ao FTC/3TC; e 2.7% (IC 95% 0.9 - 6.2%) de resistência intermediária e baixa ao IP NFV e LPV/r. Três casos apresentaram resistência múltipla a NRTIs + NNRTIs. As mutações mais frequentemente encontradas foram K103N (41.2%), M184V/I (8.8%) e M46I (5.9%). A elevada resistência transmitida do HIV-1 em pacientes atendidos em diferentes Unidades de Cuidados Integrados ao HIV demonstra a importância de analisar periodicamente a tendência de resistência em pessoas que não foram expostas aos ARVs, o que por sua vez é um marcador indireto da presença de ARVs adquiridos. resistência no país, dados que demonstram a necessidade de ações e intervenções rápidas e eficazes dado o seu impacto na saúde pública.

Resistencia genotípica del HIV a los antirretrovirales en niños de Argentina entre 2006 y 2021 / HIV genotypic drug resistance to antiretrovirals in children in Argentina between 2006 and 2021

Introducción: La resistencia del HIV a los antirretrovirales (ARVs) es una de las principales causas de fallo terapéutico en niños, niñas y adolescentes que conviven con el virus. Desde el año 2006, el Laboratorio de Biología Celular y Retrovirus del Hospital Garrahan realiza el estudio genotípico de resistencia (ER) del HIV-1 a los ARVs a fin de identificar mutaciones que disminuyen la susceptibilidad del virus a los fármacos que componen el tratamiento ARV. Objetivos: El objetivo del trabajo fue estudiar el tipo y frecuencia de resistencia del HIV a los ARVs, a través de un análisis de 371 ER realizados entre los años 2006 y 2021 en niños, niñas y adolescentes con HIV-1 adquirido por transmisión vertical y con solicitud médica de ER por presentar fallo terapéutico. Resultados: Entre los años 2006 y 2013 la proporción de casos con resistencia a al menos una clase de fármaco ARV fue mayor al 90%, sugiriendo una asociación directa entre el fallo virológico y la disminución en la susceptibilidad del HIV-1 a uno o más componentes del TARV. A partir del año 2012, se observa una disminución progresiva del nivel de resistencia de HIV-1, llegando al 50% en 2021 (p<0.0001). La frecuencia de mutaciones de resistencia fue diferente para cada una de las clases de ARVs. Mientras que la resistencia a INNTR no sufrió cambios significativos a lo largo del período de estudio, oscilando entre 27% y 75%. La proporción de mutaciones a IPs en pacientes con fallo virológico disminuyó de 87% en 2006 a 17% en 2021 y para los INTR, disminuyó de 79% en 2006 a 45% en 2021. Conclusión: El nivel de resistencia a los ARVs ha disminuido de manera sustancial a lo largo de los últimos 16 años, probablemente por el uso de nuevos fármacos ARV con alta potencia que posibilitaron la intensificación de los tratamientos ARV y la implementación de criterios de fallo terapéutico más estrictos tanto a nivel clínico como virológico (AU)

Introduction: HIV resistance to antiretroviral (ARV) drugs is one of the main causes of therapeutic failure in children and adolescents living with the virus. Since 2006, the Cell Biology and Retrovirus Laboratory of the Garrahan Hospital has been performing the genotypic study of HIV-1 resistance to ARV drugs in order to identify mutations that reduce the susceptibility of the virus to the drugs that constitute ARV treatment. Objectives: The aim of this study was to assess the type and frequency of HIV resistance to ARV drugs through an analysis of 371 genotype studies performed between 2006 and 2021 in children and adolescents with HIV-1 acquired through motherto-child transmission and with medical request for genotype study due to therapeutic failure. Results: Between 2006 and 2013, the proportion of cases with resistance to at least one ARV drug class was greater than 90%, suggesting a direct association between virologic failure and decreased susceptibility of HIV-1 to one or more components of ART. From 2012 onwards, a progressive decrease in the level of HIV-1 resistance was observed, reaching 50% in 2021 (p<0.0001). The frequency of resistant mutations was different for each of the ARV classes, while resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) did not change significantly over the study period, ranging from 27% to 75%. The proportion of drug-resistant mutations to protease inhibitors (PI) in patients with virologic failure decreased from 87% in 2006 to 17% in 2021 and for NNRTIs from 79% in 2006 to 45% in 2021. Conclusion: The level of resistance to ARV drugs has decreased substantially over the last 16 years, probably due to the use of new ARV drugs with high potency that allowed the intensification of ARV treatments and the implementation of stricter criteria for therapeutic failure both clinically and virologically (AU)

Genetic Subtypes and Pretreatment Drug Resistance in the Newly Reported Human Immunodeficiency Virus-Infected Men Aged≥50 Years Old in Guangxi / 中国医学科学院学报

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients / 中华预防医学杂志

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

Analysis of HIV-1 genetic subtype and pretreatment drug resistance among men who have sex with men infected with HIV-1 from 19 cities of 6 provinces in China / 中华流行病学杂志

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ2=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ2=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.

Chinese Medicine in Fighting against Covid-19: Role and Inspiration / 中国结合医学杂志

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.

HIV-1 genetic diversity and drug resistance mutations in the northern Brazilian region

ABSTRACT Brazil is a huge continental country with striking geographic differences which are well illustrated in the HIV/AIDS epidemic. Contrasting with the significant decline in the national AIDS detection rate in the last decade, a linear growth has been reported in the Northern region. Despite its public health and epidemiologic importance, there is scarce HIV-1 molecular data from Northern Brazil. This scoping review summarizes recent epidemiologic data with special emphasis on HIV-1 genetic diversity and antiretroviral drug resistance mutations in patients from the seven Northern states of Brazil. Studies from the Northern Brazil on different HIV-1 genomic regions, mostly pol (protease/reverse transcriptase) sequences of naïve/antiretroviral treated adults/children were retrieved from PubMed/MEDLINE electronic database. These studies indicate a consistent molecular profile largely dominated by HIV-1 subtype B with minor contribution of subtypes F1 and C and infrequent detection of other subtypes (A1, D, K), recombinants (BF1, BC), circulating recombinant forms (CRF) as the new CRF90_BF1 and CRF02_AG-like, CRF28-29_BF-like, CRF31_BC-like, and a potential new CRF_BF1. This pattern indicates a founder effect of subtype B and the introduction of non-B-subtypes and recombinants probably generated in the Southern/Southeastern regions. In naïve populations transmitted drug resistance (TDR) can impact the outcome of first-line antiretroviral treatment and prophylactic/preventive regimens. In the Northern region TDR rates are moderate while patients failing highly active antiretroviral therapy (HAART) showed high prevalence of acquired drug resistance mutations. The limited HIV-1 molecular data from Northern Brazil reflects the great challenges to generate comprehensive scientific data in isolated, underprivileged areas. It also highlights the need to invest in local capacity building which supported by adequate infrastructure and funding can promote robust research activities to help reduce the scientific asymmetries in the Northern region. Currently the impacts of the overwhelming COVID-19 pandemic on the expanding HIV/AIDS epidemic in Northern Brazil deserves to be closely monitored.

Prevalencia de resistencia transmitida a drogas antirretrovirales en pacientes con infección por VIH en Chile (2014-2018)

Background: Transmitted drug resistance (TDR) occurs in patients with HIV infection who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. Aim: To determine the prevalence of TDR and characterize HIV reverse transcriptase and protease mutation patterns. Material and Methods: HIV infected antiretroviral treatment-naive patients treated in three centers between 2014 and 2018 were studied. A genotyping study was carried out. The HIVdb Program (Stanford University) and the World Health Organization (WHO) TDR surveillance mutation list were used to register resistance-associated mutations. Results: We enrolled 220 patients aged a median of 29 (interquartile range (IQR) 24-34) years, 99% men. Median CD4 count was 365 cells/μL (IQR 250-499 cells/μL) and median viral load was 39.150 copies/mL (IQR 9,270 −120,000). The overall prevalence of RTD was 10.45% (95% CI 6.7-15.2, N = 23/220). The higher frequency of TDR was against non-nucleoside reverse transcriptase inhibitors, reaching 9.0% (95% CI 5.6-13.6), followed by nucleoside reverse transcriptase inhibitors reaching 1.8% (95% CI 0.49-4.5) and protease inhibitors reaching 0.45% (95% CI 0.01-2.5). The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. Conclusions: These results should prompt a change in recommendations for starting antiretoviral therapy, especially in first-line regimens that include non-nucleoside reverse transcriptase inhibitors.

HCMV UL97 phosphotransferase gene mutations may be associated with antiviral resistance in immunocompromised patients in Belém, PA, Northern Brazil

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.

HIV-1 genetic diversity and resistance to antiretroviral drugs among pregnant women in Ribeirão Preto (SP), Brazil. Cross-sectional study

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.

Prevalencia de resistencia a los anti-retrovirales en niños y adolescentes uruguayos infectados con el virus de la inmunodeficiencia humana en el Centro de Referencia VIH-SIDA. Centro Hospitalario Pereira Rossell. Montevideo-Uruguay / Prevalence of antiretroviral resistance in Uruguayan children and adolescents infected with the human immunodeficiency virus in the Reference Center HIV-AIDS. Centro Hospitalario Pereira Rossell, Montevideo, Uruguay

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.

Transmitted drug resistance in patients with acute/recent HIV infection in Brazil

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.

Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy

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.

An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil

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.

Resistencia de HIV-1 a drogas antirretrovirales en gestantes del área metropolitana de Buenos Aires / HIV-1 resistance to antiretroviral drugs in pregnant women from Buenos Aires metropolitan area

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.

Extensive variation in drug-resistance mutational profile of Brazilian patients failing antiretroviral therapy in five large Brazilian cities

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.

Prevalence of mutations in HBV DNA polymerase gene associated with nucleos(t)ide resistance in treatment-naive patients with Chronic Hepatitis B in Central China

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).

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

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.

Microarray-based genotyping and detection of drug-resistant HBV mutations from 620 Chinese patients with chronic HBV infection

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. .