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1.
Chinese Journal of Epidemiology ; (12): 692-695, 2022.
Article in Chinese | WPRIM | ID: wpr-935445

ABSTRACT

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /106 PBMCs) before ART, and droped rapidly (<400 copies /106 PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/106 PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.


Subject(s)
China/epidemiology , DNA/therapeutic use , HIV Infections/drug therapy , HIV Seropositivity , HIV-1/genetics , Humans , Male , Viral Load
2.
Chinese Journal of Epidemiology ; (12): 523-527, 2022.
Article in Chinese | WPRIM | ID: wpr-935421

ABSTRACT

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.


Subject(s)
China/epidemiology , Cities , Drug Resistance , Drug Resistance, Viral/genetics , Female , Genotype , HIV Infections/epidemiology , HIV Seropositivity/drug therapy , HIV-1/genetics , Homosexuality, Male , Humans , Male , Phylogeny , Reverse Transcriptase Inhibitors/therapeutic use , Sexual and Gender Minorities
3.
Braz. j. infect. dis ; 25(1): 101036, jan., 2021. tab
Article in English | LILACS | ID: biblio-1249300

ABSTRACT

ABSTRACT Homeless people are at high risk for sexually transmitted infections (STIs), such as human immunodeficiency virus (HIV) infection and syphilis. We investigated the epidemiology of HIV-1 infection and syphilis among homeless individuals in a large city in Central-Western Brazil. In this cross-sectional study, we interviewed and tested 355 individuals from September 2014 to August 2015. Rapid test samples positive for syphilis were retested using the Venereal Disease Research Laboratory (VDRL) test. Blood samples from HIV-infected participants were collected for POL sequencing using HIV-1 RNA extracted from plasma, reverse transcription, and nested polymerase chain reaction. Anti-HIV-1-positive samples were subtyped by sequencing the nucleotides of HIV-1 protease and part of the HIV-1 reverse transcriptase genes. Transmitted and acquired drug resistance mutations and susceptibility to antiretroviral drugs were also analyzed. Anti-HIV was positive in 14 patients (3.9%; 95% confidence interval [CI]: 2.3-6.4). HIV-1 RNA was detected in 8 of the 14 samples. Two of the eight (25%) isolates showed HIV-1 drug resistance mutations. Furthermore, 78 (22%; 95% CI: 17.9-26.5) and 29 (8.2%; 95% CI: 5.6-11.4) homeless individuals tested positive for syphilis using the rapid test and VDRL test, respectively. Two individuals were anti-HIV-1 and VDRL test positive. Daily alcohol use (adjusted odds ratio [AOR]: 3.2, 95% CI: 1.0-10.4), sex with people living with HIV (PLWH) infection (AOR: 6.8, 95% CI: 1.9-25.0), and sex with people of the same sex (AOR: 5.4, 95% CI: 1.7-17.5) were predictors of HIV infection. Age ≤35 years (AOR: 3.8, 95% CI: 1.4-10.8), previous syphilis testing (AOR: 3.5, 95% CI: 1.4-8.4), history of genital lesions (AOR: 4.9, 95% CI: 1.3-19.1), and crack use in the last six months (AOR: 3.1, 95% CI: 1.3-7.6) were predictors of syphilis. Our findings highlight the importance of STI prevention and control strategies among the homeless.


Subject(s)
Syphilis/epidemiology , HIV Infections/epidemiology , HIV-1/genetics , Genetic Variation , Brazil/epidemiology , Drug Resistance , Prevalence , Cross-Sectional Studies , Risk Factors , Mutation
4.
Braz. j. infect. dis ; 25(5): 101619, 2021.
Article in English | LILACS | ID: biblio-1350324

ABSTRACT

The interaction of HIV-1, human leukocyte antigen (HLA), and elite controllers (EC) compose a still intricate triad. Elite controllers maintain a very low viral load and a normal CD4 count, even without antiretrovirals. There is a lot of diversity in HIV subtypes and HLA alleles. The most common subtype in each country varies depending on its localization and epidemiological history. As we know EC appears to maintain an effective CD8 response against HIV. In this phenomenon, some alleles of HLAs are associated with a slow progression of HIV infection, others with a rapid progression. This relationship also depends on the virus subtype. Epitopes of Gag protein-restricted by HLA-B*57 generated a considerable immune response in EC. However, some mutations allow HIV to escape the CD8 response, while others do not. HLA protective alleles, like HLA-B*27, HLA-B*57 and HLA-B*58:01, that are common in Caucasians infected with HIV-1 Clade B, do not show the same protection in sub-Saharan Africans infected by HIV-1 Clade C. Endogenous pathway of antigen processing and presentation is used to present intracellular synthesized cellular peptides as well as viral protein fragments via the MHC class I molecule to the cytotoxic T-lymphocytes (CTLs). Some epitopes are immunodominant, which means that they drive the immune reaction to some virus. Mutation on an anchor residue of epitope necessary for binding on MHC class I is used by HIV to escape the immune system. Mutations inside or flanking an epitope may lead to T cell lack of recognition and CTL escape. Studying how immunodominance at epitopes drives the EC in a geographically dependent way with genetics and immunological elements orchestrating it may help future research on vaccines or immunotherapy for HIV. 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license


Subject(s)
HIV Infections/genetics , HIV Infections/drug therapy , HIV-1/genetics , T-Lymphocytes, Cytotoxic , CD8-Positive T-Lymphocytes , Viral Load , gag Gene Products, Human Immunodeficiency Virus
5.
Braz. j. infect. dis ; 25(3): 101596, 2021. tab
Article in English | LILACS | ID: biblio-1339422

ABSTRACT

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.


Subject(s)
Humans , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1/genetics , COVID-19 , Phylogeny , Brazil , Drug Resistance , Sequence Analysis, DNA , Drug Resistance, Viral/genetics , Pandemics , SARS-CoV-2 , Genotype , Mutation
6.
Mem. Inst. Oswaldo Cruz ; 115: e190461, 2020. graf
Article in English | LILACS | ID: biblio-1091243

ABSTRACT

Phylogenetic analyses were crucial to elucidate the origin and spread of the pandemic human immunodeficiency virus type 1 (HIV-1) group M virus, both during the pre-epidemic period of cryptic dissemination in human populations as well as during the epidemic phase of spread. The use of phylogenetics and phylodynamics approaches has provided important insights to track the founder events that resulted in the spread of HIV-1 strains across vast geographic areas, specific countries and within geographically restricted communities. In the recent years, the use of phylogenetic analysis combined with the huge availability of HIV sequences has become an increasingly important approach to reconstruct HIV transmission networks and understand transmission dynamics in concentrated and generalised epidemics. Significant efforts to obtain viral sequences from newly HIV-infected individuals could certainly contribute to detect rapidly expanding HIV-1 lineages, identify key populations at high-risk and understand what public health interventions should be prioritised in different scenarios.


Subject(s)
Humans , Animals , HIV Infections/transmission , HIV-1/genetics , Phylogeography , Phylogeny , Cluster Analysis , HIV Infections/virology , Gorilla gorilla
7.
Rev. Soc. Bras. Med. Trop ; 52: e20180432, 2019. tab
Article in English | LILACS | ID: biblio-1003137

ABSTRACT

Abstract By decreasing the pre-seroconversion window period, nucleic acid testing (NAT) has improved the safety of blood products and reduced the risk of transfusion-transmitted infections. Between 2011 and 2017, NAT determinations for approximately 898,202 donations were performed at Fundação Pró-Sangue/Hemocentro de São Paulo (FPS-HSP). Three seronegative HIV-viremic donations were detected. The NAT yield rate per million donations was 3.34 for HIV, and the acute HIV-1 infections detected are described, followed by a brief review of the situation in Brazil.


Subject(s)
Humans , Male , Adult , Blood Donors , DNA, Viral/blood , RNA, Viral/blood , HIV Infections/diagnosis , HIV-1/genetics , Nucleic Acid Amplification Techniques
8.
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
9.
Mem. Inst. Oswaldo Cruz ; 113(8): e170483, 2018. graf
Article in English | LILACS | ID: biblio-1040601

ABSTRACT

In Brazil, detection of the HIV-1 sub-subtype F1 has decreased with a simultaneous increase in detection of the recombinant FB and FC forms. In previous HIV-1 env molecular epidemiology studies in Rio de Janeiro, 11.4% of the detected sequences were of the F1 sub-subtype. With the goal of re-estimating the prevalence of the HIV-1 F1 sub-subtype, we performed extended analyses of these samples by examining five genomic regions, resulting in 3.3% being confirmed as F1. Moreover, genomic analysis of 11 of the 21 samples identified as F1 confirmed that nine were F1 and two were BF1. Considering the number of samples assayed, the prevalence of F1 was quite low, which supports the use of different genomic regions for the assessment of HIV-1 classification in countries where several subtypes and recombinant forms co-circulate.


Subject(s)
Humans , HIV Infections/epidemiology , HIV Infections/virology , HIV-1/genetics , Genome, Viral/genetics , Phylogeny , Brazil/epidemiology , DNA Mutational Analysis , Base Sequence , Molecular Epidemiology , Genotype
10.
Rev. chil. infectol ; 35(5): 601-605, 2018. tab
Article in Spanish | LILACS | ID: biblio-978076

ABSTRACT

Resumen La detección de virus en el líquido cefalorraquídeo (LCR) en pacientes infectados por VIH con carga viral (CV) indetectable en el plasma se ha denominado escape viral. Estas fugas pueden ser asintomáticas o asociadas con enfermedad neurológica. La discordancia de la carga viral de VIH entre plasma y LCR evidenciaría la presencia de distintos compartimentos del virus, con la posibilidad de identificar quasiespecies con mutaciones específicas que confieran resistencia a la TARV. Presentamos el caso clínico de un paciente con infección por VIH en etapa SIDA y una tuberculosis diseminada que presentó un cuadro neurológico manifestado por cefalea y un síndrome convulsivo, en que se encontró una discordancia entre la CV para VIH en plasma y LCR. El estudio genotípico del virus obtenido del LCR identificó nuevas mutaciones que determinaron un cambio de la TARV, con evolución posterior satisfactoria.


Detection of virus in cerebrospinal fluid (CSF) in HIV-infected patients with HIV viral load (VL) undetectable in plasma has been termed viral escape. These leaks may be asymptomatic from a neurological point of view, similar to plasma blips, or associated with neurological disease, with discordant VL between plasma and CSF, and may be evidence of a compartmentalization of the virus and the possibility of identifying quasispecies with mutations that confer resistance to ART. We present the case of a man with AIDS and disseminated tuberculosis who presented neurological symptomatology evidenced by headache and convulsive syndrome, who presented a discordance between plasma and CSF HIV VL; the genotypic test of the virus, obtained by lumbar puncture, identified new mutations that determined a change in ART with subsequent satisfactory evolution.


Subject(s)
Humans , Male , Adult , Tuberculosis, Meningeal/diagnosis , HIV Infections/cerebrospinal fluid , Cerebrospinal Fluid/virology , HIV-1/genetics , Viral Load , Tuberculosis, Meningeal/complications , RNA, Viral/cerebrospinal fluid , HIV Infections/complications , Mutation/genetics
11.
Rev. chil. infectol ; 35(1): 49-61, 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-899777

ABSTRACT

Resumen Introducción Las recomendaciones internacionales de tratamiento anti-retroviral incluyen pruebas de resistencia para orientar el régimen de tratamiento en cada paciente, lo que no está disponible de forma estable en Ecuador. Objetivo Describir las mutaciones que confieren resistencia a anti-retrovirales en una población de pacientes ecuatorianos. Metodología A partir de muestras de plasma de 101 pacientes con VIH-1 con fallo a la terapia anti-retroviral, 15 niños y 86 adultos, se realizó pirosecuenciación con el GS Junior (Roche) y se analizaron las secuencias con el programa DeepChek. Resultados Las mutaciones más frecuentes fueron M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M, V82T/F/A/S/L y L90M en adultos, y F77L, K103N/S, M46L/I, V82T/F/A/S/L y L90M en niños. Se encontró una elevada resistencia a los inhibidores de la transcriptasa reversa (TR) no análogos de nucleósidos en poblaciones minoritarias virales de adultos y niños (34,9 y 70%, respectivamente), en los niños, tanto las poblaciones virales mayoritarias como minoritarias, fueron resistente a inhibidores de proteasa (> 45%). Los pacientes que tuvieron un mayor número de esquemas terapéuticos presentaron mayores niveles de resistencia a los anti-retrovirales. La mayoría de las muestras fueron del subtipo B en la región de la TR y proteasa, y CRF25_cpx en integrasa. Conclusiones Se muestran las mutaciones y la resistencia a antiretrovirales en una población de pacientes ecuatorianos con infección por VIH-1, que permitirán realizar un llamado de alerta a las autoridades de salud sobre la necesidad de realizar estudios de resistencia.


Background The international recommendations of antiretroviral treatment include resistance tests to guide the treatment regimen in each patient, which is not available on a regular basis in Ecuador. Aim To describe mutations that confer resistance to antiretrovirals in a population of Ecuadorian patients. Methods Plasma samples from 101 HIV-1 patients with failure to antiretroviral therapy, divided into 15 children and 86 adults, were studied with the GS Junior (Roche) and the sequences were analyzed with the DeepChek program. Results The most frequent mutations were M184V/I, K101E/P/H, K103N/S, D30N, M46L/I, I54L/M, V82T/F/A/S/L and L90M in adults and F77L, K103N/S, M46L/I, V82T/F/A/S/L and L90M in children. High resistance to non-nucleoside reverse transcriptase (RT) inhibitors in minority viral populations of adults and children (34.9% and 70%) was detected; in children both viral populations (majority and minority viral populations) (> 45%) were protease inhibitor resistant. Patients who had a greater number of therapeutic regimens had higher levels of resistance to antiretrovirals. Most of the samples were subtype B in the TR and protease region, and CRF25_cpx in integrase. Conclusions Mutations and resistance to antiretrovirals are shown in a population of Ecuadorian patients with HIV-1. These results will make it possible to issue a warning to health authorities about the need for resistance studies.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adult , HIV Infections/genetics , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/genetics , Drug Resistance, Multiple, Viral/genetics , Anti-Retroviral Agents/pharmacology , Mutation/drug effects , HIV Infections/blood , Logistic Models , Polymerase Chain Reaction , Cross-Sectional Studies , Age Factors , CD4 Lymphocyte Count , Viral Load , Antiretroviral Therapy, Highly Active/methods , Anti-Retroviral Agents/therapeutic use , Ecuador , HIV Reverse Transcriptase/drug effects
12.
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
13.
Biomédica (Bogotá) ; 37(2): 267-273, abr.-jun. 2017. tab
Article in English | LILACS | ID: biblio-1038788

ABSTRACT

RESUMEN Introduction: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. Objective: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Materials and methods: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value <0.05 after Bonferroni correction was considered significant. Results: Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p'<0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Conclusion: Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.


ABSTRACT Introducción. Algunas variantes en genes que codifican los correceptores del HIV-1 y sus ligandos se han asociado individualmente a la resistencia natural frente a dicha infección. Sin embargo, su presencia simultánea ha sido poco estudiada. Objetivo. Evaluar la asociación de haplotipos individuales y multilocus en genes que codifican los correceptores virales CCR5 y CCR2 y sus ligandos CCL3 y CCL5 con la resistencia o la propensión a la infección por el HIV-1. Materiales y métodos. Nueve variantes en CCR5-CCR2, dos en CCL3 y dos en CCL5 fueron genotipificadas mediante reacción en cadena de la polimerasa de polimorfismos de longitud de fragmentos de restricción (Restriction Fragment Length Polymorphism-PCR-RFLP) en 35 individuos seropositivos (casos) y 49 seronegativos expuestos (controles) de Colombia. Los haplotipos se infirieron utilizando el programa Arlequín, y su frecuencia individual o combinada se comparó en los casos y los controles mediante la prueba de ji al cuadrado. Se consideró significativo un valor de p'<0,05 después de la corrección de Bonferroni. Resultados. La homocigosis del haplogrupo humano (HH) E estaba ausente en los controles y era frecuente en los casos, es decir, con tendencia hacia la propensión. Los haplotipos C-C y T-T en CCL3 se asociaron con la propensión (p'=0,016) y la resistencia (p'<0,0001), respectivamente. Por último, en el análisis multilocus, el haplotipo combinado formado por HHC en CCR5-CCR2, T-T en CCL3 y G-C en CCL5 se asoció con la resistencia (p'=0,006). Conclusión. Los resultados de este estudio sugieren que ciertas combinaciones específicas de variantes en los genes de una misma vía de señalización pueden definir un fenotipo resistente al HIV-1. Aunque el tamaño de la muestra era pequeño, las asociaciones estadísticamente significativas sugieren un efecto considerable; sin embargo, estos resultados deben validarse en cohortes de mayor tamaño.


Subject(s)
Humans , Haplotypes/genetics , HIV Infections/microbiology , HIV Infections/epidemiology , HIV-1/immunology , Receptors, CCR5/genetics , Polymorphism, Single Nucleotide/genetics , Immunity, Innate/immunology , Phenotype , HIV Infections/genetics , Cohort Studies , HIV-1/genetics , HIV-1/chemistry , Colombia , Polymorphism, Single Nucleotide/physiology , Genotype , Immunity, Innate/physiology
14.
Braz. j. infect. dis ; 21(3): 234-239, May-June 2017. tab, graf
Article in English | LILACS | ID: biblio-839219

ABSTRACT

ABSTRACT Background: Geographical distribution of HIV variants is an important way to understand the circulation and spread of such viral strains. Objectives: To evaluate the spatial distribution of HIV-1 variants in patients failing antiretroviral therapy, in Salvador, Brazil. Methods: We performed a cross-sectional evaluation of HIV resistance test reports of patients who underwent genotyping tests in a referral center in Salvador, Brazil, for the years 2008-2014. The laboratory database contains around 2500 resistance reports of patients failing antiretroviral therapy. Genotypic tests were performed by sequencing of HIV-1 POL region (TrueGene, Siemens). We assessed HIV-1 resistance mutations and subtype, as well as residential address, age, and gender of patients. Results: We evaluated 1300 reports, 772 (59.4%) of them from male patients. As expected, subtype B predominated (79%) followed by subtypes F1 (6.7%) and BF (6.5%). The most frequent mutations in HIV-1 reverse transcriptase were 184V (79.1%), 41L (33.5%), 67N (30.4%), 103N (42.4%), and 108I (11.1%). Most frequent mutations in HIV-1 protease were 63P (52.4%), 36I (47.9%), 15 V (33.0%), 62 V (28.1%) and 13 V (25.8%). Some mutations (41L, 215Y, 210W) were significantly more frequent among men. We detected a significantly higher accumulation of 103N mutation in specific areas of Salvador. We identified a more restricted circulation pattern for subtype FB (more frequent in some regions), and F1 (almost absent in a specific region). Conclusion: Our results suggest that specific subtypes/resistance mutations present a distinct frequency rate in specific areas of Salvador, probably due to a restricted circulation pattern. This trend to clustering was observed in regions covered by AIDS referral centers, suggesting that pattern of care for such patients can interfere in virological outcomes.


Subject(s)
Humans , Male , Female , Adult , HIV Infections/drug therapy , HIV-1/genetics , Anti-HIV Agents/therapeutic use , HIV Reverse Transcriptase/genetics , Mutation , RNA, Viral/genetics , HIV Infections/virology , Cross-Sectional Studies , HIV-1/drug effects , Treatment Failure , Viral Load , Spatial Analysis , Genotype
15.
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
16.
Braz. j. infect. dis ; 21(2): 148-154, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-839202

ABSTRACT

Abstract Several studies show that the prevalence of multidrug-resistant HIV-1 virus is declining over time. A retrospective cohort study was carried out to evaluate the trends of drug resistance in antiretroviral treatment-exposed individuals in a state of a middle-income country, Minas Gerais, southeast region of Brazil. We analyzed 2115 HIV-1 sequences from 2002 up to 2012, from 52 cities of Minas Gerais. The groups were analyzed according to the definitions: "IAS – 3 class mutations", if ≥1 drug resistance mutation from IAS 2015 list (DRM) was present in each class; "No fully susceptible drugs" as the absence of any fully susceptible drug in Stanford algorithm; and "GSS ≥ 2″, when a maximum calculated GSS (genotypic susceptibility score) was ≥2 or ≥3, counting only drugs available in Brazil and USA at given calendar years. Time trends of resistance were analyzed by Cochran–Armitage test. We observed a decrease in the rate resistance mutations for PI, NRTI, "IAS – 3 class mutations", and "No fully susceptible drugs" over these 11 years, from 69.2% to 20.7%, 92.3% to 90.2%, 46.2% to 22.5%, and 12.8% to 5.7%, respectively (p < 0.05). Resistance to NNRTI increased from 74.4% to 81.6%, mainly because of K103N mutation. The GSS score ≥2 increased during the years from 35.9% to 87.3% (p < 0.001). We demonstrate that resistance to PI and to the three main classes simultaneously are declining, although the number of patients on of antiretroviral therapy has doubled in the last ten years in Brazil (125,000 in 2002 to 400,000 in 2014). Broader resistance testing and the availability of more therapeutic options might have influenced this decline. The increase in NNRTI resistance can limit this class as first line treatment in Brazil in the future.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , HIV Infections/virology , HIV-1/drug effects , Anti-HIV Agents/therapeutic use , Drug Resistance, Multiple, Viral/genetics , Brazil , HIV Infections/drug therapy , Prevalence , Retrospective Studies , Cohort Studies , HIV-1/genetics , Anti-HIV Agents/pharmacology , Genotype , Mutation
17.
Rev. Soc. Bras. Med. Trop ; 50(1): 110-112, Jan.-Feb. 2017. tab
Article in English | LILACS | ID: biblio-1041396

ABSTRACT

Abstract INTRODUCTION: Improving HIV diagnostics and treatment is necessary to end the AIDS epidemic. Pooled plasma can be used to identify patients with acute HIV disease, even before serological tests. During dengue outbreaks, patients having symptoms common to other acute viral diseases might seek medical care. METHODS: We evaluated HIV RNA in pooled seronegative dengue samples. RESULTS: After excluding individuals with a known HIV diagnosis, an HIV-1 prevalence of 0.73% [95% confidence interval (CI) 0.23-1.76; 4/546 samples] was found. CONCLUSIONS: Promoting strategies to diagnose these individuals and provide them with medical treatment might be instrumental for controlling the HIV epidemic.


Subject(s)
Humans , Male , Female , Adult , RNA, Viral/blood , HIV Infections/diagnosis , Disease Outbreaks , HIV-1/genetics , Dengue/epidemiology , Brazil/epidemiology , HIV Infections/epidemiology , Acute Disease , Prevalence , Middle Aged
18.
Biol. Res ; 50: 3, 2017. tab, graf
Article in English | LILACS | ID: biblio-838974

ABSTRACT

Direct tests of the random or non-random distribution of nucleotides on genomes have been devised to test the hypothesis of neutral, nearly-neutral or selective evolution. These tests are based on the direct base distribution and are independent of the functional (coding or non-coding) or structural (repeated or unique sequences) properties of the DNA. The first approach described the longitudinal distribution of bases in tandem repeats under the Bose-Einstein statistics. A huge deviation from randomness was found. A second approach was the study of the base distribution within dinucleotides whose bases were separated by 0, 1, 2... K nucleotides. Again an enormous difference from the random distribution was found with significances out of tables and programs. These test values were periodical and included the 16 dinucleotides. For example a high ¨positive¨ (more observed than expected dinucleotides) value, found in dinucleotides whose bases were separated by (3K + 2) sites, was preceded by two smaller ¨negative¨ (less observed than expected dinucleotides) values, whose bases were separated by (3K) or (3K + 1) sites. We examined mtDNAs, prokaryote genomes and some eukaryote chromosomes and found that the significant non-random interactions and periodicities were present up to 1000 or more sites of base separation and in human chromosome 21 until separations of more than 10 millions sites. Each nucleotide has its own significant value of its distance to neutrality; this yields 16 hierarchical significances. A three dimensional table with the number of sites of separation between the bases and the 16 significances (the third dimension is the dinucleotide, individual or taxon involved) gives directly an evolutionary state of the analyzed genome that can be used to obtain phylogenies. An example is provided.


Subject(s)
Humans , Animals , Phylogeny , Base Sequence/genetics , Genome , Sequence Analysis, DNA/methods , Nucleotides/genetics , Periodicity , Prokaryotic Cells/chemistry , Reference Values , Algorithms , DNA, Mitochondrial/genetics , Chi-Square Distribution , Collagen/genetics , HIV-1/genetics , Evolution, Molecular , Tandem Repeat Sequences , Chromosome Structures , Genetic Drift , Drosophila melanogaster/genetics , Epistasis, Genetic/genetics , Nucleotides/chemistry
19.
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
20.
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
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