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1.
Medicine (Baltimore) ; 99(7): e18777, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049783

RESUMEN

This study sought to determine the dominant circulating human immunodeficiency virus type 1 (HIV-1) subtype and associated drug resistance mutations in Ghana.This cross-sectional study was conducted with archived samples collected from patients who received care at 2 hospitals in Ghana from 2014 to 2016. Blood samples were earlier processed into plasma and peripheral blood mononuclear cells and stored at -80 °C. Ribonucleic acid (RNA) was extracted from the archived plasma. Two HIV-1 genes; protease and reverse transcriptase, were amplified, sequenced using gene-specific primers and analyzed for subtype and drug resistance mutations using the Stanford HIV Database.Of 16 patient samples successfully sequenced, we identified the predominance of HIV-1 subtype CRF02_AG (11/16, 68%). Subtypes G (2/16, 13%), dual CRF02_AG/G (2/16, 13%), and CRF01_AE (1/16, 6%) were also observed. Major nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, M184I/V, D67N, T215F, and K70R/E were found. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, K103N, Y181C, V90I, F227L, and V106A were also prevalent. Additionally, and at a lower level, protease inhibitor (PI)-resistance mutations, M46I, I54 V, V82A, L90 M, and I471 V, were also present in the sequences from antiretroviral therapy (ART)-experienced individuals. Two NRTI-associated drug resistance mutations (DRMs) (D67N and T69N) were present in sequences from 1 ART-naive individual.HIV-1 subtype CRF02_AG was most frequently detected in this study thus confirming earlier reports of dominance of this subtype in the West-African sub-region and Ghana in particular. The detection of these drug resistance mutations in individuals on first-line regimen composed of NRTI and NNRTI is an indication of prolonged drug exposure without viral load monitoring. Routine viral load monitoring is necessary for early detection of virologic failure and drug resistance testing will inform appropriate choice of regimens for such patients.


Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/clasificación , Mutación , Adulto , Fármacos Anti-VIH/uso terapéutico , Estudios Transversales , Evolución Molecular , Femenino , Ghana , Infecciones por VIH/tratamiento farmacológico , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , VIH-1/genética , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral
2.
Int J Infect Dis ; 90: 125-131, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31682961

RESUMEN

OBJECTIVES: Men who have sex with men (MSM) represent one of the major risk groups for HIV-1 infection in China, and the predominant subtypes among this population has changed over the last two decades. The objective of this study was to determine the evolutionary characteristics and transmission patterns of the dominant HIV-1 strains in the Chinese MSM population. METHODS: A total of 4980 published HIV-1 pol gene sequences from MSM in China were retrieved and comprehensive evolutionary and transmission analyses were then conducted. Bayesian coalescent-based methods and selection pressure analyses were used to reconstruct the time-scale and demographic history and to estimate other evolutionary parameters. Transmission patterns were characterized using network analyses. RESULTS: There were 2546 (51.12%) CRF01_AE, 1263 (25.36%) CRF07_BC, and 623 (12.51%) subtype B, accounting for 88.99% of the total sequences. From 2000 to 2016, the prevalence of CRF01_AE was stable, comprising nearly half of all sequences over time (58.33-45.38%, p=0.071). CRF07_BC increased slightly from 13.3% to 22.49% (p<0.001), while subtype B decreased dramatically from 41.67% to 9.04% (p<0.001). Demographic reconstruction showed that the greatest expansion of the HIV epidemic occurred between 1999 and 2005. CRF01_AE had a higher estimated evolutionary rate (2.97×10-3 substitutions/site/year) and exhibited more sites under positive selection (25/351 codons) compared to the other subtypes. Network analyses showed that CRF07_BC (68.29%, 84/123) had a higher proportion of cross-region networks than CRF01_AE (49.1%, 174/354) and subtype B (36.46%, 35/96) (p<0.001). CONCLUSIONS: The predominant subtypes of HIV-1 in Chinese MSM have different evolutionary characteristics and transmission patterns, which poses a significant challenge to HIV treatment and disease prevention.


Asunto(s)
Infecciones por VIH/virología , VIH-1/genética , Homosexualidad Masculina , Teorema de Bayes , Evolución Biológica , China/epidemiología , Epidemias , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , VIH-1/clasificación , Humanos , Masculino , Minorías Sexuales y de Género , Adulto Joven
3.
Arch Virol ; 165(1): 115-125, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31741096

RESUMEN

The latest class of antiretrovirals (ARVs), including integrase strand transfer inhibitors (INSTIs), has been demonstrated to be effective for antiretroviral therapy (ART). Despite all the distinguishing characteristics of these drugs, including a high genetic barrier to resistance and lower toxicity than other ARVs, unfortunately, INSTI drug resistance mutations (DRMs) have occasionally been observed. The aim of this study was to investigate the presence of DRMs associated with INSTIs among treatment-experienced HIV-1-infected patients. From June 2012 to December 2018, a total of 655 treatment-experienced HIV-1-infected patients enrolled in this cross-sectional survey. Following amplification and sequencing of the HIV-1 integrase region of the pol gene, DRM and phylogenetic analysis were successfully carried out on the plasma samples of patients who had a viral load over 1,000 IU/ml after at least 6 months of ART. Out of the 655 patients evaluated, 62 (9.5%) had a viral load higher than 1,000 IU/ml after at least 6 months of ART. Phylogenetic analysis showed that all of the 62 HIV-1 patients experiencing treatment failure were infected with CRF35_AD, and one of these patients (1.6%) was infected with HIV-1 variants with DRMs. The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R. This survey shows that DRMs belonging to the INSTI class were detected in an Iranian HIV patient who has experienced treatment failure. Therefore, regarding the presence of DRMs to INSTIs in ART-experienced patients, it seems better to perform drug resistance mutation testing in HIV patients experiencing treatment failure before changing the ART regimen and prescribing this class of medication.


Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH/virología , Integrasa de VIH/genética , VIH-1/clasificación , Mutación , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/enzimología , VIH-1/genética , Humanos , Lactante , Irán , Masculino , Persona de Mediana Edad , Filogenia , Análisis de Secuencia de ARN , Adulto Joven
4.
Emerg Microbes Infect ; 9(1): 32-41, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31859609

RESUMEN

To better evaluate HIV-1 vaccines and therapeutics, the National Institutes for Food and Drug Control of China developed a panel of HIV-1 pseudoviruses including 462 viral strains derived from China, covering the majority of contemporaneous subtypes and circulating recombinant forms. Compared with the standard pseudovirus panels derived from other countries/regions, the Chinese isolates are more susceptible to neutralization by the sera obtained in China, revealing the strain/subtype specificity. Some of these pseudoviruses have already been used for the evaluation of HIV vaccines and drug candidates in Chinese clinical trials. The pseudoviruses panel is widely shared with interested scientists involved in the research and development of vaccines and antiviral drugs against HIV-1 strains prevalent in China.


Asunto(s)
Investigación Biomédica , VIH-1/genética , Vacunas contra el SIDA , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , China , Farmacorresistencia Viral , VIH-1/clasificación , VIH-1/inmunología , Humanos , Filogenia , Recombinación Genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(11): 1487-1491, 2019 Nov 10.
Artículo en Chino | MEDLINE | ID: mdl-31838826

RESUMEN

HIV molecular network is a recently reported method for studying the transmission characteristics of HIV-infected people. Countries have used this method to conduct a large number of researches on transmission relations, transmission hotspots and epidemic surveillance for the purpose of providing evidence for precise AIDS intervention and control. At present, there are three major methods for constructing molecular networks in the world, i.e. genetic distance method based on pairwise alignment, phylogenetic node support method, and joint parameter method based on the two methods. This paper reviews the progress of the three methods for constructing HIV molecular network to study the transmission characteristics of HIV-infected patients, in order to provide data support for the prevention and control of HIV. Since the emergence of the molecular network method, Beijing, Shanghai, Zhejiang, Sichuan and other provinces in China have reported relevant research results using molecular network analysis, which provided scientific data for further precise AIDS prevention and control. Recent international studies have also predicted that molecular network based transmission cluster detection is expected to become a new method to stop AIDS epidemic.


Asunto(s)
Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , VIH-1/clasificación , VIH-1/genética , Síndrome de Inmunodeficiencia Adquirida , Beijing , China , Infecciones por VIH/diagnóstico , Infecciones por VIH/genética , VIH-1/aislamiento & purificación , Humanos , Modelos Moleculares , Epidemiología Molecular , Filogenia
6.
Mikrobiyol Bul ; 53(4): 374-387, 2019 Oct.
Artículo en Turco | MEDLINE | ID: mdl-31709935

RESUMEN

Human immunodeficiency virus (HIV) comprises two genotypes, namely HIV-1 (group M, N, O and P) and HIV-2 (group A to H), which differ in their envelope glycoproteins and other antigenic epitopes despite their morphological and biological resemblance.Group M of HIV-1 responsible for 95% of HIV infections worldwide is composed of nine subgroups. In addition to subgroups, group M contains also two recombinant forms, known as circulating recombinant form (CRF) and unique recombinant form (URF). The first case of HIV/acquired immun deficiency virus (AIDS) in Turkey was reported in 1985 and the current number of cases reached a total of 18.557 including 1736 with AIDS based upon the surveillance data of Ministry of Health between October 1985 and November 2018. The aim of this study was to determine the prevalence of HIV-1 strains isolated from HIV positive autopsy cases detected by HIV polymerase chain reaction (PCR) and determine drug resistance. Twenty eight cases [17 males, 11 female: age ranged between 3 months and 66 years (median: 35 years)] found to be HIV positive among the autopsy cases sent for HIV1 PCR study and serological screening between 2011-2017 were recruited in the study. For identification of subtypes in HIV-1 isolates, most-preferred analysis tool was used [HIVdb Stanford University Genotypic Resistance Interpretation Algorithm (www.hivdb.stanford.edu)]. Phylogenetic tree was made according to direct sequencing of HIV-1 reverse transcriptase (pol) region and phylogenetic analysis was evaluated in 23 cases. Los Alamos National Laboratory were trimmed from full-length genomes. Phylogenetic analysis of the 870 base pair of the pol gene region was performed using CLC Sequence Viewer v8.0 (Qiagen Aarhus A/S, www.qiagenbioinformatics.com) software. The phylogenetic tree was obtained according to the neighbor-joining method and the Jukes-Cantor nucleotide distance scale and bootstrap value was set at 1000. In our study, subtype B was found to be most frequent type (39.3%; 11/28). Subtype A (17.9%; 5/28), CRF02_AG (14.3%; 4/28), subtype C (10.7%; 3/28), B+CRF02_AG recombinant (3.6%; 1/28), CRF01_AE (3.6%; 1/28), subtype D (3.6%; 1/28), as well as subtype F (3.6%; 1/28) and subtype G (3.6%; 1/28) strains were also detected in the circulation. Analysis of our results showed that 32.1% (9/28) of the samples exhibited resistance mutations. Detected mutations were as follows: M41L, T215C, K65R, M184V, responsible for nucleoside reverse transcriptase inhibitor (NRTI) resistance; K103N, Y181C, G190A, responsible for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance; D30N, M46I, responsible for protease inhibitor (PI) resistance. NRTI, NNRTI and PI mutation rates in the samples were found as 21.4%, 7.1% and 3.6%, respectively. Although number of samples analyzed in our study is low, we can propose that they resemble the strains circulating in Turkey. The results of our study; although the subtype B is still dominant in our country, it supports other studies reporting that there are non-B subtypes and an increase in CRF rates in recent years. Phylogenetic analysis is widely regarded as the gold standard technique to determine the subtypes of HIV-1. Molecular epidemiologic studies related to HIV may be important in monitoring HIV subtype patterns and spreading pathways in that country. As a result; the opportunity to collect postmortem HIV sequences in a database appears to have occurred, and as this database expands, its usability is available. Therefore, it is thought that HIV subtypes and mutation information may be useful.


Asunto(s)
Infecciones por VIH , VIH-1 , Epidemiología Molecular , Adolescente , Adulto , Anciano , Antivirales/farmacología , Autopsia , Niño , Preescolar , Farmacorresistencia Viral , Femenino , Genotipo , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/efectos de los fármacos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación , Filogenia , Turquia/epidemiología
7.
Arch Virol ; 164(12): 3081-3087, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31576459

RESUMEN

Owing to consistent genetic mutation and recombination, various escape mutants and/or drug-resistant mutants of human immunodeficiency virus (HIV-1) are now emerging worldwide. Therefore, an understanding of the genetic characteristics of prevailing strains, particularly with regard to drug-resistance-associated substitutions, is essential for devising and implementing treatments and disease control interventions in endemic settings such as Pakistan. We processed a total of 130 plasma samples originating from HIV-treatment centers in selected districts of Punjab province, Pakistan. The samples were first screened using an HIV-1 Ag/Ab Combo test followed by amplification of the pol gene (1084 bp) from samples that were positive either for the antigen or for both the antigen and antibodies simultaneously. Screening revealed that a total of 45 samples were positive (34.62%; 95% CI: 26.99-43.13) for either antigen or both antigen and antibodies (n = 18, 40%; 95% CI: 27.02-54.55) or for antibodies alone (n = 27, 60%; 95% CI: 45.45-72.98). A largest number of positive samples was from the district of Lahore (n = 19/43, 44.18%; 95% CI: 30.44-58.9) followed by Faisalabad (n= 12/36, 33.33%; 95% CI: 20.21-49.66), Gujranwala (n = 05/23, 21.7%; 95% CI: 9.66-41.9) and Sargodha (n = 09/28, 32.1%; 95% CI: 17.93-50.66). The probability of occurrence of HIV infection was significantly associated with individuals having a history of injecting drug use (68.08%; OR = 11.15; 95% CI: 53.84-79.61, p = 0.0001). Phylogenetic analysis based on the pol gene showed that the sequences from this study clustered into three distinct clades representing recombinant form 02_AG (n = 14, 77.0%; 95% CI: 54.79-91.00), and subtypes A (n = 2, 11.1%; 95% CI: 3.1-32.8) and G (n = 2, 11.1%; 95% CI: 3.1-32.8). Although we screened 18 samples for drug-resistance-associated mutations, except for an accessory mutation (M46K) in the protease (PR) region in one subject, we found a lack of drug-resistance-associated substitutions in the PR region. On the other hand, we found two subjects (2/18) carrying a resistance-associated mutation (V106I) conferring a low level of resistance against non-nucleoside reverse transcriptase inhibitors. The present study shows that multiple subtypes of HIV-1 are present in the affected population. Continuous disease surveillance coupled with evaluation of drug resistance at higher resolution should be done in future studies.


Asunto(s)
Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/aislamiento & purificación , Adulto , Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral , Femenino , Infecciones por VIH/epidemiología , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pakistán/epidemiología , Filogenia , Adulto Joven , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética
8.
Ann Clin Microbiol Antimicrob ; 18(1): 27, 2019 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-31551072

RESUMEN

BACKGROUND: Identification of all possible HIV reservoirs is an important aspect in HIV eradication efforts. The urinary tract has however not been well studied as a potential HIV reservoir. In this pilot study we molecularly characterized HIV-1 viruses in urine and plasma samples to investigate HIV-1 replication, compartmentalization and persistence in the urinary tract. METHODS: Prospectively collected urine and blood samples collected over 12-36 months from 20 HIV-1 infected individuals were analysed including sampling points from prior to and after ART initiation. HIV-1 pol gene RNA and DNA from urine supernatant and urine pellets respectively were analysed and compared to plasma RNA viruses from the same individual. RESULTS: HIV-1 nucleic acid was detected in urine samples from at least one time point in 8/20 (40%) treatment-naïve subjects compared to 1/13 (7.7%) individuals on antiretroviral treatment (ART) during periods of plasma viral suppression and 1/7 (14.3%) individuals with virological failure. HIV-1 RNA was undetectable in urine samples after ART initiation but HIV-1 DNA was detectable in one patient more than 6 months after treatment initiation. There was co-clustering of urine-derived pol sequences but some urine-derived sequences were interspersed among the plasma-derived sequences. CONCLUSIONS: Suppressive ART reduces HIV-1 replication in the urinary tract but HIV-1 DNA may persist in these cells despite treatment. A larger number of sequences would be required to confirm HIV compartmentalization in the urinary tract.


Asunto(s)
Genotipo , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/aislamiento & purificación , Sistema Urinario/virología , Adulto , Antirretrovirales/uso terapéutico , ADN Viral/genética , ADN Viral/aislamiento & purificación , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Masculino , Proyectos Piloto , Plasma/virología , Estudios Prospectivos , ARN Viral/genética , ARN Viral/aislamiento & purificación , Análisis de Secuencia de ADN , Carga Viral , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética
9.
Molecules ; 24(19)2019 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-31561445

RESUMEN

In spite of significant advancements and success in antiretroviral therapies directed against HIV infection, there is no cure for HIV, which scan persist in a human body in its latent form and become reactivated under favorable conditions. Therefore, novel antiretroviral drugs with different modes of actions are still a major focus for researchers. In particular, novel lead structures are being sought from natural sources. So far, a number of compounds from marine organisms have been identified as promising therapeutics for HIV infection. Therefore, in this paper, we provide an overview of marine natural products that were first identified in the period between 2013 and 2018 that could be potentially used, or further optimized, as novel antiretroviral agents. This pipeline includes the systematization of antiretroviral activities for several categories of marine structures including chitosan and its derivatives, sulfated polysaccharides, lectins, bromotyrosine derivatives, peptides, alkaloids, diterpenes, phlorotannins, and xanthones as well as adjuvants to the HAART therapy such as fish oil. We critically discuss the structures and activities of the most promising new marine anti-HIV compounds.


Asunto(s)
Antirretrovirales/química , Antirretrovirales/farmacología , Organismos Acuáticos/química , Productos Biológicos/química , Productos Biológicos/farmacología , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , Desarrollo de Medicamentos , Aceites de Pescado/química , Aceites de Pescado/farmacología , VIH-1/clasificación , VIH-1/efectos de los fármacos , Humanos , Relación Estructura-Actividad
10.
Virol J ; 16(1): 103, 2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31416460

RESUMEN

BACKGROUND: The high genetic diversity of HIV-1 has been shown to influence the global distribution, disease progression, treatment success, and the development of an effective vaccine. Despite the low HIV prevalence in Cameroon, all the major HIV subtypes alongside several circulating recombinant forms (CRFs) and unique recombinant forms (URFs) have been reported in Cameroon. To date, HIV-1 diversity in some parts of Cameroon has been largely studied however, information on circulating HIV-1 subtypes in the Northwest region (NWR) of Cameroon is dearth. Therefore the aim of this study was to determine the current circulating HIV-1 subtypes among adults in the NWR of Cameroon. METHODS: The genetic analysis of the reverse transcriptase region of the pol gene was performed on 81 samples. The samples were collected from drug naïve patients aged between 18 and 61 years residing within the rural and urban towns in the NWR during the period between February and April 2016. Viral RNA was extracted from plasma, reverse-transcribed, further amplified by nested-PCR before sequencing using an in-house protocol. Generated sequences were then phylogenetically analyzed together with references using MEGA 7. RESULTS: Phylogenetic analysis revealed a broad viral diversity including CRF02 _AG (74.1%), F2 (7.4%), D (7.4%), G (3.7%), A1 (1.2%), CRF22_01A1 (2.5%), CRF06_cpx (1.2%), CRF09_cpx (1.2%), CRF11_cpx (1.2%). Three close epidemic clusters were found among F2 (1) and CRF02_AG (2) variants. For the first time we are reporting the CRF22_01A1 subtype in this region. CONCLUSION: Our findings update HIV-1 subtypes information in Cameroon and uphold previous studies that CRF02_AG is the most prevalent subtype. This CRF02_AG subtype may have important public health, research, and clinical consequences.


Asunto(s)
Variación Genética , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/clasificación , Filogenia , Adolescente , Adulto , Camerún/epidemiología , Estudios Transversales , Evolución Molecular , Femenino , Genes pol , Genotipo , Geografía , VIH-1/enzimología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ADN Polimerasa Dirigida por ARN/genética , Recombinación Genética , Análisis de Secuencia de ADN , Adulto Joven
11.
Cell Host Microbe ; 26(1): 73-85.e4, 2019 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-31295427

RESUMEN

Evaluation of HIV cure strategies is complicated by defective proviruses that persist in ART-treated patients but are irrelevant to cure. Non-human primates (NHP) are essential for testing cure strategies. However, the persisting proviral landscape in ART-treated NHPs is uncharacterized. Here, we describe viral genomes persisting in ART-treated, simian immunodeficiency virus (SIV)-infected NHPs, simian-human immunodeficiency virus (SHIV)-infected NHPs, and humans infected with HIV-2, an SIV-related virus. The landscapes of persisting SIV, SHIV, and HIV-2 genomes are also dominated by defective sequences. However, there was a significantly higher fraction of intact SIV proviral genomes compared to ART-treated HIV-1 or HIV-2 infected humans. Compared to humans with HIV-1, SIV-infected NHPs had more hypermutated genomes, a relative paucity of clonal SIV sequences, and a lower frequency of deleted genomes. Finally, we report an assay for measuring intact SIV genomes which may have value in cure research.


Asunto(s)
Antirretrovirales/uso terapéutico , Variación Genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-2/efectos de los fármacos , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Animales , Virus Defectuosos/genética , Genoma Viral , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , VIH-2/clasificación , VIH-2/genética , Humanos , Macaca mulatta , Provirus/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/clasificación , Virus de la Inmunodeficiencia de los Simios/genética
12.
BMC Infect Dis ; 19(1): 669, 2019 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-31357947

RESUMEN

BACKGROUND: As a gateway for HIV-1 in China, Yunnan has experienced dramatic changes in HIV-1 epidemics, during which HIV-1 genotypes have become complex. To track dynamic changes in HIV-1 genotypes, an HIV-1 molecular epidemiological study was implemented in the recently infected population in Yunnan. METHODS: From 6,357 HIV-1-positive samples diagnosed during the first half of 2015 in Yunnan, 586 samples were identified as recent infections with BED-capture enzyme immunoassay (CEIA) and were subjected to phylogenetic analyses. Spatial scanning analyses for the main HIV-1 genotypes were also performed. RESULTS: Among the 439 specimens successfully genotyped, more than ten genotypes were detected, including CRF08_BC (45.3%), CRF07_BC (19.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (11.4%), subtype C (2.1%), CRF85_BC (1.1%), CRF55_01B (0.9%), subtype B (0.5%), CRF64_BC (0.5%), CRF59_01B (0.2%), CRF83_cpx (0.2%) and CRF87_cpx (0.2%). Females, Chinese, heterosexual contact and intravenous drug injection were significantly associated with CRF08_BC infection; homosexual contact was significantly associated with CRF01_AE and CRF07_BC infection; males and non-Chinese had a higher risk of URF infection than females. Among all HIV-1 genotypes, the geographic coverage of CRF08_BC was the largest. For CRF08_BC, CRF07_BC, URFs and CRF01_AE, spatial clusters were detected. The two CRF08_BC clusters and one URF cluster were associated with heterosexual transmission, and two of CRF01_AE clusters were associated with homosexual transmission. Transmitted drug resistance (TDR)-associated mutations were detected in 2.4% of individuals. CONCLUSIONS: The diversity of HIV-1 genotypes increased in recent infections because of a long-term HIV-1 epidemic in Yunnan. The predominant HIV-1 strains showed distinct demographic characteristics and formed spatial clusters. These findings improved our understanding of the evolution of HIV-1 in Yunnan and provided information for further HIV-1 control and prevention.


Asunto(s)
Farmacorresistencia Viral/genética , Epidemias , Variación Genética , Infecciones por VIH/virología , VIH-1/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Genotipo , Infecciones por VIH/epidemiología , VIH-1/clasificación , Heterosexualidad , Homosexualidad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Filogenia , Análisis Espacial , Adulto Joven
13.
AIDS Rev ; 21(2): 76-83, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31332398

RESUMEN

With the introduction of combinatory antiretroviral therapy, patients infected with human immunodeficiency virus type 1 (HIV-1) can live much longer than before. However, the identification of HIV-associated neurocognitive disorder (HAND), especially HIV-associated dementia in 15-20% of patients infected with HIV-1, indicates additional complexity. These disorders turn out to be subtype dependent. Recently, many studies are ongoing trying to understand how the virus induces neuronal injury which could lead to neurological dysfunction. Most of these studies are focusing on the HIV-1 release of proteins such as Tat. However, the exact role of these proteins and their involvement in neuronal degeneration remains unidentified; this is especially true since viral proteins from different HIV-1 subtypes differ in their ability to cause neuronal damage. This review describes the role of different HIV-1 subtypes, identifies probable pathways involved in neuronal damage, the contribution of different HIV-1 subtypes to the progression of HAND, and potential treatments for HAND.


Asunto(s)
Complejo SIDA Demencia/epidemiología , Genotipo , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/patogenicidad , VIH-1/genética , Interacciones Huésped-Patógeno , Humanos
14.
PLoS One ; 14(6): e0218369, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31246963

RESUMEN

BACKGROUND: Point of-care (POC) HIV-1 RNA tests which are accurate and easy to use with limited infrastructure are needed in resource-limited settings (RLS). We systematically reviewed evidence of POC test performance compared to laboratory-based HIV-1 RNA assays and the potential utility of these tests for diagnosis and care in RLS. METHODS: Studies published up to July 2018 were identified by a search of PUBMED, EMBASE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials. Studies evaluating the use of POC HIV-1 RNA testing for early infant diagnosis (EID), acute HIV infection (AHI) diagnosis, or viral load monitoring (VL), compared to centralized testing, were included. Separate search strategies were used for each testing objective. RESULTS: 197 abstracts were screened and 34 full-text articles were assessed, of which 32 met inclusion criteria. Thirty studies evaluated performance and diagnostic accuracy of POC tests compared to standard reference tests. Two of the thirty and two additional studies with no comparative testing reported on clinical utility of POC results. Five different POC tests (Cepheid GeneXpert HIV-1 Quantitative and Qualitative assays, Alere q HIV-1/2 Detect, SAMBA, Liat HIV Quant and Aptima HIV-1 Quant) were used in 21 studies of VL, 11 of EID and 2 of AHI. POC tests were easy to use, had rapid turnaround times, and comparable accuracy and precision to reference technologies. Sensitivity and specificity were high for EID and AHI but lower for VL. For VL, lower sensitivity was reported for whole blood and dried blood spots compared to plasma samples. Reported error rates for Cepheid GeneXpert Qual (2.0%-5.0%), GeneXpert Quant (2.5%-17.0%) and Alere q HIV-1/2 Detect (3.1%-11.0%) were higher than in WHO prequalification reports. Most errors resolved with retesting; however, inadequate sample volumes often precluded repeat testing. Only two studies used POC results for clinical management, one for EID and another for VL. POC EID resulted in shorter time-to-result, rapid ART initiation, and better retention in care compared to centralised testing. CONCLUSIONS: Performance of POC HIV-1 RNA tests is comparable to reference assays, and have potential to improve patient outcomes. Additional studies on implementation in limited-resources settings are needed.


Asunto(s)
Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , VIH-1/genética , Pruebas en el Punto de Atención , ARN Viral , Factores de Edad , Infecciones por VIH/tratamiento farmacológico , VIH-1/clasificación , Humanos , Sistemas de Atención de Punto/normas , Pruebas en el Punto de Atención/normas , Reacción en Cadena de la Polimerasa , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Carga Viral/métodos
15.
BMC Infect Dis ; 19(1): 562, 2019 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-31248372

RESUMEN

BACKGROUND: The proportion of older HIV-1 infected people in China has increased rapidly in recent years. Elucidation of the transmission characteristics of this high-risk population subgroup is helpful for the development of tailored interventions. METHODS: A phylogenetic analysis was performed that uses available HIV-1 pol sequences amplified with nested RT-PCR from plasma samples of all newly diagnosed participants spanning from October 2017 to September 2018 in Fuyang, Anhui Province. Transmission clusters were identified as two or more sequences that shared a corresponding node with an aLRT-SH value ≥90 in the maximum-likelihood phylogenetic tree and had an overall mean genetic distance of ≤1.5%. A local transmission cluster was defined as a cluster that had more than 80% of its sequences from Fuyang. The role of older people in local HIV-1 transmission was determined using an integration of molecular and demographic data. RESULTS: Of 362 available sequences, 14 subtypes, and 28 local transmission clusters were identified. It was found that the proportion of older people in the local transmission cluster (69/77, 89.61%) was much higher than that of younger people (46/114, 40.35%) (χ2 test, P < 0.001). In the pretreatment drug resistance analysis, the proportion of sequences with PDRMs in the local transmission cluster was not significantly different between the older people group (57.14%, 4/7) and non-old-aged group (11.11%, 1/9) (Fisher's exact test, P > 0.05). CONCLUSION: By combining phylogenetic analyses with demographic data, more detailed information was provided about the local transmission structure in Fuyang. These findings suggested that older people play an important role in local transmission, and more tailored interventions for this population subgroup are urgently needed.


Asunto(s)
Infecciones por VIH/diagnóstico , VIH-1/clasificación , Adulto , Anciano , Antirretrovirales/uso terapéutico , China/epidemiología , Farmacorresistencia Viral/genética , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa , ARN Viral/aislamiento & purificación , ARN Viral/metabolismo
16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(5): 580-584, 2019 May 10.
Artículo en Chino | MEDLINE | ID: mdl-31177742

RESUMEN

Objective: To analyze the change trend of HIV genetic subtypes and compare the first CD(4)(+)T cell counts of newly diagnosed HIV infected patients in Liuzhou from 1998 to 2012, and provide a reference for AIDS prevention and control. Methods: Newly diagnosed HIV-infected patients from 1998 to 2012 in Liuzhou were selected through national HIV/ADIS comprehensive response information management system. Their plasma samples were used for RNA gene extraction, amplification, sequencing and genotyping. Coharan-Armitage trend test was used to analyze the ratio trend of genetic subtypes and phylogenetic clusters of HIV and Wilcoxon Rank Sum Test was used to compare the first CD(4)(+)T cell counts (CD(4)) of the different subtype HIV infected patients. Results: A total of 1 877 newly diagnosed HIV infected patients were included in the study. From 1998 to 2012, the proportions of CRF01_AE and CRF01_AE (Cluster 1) increased from 78.4% (76/97) to 91.5% (1 441/1 574), from 63.9% (62/97) to 74.0% (1 164/1 574), and the proportion of CRF07_BC decreased from 17.5% (17/97) to 4.6% (72/1 574), respectively (Z=4.632, P<0.001; Z=2.455, P=0.014; Z=-5.943, P<0.001). The median and interquartile range of the first CD(4) of the patients infected with subtype CRF01_AE (Cluster 1), CRF01_AE (Cluster 2), CRF07_BC and CRF08_BC were 230 (83-375), 215 (48-351), 365 (254-503) and 334 (206-479) cell/µl, respectively. The first CD(4) levels of the patients infected with subtype CRF01_AE (Cluster 1) or CRF01_AE (Cluster 2) were significantly lower than those of CRF07_BC (Z=-4.795, P<0.001; Z=-4.238, P<0.001). Conclusion: The genetic subtypes of HIV were mainly CRF01_AE in newly diagnosed HIV-infected patients and this subtype proportion was in increase and the first CD(4) levels of the patients were low in Liuzhou during 1998 to 2012.


Asunto(s)
Infecciones por VIH/diagnóstico , VIH-1/clasificación , VIH-1/genética , ARN Viral/aislamiento & purificación , Linfocitos T , Recuento de Células , China/epidemiología , ADN Viral/genética , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Filogenia , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN
17.
Curr HIV Res ; 17(2): 114-125, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31210113

RESUMEN

BACKGROUND: The information about the dynamics of the viral population and migration events that affect the epidemic in different parts of the Russia is insufficient. Possibly, the huge size of the country and limited transport accessibility to certain territories may determine unique traits of the HIV-1 evolutionary history in different regions. OBJECTIVE: The aim of this study was to explore the genetic diversity of HIV-1 in the Krasnoyarsk region and reconstruct spatial-temporal dynamics of the infection in the region. METHODS: The demographic and virologic data from 281 HIV-infected individuals in Krasnoyarsk region collected during 2011-2016 were analyzed. The time to the most recent common ancestor, evolutionary rates, population growth, and ancestral geographic movements was estimated using Bayesian coalescent-based methods. RESULTS: The study revealed moderate diversity of the HIV-1 subtypes found in the region, which included A6 (92.3%), CRF063_02A (4.3%), B (1.1%), and unique recombinants (2.5%). Phylogenetic reconstruction revealed that the A6 subtype was introduced into Krasnoyarsk region by one viral lineage, which arose around 1996.9 (1994.5-1999.5). The phylogeography analysis pointed to Krasnoyarsk city as the geographical center of the epidemic, which further spread to central neighboring districts of the region. At least two epidemic growth phases of subtype A6 were identified which included exponential growth in early-2000s followed by the decline in the mid/late 2010s. CONCLUSION: This study demonstrates a change in the genetic diversity of HIV-1 in the Krasnoyarsk region. At the beginning of the epidemic, subtype A6 prevailed, subtypes B and CRF063_02A appeared in the region later.


Asunto(s)
Variación Genética , Infecciones por VIH/epidemiología , VIH-1/genética , Epidemiología Molecular , VIH-1/clasificación , Humanos , Filogenia , Filogeografía , Vigilancia de la Población , Federación de Rusia/epidemiología
18.
PLoS One ; 14(6): e0217817, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31166970

RESUMEN

Population-level phylogenetic patterns reflect both transmission dynamics and genetic changes, which accumulate because of selection or drift. In this study, we determined whether a longitudinally sampled dataset derived from human immunodeficiency virus (HIV)-1-infected individuals over a 14-year period (1999-2012) could shed light on the transmission processes involved in the initiation of the HIV-1 epidemic in Korea. In total, 927 sequences were acquired from 1999 to 2012; each sequence was acquired from an individual patient who had not received treatment. Sequences were used for drug resistance and phylogenetic analyses. Phylogenetic and other analyses were conducted using MEGA version 6.06 based on the GTR G+I parameter model and SAS. Of the 927 samples, 863 (93.1%) were classified as subtype B and 64 were classified as other subtypes. Phylogenetic analysis demonstrated that 104 of 927 patient samples (11.2%) were grouped into 37 clusters. Being part of a transmission cluster was significantly associated with subtype-B viruses, infection via sexual contact, and the infection of young males. Of all clusters, three (~8.1%) that comprised 10 individual samples (22.2% of 45 individuals) included at least one member with total transmitted drug resistance (TDR). In summary, HIV transmission cluster analyses can integrate laboratory data with behavioral data to enable the identification of key transmission patterns to develop tailored interventions aimed at interrupting transmission chains.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , VIH-1/clasificación , Filogenia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Farmacorresistencia Viral/genética , Femenino , Genotipo , Infecciones por VIH/diagnóstico , VIH-1/genética , Homosexualidad Masculina , Humanos , Lactante , Masculino , Persona de Mediana Edad , Recombinación Genética/genética , República de Corea , Adulto Joven
19.
Cell Host Microbe ; 25(6): 858-872.e13, 2019 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-31175045

RESUMEN

The interferon γ-inducible protein 16 (IFI16) is known as immune sensor of retroviral DNA intermediates. We show that IFI16 restricts HIV-1 independently of immune sensing by binding and inhibiting the host transcription factor Sp1 that drives viral gene expression. This antiretroviral activity and ability to bind Sp1 require the N-terminal pyrin domain and nuclear localization of IFI16, but not the HIN domains involved in DNA binding. Highly prevalent clade C HIV-1 strains are more resistant to IFI16 and less dependent on Sp1 than other HIV-1 subtypes. Furthermore, inhibition of Sp1 by IFI16 or pharmacologically by Mithramycin A suppresses reactivation of latent HIV-1 in CD4+ T cells. Finally, IFI16 also inhibits retrotransposition of LINE-1, known to engage Sp1, and murine IFI16 homologs restrict Friend retrovirus replication in mice. Thus, IFI16 restricts retroviruses and retrotransposons by interfering with Sp1-dependent gene expression, and evasion from this restriction may facilitate spread of HIV-1 subtype C.


Asunto(s)
VIH-1/inmunología , Factores Inmunológicos/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Factor de Transcripción Sp1/antagonistas & inhibidores , Transcripción Genética , Activación Viral , Latencia del Virus , Animales , Linfocitos T CD4-Positivos/virología , Células Cultivadas , Genotipo , VIH-1/clasificación , VIH-1/genética , VIH-1/crecimiento & desarrollo , Ratones
20.
BMC Infect Dis ; 19(1): 566, 2019 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-31253127

RESUMEN

BACKGROUND: To infer transmission direction of a HIV transmission chain is helpful not only in legal jurisdiction but also in precise intervention to prevent HIV spread. Recently, the direction of transmission is inferred by whether paraphyletic-monophyletic (PM) or a combination of paraphyletic and polyphyletic (PP) topologies is observed or not between the sequences of source and recipient in the phylogenetic tree. However, paraphyly between them often declines over time and may disappear between spouses due to bidirectional transmission after primary infection. In this study, our aim is to test the reliability of inferring HIV transmission direction between epidemiologically linked HIV-1 positive couples using whether or not paraphyly is observed in phylogenetic tree. METHODS: HIV quasi-species were sequenced using PCR product clones, and then Bayesian analysis of molecular sequences with MCMC was employed to construct phylogenetic relationship of env, gag, pol gene fragments of HIV-1 positive couples using BEAST software. RESULTS: Our results showed that all sequences of seven couples except pol sequences of couple 12 and 13 form their own monophyletic cluster in phylogenetic tree including the closest control sequences from GenBank or other studies on local samples, which are supported by significant Bayesian posterior probabilities more than 0.9932. Of seven couples, paraphyly is only observed in phylogenetic tree constructed with env and pol gene sequences of three couples and gag gene sequences of four couples. Paraphyly is not observed in half of HIV positive couples. Pol sequences of couple 13 is separated by Blast selected controls; pol sequences of couple 12 in phylogenetic tree is supported by a lower Bayesian posterior value. CONCLUSION: Paraphyly relationship between sequences of donator and recipient is only observed among partial HIV-1 positive couples with epidemiological link. Phylogenetic relationship is not always the same when various gene regions of HIV are used to conduct phylogenetic analysis. The combination of phylogenetic analysis based on various gene regions of HIV and enough epidemiology investigation is essential when inferring transmission direction of HIV in a transmission chain or in one couple. However, while observed paraphyly can be used to infer transmission direction in HIV-1 positive couple, no observed paraphyly cannot deny it.


Asunto(s)
Infecciones por VIH/transmisión , VIH-1/genética , Cuasiespecies , Teorema de Bayes , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/clasificación , Humanos , Masculino , Filogenia , Reacción en Cadena de la Polimerasa , ARN Viral/genética , ARN Viral/aislamiento & purificación , ARN Viral/metabolismo , Conducta Sexual , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/clasificación , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/clasificación
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