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1.
Medicine (Baltimore) ; 99(2): e18499, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914019

RESUMO

BACKGROUND: Previous studies have reported the association between Mycoplasma fermentans (M. fermentans) and the risk of human immunodeficiency virus 1 (HIV-1) infection, but the results were inconsistent. The present study aims to systematically review reported studies on M. fermentans and its association with HIV-1 infection, as well as to summarize the findings using a meta-analysis. METHODS: Studies meeting the inclusion criteria in the PubMed, Embase, China National Knowledge Infrastructure, WanFang Data, and Chongqing VIP databases up to March 2019 were identified. Cochran Q and I statistics were used to assess heterogeneity. Additionally, pooled odds ratio (OR) with 95% confidence intervals (CI) were calculated and displayed by Forest plots. Also, the funnel plot, Begg test, and Egger test were used to evaluate potential publication bias. In addition, the source of heterogeneity was investigated by subgroup and sensitivity analyses. RESULTS: A total of 11 studies comprising 1028 HIV-1-positive patients and 1298 controls were ultimately included in this meta-analysis. Our results indicated that M. fermentans could increase the risk of HIV-1 infection among humans (OR = 3.66, 95%CI 1.26-10.64). Subgroup analysis showed that the risk of HIV-1 infection associated with M. fermentans was, based on the geographical distribution, 1.19 (95%CI 0.33-4.33) in Europe, 2.83 (95%CI 0.94-8.52) in United States, 11.92 (95%CI 3.93-36.15) in Asia; based on the source of the sample, 2.97 (95%CI 0.89-9.95) in blood samples, 4.36 (95%CI 1.63-11.68) in urine samples; based on the detection method, 2.80 (95%CI 0.72-10.96) with the polymerase chain reaction method, 5.54 (95%CI 1.21-25.28) with other detection methods; based on the source of controls, 1.91 (95%CI 0.53-6.89) in sexually transmitted diseases individuals, and 8.25 (95%CI 2.16-31.60) in health individuals. CONCLUSION: Our study revealed evidence of the association between M. fermentans and HIV-1 infection. Considering the heterogeneity, further studies are warranted to understand the relationship between M. fermentans and HIV-1 infection.


Assuntos
Infecções por HIV/etiologia , Soropositividade para HIV/diagnóstico , Infecções por Mycoplasma/complicações , Mycoplasma fermentans/metabolismo , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/diagnóstico , Soropositividade para HIV/complicações , Soropositividade para HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Infecções por Mycoplasma/microbiologia , Mycoplasma fermentans/isolamento & purificação , Fatores de Risco , Estados Unidos/epidemiologia
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(11): 1487-1491, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31838826

RESUMO

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.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/classificação , HIV-1/genética , Síndrome de Imunodeficiência Adquirida , Pequim , China , Infecções por HIV/diagnóstico , Infecções por HIV/genética , HIV-1/isolamento & purificação , Humanos , Modelos Moleculares , Epidemiologia Molecular , Filogenia
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(12): 1278-1283, 2019 Dec 06.
Artigo em Chinês | MEDLINE | ID: mdl-31795586

RESUMO

Objective: Using field epidemiological investigation and molecular analysis to construct the molecular transmission network of human immunodeficiency virus/acquired immunodeficiency syndrome cases (HIV/AIDS) newly diagnosed in Huzhou in 2017, Zhejiang Province. Methods: A total of 160 participants were obtained through a web-based system from Chinese Center for Disease Control and Prevention (CCDC) with the features of diagnosed in Huzhou in 2017 who also had been collected samples for the first follow-up. The basic information of demographic characteristics and risk factors was extracted from the website. RNA was extracted from plasma samples of untreated cases, followed by RT-PCR and nest-PCR for pol gene amplification, sequencing. Phylogenetic tree was constructed by MEGA software for HIV gene subtyping. TN93 model was used for calculating the distance between two sequences. Cytoscape software was used for drawing molecular transmission network. And then an epidemiological survey was conducted to cases in the primary cluster. Results: A total of 138 sequenced individuals (86.3%) were acquired from 160 individuals. Among which, 123 (89.1%) were male. The highest proportion of subtype was CRF07_BC (60, 43.5%), followed by CRF01_AE (46, 33.3%), and with four cases of Unique Recombinant Form (URF, CRF01_AE and CRF07_BC) and one case of URF (subtype B and C). A total of 18 molecular clusters included 56 individuals (40.6%) were found in the transmission network under the optimal genetic distance threshold (1.0%). The clustering proportion of CRF07_BC (66.1%, 37 cases) was higher than that of CRF01_AE. There were 9 clusters formed among CRF07_BC, including 37 cases (accounting for 61.7%, 37/60). The primary transmission cluster contained 11 cases, among which 9 cases were transmitted by homosexual sex. The first time of the cases to have homosexual behavior is range from 2010 to 2016, whose media number (P(25), P(75)) of partners was 6 (3.5, 8.5). Most of the cases come from Anhui Province and engaged in garment industry (5 cases), between which there were 8 cases used Blued software to seek for casual partners, 1 case seeking for casual partners in garden. Conclusion: With CRF07_BC and CRF01_AE predominantly circulating, HIV genetic diversity had been noticed in this area. The primary cluster was consisted of high proportion of locally new infections, and a specific population aggregation in limited place existed.


Assuntos
Síndrome de Imunodeficiência Adquirida/transmissão , Infecções por HIV/transmissão , HIV-1/genética , Síndrome de Imunodeficiência Adquirida/diagnóstico , China , Amplificação de Genes , Genótipo , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Humanos , Masculino , Epidemiologia Molecular , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
4.
Arch Virol ; 164(12): 3081-3087, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576459

RESUMO

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.


Assuntos
Infecções por HIV/virologia , HIV-1/classificação , HIV-1/isolamento & purificação , Adulto , Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Feminino , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Paquistão/epidemiologia , Filogenia , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
5.
BMC Infect Dis ; 19(1): 815, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533639

RESUMO

BACKGROUND: Elite controllers (EC), a small subset of the HIV-positive population (< 1%), suppress HIV viremia below the limit of quantification of clinical viral load assays in the absence of antiretroviral therapy (ART). However, there is a paucity of longitudinal data detailing the viral and immune dynamics or HIV reservoir seeding during acute infection in individuals that go on to become Elite Controllers. CASE PRESENTATION: In this report, we describe a case of a 42 year old woman diagnosed during acute infection who rapidly and permanently suppressed her viremia in the absence of antiretroviral therapy (ART). Rapid antibody/antigen testing was either negative or equivocal during acute infection, despite subsequent viral load testing at that time point with 71,550 plasma HIV RNA copies/mL, making initial diagnosis challenging. The patient subsequently developed detectable anti-HIV antibodies and an increase in HIV-specific CD8+ T cell responses to overlapping subtype C HIV gag peptide; very low-level plasma viremia (0.84 RNA copies/mL) was detected by an ultrasensitive assay 2 years following infection. Subsequently, she was started on ART for multifocal furunculosis despite continued suppression of virus and stable CD4+ T cell counts. Following ART initiation, HIV specific antibody levels and CD8+ T cell responses increased, but no HIV DNA or RNA was able to be isolated from large numbers of peripheral blood CD4+ T cells. CONCLUSION: This case provides important information regarding the establishment of elite HIV control during acute infection and also demonstrates an increase in HIV-specific immune responses following ART despite undetectable peripheral blood cellular measures of HIV persistence. This case also highlights the challenges in diagnosing acute HIV infection without the use of viral load testing in this rare elite controller phenotype.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1/genética , Humanos , RNA Viral/sangue , Carga Viral
6.
BMC Infect Dis ; 19(Suppl 1): 787, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31526373

RESUMO

BACKGROUND: South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. METHODS: Three nationally representative surveys were conducted in 2010, 2011-12 and 2012-13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4-8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. RESULTS: Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45-58%]) of HIV PCR positive infants, 37% (95% CI [28-47%]) in 2010, 64% (95% CI [53-74%]) in 2011 and 63% (95% CI [47-77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. CONCLUSIONS: These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/imunologia , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Aleitamento Materno , Contagem de Linfócito CD4 , Pré-Escolar , Estudos Transversais , Teste em Amostras de Sangue Seco , Feminino , Infecções por HIV/diagnóstico , Soropositividade para HIV , HIV-1/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Lactação , Mães , Período Pós-Parto , Gravidez , Prevalência , Inibidores da Transcriptase Reversa/uso terapêutico , Autorrelato , África do Sul/epidemiologia
7.
Cell Host Microbe ; 26(3): 347-358.e7, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31471273

RESUMO

Viral rebound upon stopping combined antiretroviral therapy poses a major barrier toward an HIV cure. Cellular and anatomical sources responsible for reinitiating viral replication remain a subject of ardent debate, despite extensive research efforts. To unravel the source of rebounding viruses, we conducted a large-scale HIV-STAR (HIV-1 sequencing before analytical treatment interruption to identify the anatomically relevant HIV reservoir) clinical trial. We collected samples from 11 participants and compared the genetic composition of (pro)viruses collected under treatment from different cellular and anatomical compartments with that of plasma viruses sampled during analytical treatment interruption. We found a remarkably heterogeneous source of viral rebound. In addition, irrespective of the compartment or cell subset, genetically identical viral expansions played a significant role in viral rebound. Our study suggests that although there does not seem to be a primary source for rebound HIV, cellular proliferation is an important driver of HIV persistence and should therefore be considered in future curative strategies.


Assuntos
Infecções por HIV/virologia , HIV-1/genética , Dispositivos de Acesso Vascular/virologia , Antirretrovirais/uso terapêutico , Medula Óssea/virologia , Proliferação de Células , Líquido Cefalorraquidiano/virologia , Feminino , Genes Virais , HIV-1/isolamento & purificação , Humanos , Cinética , Linfonodos/virologia , Tecido Linfoide/virologia , Masculino , Plasma , Carga Viral , Replicação Viral
8.
Int J Infect Dis ; 88: 73-79, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401201

RESUMO

BACKGROUND: Severe cases of primary HIV infection have been described in patients presenting with neurological involvement, AIDS defining events or other life-threatening events. These severe forms have not been fully studied. OBJECTIVES: To determine the prevalence and characteristics of severe PHI in a hospital-based cohort of primary HIV infection, and the response to the early initiation of antiretroviral therapy (ART) at 12 months. METHODS: Every patient with PHI attending Hospital Clínic of Barcelona (1997-2015) was evaluated. Severe PHI was defined using clinical, analytical and immunological criteria. Chi-squared test was used for categorical variables and Student's t-test for quantitative variables. RESULTS: 33% of 224 PHI patients (95% CI: 26.84%-39.16%) had a severe PHI. These patients had more symptoms, abnormal analytical parameters and hospital admissions. The severe PHI group had a significantly higher viral load although no differences were observed at 12 months in terms of viral suppression or CD4 count recovery. None died during PHI. CONCLUSIONS: Up to one third of patients in our cohort presented with a severe PHI, which was associated with higher hospitalization rates and higher plasma HIV RNA viral load. However, severe forms were not associated to a worse clinical, immunological or virological outcome at 12 months.


Assuntos
Infecções por HIV/tratamento farmacológico , Adulto , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/isolamento & purificação , HIV-1/fisiologia , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Carga Viral
10.
Pan Afr Med J ; 32: 215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404285

RESUMO

Introduction: Kaposi's sarcoma (KS) is a kind of cancer that causes flat or raised lesions containing Human herpes virus 8 (HHV8). The KS lesions are common among immunosuppressed HIV patients. Highly Active Antiretroviral (HHART) treats and prevents the development of KS. The objective of this study was to determine the presence of K1 and K15 (predominant alleles) genes in Kaposi's sarcoma-associated herpes virus (KSHV) among immunosuppressed patients due to HIV-1. Methods: This was a cross-sectional descriptive study where consecutive sampling technique was adopted to pick archived tissue blocks from the Thematic Unit of Anatomic Pathology, Department of Human Pathology, College of Health Sciences, University of Nairobi and Department of Laboratory Medicine, Histology Section, Kenyatta National Hospital. Results: Upon staining 81 tissue blocks with H & E, 84% (68/81) were diagnosed as KS and 16% (13/81) as KS-like. The K1 and K15 (P) genes were both detected at 88.9% (72/81) in the tissue blocks, with 95.8% (69/72) detection from KS and 4.2% (3/72) from the KS-like. Conclusion: The K1 and K15 (P) genes of KSHV were present among the immunosuppressed patients with Human Immunodeficiency Virus (HIV)-1. It is important to carry out K1 and K15 (P) genes detection on tissues that are diagnosed as KS or KS-like by histology technique.


Assuntos
Infecções por HIV/complicações , Sarcoma de Kaposi/genética , Proteínas Virais/genética , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/genética , Adolescente , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , HIV-1/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/etiologia , Adulto Jovem
11.
BMC Bioinformatics ; 20(1): 410, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362714

RESUMO

BACKGROUND: Antiretroviral drugs are a very effective therapy against HIV infection. However, the high mutation rate of HIV permits the emergence of variants that can be resistant to the drug treatment. Predicting drug resistance to previously unobserved variants is therefore very important for an optimum medical treatment. In this paper, we propose the use of weighted categorical kernel functions to predict drug resistance from virus sequence data. These kernel functions are very simple to implement and are able to take into account HIV data particularities, such as allele mixtures, and to weigh the different importance of each protein residue, as it is known that not all positions contribute equally to the resistance. RESULTS: We analyzed 21 drugs of four classes: protease inhibitors (PI), integrase inhibitors (INI), nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI). We compared two categorical kernel functions, Overlap and Jaccard, against two well-known noncategorical kernel functions (Linear and RBF) and Random Forest (RF). Weighted versions of these kernels were also considered, where the weights were obtained from the RF decrease in node impurity. The Jaccard kernel was the best method, either in its weighted or unweighted form, for 20 out of the 21 drugs. CONCLUSIONS: Results show that kernels that take into account both the categorical nature of the data and the presence of mixtures consistently result in the best prediction model. The advantage of including weights depended on the protein targeted by the drug. In the case of reverse transcriptase, weights based in the relative importance of each position clearly increased the prediction performance, while the improvement in the protease was much smaller. This seems to be related to the distribution of weights, as measured by the Gini index. All methods described, together with documentation and examples, are freely available at https://bitbucket.org/elies_ramon/catkern.


Assuntos
Algoritmos , Biologia Computacional/métodos , Farmacorresistência Viral/genética , HIV-1/genética , Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/efeitos dos fármacos , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Humanos , Modelos Lineares , Análise de Componente Principal
12.
N Engl J Med ; 381(9): 816-826, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31339676

RESUMO

BACKGROUND: An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings. METHODS: We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points. RESULTS: A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P<0.001 for noninferiority). Among those with a baseline viral load of at least 100,000 copies per milliliter, a viral load of less than 50 copies per milliliter was observed in 137 of 207 participants (66.2%) in the dolutegravir group and in 123 of 200 participants (61.5%) in the EFV400 group, with a difference of 4.7 percentage points (95% CI, -4.6 to 14.0). Virologic failure (a viral load of >1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%). CONCLUSIONS: In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.).


Assuntos
Benzoxazinas/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Adulto , Benzoxazinas/efeitos adversos , Quimioterapia Combinada , Feminino , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lamivudina/administração & dosagem , Masculino , Obesidade/induzido quimicamente , Gravidez , RNA Viral/sangue , Tenofovir/administração & dosagem , Carga Viral/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
13.
N Engl J Med ; 381(9): 803-815, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31339677

RESUMO

BACKGROUND: Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries. METHODS: We conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs - TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) - against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48-week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, -10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTS: A total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONS: Treatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.).


Assuntos
Adenina/análogos & derivados , Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Ácidos Fosforosos/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Inibidores de Integrase de HIV/administração & dosagem , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Ácidos Fosforosos/efeitos adversos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Pró-Fármacos/administração & dosagem , RNA Viral/sangue , Uracila/administração & dosagem , Uracila/análogos & derivados , Carga Viral , Adulto Jovem
14.
Nat Commun ; 10(1): 3193, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324762

RESUMO

The HIV-1 reservoir is the major hurdle to a cure. We here evaluate viral and host characteristics associated with reservoir size and long-term dynamics in 1,057 individuals on suppressive antiretroviral therapy for a median of 5.4 years. At the population level, the reservoir decreases with diminishing differences over time, but increases in 26.6% of individuals. Viral blips and low-level viremia are significantly associated with slower reservoir decay. Initiation of ART within the first year of infection, pretreatment viral load, and ethnicity affect reservoir size, but less so long-term dynamics. Viral blips and low-level viremia are thus relevant for reservoir and cure studies.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Reservatórios de Doenças , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Adulto , Feminino , Infecções por HIV/sangue , HIV-1/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , RNA Viral/sangue , Carga Viral , Viremia , Latência Viral/efeitos dos fármacos
17.
Georgian Med News ; (290): 73-77, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31322519

RESUMO

The problem of HBV and HCV infections in addition to the HIV-infection in sub-Saharan African countries remains important due to the high prevalence and mortality after fast progressing fibrogenesis and development of hepatocellular carcinoma. Despite of the large number of investigations on diagnostics and prediction of the disease course, the exact role of the proinflammatory influence of IP-10 and IL-17A on the fibrogenesis during HIV/HBV-co-infection is still unknown. The aim of the study was to investigate IP-10 and IL-17A concentration in blood serum among HIV/HBV patients to consider their potential role in improvement of diagnostics of liver fibrosis progression. 53 HIV/HBV patients of Lewanika General Hospital (West Zambia) and 21 healthy blood donors were checked for serological markers, liver biopsy and IP-10, IL-17A in blood serum. The obtained results were analyzed by statistical package SPSS 12.0. Mean IP-10 was 753,6 pg/ml among HIV/HBV co-infected patients with F3-4 and it was reliably higher than in F1-2 patients and healthy responders (р=0,005). This group had also higher level of IL-17A (37,54 pg/ml) than comparison groups (р=0,032). We found out strong correlation between increasing IP-10 (r=0,6), IL-17A (r=0,52) and fibrotic severity (р<0,05). High IP-10, IL-17A amount increases the risk of F3-4 formation in HIV/HBV patients.


Assuntos
Quimiocina CXCL10/sangue , Coinfecção/epidemiologia , Infecções por HIV/complicações , HIV-1/isolamento & purificação , Hepatite B/complicações , Interleucina-17/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Fígado/virologia , Soro/virologia , Adulto , Biomarcadores/sangue , Biópsia , Estudos de Casos e Controles , Quimiocina CXCL10/imunologia , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Hepatite B/sangue , Hepatite B/epidemiologia , Vírus da Hepatite B , Humanos , Interleucina-17/imunologia , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Zâmbia/epidemiologia
18.
BMC Infect Dis ; 19(1): 588, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277590

RESUMO

BACKGROUND: HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described. CASE PRESENTATION: Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4+ T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009-2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B1). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B2) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B2 variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8+ and CD4+ T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period. CONCLUSIONS: Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Superinfecção/virologia , Replicação Viral/fisiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , HIV-1/patogenicidade , Antígenos HLA-B/genética , Humanos , Leucócitos Mononucleares/virologia , Masculino , Filogenia , RNA Viral/sangue , Sífilis/diagnóstico , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(6): 648-653, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31238613

RESUMO

Objective: To explore HIV-1 drug resistance and influencing factors among people living with HIV/AIDS before antiretroviral therapy in Liangshan Yi Autonomous Prefecture (Liangshan). Methods: Between January 1 and June 30, in both 2017 and 2018, a cross-sectional survey was conducted in Liangshan HIV-1 pol sequences were gathered and analyzed according to WHO Guidelines on HIV drug resistance surveillance of 2014. Both HyPhy 2.2.4 and Cytoscape 3.6.1 software were used to analyze the drug resistant strains of HIV-1 transmission network. Results: A total of 464 people living with HIV/AIDS was recruited. The proportion of HIV-1 CRF07_BC subtype was 88.6% (411/464), with HIV-1 drug resistance rate was 9.9% (46/464). The HIV-1 drug resistance rates of non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors(NRTI) and protease inhibitors (PI) were 6.7% (31/464), 1.9% (9/464) and 0.4% (2/464) respectively. New recombinant strains of HIV-1 URF_01BC subtype was independently clustered according to the drug resistant mutation sites. Results from the multivariate logistic analysis showed that injected drug users group had higher risk on HIV-1 drug resistance (aOR=3.03, 95%CI:1.40-6.54) than heterosexual group among people living with HIV/AIDS. Conclusions: HIV-1 drug resistance rate had already been in a high level before antiretroviral therapy was in place. The newly identified recombinant strains of HIV-1 URF_01BC subtype were independently clustered according to the drug resistant mutation sites. It was necessary to strengthen the prevention of the HIV-1 drug resistant strains transmission.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , China/epidemiologia , Estudos Transversais , Infecções por HIV/epidemiologia , HIV-1/isolamento & purificação , Humanos , Mutação , Análise de Sequência de DNA , Carga Viral
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