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1.
Science ; 371(6526): 284-288, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33446556

RESUMO

The ability for viruses to mutate and evade the human immune system and cause infection, called viral escape, remains an obstacle to antiviral and vaccine development. Understanding the complex rules that govern escape could inform therapeutic design. We modeled viral escape with machine learning algorithms originally developed for human natural language. We identified escape mutations as those that preserve viral infectivity but cause a virus to look different to the immune system, akin to word changes that preserve a sentence's grammaticality but change its meaning. With this approach, language models of influenza hemagglutinin, HIV-1 envelope glycoprotein (HIV Env), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike viral proteins can accurately predict structural escape patterns using sequence data alone. Our study represents a promising conceptual bridge between natural language and viral evolution.


Assuntos
Síndrome de Imunodeficiência Adquirida/imunologia , HIV-1/genética , Vírus da Influenza A/genética , Influenza Humana/imunologia , /genética , Síndrome de Imunodeficiência Adquirida/virologia , Sítios de Ligação , Evolução Molecular , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Influenza Humana/virologia , Mutação , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/química , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
2.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375194

RESUMO

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients' prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.


Assuntos
Infecções Bacterianas/complicações , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , Viroses/complicações , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/patologia , Síndrome de Imunodeficiência Adquirida/terapia , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/patologia , /patologia , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Carcinoma Pulmonar de Células não Pequenas/virologia , HIV/efeitos dos fármacos , Hepatite B/complicações , Hepatite B/imunologia , Hepatite B/patologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Humanos , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/virologia , Microbiota/efeitos dos fármacos , Microbiota/imunologia
3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(12): 2093-2097, 2020 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-33378822

RESUMO

Objective: To analyze influencing factors of instant antiretroviral therapy (ART) and explore associution between strategies of ART and immunological effects among HIV/AIDS patients in Taizhou city during 2006-2019. Methods: A retrospective cohort study was conducted on HIV/AIDS patients under ART, and a logistic regression model was used to analyze factors of instant ART. The student t-test and chi-square test were used to compare immunological effect of different ART strategies while the Kaplan-Meier method was used to generate a survival curve. Results: A total of 2 971 HIV/AIDS patients were enrolled with 1 786 cases (60.1%) having instant ART strategy. The proportion of instant ART were 77.8% (1 170/1 504) during 2016 to 2019. The treatment success rate of the instant ART group (87.4%, 1 561/1 786) were higher than the delayed ART group (84.4%, 1 000/1 185). The results of multivariate logistic regression model indicated that male (aOR=1.28, 95%CI: 1.03-1.59), married (aOR=1.71, 95%CI: 1.33-2.19) and baseline CD(4)(+)T lymphocyte cells (CD(4)) counts ≤200 cells/µl (aOR=1.60, 95%CI: 1.27-2.02) were factors positively related to instant ART while 31-40 years old (aOR=0.63, 95%CI: 0.48-0.84), infected through heterosexual transmission(aOR=0.60, 95%CI: 0.49-0.74) and diagnosed before 2015 (aOR=0.20, 95%CI: 0.17-0.23) were inversely related to instant ART. The increase of the CD(4)/CD(8) ratio was greater, and the cumulative ART success rate was higher each year in the instant ART group than in the delayed ART group (P<0.05). Conclusions: The instant ART strategy has been well implemented in Taizhou city during 2006-2019, and the immunological effect was better in instant ART group. The proportion of instant ART were more than 60.0% among HIV/AIDS patients. Instant ART strategy needs to be strengthened for those who are 31-40 years old, women, unmarried, and infected through heterosexual transmission in an attempt to further increase treatment level and improve treatment effect.


Assuntos
Síndrome de Imunodeficiência Adquirida , Antirretrovirais , Infecções por HIV , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/imunologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4/estatística & dados numéricos , China/epidemiologia , Cidades/epidemiologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Masculino , Estudos Retrospectivos , Fatores Socioeconômicos , Resultado do Tratamento
4.
PLoS One ; 15(12): e0243773, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33351812

RESUMO

The objective of this study was to elucidate the burden, risk factors, and prognosis of serious non-AIDS-defining events among admitted cART-naive AIDS patients in China. The evaluation of the burden, risk factors and prognosis of serious NADEs was carried out among 1309 cART-naive AIDS patients (median age: 38.2 years, range: 18-78 years) admitted in Beijing Ditan Hospital between January 2009 and December 2018. Among 1309 patients, 143 patients (10.9%) had at least one serious NADEs, including 49 (3.8%) with cerebrovascular diseases, 37 (2.8%) with non-AIDS-defining cancers, 28 (2.1%) with chronic kidney diseases, 26 (2.0%) with cardiovascular diseases, and 18 (1.4%) with liver cirrhosis. Serious NADEs distributed in different age and CD4 levels, especially with age ≥50 years and CD4 ≤350 cells/ul. Other traditional risk factors, including cigarette smoking (OR = 1.9, 95%CI = 1.3-2.8, p = 0.002), hypertension (OR = 2.5, 95%CI = 1.7-3.7, p<0.001), chronic HCV infection (OR = 2.8, 95%CI = 1.4-5.6, p = 0.004), and hypercholesterolemia (OR = 4.1, 95% CI = 1.2-14.1, p = 0.026), were also associated with serious NADEs. Seventeen cases (1.3%) with serious NADEs died among hospitalized cART-naive AIDS patients, and severe pneumonia (HR = 5.5, 95%CI = 1.9-15.9, p<0.001) and AIDS-defining cancers (HR = 3.8, 95%CI = 1.1-13.2, p = 0.038) were identified as risk factors associated with an increased hazard of mortality among these patients with serious NADEs. Serious NADEs also occurred in cART-naive AIDS patients in China with low prevalence. Our results reminded physicians that early screening of serious NADEs, timely intervention of their risk factors, management of severe AIDS-defining events, multi-disciplinary cooperation, and early initiation of cART were essential to reduce the burden of serious NADEs.


Assuntos
Síndrome de Imunodeficiência Adquirida/epidemiologia , Efeitos Psicossociais da Doença , Síndrome de Imunodeficiência Adquirida/diagnóstico , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/imunologia , Distribuição por Idade , Idoso , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , China/epidemiologia , Estudos de Coortes , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
5.
BMC Infect Dis ; 20(1): 546, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711474

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV-1) infection is characterized by high viral replication and a decrease in CD4+ T cells (CD4+TC), resulting in AIDS, which can lead to death. In elite controllers and viremia controllers, viral replication is naturally controlled, with maintenance of CD4+TC levels without the use of antiretroviral therapy (ART). METHODS: The aim of the present study was to describe virological and immunological risk factors among HIV-1-infected individuals according to characteristics of progression to AIDS. The sample included 30 treatment-naive patients classified into three groups based on infection duration (> 6 years), CD4+TC count and viral load: (i) 2 elite controllers (ECs), (ii) 7 viremia controllers (VCs) and (iii) 21 nonviremia controllers (NVCs). Nested PCR was employed to amplify the virus genome, which was later sequenced using the Ion PGM platform for subtyping and analysis of immune escape mutations. RESULTS: Viral samples were classified as HIV-1 subtypes B and F. Greater selection pressure on mutations was observed in the group of viremia controllers, with a higher frequency of immunological escape mutations in the genes investigated, including two new mutations in gag. The viral sequences of viremia controllers and nonviremia controllers did not differ significantly regarding the presence of immune escape mutations. CONCLUSION: The results suggest that progression to AIDS is not dependent on a single variable but rather on a set of characteristics and pressures exerted by virus biology and interactions with immunogenetic host factors.


Assuntos
Síndrome de Imunodeficiência Adquirida/imunologia , HIV-1/genética , Evasão da Resposta Imune/genética , Mutação/imunologia , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Brasil , Linfócitos T CD4-Positivos/imunologia , Estudos Transversais , Feminino , Genes gag/genética , Humanos , Masculino , Filogenia , Conformação Proteica , Estudos Retrospectivos , Carga Viral , Viremia/genética , Replicação Viral/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/química , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
6.
Adv Exp Med Biol ; 1228: 411-421, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32342474

RESUMO

Physical exercise is a common type of planned physical activity in order to enhance or maintain a person's physical fitness. Physical exercise may act as an effective strategy to take control of certain conditions associated with HIV-1 infection. HIV infection and its related treatments not only affect the immune system but also cause several musculoskeletal disorders including pre-sarcopenia or sarcopenia, myalgia, and low bone mineral density. Moderate- to high-intensity aerobic exercise, progressive resistance exercise, or a combination of both is considered as a complementary part of medical care and treatment of HIV-infected individuals. In the present chapter, the results of recent investigations regarding the effects of physical activity on muscle strength and function, mental health, and immune system of HIV infected individuals will be discussed.


Assuntos
Exercício Físico/fisiologia , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Saúde Mental , Qualidade de Vida , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/psicologia , Síndrome de Imunodeficiência Adquirida/terapia , HIV/imunologia , HIV/patogenicidade , Infecções por HIV/terapia , Humanos
7.
PLoS One ; 15(3): e0228163, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130229

RESUMO

Anti-retroviral therapy (ART) has been highly successful in controlling HIV replication, reducing viral burden, and preventing both progression to AIDS and viral transmission. Yet, ART alone cannot cure the infection. Even after years of successful therapy, ART withdrawal leads inevitably to viral rebound within a few weeks or months. Our hypothesis: effective therapy must control both the replicating virus pool and the reactivatable latent viral reservoir. To do this, we have combined ART and immunotherapy to attack both viral pools simultaneously. The vaccine regimen consisted of DNA vaccine expressing SIV Gag, followed by a boost with live attenuated rubella/gag vectors. The vectors grow well in rhesus macaques, and they are potent immunogens when used in a prime and boost strategy. We infected rhesus macaques by high dose mucosal challenge with virulent SIVmac251 and waited three days to allow viral dissemination and establishment of a reactivatable viral reservoir before starting ART. While on ART, the control group received control DNA and empty rubella vaccine, while the immunotherapy group received DNA/gag prime, followed by boosts with rubella vectors expressing SIV gag over 27 weeks. Both groups had a vaccine "take" to rubella, and the vaccine group developed antibodies and T cells specific for Gag. Five weeks after the last immunization, we stopped ART and monitored virus rebound. All four control animals eventually had a viral rebound, and two were euthanized for AIDS. One control macaque did not rebound until 2 years after ART release. In contrast, there was only one viral rebound in the vaccine group. Three out of four vaccinees had no viral rebound, even after CD8 depletion, and they remain in drug-free viral remission more than 2.5 years later. The strategy of early ART combined with immunotherapy can produce a sustained SIV remission in macaques and may be relevant for immunotherapy of HIV in humans.


Assuntos
Síndrome de Imunodeficiência Adquirida/terapia , Fármacos Anti-HIV/uso terapêutico , Vacinas contra a SAIDS/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/terapia , Vírus da Imunodeficiência Símia/imunologia , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/virologia , Animais , Terapia Combinada/métodos , Modelos Animais de Doenças , Esquema de Medicação , Quimioterapia Combinada/métodos , Produtos do Gene gag/genética , Produtos do Gene gag/imunologia , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Macaca mulatta , Plasmídeos/administração & dosagem , Plasmídeos/genética , Vírus da Rubéola/imunologia , Vacinas contra a SAIDS/genética , Síndrome de Imunodeficiência Adquirida dos Símios/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/isolamento & purificação , Fatores de Tempo , Resultado do Tratamento , Vacinas Atenuadas/administração & dosagem , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Latência Viral/efeitos dos fármacos , Latência Viral/imunologia , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
8.
Gastroenterology ; 158(6): 1546-1547, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32017908

Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Coinfecção/diagnóstico , Granuloma/diagnóstico , Proctite/diagnóstico , Doenças Sexualmente Transmissíveis/diagnóstico , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/imunologia , Antibacterianos/administração & dosagem , Antivirais/administração & dosagem , Ceftriaxona/administração & dosagem , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Coinfecção/tratamento farmacológico , Coinfecção/imunologia , Coinfecção/microbiologia , Colonoscopia , Citomegalovirus/isolamento & purificação , DNA Bacteriano/isolamento & purificação , Doxiciclina/administração & dosagem , Quimioterapia Combinada/métodos , Granuloma/tratamento farmacológico , Granuloma/imunologia , Granuloma/microbiologia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , Proctite/tratamento farmacológico , Proctite/imunologia , Proctite/microbiologia , Reto/diagnóstico por imagem , Reto/microbiologia , Reto/patologia , Doenças Sexualmente Transmissíveis/tratamento farmacológico , Doenças Sexualmente Transmissíveis/imunologia , Doenças Sexualmente Transmissíveis/microbiologia , Resultado do Tratamento , Valganciclovir/administração & dosagem
9.
J Leukoc Biol ; 107(4): 597-612, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31965635

RESUMO

The morbidity and mortality of HIV type-1 (HIV-1)-related diseases were dramatically diminished by the grounds of the introduction of potent antiretroviral therapy, which induces persistent suppression of HIV-1 replication and gradual recovery of CD4+ T-cell counts. However, ∼10-40% of HIV-1-infected individuals fail to achieve normalization of CD4+ T-cell counts despite persistent virological suppression. These patients are referred to as "inadequate immunological responders," "immunodiscordant responders," or "immunological non-responders (INRs)" who show severe immunological dysfunction. Indeed, INRs are at an increased risk of clinical progression to AIDS and non-AIDS events and present higher rates of mortality than HIV-1-infected individuals with adequate immune reconstitution. To date, the underlying mechanism of incomplete immune reconstitution in HIV-1-infected patients has not been fully elucidated. In light of this limitation, it is of substantial practical significance to deeply understand the mechanism of immune reconstitution and design effective individualized treatment strategies. Therefore, in this review, we aim to highlight the mechanism and risk factors of incomplete immune reconstitution and strategies to intervene.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/imunologia , Terapia Antirretroviral de Alta Atividade , Reconstituição Imune , Síndrome de Imunodeficiência Adquirida/genética , Síndrome de Imunodeficiência Adquirida/microbiologia , Microbioma Gastrointestinal , Humanos
10.
PLoS One ; 15(1): e0225861, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31999715

RESUMO

Chemoprophylaxis (antibiotic prophylaxis) is a long relied-upon means of opportunistic infection management among HIV/AIDS patients, but its use represents an evolutionary tradeoff: Despite the benefits of chemoprophylaxis, widespread use of antibiotics creates a selective advantage for drug-resistant bacterial strains. Especially in the developing world, with combined resource limitations, antibiotic misuse, and often-poor infection control, the emergence of antibiotic resistance may pose a critical health risk. Extending previous work that demonstrated that this risk is heightened when a significant proportion of the population is HIV/AIDS-immunocompromised, we work to address the relationship between HIV/AIDS patients' use of antibiotic chemoprophylaxis and the emergence of resistance. We apply an SEIR compartmental model, parameterized to reflect varying percentages of chemoprophylaxis use among HIV/AIDS+ patients in a resource-limited setting, to investigate the magnitude of the risk of prophylaxis-associated emergence versus the individual-level benefits it is presumed to provide. The results from this model suggest that, while still providing tangible benefits to the individual, chemoprophylaxis is associated with negligible decreases in population-wide morbidity and mortality from bacterial infection, and may also fail to provide assumed efficacy in reduction of TB prevalence.


Assuntos
Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Hospedeiro Imunocomprometido , Políticas , Humanos , Probabilidade
11.
J Infect Chemother ; 26(2): 279-281, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31543435

RESUMO

We report an AIDS patient with a high HIV RNA copy number in the plasma who was successfully treated for prolonged Mycobacterium avium bacteremia and other complications. An HIV-infected patient with high fever, anemia, high alkaline phosphatase, cystic lung lesions, hepatitis B virus infection and Kaposi's sarcoma was referred to our hospital. PCR of the blood revealed Mycobacterium avium bacteremia and the time to blood culture positivity was 8 days. The HIV-1 RNA copy number in the plasma was more than ten million copies/ml and the CD4-positive T cell count was 21 cells/µL. Although the high fever resolved five days after therapy for Mycobacterium avium was started, the fever recurred just before starting anti-retroviral therapy (ART) including dolutegravir. The patient experienced repeated but self-limiting bouts of severe inflammation. Mycobacteremia was intermittently detected up to 79 days, suggesting that the recurrent episodes of inflammation were due to the intermittent dissemination of mycobacteria, and that persistent treatment is needed. Five months after the beginning of ART, the HIV-1 RNA copy number in the plasma was still 28,000 copies/ml. An HIV drug-resistance test revealed sensitivity to all anti-retroviral drugs. Eleven months after the initiation of ART, the HIV RNA copy number in the plasma decreased to 45 copies/mL and the CD4-positive T cell count recovered to 205 cells/µL. Our case also suggests that dolutegravir can be effective in cases with prolonged high levels of HIV RNA. Our findings emphasize that prompt diagnosis and persistent therapy for mycobacterial infection are important for successful treatment.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Bacteriemia/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , RNA Viral/sangue , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/imunologia , Adulto , Antibacterianos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Bacteriemia/complicações , Contagem de Linfócito CD4 , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inflamação/complicações , Masculino , Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/complicações , Oxazinas , Piperazinas , Piridonas , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Resultado do Tratamento
12.
J Infect Dis ; 221(5): 756-765, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-31581292

RESUMO

BACKGROUND: Multiple factors influence the human immunodeficiency virus (HIV) antibody response produced during natural infection, leading to responses that can vary in specificity, strength, and breadth. METHODS: People who inject drugs identified as recently infected with HIV (n = 23) were analyzed for clustering of their viral sequences (genetic distance, <2%). Longitudinal antibody responses were identified for neutralizing antibody (Nab) potential, and differences in antibody subclass, specificity, and Fc receptor ligation using pseudovirus entry and multiplexed Fc array assays, respectively. Responses were analyzed for differences between subject groups, defined by similarity in the sequence of the infecting virus. RESULTS: Viral sequences from infected individuals were grouped into 3 distinct clusters with 7 unclustered individuals. Subjects in cluster 1 generally had lower antibody response magnitudes, except for antibodies targeting the V1/V2 region. Subjects in clusters 2 and 3 typically had higher antibody response magnitudes, with the Fv specificity of cluster 2 favoring gp140 recognition. NAb responses differed significantly between clusters for 3 of 18 pseudoviruses examined (P < .05), but there were no differences in overall NAb breadth (P = .62). DISCUSSION: These data demonstrate that individuals infected with similar viral strains can generate partially similar antibody responses, but these do not drastically differ from those in individuals infected with relatively unrelated strains.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/epidemiologia , Epidemias , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Abuso de Substâncias por Via Intravenosa/complicações , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Anticorpos Neutralizantes/imunologia , Baltimore/epidemiologia , Sequência de Bases/genética , Análise por Conglomerados , Feminino , Seguimentos , Proteína gp41 do Envelope de HIV/genética , HIV-1/genética , Humanos , Estudos Longitudinais , Masculino , Filogenia , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
13.
Mol Cell Biochem ; 464(1-2): 65-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31732831

RESUMO

Human leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8+ T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC-II-encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR-RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 (C/T intron 7) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06-1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56-7.46), P = 0.0010] variants of TAP2 (A/G exon 11) (T665A) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case-control analysis might suggest a possible role of TAP2 (A/G exon 11) (T665A) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.


Assuntos
Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Síndrome de Imunodeficiência Adquirida/genética , Apresentação do Antígeno/genética , Predisposição Genética para Doença , HIV-1 , Polimorfismo Genético , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/imunologia , Membro 3 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/imunologia , Síndrome de Imunodeficiência Adquirida/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Int J Dermatol ; 59(3): 308-313, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31846069

RESUMO

BACKGROUND: The affecting factors of mucocutaneous manifestations in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients remain unclear in China. METHODS: A retrospective analysis was conducted among HIV/AIDS patients in Yunnan, China. The demographic data, mucocutaneous manifestations, CD4 cell counts, and antiretroviral therapy (ART) regimens were collected. The effects of CD4 cell count and ART on the spectrum of mucocutaneous manifestations were evaluated. RESULTS: Among 508 HIV/AIDS patients, 86.0% of cases showed mucocutaneous manifestations. The average CD4 cell count (176 cells/µl) of the patients with manifestations was significantly lower than those without manifestations (328 cells/µl) (P < 0.001). Diseases such as herpes zoster, oral candidiasis, condyloma acuminatum, genital herpes, oral leukoplakia, talaromycosis, cryptococcosis, and HIV-PPE (pruritic papular eruption) were represented quite frequently in patients with CD4 cell count <200 cells/µl (P < 0.05), but eczema was suffered by those with CD4 cell count ≥200 cells/µl (P < 0.05). ART could decline the incidence of herpes zoster, oral candidiasis, condyloma acuminatum, genital herpes, oral leukoplakia, talaromycosis, and cryptococcosis (P < 0.05). CONCLUSIONS: Mucocutaneous manifestations are closely related to the CD4 cell count and can be used as early predictors of HIV/AIDS and immune status in clinic. ART could reduce the incidence of certain mucocutaneous manifestations.


Assuntos
Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Infecções por HIV/epidemiologia , Dermatopatias/epidemiologia , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Síndrome de Imunodeficiência Adquirida/imunologia , Adolescente , Adulto , Idoso , Antirretrovirais/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatopatias/sangue , Dermatopatias/induzido quimicamente , Dermatopatias/imunologia , Adulto Jovem
15.
Viruses ; 12(1)2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878130

RESUMO

Dendritic cells (DCs) are involved in human and simian immunodeficiency virus (HIV and SIV) pathogenesis but also play a critical role in orchestrating innate and adaptive vaccine-specific immune responses. Effective HIV/SIV vaccines require strong antigen-specific CD4 T cell responses, cytotoxic activity of CD8 T cells, and neutralizing/non-neutralizing antibody production at mucosal and systemic sites. To develop a protective HIV/SIV vaccine, vaccine regimens including DCs themselves, protein, DNA, mRNA, virus vectors, and various combinations have been evaluated in different animal and human models. Recent studies have shown that DCs enhanced prophylactic HIV/SIV vaccine efficacy by producing pro-inflammatory cytokines, improving T cell responses, and recruiting effector cells to target tissues. DCs are also targets for therapeutic HIV/SIV vaccines due to their ability to reverse latency, present antigen, and augment T and B cell immunity. Here, we review the complex interactions of DCs over the course of HIV/SIV prophylactic and therapeutic immunizations, providing new insights into development of advanced DC-targeted HIV/SIV vaccines.


Assuntos
Vacinas contra a AIDS/imunologia , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/terapia , Células Dendríticas/imunologia , Vírus da Imunodeficiência Símia/imunologia , Síndrome de Imunodeficiência Adquirida/prevenção & controle , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Humanos , Macaca mulatta/imunologia
16.
Medicine (Baltimore) ; 98(41): e17525, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593126

RESUMO

To assess the intra-individual and inter-individuals biological variation and the effect of aging on lymphocyte T-cells subsets.We assessed lymphocyte phenotypes (CD3, CD4, and CD8 T-cells) in 89 HIV-1-infected and 88 uninfected white non-Hispanic men every 6 months, to examine the biological variation for those measurements, and the average change in lymphocyte phenotype over 34 years.The markers showed significant intra-individuality in HIV-infected and uninfected individuals with index of individuality of <1.4. No mean changes were seen over the 34 years, with the exception of percentage CD4T-cells in HIV-uninfected individuals.In the pre-HAART era, HIV-infected individuals experienced an increase in mean absolute CD3 T-cell numbers (11.21 cells/µL, P = 0.02) and absolute CD8 T-cell numbers (34.57 cell/µl, P < .001), and in the percentage of CD8 T-cells (1.45%, P < .001) per year and a significant decrease in mean absolute CD4 T-cell numbers (23.68 cells/µl, P < .001) and in the percentage of CD4 T-cells (1.49%, P < .001) per year.In the post-HAART era, no changes in mean levels were observed in absolute CD3 T-cell count (P = .15) or percentage (P = .99). Significant decreases were seen in mean count (8.56 cells/µl, P < .001) and percentage (0.59%, P < .001) of CD8 T-cells, and increases in mean absolute count (10.72 cells/µl, P < .001) and percentage (0.47%, P < .001) of CD4 T-cells.With the exception of CD4 (%), no average changes per year were seen in lymphocyte phenotype of HIV-uninfected men. The results of coefficients of variation of intra and inter-individuals of this study can be useful for HIV-1 infection monitoring and in addition the observation could be a useful guide for intra- and inter-individual coefficient variations, and establishing quality goal studies of different blood biomarkers in healthy and other diseases.


Assuntos
Síndrome de Imunodeficiência Adquirida/imunologia , Variação Biológica da População/imunologia , Infecções por HIV/imunologia , Subpopulações de Linfócitos T/imunologia , Síndrome de Imunodeficiência Adquirida/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Variação Biológica da População/etnologia , Biomarcadores/sangue , Complexo CD3/efeitos dos fármacos , Complexo CD3/imunologia , Complexo CD3/metabolismo , Antígenos CD4/imunologia , Antígenos CD4/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Senescência Celular/imunologia , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Los Angeles/epidemiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Fenótipo , Subpopulações de Linfócitos T/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3448-3453, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602908

RESUMO

The aim of this paper was to study the influence of triptolide in the immune response pathways of acquired immune deficiency syndrome( AIDS). Target proteins of triptolide and related genes of AIDS were searched in PubChem and Gene databases on line. Molecular networks and canonical pathways comparison analyses were performed by bioinformatics software( IPA). There were 15 targets proteins of triptolide and 258 related genes of AIDS. Close biological relationships of molecules of triptolide and AIDS were established by networks analysis. There were 21 common immune response pathways of triptolide and AIDS,including neuroinflammation signaling pathway,Th1 and Th2 activation pathway and role of pattern recognition receptors in recognition of bacteria and viruses. Triptolide stimulated immune response pathways by the main molecules of IFNγ,JAK2,NOD1,PTGS2,RORC. IFNγ is the focus nodes of triptolide and AIDS,and regulates genes of AIDS directly or indirectly. Triptolide may against AIDS by regulating molecules IFNγ in immune response pathways.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Diterpenos/farmacologia , Interferon gama/genética , Fenantrenos/farmacologia , Síndrome de Imunodeficiência Adquirida/imunologia , Biologia Computacional , Compostos de Epóxi/farmacologia , Redes Reguladoras de Genes , Humanos , Receptores de Reconhecimento de Padrão/imunologia , Transdução de Sinais , Linfócitos T/imunologia
18.
Turkiye Parazitol Derg ; 43(Suppl 1): 1-7, 2019 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-31587535

RESUMO

Objective: Since symptomatic toxoplasmosis in in human immunodeficiency virus (HIV)/Acquired immunodeficiency syndrome (AIDS) almost always occurs as a result of reactivation of chronic infection, screening Toxoplasma serology has an important role in the follow up of the main disease in these populations. In this meta-analysis, we aimed to reveal the difference in the seroprevalence rates of Toxoplasma gondii infection between groups in relation to CD4 counts (CD4-counts ≥200 and <200 cells/mm3) HIV-infected population. Methods: The meta-analysis was performed by searching for the studies in English that were published in the last 20-year period in databases including PubMed, Google Scholar, Embase, Science Direct and Web of Science. The process of searching was carried out using the keywords: "Acquired immunodeficiency syndrome", "AIDS", "Human immunodeficiency virus", "HIV", "Toxoplasma", "Toxoplasmosis", "Toxoplasma gondii", "seroprevalence", "prevalence" and "immunoglobulin G". Results: A total of 16 studies including 3982 seropositive samples of T. gondii, 2792 of which were in first group (HIV positive patients with CD4-counts ≥200 cells/mm3) and 1190 were in second group (HIV positive patients with CD4-counts <200 cells/mm3), were included in the meta-analysis. The seroprevalence of T. gondii was 40.03% in HIV-positive patients with CD4 counts ≥200 cells/mm3, and 43.5% in the group with CD4 counts <200 cells/mm3. Seroprevalence rates in the studies included in the meta-analysis showed variability (heterogeneity) in both groups and heterogeneity between studies was higher in group 1 [Group 1; Cochran Q=994.16, DF=15, I²=98.49%, p<0.0001 and group 2; Cochran Q=368.50, DF=15, I²=95.93%, p<0.0001]. Conclusion: We concluded that HIV/AIDS patients with low CD4 counts have higher epidemiological risk as well as immunological risk of toxoplasmosis. To the best of our knowledge, this is the first meta-analysis evaluating the seroprevalence of T. gondii in AIDS/HIV population by comparing the seroprevalance of T. gondii in subgroups formed according to CD4 counts.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Síndrome de Imunodeficiência Adquirida/imunologia , Anticorpos Antiprotozoários/sangue , Contagem de Linfócito CD4 , Gerenciamento de Dados , Feminino , Infecções por HIV/complicações , Infecções por HIV/imunologia , Humanos , Imunoglobulina G/sangue , Masculino , Fatores de Risco , Estudos Soroepidemiológicos , Toxoplasmose/complicações , Toxoplasmose/imunologia
19.
J Zhejiang Univ Sci B ; 20(10): 793-802, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489799

RESUMO

OBJECTIVE: In this study, we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive individuals (AIDS/HIV patients), and explored the relationships among intestinal flora, peripheral blood inflammatory factors, and CD4+ T lymphocytes. METHODS: Thirty blood and stool samples from an AIDS group and a control group were collected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA), and the number of CD4+ T lymphocytes by a FACSCount automated instrument. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the messenger RNA (mRNA) levels of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Correlations among intestinal flora, inflammatory factor levels, and CD4+ T lymphocyte values were evaluated using the Spearman correlation coefficient. RESULTS: The levels of TNF-α and IL-6 in the AIDS group were higher than those in the control group, while the number of CD4+ T lymphocytes was lower. The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group, while the amounts of E. coli, E. faecalis, and E. faecium were much higher. The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-α and IL-6 and the CD4+ T lymphocyte count, while those correlations were reversed for E. coli, E. faecalis, and E. faecium. CONCLUSIONS: The intestinal microbiota of AIDS/HIV patients were disordered, and there was a correlation between the amount of intestinal flora and the number of CD4+ T lymphocytes and the levels of TNF-α and IL-6.


Assuntos
Síndrome de Imunodeficiência Adquirida/imunologia , Microbioma Gastrointestinal , Infecções por HIV/imunologia , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Síndrome de Imunodeficiência Adquirida/microbiologia , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Clin Hypertens (Greenwich) ; 21(10): 1558-1566, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31448551

RESUMO

HIV infection is associated with increased risk and progression of cardiovascular disease (CVD), yet little is known about the prevalence of CVD risk factors among long-term AIDS survivors in resource-limited settings. Using routinely collected data, we conducted a retrospective study to describe the prevalence of CVD risk factors among a cohort of HIV-infected patients followed for over 10 years in Port-au Prince, Haiti. This cohort includes 910 adults who initiated antiretroviral therapy (ART) between 2003 and 2004 and remained in care between 2014 and 2016 when routine screening for CVD risk factors was implemented at a large clinic in Haiti. A total of 397 remained in care ≥10 years and received screening. At ART initiation, 59% were female, median age was 38 years (IQR 33-44), and median CD4 count was 117 cells/mm3 (IQR 34-201). Median follow-up time from ART initiation was 12.1 years (IQR 11.7-12.7). At screening, median CD4 count was 574 cells/mm3 (IQR 378-771), and 84% (282 of 336 screened) had HIV-1 RNA < 1000 copies/mL. Seventy-four percent of patients had at least 1 risk factor including 58% (224/385) with hypertension, 8% (24/297) diabetes, 43% (119/275) hypercholesterolemia, 8% (20/248) active smoking, and 10% (25/245) obesity. Factors associated with hypertension were age (adjusted OR 1.06, P < .001) and weight at screening (adjusted OR 1.02, P = .019). Long-term AIDS survivors have a high prevalence of CVD risk factors, primarily hypertension. Integration of cardiovascular screening and management into routine HIV care is needed to maximize health outcomes among aging HIV patients in resource-limited settings.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/complicações , Hipertensão/epidemiologia , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4/métodos , Contagem de Linfócito CD4/estatística & dados numéricos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Programas de Triagem Diagnóstica/normas , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , Haiti/epidemiologia , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/diagnóstico , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fumar/epidemiologia , Sobreviventes/estatística & dados numéricos
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