RESUMEN
Persistent inflammation contributes to the exhaustion of immune system and non-AIDS-defining events in HIV-infected patients. Transforming growth factor ß (TGF-ß) is generally considered an anti-inflammatory cytokine. It is unclear that why high-level TGF-ß coexists with chronic inflammation during HIV infection. In this study, it was found that HIV-infected patients had lower proportion of phosphorylated SMAD2/3-positive cells among total CD3+ T cells and subsets of CD3+CD8+ and CD3+CD8- T cells when compared with health subjects. The findings implied that phosphorylation of SMAD2/3 is inhibited in HIV-infected patients, and that disturbance of TGF-ß/SMAD2/3 signaling pathway may be involved in HIV-related chronic inflammation.
Asunto(s)
Infecciones por VIH , Transducción de Señal , Linfocitos T , Humanos , Inflamación , Fosforilación , Proteína Smad2/metabolismo , Factor de Crecimiento Transformador beta , Linfocitos T/metabolismoRESUMEN
Background: The immune activation caused by microbial translocation has been considered to be a major driver of HIV infection progression. The dysbiosis of gut microbiota has been demonstrated in HIV infection, but the interplay between gut microbiota and its metabolites in the pathogenesis of HIV is seldom reported. Methods: We conducted a case-controlled study including 41 AIDS patients, 39 pre-AIDS patients and 34 healthy controls. Both AIDS group and pre-AIDS group were divided according to clinical manifestations and CD4 + T cell count. We collected stool samples for 16S rDNA sequencing and untargeted metabolomics analysis, and examined immune activation and microbial translocation for blood samples. Results: The pre-AIDS and AIDS groups had higher levels of microbial translocation and immune activation. There were significant differences in gut microbiota and metabolites at different stages of HIV infection. Higher abundances of pathogenic bacteria or opportunistic pathogen, as well as lower abundances of butyrate-producing bacteria and bacteria with anti-inflammatory potential were associated with HIV severity. The metabolism of tryptophan was disordered after HIV infection. Lower level of anti-inflammatory metabolites and phosphonoacetate, and higher level of phenylethylamine and polyamines were observed in HIV infection. And microbial metabolic pathways related to altered metabolites differed. Moreover, disrupted metabolites contributed by altered microbiota were found to be correlated to microbial translocation and immune activation. Conclusions: Metabolites caused by dysbiosis of gut microbiota and related metabolic function are correlated to immune activation and microbial translocation, suggesting that the effect of microbiota on metabolites is related to intestinal barrier disruption in HIV infection.
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Síndrome de Inmunodeficiencia Adquirida , Microbioma Gastrointestinal , Infecciones por VIH , Humanos , Microbioma Gastrointestinal/genética , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Disbiosis/microbiología , Antiinflamatorios/uso terapéuticoRESUMEN
Shenlin Fuzheng Capsule (SLFZC) is a herbal preparation used for HIV/AIDS in Guangxi, China. This study was designed to evaluate the influence of SLFZC on the pharmacokinetics of highly active antiretroviral therapy (HAART) drugs, zidovudine (3'-azido-3'-deoythymidine, AZT), 2',3'-dideoxy-3'-thiacytidine (3TC) and efavirenz (EFV). Thirty-six male SD rats were divided into three groups. Group A was given a combination of AZT, 3TC and EFV (AZT/3TC/EFV). Group B rats were given AZT/3TC/EFV simultaneously with SLFZC. Group C rats were given AZT/3TC/EFV 2h prior to SLFZC. Blood samples were collected at fixed time intervals. Plasma concentration of each antiretroviral drug was tested for calculation of pharmacokinetic parameters. There was significant difference among groups with respect to t1/2 for AZT (F=3.371, P<0.05), but the Student-Newman-Keuls (SNK) pairwise multiple comparison procedure showed no statistical differences in all pairwise comparisons (P>0.05). There were no significant differences among groups in terms of Cmax, T max, AUC0-12h and CL for AZT, and t1/2, Cmax, Tmax, AUC0-12h and CL for 3TC and EFV, respectively. The results indicate that SLFZC has little impact on pharmacokinetic properties of AZT, 3TC and EFV.
Asunto(s)
Alquinos/farmacocinética , Benzoxazinas/farmacocinética , Ciclopropanos/farmacocinética , Interacciones de Hierba-Droga , Lamivudine/farmacocinética , Zidovudina/farmacocinética , Alquinos/sangre , Animales , Benzoxazinas/sangre , Ciclopropanos/sangre , Lamivudine/sangre , Masculino , Ratas , Zidovudina/sangreRESUMEN
Exosomes play an important role in cell-to-cell communication as they can transfer functional molecules such as microRNAs (miRNAs) from one cell to another, exerting biological and immunological functions. Here, we investigated the impact of HIV infection and/or heroin use on the expression of the miRNAs in plasma exosomes. We found that HIV infection or heroin use upregulated the majority (98%) of a panel of plasma exosomal miRNAs associated with immune regulation and inflammation. We also observed the enhanced effect of HIV infection and heroin use on some of these upregulated miRNAs. Our further investigation showed that the levels of four of neuro-inflammation-related miRNAs (146a, 126, 21, and let-7a) were higher in HIV-infected heroin users as compared with the control subjects. These findings indicate that the dysregulations of the plasma exosomal miRNAs support further studies to determine the role of the miRNAs in HIV and/or heroin use-mediated immune modulation and neuro-inflammation. Graphical abstract.
Asunto(s)
Exosomas/metabolismo , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Dependencia de Heroína/genética , Dependencia de Heroína/metabolismo , MicroARNs/sangre , Adulto , Comunicación Celular , Encefalitis/genética , Encefalitis/metabolismo , Femenino , Infecciones por VIH/inmunología , Dependencia de Heroína/inmunología , Humanos , Masculino , Persona de Mediana Edad , Síndromes de Neurotoxicidad/genética , Síndromes de Neurotoxicidad/metabolismo , Regulación hacia Arriba , Adulto JovenRESUMEN
OBJECTIVE: To investigate the impacts of two herbal preparations for human immunodeficiency virus/aquired immune deficiency syndrome (HIV/AIDS) patients, Shenling Fuzheng Capsule (, SLFZC) and Qingdu Capsule (, QDC), on the efficacy of highly active antiretroviral therapy (HAART). METHODS: HIV/AIDS patients met the criteria were all enrolled in a 1-year cohort study, in which patients receiving HAART alone were designated as Group A, those receiving HAART in combination with SLFZC were designated as Group B, and those receiving HAART in combination with QDC were designated as Group C, 100 cases in each group. The dose of SLFZC was 1.48 g (4 capsules), 3 times daily, and QDC 1.56 g (4 capsules), 3 times daily. T cell subsets, HIV RNA and HIV-1 drug resistance were detected at enrollment and 1 year after treatment. Patients were followed up every 3 months, during which side-effects and other clinical data were recorded. RESULTS: After 1-year treatment, the median increment in CD4 counts was 165.0, 178.0 and 145.0 cells/µL for Group A, B and C, respectively. HIV RNA was undetectable in 94% of patients in Group A, 96% in Group B and 92% in Group C. There were no differences regarding the increment in CD4 counts, HIV RNA and frequency of HIV-1 drug resistance mutations. Two of the 14 suspected side-effect symptoms, i.e. fatigue and dizziness, were lower in Groups B and C than in Group A (P<0.05, respectively) CONCLUSIONS: SLFZC and QDC do not have a negative impact on immunological and virological response to HAART; however, these preparations are not as potent in reducing HAART-associated side-effects as anticipated.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Fitoterapia/métodos , Preparaciones de Plantas/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Cápsulas , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The recently discovered IFN-λ4 has been found to have antiviral activity against several viruses. However, it's unknown whether IFN-λ4 can inhibit HIV infection. Here, we show that IFN-λ4 could suppress HIV infection of macrophages. This IFN-λ4-mediated HIV inhibition was compromised by the antibodies against IFN-λ receptor complex, IFN-λR1/IL-10R2. IFN-λ4 enhanced the phosphorylation of STAT1, and induced antiviral interferon-stimulated genes. These findings indicated that IFN-λ4 can inhibit HIV via JAK/STAT signalling pathway.
Asunto(s)
Fármacos Anti-VIH/farmacología , Infecciones por VIH/inmunología , Subunidad beta del Receptor de Interleucina-10/metabolismo , Interleucinas/metabolismo , Interleucinas/farmacología , Macrófagos/inmunología , Macrófagos/virología , Receptores de Citocinas/metabolismo , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Humanos , Técnicas In Vitro , Macrófagos/metabolismo , Receptores de Interferón , Proteínas Recombinantes/farmacología , Factor de Transcripción STAT1/metabolismo , Transducción de Señal , Replicación Viral/inmunologíaRESUMEN
Although it has been shown that some mannose-binding lectins (MBLs) exhibit significant activity against HIV infection, little is known about whether N-acetylgalactosamine (GalNAc)-binding lectins have the ability to inhibit HIV infection. Here, we demonstrate that a soybean-derived lectin (SBL) with GalNAc-binding affinity could potently suppress HIV infection of macrophages in a dose-dependent fashion. Unlike the MBLs, which block HIV only through binding to the glycosylated envelope proteins (gp120 and gp41) of the virus, SBL inhibited HIV at multiple steps of the virus infection/replication cycle. SBL could activate the beta interferon (IFN-ß)-STAT signaling pathway, resulting in the upregulation of a number of antiviral interferon-stimulated genes (ISGs) in macrophages. In addition, SBL treatment of macrophages induced the production of C-C chemokines, which bind to HIV entry coreceptor CCR5. Deglycosylation of cell surface galactosyl moieties or presaturation of GalNAc-binding capacity could compromise SBL-mediated induction of the antiviral factors. Furthermore, SBL exerted its anti-HIV activity in the low nanomolar range with no mitogenic effect on CD4+ T cells, a major advantage in the development of SBL as a potential anti-HIV agent compared with MBLs. These data indicate a necessity to further investigate SBL as an alternative and cost-effective anti-HIV natural product.IMPORTANCE Mannose-binding lectins (MBLs) can block the attachment of HIV to target cells and have been suggested as anti-HIV microbicides. However, the mitogenic effect of MBLs on CD4+ T cells limits this potential in clinical settings. Lectins with galactose (Gal)- or N-acetylgalactosamine (GalNAc)-binding specificity are another important category of carbohydrate-binding proteins (CBP). Compared to high-mannose N-linked glycans, GalNAc-type glycans present much less in HIV gp120 or gp41 glycosylation. Here, we demonstrate that GalNAc-specific soybean lectin (SBL) triggers antiviral signaling via recognition of the cell surface galactosyl group of macrophages, which results in the suppression of HIV at multiple steps. More importantly, SBL has no mitogenic effect on the activation of CD4+ T cells, a major advantage in the development of Gal/GalNAc-specific lectins as naturopathic anti-HIV agents.
Asunto(s)
Fármacos Anti-VIH/farmacología , Infecciones por VIH/tratamiento farmacológico , VIH-1/inmunología , Macrófagos/inmunología , Lectinas de Plantas/farmacología , Proteínas de Soja/farmacología , Internalización del Virus/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Proteína gp120 de Envoltorio del VIH/inmunología , Proteína gp41 de Envoltorio del VIH/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/patología , VIH-1/patogenicidad , Humanos , Interferón beta/inmunología , Macrófagos/patología , Macrófagos/virología , Receptores CCR5/inmunología , Factores de Transcripción STAT/inmunología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunologíaRESUMEN
Epidemiological studies have demonstrated that the human immunodeficiency virus (HIV)-1 drug-resistant rate among injecting drug users is higher than that in other HIV-1-positive populations, which is generally believed to be largely due to clinical nonadherence. Little is known, however, about whether heroin abuse has a direct impact on the generation of HIV-1 drug-resistant mutations. In this study, we investigated the impacts of morphine, the active metabolite of heroin, on HIV-1 infection/replication and HIV-1 drug-resistant mutations through an in vitro HIV-1-CD4+ T cell system under selective pressure from two typical antiviral drugs, Lamivudine and Nevirapine. We found that morphine treatment of MT4 cells (a CD4+ T cell line) significantly increased HIV-1 III B (a T-tropic viral strain) infection and replication in MT4 cells, and the effect of morphine on HIV-1 was mediated through an opioid receptor. More importantly, our results showed that morphine treatment not only induced more drug-resistant mutations under selective pressure from antiretroviral drugs but also shortened the mutations' generation time, compared with the control groups that were treated with antiretroviral drugs alone. Although the in vivo relevance remains to be determined, these findings provide direct in vitro evidence to support the possibility that heroin abuse itself can act as an independent factor contributing to the generation of HIV-1 drug resistance during clinical antiretroviral therapy. Therapeutic guidelines should consider this issue for heroin users with HIV infection.
Asunto(s)
Farmacorresistencia Viral/efectos de los fármacos , VIH-1/efectos de los fármacos , VIH-1/genética , Lamivudine/farmacología , Morfina/farmacología , Mutación/efectos de los fármacos , Nevirapina/farmacología , Fármacos Anti-VIH/farmacología , Línea Celular , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Humanos , Mutación/genética , Replicación Viral/efectos de los fármacos , Replicación Viral/genéticaRESUMEN
BACKGROUND: Although a number of in vitro studies have shown that methamphetamine (METH) can increase HIV-1 replication in human immune cells, a direct link between METH use and HIV-1 pathogenesis remains to be determined among HIV-1 patients. METHODS: According to the status of METH use and HIV-1 infection, we enrolled participants and divided them into four groups: METH+HIV+, METH-HIV+, METH+HIV-, and METH-HIV-. HIV viral loads and HIV-1-related cellular factors were measured and compared among different groups. RESULTS: A total of 60 participants were enrolled into this study, 15 within each group. HIV viral loads in METH+HIV+ group were significantly higher than those in METH-HIV+ group, while CD4+ T cell counts had an inverse trend between the two groups (p<0.05). METH users or HIV-1 infected patients had lower CCR5+, CXCR4+ percentages in CD4+ T cells than METH-HIV- subjects (p<0.01). However, METH use had little effect on CD3 expression in PBMCs and the levels of MIP-1α, MIP-1ß and IL-6 in PBMCs or plasma, which were increased by HIV-1 infection with or without METH. TLR-9 and IFN-α levels in PBMCs of METH users with or without HIV infection were higher than non-METH users (p<0.05). CONCLUSIONS: METH use is associated with higher viral loads and lower CD4+ T cell counts in HIV-infected individuals. This finding may be mediated by activation of innate immunity (TLR-9, IFN-α) by METH use.
Asunto(s)
Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/crecimiento & desarrollo , Metanfetamina/farmacología , Carga Viral/efectos de los fármacos , Adulto , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Quimiocina CCL3/sangre , Quimiocina CCL3/metabolismo , Quimiocina CCL4/sangre , Quimiocina CCL4/metabolismo , Regulación hacia Abajo , Femenino , Infecciones por VIH/inmunología , Humanos , Inmunidad Innata/efectos de los fármacos , Interferón-alfa/biosíntesis , Interleucina-6/sangre , Interleucina-6/metabolismo , Masculino , Metanfetamina/orina , Persona de Mediana Edad , Receptores CCR5/biosíntesis , Receptores CXCR4/biosíntesis , Receptor Toll-Like 9/biosíntesisRESUMEN
OBJECTIVE: To study pharmacokinetic effect of Aikeqing Granule (AG) by different medication ways on zidovudine (AZT) in highly active antiretroviral therapy ( HAART) of rats. METHODS: Totally 36 rats were administered with corresponding medications by gastrogavage, group I [HAART: AZT 31.5 mg/kg +3TC 31.5 mg/kg + Efavirenz (EFV) 63.0 mg/kg], group II (HAART+AG525 mg/kg), group III (HAART and AG 525 mg/kg after a 2-h interval). Drug concentrations of AZT were determined by high performance liquid chromatography-mass spectroscopy (HPLC-MS) before HAART, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after HAART, respectively. Pharmacokinetic parameters [such as t1/2, Tmax, Cmax, AUCo-t, plasma clearance rate (CL)] were calculated by DAS2.0 Software. RESULTS: The-equation of linear regression of AZT was good, with the precision, coefficient of recovery, and stability definitely confirmed. AUC in group II and III was larger than that of group I. There was no statistical difference in t1/2, Tmax, Cmax, AUC0-12 h, or AUC0-∞ among groups (P > 0.05). CONCLUSION: AG combined HAART could enhance the Cmax of AZT.
Asunto(s)
Medicamentos Herbarios Chinos/farmacocinética , Zidovudina/farmacocinética , Alquinos , Animales , Terapia Antirretroviral Altamente Activa , Benzoxazinas , Cromatografía Líquida de Alta Presión , Ciclopropanos , Medicamentos Herbarios Chinos/farmacología , Espectrometría de Masas , Ratas , Zidovudina/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Acanthus ilicifolius L. is an important medicinal mangrove plant. It is popularly used for its anti-inflammatory, antioxidant activity and hepatoprotective effects. The present study was conducted to evaluate the effect of treatment with alcohol extract of Acanthus ilicifolius L. on duck hepatitis B. MATERIALS AND METHODS: One-day-old Guangxi shelducks injected intraperitoneally with strong positive duck hepatitis B virus (DHBV) serum were used to establish a duck hepatitis B animal model in the study. The ducks were respectively administered in different groups with low-, middle- and high-dose alcohol extracts of Acanthus ilicifolius L., the positive control drug acyclovir (ACV) and double-distilled water. The levels of serum DHBV DNA were detected by fluorescence quantitative PCR (FQ-PCR). Duck hepatitis B surface antigen (DHBsAg) and duck hepatitis B e antigen (DHBeAg) OD values in the serum were measured by ELISA. The activity of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) in the serum was measured, and the livers were taken for histopathological examination. RESULTS: The levels of serum DHBV DNA and the values of DHBsAg and DHBeAg OD were not significant in any of the dose extract groups. However, the ALT activity was obviously lower in the middle- and high-dose extract groups. It was also found that a high dose of alcohol extract could reduce the activity of AST significantly and significantly improve hepatic pathological effects. CONCLUSIONS: High-dose alcohol extract of Acanthus ilicifolius L. has an obvious protective effect on the liver function and liver tissue. However, the present study finds that Acanthus ilicifolius L. cannot inhibit the replication of duck hepatitis B virus.
Asunto(s)
Acanthaceae/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Infecciones por Hepadnaviridae/tratamiento farmacológico , Virus de la Hepatitis B del Pato/efectos de los fármacos , Hepatitis Viral Animal/tratamiento farmacológico , Hígado/efectos de los fármacos , Fitoterapia , Aciclovir/farmacología , Aciclovir/uso terapéutico , Alanina Transaminasa/sangre , Animales , Animales Recién Nacidos , Antivirales/farmacología , Antivirales/uso terapéutico , Aspartato Aminotransferasas/sangre , ADN Viral/sangre , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Patos , Infecciones por Hepadnaviridae/patología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis Viral Animal/patología , Hígado/patología , Carga Viral/efectos de los fármacosRESUMEN
We conducted a study to determine whether an immunomodulator, polyactin A, is able to enhance the immunologic response in patients with insufficient immunologic response to highly active antiretroviral therapy. From 783 patients, 48 were eligible and were randomly assigned to an experimental group receiving polyactin A for 3 months or a control group. CD4(+) T-cell counts in the experimental group increased from 201 ± 31 to 228 ± 38 cells/µl after treatment (p < 0.001). CD4(+) T-cell counts in the control group and CD8(+) T-cell counts and CD4(+)/CD8(+) ratios in both groups did not differ significantly between baseline and month 3. The experimental group had a higher CD4(+) T-cell count than the control group at month 3 (228 ± 38 versus 205 ± 35, p < 0.05). Our work demonstrated that polyactin A can increase CD4(+) T-cell counts in patients with insufficient immunologic response to highly active antiretroviral therapy, but further studies are required to determine its clinical benefits.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Linfocitos T CD4-Positivos/efectos de los fármacos , Glicopéptidos/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/virología , Femenino , Glicopéptidos/sangre , Infecciones por VIH/virología , VIH-1/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Carga ViralRESUMEN
Toll-like receptor 9 (TLR9) is one of the key sensors that recognize viral infection/replication in the host cells. Studies have demonstrated that methamphetamine (METH) dysregulated host cell innate immunity and facilitated HIV infection of macrophages. In this study, we present new evidence that METH suppressed TLR9-mediated anti-HIV activity in macrophages. Activation of TLR9 by its agonist CpG-ODN 2216 inhibits HIV replication, which was demonstrated by increased expression of TLR9, interferon (IFN)-α, IFN regulatory factor-7 (IRF-7), myeloid differentiation factor 88 (MyD88), and myxovirus resistance gene A (MxA) in macrophages. However, METH treatment of macrophages greatly compromised the TLR9 signaling-mediated anti-HIV effect and inhibited the expression of TLR9 downstream signaling factors. Dopamine D1 receptor (D1R) antagonists (SCH23390) could block METH-mediated inhibition of anti-HIV activity of TLR9 signaling. Investigation of the underlying mechanisms of the METH action showed that METH treatment selectively down-regulated the expression of TLR9 on macrophages, whereas it had little effect on the expression of other TLRs. Collectively, our results provide further evidence that METH suppresses host cell innate immunity against HIV infection by down-regulating TLR9 expression and its signaling-mediated antiviral effect in macrophages.
Asunto(s)
Estimulantes del Sistema Nervioso Central/efectos adversos , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , Macrófagos/efectos de los fármacos , Metanfetamina/efectos adversos , Receptor Toll-Like 9/antagonistas & inhibidores , Replicación Viral/efectos de los fármacos , Adulto , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Infecciones por VIH/metabolismo , Humanos , Factor 7 Regulador del Interferón/metabolismo , Interferón-alfa/metabolismo , Macrófagos/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Receptor Toll-Like 9/inmunología , Replicación Viral/inmunologíaRESUMEN
OBJECTIVE: To analyze the clinical effectiveness of Shenling Fuzheng Capsule (SFC) and Qingdu Capsule (QC) in treating HIV/AIDS patients. METHODS: Totally 220 patients with complete clinical data, who received consecutive treatment for 6 months were selected from the database. They were assigned to two groups whether they would rather receive antiretroviral drugs, the Chinese medicine (CM) treatment group and the integrative medicine (IM) group. The 129 patients in the CM group were treated with SFC or QC, while the 91 patients in the IM group were treated with SFC or QC combined highly active antiretroviral agents. Total score and single score of clinical symptoms and signs, Karnofsky Performance Status (KPS), and changes of body weight before treatment, 3 and 6 months after treatment were compared. CD4+ cell counts were compared between before treatment and 6 months after treatment. RESULTS: The total score of clinical symptoms and signs were lower at 3 and 6 months of treatment than before treatment respectively (P < 0.01). The single score of clinical symptoms and signs such as cough, weakness, shortness of breath, vomit, spontaneous perspiration, hair loss,and chest pain were also lowered at 3 and 6 months of treatment (P < 0.05, P < 0.01), and the KPS increased (P < 0.05). The body weight increased (P < 0.05) and CD4 cell counts decreased (P < 0.05) in the CM group. There was no statistical difference in body weight or CD4 cell counts in the IM group between before and after treatment. CONCLUSION: SFC and QC could improve clinical symptoms and signs of HIV/ AIDS patients, but failed to deter the decrease of CD4+ cell counts.
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Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Adolescente , Adulto , Anciano , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Cápsulas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We investigated the distribution of HIV-1 subtypes and the prevalence of HIV-1 drug resistance among HIV-infected antiretroviral-naive patients in Guangxi, southern China. A total of 144 subjects from Liuzhou or Nanning, two cities having the most HIV-infected cases in Guangxi, were enrolled. HIV-1 pol fragments were amplified and sequenced from plasma of all patients. In all, 124 sequences were obtained, with 67 from Liuzhou and 57 from Nanning. All sequences were subtyped by phylogenetic analysis and analyzed for antiretroviral resistance using the HIVdb program. Our data showed that the sequences from Liuzhou were subtyped as CRF01_AE (77.6%), CRF07_BC(20.9%), and BC (1.5%), respectively, and the sequences from Nanning as CRF01_AE (78.9%), CRF08_BC (15.8%), B (3.5%), and C (1.8%), respectively. Of the sequences 11.9% from Liuzhou and 28.1% from Nanning harbored drug resistance-associated mutations, but there were only two sequences with mutations associated with significantly reduced phenotypic susceptibility to antiretroviral drugs.
Asunto(s)
Farmacorresistencia Viral/genética , Genes pol/inmunología , Seropositividad para VIH/inmunología , VIH-1/inmunología , Mutación , Subgrupos de Linfocitos T/inmunología , Adulto , Fármacos Anti-VIH/administración & dosificación , China/epidemiología , Femenino , Genes pol/genética , Seropositividad para VIH/epidemiología , Seropositividad para VIH/genética , Humanos , Masculino , Datos de Secuencia Molecular , FilogeniaRESUMEN
OBJECTIVE: To determine whether morphine having the ability to influence the antiviral effect of lamivudine (3TC) in vitro study. METHODS: MT2 cells were randomly assigned into morphine + 3TC treatment group, morphine + naloxone + 3TC treatment group, naloxone + 3TC treatment group. Both 3TC and virus control groups were set up. The corresponding MT2 cells were treated with opiates antagonist (naloxone) for 0.5 hours before the 24-hours morphine treatment program was implemented while all of the groups were then infected with equal amounts of cell-free HIV-1 IIIB strain and 3TC. HIV-1 p24 antigen in culture supernatants collected at days 3, 4, 5 and 6 after infection status was tested and the inhibition of 3TC anti-HIV-1 p24 antigen of various treatment groups calculated. RESULTS: Inhibition of 3TC anti-HIV-1 p24 antigen of Morphine + 3TC treatment group was the lowest when HIV-1 infected cells at 3(rd)and 4(th) day and showed significant difference (P < 0.05) when compared to the 3TC control. However, there was no statistically significant difference among them (P > 0.05), when virus was infected the cells at 5(th)and 6(th) day. The difference of 3TC anti-HIV-1 p24 antigen inhibition between the morphine + naloxone + 3TC treatment group and the naloxone + 3TC treatment group was not significant (P > 0.05). Similar results were obtained when these two groups were compared to the 3TC control group (P > 0.05), respectively. The 3TC anti-HIV-1 p24 antigen inhibition of each treatment group reduced as the time of infection prolonged, showing a significant and time-course effect. CONCLUSION: The 3TC antiviral effect was reduced by morphine in the early stage of infection, and could be blocked by naloxone.
Asunto(s)
Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , Lamivudine/farmacología , Morfina/farmacología , Línea Celular , Humanos , Naloxona/farmacología , Carga ViralRESUMEN
A subtype-specific PCR approach is described for the identification of HIV-1 intersubtype CRF01_AE and BC recombinants, the two predominant subtypes in Southern China. Primers were designed based on the env and gag regions of the HIV-1 genome. Nested PCRs with primers targeting the env region were performed to amplify subtype C, CRF01_AE, or BC recombinants. To differentiate BC recombinants from subtype C virus, a BC recombinant specific gag PCR was then performed. In order to identify the CRF07_BC and CRF08_BC recombinant forms, an additional PCR step was included. Four HIV-1 samples of known subtype, 77 samples with unknown-subtype, and 30 HIV-negative control samples were tested by the new assay. The results of this PCR-based subtyping approach were compared with that of a sequence-based phylogenetic analysis. In total, 73 (94.8%) samples were amplified by the subtype-specific PCR reactions, of which 39 were identified as CRF01_AE, 14 as CRF07_BC, and 20 as CRF08_BC. The sensitivity of this assay was 90.7% for the CRF01_AE recombinant and 100% for BC recombinants. The specificity was 100% when used to identify 30 HIV-negative samples. The reproducibility was 93.8% for CRF01_AE, and 100% for BC recombinants. This subtype-specific PCR technique represents a simple, rapid, and low-cost assay for the identification of HIV-1 CRF01_AE and BC recombinants in Southern China.
Asunto(s)
Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Reacción en Cadena de la Polimerasa/métodos , Recombinación Genética , Virología/métodos , China , Cartilla de ADN/genética , Genotipo , VIH-1/aislamiento & purificación , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
To investigate HIV-1 subtype distribution and prevalence of HIV-1 drug resistance in Liuzhou and Nanning, a total of 304 HIV-infected subjects or AIDS patients from Liuzhou and Nanning were recruited. Whole blood was withdrawn from a peripheral vein of each subject. HIV RNA were extracted from plasma, and subjected to PCR amplification targeting HIV pol gene fragment and DNA sequencing. Sequences obtained were subtyped by phylogenetic analysis. Two subtypes, CRF01_AE and CRF07_BC, were found in subjects from Liuzhou, accounting for 75.2% and 24.8%, respectively. Subtype CRF01 AE, CRFO8_BC, B, and C were found in subjects from Nanning. CRF01_AE and CRF08 BC were still the dominant strains in Nanning, accounting for 85.8% and 11.5%, respectively. Sequences were also analyzed for drug resistance mutations, and rates of drug resistance were calculated. The rate of drug resistance was 3.3% in ART-naive subjects from Liuzhou, and 8.7% in the ART-experienced. For patients from Nanning, the rate was 1.4% in ART-naive subjects, and 27.5% in ART-experienced subjects.
Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH/epidemiología , VIH-1/aislamiento & purificación , Fármacos Anti-VIH/farmacología , China/epidemiología , Genotipo , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Datos de Secuencia Molecular , FilogeniaRESUMEN
OBJECTIVE: To establish a rapid nested multiplex PCR assay for subtyping HIV-1 CRF01_AE, CRF07_BC, CRF08_BC, B, and C strains prevailing in Guangxi. METHOD: Subtype-specific primers were designed for these subtypes based on their gag sequences. The subtypes of HIV-1 samples from Guangxi were determined by nested multiplex PCR and DNA sequencing and phylogenetic analysis, respectively, and then the sensitivity and the specificity of nested multiplex PCR were calculated. RESULTS: Nested multiplex PCR could correctly classify the 5 known-subtype samples, and were not reactive to all HIV-negative samples. Of the 72 HIV-positive samples, 66 were correctly identified as CRF01_AE, CRF07_BC, CRF08_BC, and B by this assay, giving a sensitivity of 91.7% (66/72), and a specificity of 100%. CONCLUSION: This assay is a simple, fast, and cost-effective subtyping method for HIV-1 CRF01-AE, CRF07_BC, CRF08_BC, and B strains prevailing in Guangxi.