Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24.974
Filtrar
1.
Am J Health Behav ; 46(5): 558-566, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36333826

RESUMO

OBJECTIVES: Asymptomatic sexually transmitted infections (STI) are frequent among men who have sex with men (MSM). Identifying asymptomatic STIs is a crucial issue, not only for secondary but also for primary prevention, as early treatment can reduce transmission risk. We aimed to develop a self-reported predictive score for early identification of asymptomatic STIs. METHODS: Participants provided clinical data and completed a self-administered questionnaire including sociodemographic variables and behaviors during the 6 previous months. We used multivariable logistic regression to identify factors associated with asymptomatic STIs. We calculated the accuracy of the model by the non-parametric area (AUC) under the receiver-operating-characteristic (ROC) curve to find the optimal discriminant threshold for screening. RESULTS: A total of 781 HIV-positive MSM were included with a mean age of 46.8 years. Asymptomatic STI prevalence was 13.2%. Detectable plasma HIV RNA (adjusted odds ratio (aOR [95% CI): 2.54 [1.23;5.25]), inconsistent condom use during anal sex (2.20 [1.36;3.56]), group sex (2.00 [1.15;3.45]), during or-genital practices (1.83 [1.12;3.01]), not being in stable relationship (1.70 [1.01;2.66] and an item from a sensation-seeking behavioral scale "I don't like watching porn videos" (1.61 [1.01;2.59] were associated with asymptomatic STI. AUC was 0.7 and with optimal threshold of 0.1082 for this model; sensitivity was 80.4%. Self-reported asymptomatic STI predictive score was built with this threshold according to the 6 factors in the final model. CONCLUSIONS: As this predictive score is not designed to be diagnostic, but to provide indications for diagnostic tests, its ease of administration and sensitivity remain the most important features. Its use in clinical practice for early detection of asymptomatic STIs potentially can reinforce STI primary and secondary prevention.


Assuntos
Infecções por HIV , Soropositividade para HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Masculino , Humanos , Pessoa de Meia-Idade , Homossexualidade Masculina , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Comportamento Sexual
2.
Cell Rep ; 41(8): 111674, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417867

RESUMO

A possible explanation for chronic inflammation in HIV-infected individuals treated with anti-retroviral therapy is hyperreactivity of myeloid cells due to a phenomenon called "trained immunity." Here, we demonstrate that human monocyte-derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, release increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect is associated with chromatin changes at the genes involved in inflammation and cholesterol metabolism pathways and upregulation of the lipid rafts and is blocked by methyl-ß-cyclodextrin, statin, and an inhibitor of the lipid raft-associated receptor IGF1R. Bone-marrow-derived macrophages from exNef-injected mice, as well as from mice transplanted with bone marrow from exNef-injected animals, produce elevated levels of tumor necrosis factor α (TNF-α) upon stimulation. These phenomena are consistent with exNef-induced trained immunity that may contribute to persistent inflammation and associated co-morbidities in HIV-infected individuals with undetectable HIV load.


Assuntos
Vesículas Extracelulares , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Camundongos , Animais , HIV-1/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo
3.
AIDS Res Ther ; 19(1): 53, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36419079

RESUMO

OBJECTIVE: We aimed to observe the clinical effect of single-stage posterior surgery on HIV-positive patients with thoracolumbar tuberculosis. METHODS: From October 2015 to October 2019, 13 HIV-positive patients with thoracolumbar tuberculosis who underwent single-stage posterior surgery were retrospectively analyzed (observation group), and 13 HIV-negative patients with thoracolumbar tuberculosis who were matched with the gender, age, operative site, and surgical approach during the same period were selected as the control group. Postoperative complications, hemoglobin, albumin, CD4+T lymphocyte count, operative site, operative time, and blood loss were recorded between the two groups. The clinical efficacy was evaluated by the visual analog scale (VAS), American Spinal Injury Association (ASIA) scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), kyphotic angle, correction rate of kyphosis, angle loss, and bone graft fusion time. RESULTS: In the observation group, 7 patients had postoperative complications, including 1 patient with cerebrospinal fluid leakage, 1 patient with nerve root irritation, 1 patient with an opportunistic infection, and 4 with delayed wound healing. In the control group, 2 patients developed postoperative complications, including 1 with nerve root irritation and 1 with delayed wound healing. There was no statistically significant difference in the incidence of postoperative complications between the two groups (P > 0.05). CD4+T lymphocyte count, hemoglobin, and albumin in HIV-positive patients with postoperative complications were statistically different from those without postoperative complications (P all < 0.05). No tuberculosis recurrence was found at the last follow-up, ESR and CRP returned to normal, and there were no statistically significant differences in bone graft fusion time, VAS score, ASIA scale, correction rate of kyphosis, and angle loss between two groups (P all > 0.05). CONCLUSION: Single-stage posterior surgery for HIV-positive patients with thoracolumbar tuberculosis could achieve satisfactory clinical efficacy through comprehensive preoperative evaluation, standardized perioperative antiviral and anti-tuberculosis treatments, and prevention of postoperative complications.


Assuntos
Infecções por HIV , Soropositividade para HIV , Cifose , Tuberculose , Humanos , Estudos Retrospectivos , Proteína C-Reativa , Complicações Pós-Operatórias , Albuminas
4.
Front Immunol ; 13: 878273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420277

RESUMO

Follicular helper CD4+ T cells (TFH) are highly permissive to HIV and major foci of virus expression in both untreated and treated infection. Follicular regulatory CD4+ T cells (TFR) limit TFH numbers and function in vitro and in vivo. We evaluated the hypothesis that TFR suppress HIV replication in TFH using a well-established model of ex vivo HIV infection that employs tonsil cells from HIV uninfected individuals spinoculated with CXCR4- and CCR5-tropic HIV-GFP reporter viruses. Both CXCR4 and CCR5-tropic HIV replication were reduced in TFH cultured with TFR as compared to controls. Blocking antibodies to CD39, CTLA-4, IL-10, and TGF-beta failed to reverse suppression of HIV replication by TFR, and there were no sex differences in TFR suppressive activity. TFR reduced viability of TFH and even more so reduced HIV infected TFH as assessed by total and integrated HIV DNA. Exogenous IL-2 enhanced TFH viability and particularly numbers of GFP+ TFH in a concentration dependent manner. TFR reduced productively infected TFH at low and moderate IL-2 concentrations, and this was associated with decreases in extracellular IL-2. Both IL-2 expressing cells and larger numbers of FoxP3+CD4+ cells were detected in follicles and germinal centers of lymph nodes of people living with HIV. TFR may deplete TFH in vivo through restriction of IL-2 and thereby contribute to decay of HIV expressing cells in B cell follicles during HIV infection.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Células T Auxiliares Foliculares , Linfócitos T Reguladores , Interleucina-2
5.
Proc Natl Acad Sci U S A ; 119(48): e2210584119, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36413502

RESUMO

Antiretroviral therapy (ART) can attain prolonged undetectable HIV-1 in plasma and cerebrospinal fluid (CSF), but brain injury remains prevalent in people living with HIV-1 infection (PLHIV). We investigated cell-associated (CA)-HIV-1 RNA transcripts in cells in CSF and blood, using the highly sensitive Double-R assay, together with proton Magnetic Resonance Spectroscopy (1H MRS) of major brain metabolites, in sixteen PLHIV. 14/16 CSF cell samples had quantifiable CA-HIV-1 RNA, at levels significantly higher than in their PBMCs (median 9,266 vs 185 copies /106 CD4+ T-cells; p<0.0001). In individual PLHIV, higher levels of HIV-1 transcripts in CSF cells were associated with greater brain injury in the frontal white matter (Std ß=-0.73; p=0.007) and posterior cingulate (Std ß=-0.61; p=0.03). 18-colour flow cytometry revealed that the CSF cells were 91% memory T-cells, equally CD4+ and CD8+ T-cells, but fewer B cells (0.4 %), and monocytes (3.1%). CXCR3+CD49d+integrin ß7-, CCR5+CD4+ T-cells were highly enriched in CSF, compared with PBMC (p <0.001). However, CA-HIV-1 RNA could not be detected in 10/16 preparations of highly purified monocytes from PBMC, and was extremely low in the other six. Our data show that elevated HIV-1 transcripts in CSF cells were associated with brain injury, despite suppressive ART. The cellular source is most likely memory CD4+ T cells from blood, rather than trafficking monocytes. Future research should focus on inhibitors of this transcription to reduce local production of potentially neurotoxic and inflammatory viral products.


Assuntos
Lesões Encefálicas , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Linfócitos T CD4-Positivos , Leucócitos Mononucleares , Infecções por HIV/tratamento farmacológico
6.
PLoS One ; 17(11): e0277231, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36409740

RESUMO

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15-21) years in men and 18 (IQR 15-21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5-8.9) years in men and 8.2 (IQR 6.1-10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Masculino , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Densidade Óssea , Estudos Transversais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Asiáticos , Absorciometria de Fóton
7.
BMC Pediatr ; 22(1): 670, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411424

RESUMO

BACKGROUND: Acquired immune deficiency syndrome is an infectious disease caused by the human immunodeficiency virus (HIV) that primarily targets an individual's immune system. In Ethiopia, nearly 24% of HIV-related deaths occur in children under the age of five. However, studies regarding the survival time of HIV-positive under-five children after anti-retroviral therapy initiation are limited with poor evidence of predictors of death. OBJECTIVE: To assess survival time and predictors of death among HIV infected under-five children after initiation of anti-retroviral therapy in West Amhara Referral Hospitals, Northwest Ethiopia, 2021. METHODS: A multicenter institution-based retrospective follow-up study was conducted among 432 HIV-positive under-five children on anti-retroviral therapy selected by simple random sampling from January 2010 to December 2019. A standardized data extraction tool was employed, which was adapted from anti-retroviral therapy entry and follow-up forms. The event of interest for this study is death, whereas the absence of experience of death is censored. Data were entered into Epi-Data version 3.1 and exported to STATA version 14. The Kaplan-Meier curve was used to estimate the survival probability. The Cox regression model was used to identify independent predictors of death. RESULTS: Among the 415 records included in the final analysis, 25 (6.02%) of the individuals were died. The incidence rate of death was found to be 2.87 per 1000 child-months (95%CI: 1.94-4.25). The cumulative survival probabilities of children after 6, 12, 24, and 36 months were 0.97, 0.95, 0.92, and 0.85 respectively. HIV-infected under-five children who lived in rural areas (AHR 3.32:-95% CI 1.17-9.39), with poor adherence to anti-retroviral therapy (AHR = 3.36; CI: 1.06, 10.69), without Isoniazide prophylaxis (AHR = 3.15; CI: 1.11, 8.94) and with anemia (AHR: 3.05, 95% CI: 1.16, 8.03) were at higher risk of death. CONCLUSION AND RECOMMENDATION: Death of HIV-infected under-five children on anti-retroviral therapy is high within the first one year after enrolment. Living in rural area, had poor adherence, lacked Isoniazide prophylaxis, and anemia were predictors of death. Therefore, clinicians shall emphasize for those specific risk factors of death and take action accordingly.


Assuntos
Anemia , Infecções por HIV , Soropositividade para HIV , Humanos , Etiópia/epidemiologia , Estudos Retrospectivos , Seguimentos , Infecções por HIV/tratamento farmacológico , Encaminhamento e Consulta , Hospitais
8.
J Cancer Res Ther ; 18(6): 1537-1540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412406

RESUMO

Objective: To find out the epidemiological factors and oncology treatment outcome in human immunodeficiency virus-positive cancer cervix patients (HPCCP). Materials and Methods: After institutional ethics committee approval, hospital case records of HPCCP registered at the radiation oncology department from January 2011 to December 2018 were retrospectively studied. Results: The case records of 22 eligible HPCCP were studied. Median age at presentation was 42.5 years. 90.90% of the patients were below 55 years of age. The duration of symptom was <3 months in 63.64% of patients. 68.18% of the patients were FIGO Stage III. Only 11 patients completed the planned treatment. Total target equivalent dose of 2 Gy per fraction delivered was 66 Gy. Seven patients had complete response. Four patients had local recurrence. Median disease-free and overall survival was 27 (14-38) and 18 months (2-48), respectively. Conclusion: HPCCP present at relatively early age and advanced stage despite short symptom duration. Poor patient compliance and treatment alteration have led to suboptimal outcome.


Assuntos
Soropositividade para HIV , Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Estudos Retrospectivos , Colo do Útero , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/tratamento farmacológico , Resultado do Tratamento , HIV
9.
J Virol ; 96(22): e0124822, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36326273

RESUMO

Rare HLA alleles such as HLA-B57 are associated with slow progression to AIDS. However, the evidence for the advantage of rare protective alleles is limited, and the mechanism is still unclear. Although the prevalence of HLA-B*67:01 is only 1.2% in Japan, HLA-B*67:01-positive (HLA-B*67:01+) individuals had the lowest plasma viral load (pVL) and highest CD4 count in HIV-1 clade B-infected Japanese individuals. We investigated the mechanism of immunological control of HIV-1 by a rare protective allele, HLA-B*67:01. We identified six novel HLA-B*67:01-restricted epitopes and found that T cells specific for four epitopes were significantly associated with good clinical outcomes, pVL and/or CD4 count. The wild type or cross-reactive sequences of three protective and immunodominant Pol and Gag epitopes were found in around 95% of the circulating HIV-1, indicating that T cells specific for three conserved or cross-reactive epitopes contributed to good clinical outcomes. One escape mutation (Nef71K) in the Nef protective epitope, which was selected by T cells restricted by either HLA allele in the HLA-B*67:01-C*07:02 haplotype, affected the HLA-B*67:01-restricted RY11-specific T-cell recognition. These results imply that the further accumulation of the Nef71K mutation in the population will negatively affect the control of HIV-1 replication by RY11-specific CD8+ T cells in HIV-1-infected HLA-B*67:01+ individuals. The present study demonstrated that conserved or cross-reactive epitope-specific T cells mainly contribute to control of HIV-1 by a rare protective allele, HLA-B*67:01. IMPORTANCE HLA-B57 is a relatively rare allele around world and the strongest protective HLA allele in Caucasians and African black individuals infected with HIV-1. Previous studies suggested that the advantage of this allele in HIV-1 disease progression is due to a strong functional ability of HLA-B57-restricted Gag-specific T cells and lower fitness of mutant viruses selected by the T cells. HLA-B*57 is a very rare allele and has not been reported as a protective allele in Asian countries, whereas a rare allele, HLA-B*67:01, was shown to be a protective allele in Japan. Therefore, the analysis of HLA-B*67:01-restricted T cells is important to clarify the mechanism of immunological control of HIV-1 by a rare protective HLA allele in Asia. We found that HLA-B*67:01-restricted T cells specific for three conserved or cross-reactive Gag and Pol epitopes are associated with good clinical outcomes in HLA-B*67:01+ individuals. It is expected that T cells specific for conserved or cross-reactive epitopes contribute to a curing treatment.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Alelos , Linfócitos T CD8-Positivos , Replicação Viral , Antígenos HLA-B/genética , Soropositividade para HIV/genética , Epitopos , Progressão da Doença , Epitopos de Linfócito T/genética
10.
Afr Health Sci ; 22(2): 1-11, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36407401

RESUMO

Background: Moringa oleifera Lam. is known to be of high nutritional and medicinal importance and has been demonstrated to possess a variety of biological activities. Objective: This study investigated the beneficial role of M. oleifera (moringa) supplementation in HIV positive subjects receiving antiretroviral drugs. Methods: Adult HIV positive individuals (104) attending the medical outpatient clinic in a tertiary health institution in Nigeria receiving highly active anti-retroviral therapies (HAARTs) were recruited in a randomized fashion for the study. Half of the subjects received moringa supplement (20 mg daily) additionally, while the others received only HAART and represented the control group. All subjects were monitored for 3 months during which their immunological status (CD4 counts and TNF-α), and hematological abnormalities at pre (baseline) and post study periods were determined. Results: Baseline levels of CD4 increased while TNF-α decreased significantly in control and moringa supplemented groups (p < 0.01). However, the post study CD4 values in the moringa group were higher and TNF-α values were lower compared to the control group (p < 0.01). In addition, baseline hematological abnormalities (anemia, thrombocytopenia, leucopenia, lymphopenia, and neutropenia) were improved but most significantly in the moringa supplemented subjects. Conclusion: The results suggest that moringa has immune-beneficial properties and improved hematological abnormalities in HIV positive individuals receiving antiretroviral therapy.


Assuntos
Anemia , Infecções por HIV , Soropositividade para HIV , Moringa , Humanos , Adulto , Terapia Antirretroviral de Alta Atividade , Fator de Necrose Tumoral alfa , Infecções por HIV/tratamento farmacológico , Suplementos Nutricionais , Soropositividade para HIV/tratamento farmacológico
11.
Artigo em Inglês | MEDLINE | ID: mdl-36361428

RESUMO

HIV-1 patients place an economic burden on the health system. The objectives of this study were to estimate the direct HIV-1 costs and cost-related factors of HIV-1 patients in Israel and identify cost predictors. We conducted a retrospective study of randomly selected HIV-1 patients aged ≥18 who visited a large outpatient clinic in 2015 and/or 2019. Yearly costs of physician and nurse visits, antiretroviral therapy (ART) and laboratory tests were calculated in USD using the 2020 purchasing power parities. Associations between disease characteristics and costs were analyzed using univariate and multivariable analysis. The median (IQR) total direct costs per patient per year were USD 12,387 (9813-14,124) and USD 12,835 (11,651-13,970) in 2015 (n = 284) and 2019 (n = 290), respectively. ART accounted for approximately 77% of all direct costs, followed by laboratory tests (20%) and medical visits (3%) in both studied years. Being female (USD +710), first yearly viral load <50 c/mL (+$1984) and ≥20 years with HIV-1 (USD +1056) were independently associated with higher costs. In conclusion, HIV-1 cost was stable in the studied period. Viral load and time since diagnosis were the major determinants associated with HIV-1 costs. ART and laboratory tests accounted for 97% of the costs. Therefore, these factors should be considered when planning future expenditures.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Feminino , Masculino , Estudos Retrospectivos , Custos de Cuidados de Saúde , Israel/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Assistência Ambulatorial
12.
PLoS One ; 17(11): e0277650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36378657

RESUMO

Lithuania has a long history of remunerated donations. The first steps towards voluntary, non-remunerated blood and blood component donations started in 2004. Lithuania achieved 99.98% voluntary non-remunerated donations (VNRDs) in 2020. This study aimed to assess the risk of transfusion-transmitted infectious (TTI) disease markers for remunerated donations in comparison with VNRDs in Lithuania from 2013 to 2020. Data were obtained from the Lithuanian Blood Donor Register. The prevalence was calculated as the rate between the number of confirmed positive results for all TTI disease markers (serological anti-HCV, HBsAg, Ag/anti-HIV 1 and 2, and syphilis, and/or HCV, HBV, and HIV-1 NAT) per 100 donations. The relative risk of infectious disease markers for remunerated donations was then estimated. In total, 796310 donations were made. Altogether, 2743 donations were positive for TTI markers as follows: HCV, 1318; HBV, 768; syphilis, 583; and HIV 1 and 2, 74. The prevalence of confirmed TTI markers were 2.86, 0.97, 0.18, and 0.04 per 100 first-time remunerated donations, first-time VNRDs, repeat remunerated donations, and repeat VNRDs, respectively. Remunerated first-time and repeat donations had a statistically higher prevalence of TTI disease markers than VNRDs. First-time and repeat remunerated donations had statistically significantly higher relative risks of confirmed TTI disease markers than VNRD. In conclusion, the risks of TTI disease markers for remunerated first-time and repeat blood and its component donations are significantly higher than those for VNRDs.


Assuntos
Doenças Transmissíveis , Infecções por HIV , Soropositividade para HIV , HIV-1 , Sífilis , Reação Transfusional , Humanos , Doadores de Sangue , Sífilis/epidemiologia , Lituânia/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle
13.
Viruses ; 14(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36366513

RESUMO

With the aim of rationally devising a refined and potent HIV-1 blocker, the cDNA of CCL5 5p12 5m, an extremely potent CCR5 antagonist, was fused to that of C37, a gp41-targeted fusion inhibitor. The resulting CCL5 5p12 5m-C37 fusion protein was expressed in E. coli and proved to be capable of inhibiting R5 HIV-1 strains with low to sub-picomolar IC50, maintaining its antagonism toward CCR5. In addition, CCL5 5p12 5m-C37 inhibits R5/X4 and X4 HIV-1 strains in the picomolar concentration range. The combination of CCL5 5p12 5m-C37 with tenofovir (TDF) exhibited a synergic effect, promoting this antiviral cocktail. Interestingly, a CCR5-targeted combination of maraviroc (MVC) with CCL5 5p12 5m-C37 led to a synergic effect that could be explained by an extensive engagement of different CCR5 conformational populations. Within the mechanism of HIV-1 entry, the CCL5 5p12 5m-C37 chimera may fit as a powerful blocker in several instances. In its possible consideration for systemic therapy or pre-exposure prophylaxis, this protein design represents an interesting lead in the combat of HIV-1 infection.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Receptores CCR5/genética , Receptores CCR5/metabolismo , Escherichia coli/metabolismo , Maraviroc/farmacologia , Maraviroc/uso terapêutico , Infecções por HIV/metabolismo , Antagonistas dos Receptores CCR5/farmacologia , Antagonistas dos Receptores CCR5/uso terapêutico
14.
Viruses ; 14(11)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36366418

RESUMO

The increased antiretroviral therapy (ART) coverage of patients in the absence of routine genotyping tests and in the context of active labor migration highlight the importance of HIV-1 drug resistance (DR) surveillance in Armenia. We conducted a two-phase pretreatment DR (PDR) study in 2017-2018 (phase I; 120 patients) and 2020-2021 (phase II; 133 patients) according to the WHO-approved protocol. The analysis of HIV-1 genetic variants showed high degrees of viral diversity, with the predominance of A6. The prevalence of any PDR was 9.2% in phase I and 7.5% in phase II. PDR to protease inhibitors was found only in 0.8% in phase II. PDR to efavirenz and nevirapine was found among 5.0% and 6.7% of patients in phase I, and 6.0% and 6.8% of patients in phase II, respectively. The prevalence of PDR to nucleoside reverse-transcriptase inhibitors decreased from 5.0% in phase I to 0.8% in phase II. In addition, we identified risk factors associated with the emergence of DR-male, MSM, subtype B, and residence in or around the capital of Armenia-and showed the active spread of HIV-1 among MSM in transmission clusters, i.e., harboring DR, which requires the immediate attention of public health policymakers for the prevention of HIV-1 DR spread in the country.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Minorias Sexuais e de Gênero , Humanos , Masculino , Gravidez , Feminino , HIV-1/genética , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Prevalência , Homossexualidade Masculina , Armênia/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Organização Mundial da Saúde , Genótipo , Mutação
15.
Viruses ; 14(11)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36423103

RESUMO

The integration of the HIV-1 genome into the host genome is an essential step in the life cycle of the virus and it plays a critical role in the expression, long-term persistence, and reactivation of HIV expression. To better understand the local genomic environment surrounding HIV-1 proviruses, we assessed the influence of non-canonical B-form DNA (non-B DNA) on the HIV-1 integration site selection. We showed that productively and latently infected cells exhibit different integration site biases towards non-B DNA motifs. We identified a correlation between the integration sites of the latent proviruses and non-B DNA features known to potently influence gene expression (e.g., cruciform, guanine-quadruplex (G4), triplex, and Z-DNA). The reactivation potential of latent proviruses with latency reversal agents also correlated with their proximity to specific non-B DNA motifs. The perturbation of G4 structures in vitro using G4 structure-destabilizing or -stabilizing ligands resulted in a significant reduction in integration within 100 base pairs of G4 motifs. The stabilization of G4 structures increased the integration within 300-500 base pairs from G4 motifs, increased integration near transcription start sites, and increased the proportion of latently infected cells. Moreover, we showed that host lens epithelium-derived growth factor (LEDGF)/p75 and cleavage and polyadenylation specificity factor 6 (CPSF6) influenced the distribution of integration sites near several non-B DNA motifs, especially G4 DNA. Our findings identify non-B DNA motifs as important factors that influence productive and latent HIV-1 integration and the reactivation potential of latent proviruses.


Assuntos
DNA de Forma B , Quadruplex G , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Motivos de Nucleotídeos , Latência Viral , DNA , Provírus/genética
16.
Viruses ; 14(11)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36423152

RESUMO

Since it was clearly established that HIV/AIDS predisposes to the infection, persistence or reactivation of latent viruses, the prevalence of human polyomaviruses (HPyVs) among HIV-1-infected patients and a possible correlation between HPyVs and HIV sero-status were investigated. PCR was performed to detect and quantify JCPyV, BKPyV, MCPyV, HPyV6, HPyV7 and QPyV DNA in the urine and plasma samples of 103 HIV-1-infected patients. Subsequently, NCCR, VP1 and MCPyV LT sequences were examined. In addition, for MCPyV, the expression of transcripts for the LT gene was investigated. JCPyV, BKPyV and MCPyV's presence was reported, whereas HPyV6, HPyV7 and QPyV were not detected in any sample. Co-infection patterns of JCPyV, BKPyV and MCPyV were found. Archetype-like NCCRs were observed with some point mutations in plasma samples positive for JCPyV and BKPyV. The VP1 region was found to be highly conserved among these subjects. LT did not show mutations causing stop codons, and LT transcripts were expressed in MCPyV positive samples. A significant correlation between HPyVs' detection and a low level of CD4+ was reported. In conclusion, HPyV6, HPyV7 and QPyV seem to not have a clinical relevance in HIV-1 patients, whereas further studies are warranted to define the clinical importance of JCPyV, BKPyV and MCPyV DNA detection in these subjects.


Assuntos
Líquidos Corporais , Soropositividade para HIV , HIV-1 , Poliomavírus das Células de Merkel , Polyomavirus , Humanos , HIV-1/genética , Plasma , Genômica
17.
Artigo em Inglês | MEDLINE | ID: mdl-36429944

RESUMO

Our lab investigates the anti-HIV-1 activity in Momordica balsamina (M. balsamina) leaf extract. Traditional Senegalese healers have used M. balsamina leaf extract as a part of a plant-based treatment for HIV/AIDS infections. Our overall goal is to define and validate the scientific basis for using M. balsamina leaf extract as a part of the traditional Senegalese treatment. As an initial characterization of this extract, we used activity-guided fractionation to determine the active ingredient's solubility and relative size. We found that M. balsamina leaf extract inhibits HIV-1 infection by >50% at concentrations of 0.02 mg/mL and above and is not toxic over its inhibitory range (0-0.5 mg/mL). We observed significantly more antiviral activity in direct water and acetonitrile extractions (p ≤ 0.05). We also observed significantly more antiviral activity in the aqueous phases of ethyl acetate, chloroform, and diethyl ether extractions (p ≤ 0.05). Though most of the antiviral activity partitioned into the aqueous layers, some antiviral activity was present in the organic layers. We show that the active agent in the plant extracts is at least 30 kD in size. Significantly more antiviral activity was retained in 3, 10, and 30 kD molecular weight cutoff filters (p ≤ 0.05). In contrast, most of the antiviral activity passed through the 100 kD filter (p ≤ 0.05). Because the active anti-HIV-1 agent presented as a large, amphiphilic molecule we ran the purified extract on an SDS-page gel. We show that the anti-HIV-1 activity in the leaf extracts is attributed to a 30 kDa protein we call MoMo30. This article describes how MoMo30 was determined to be responsible for its anti-HIV-1 activity.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Momordica , Extratos Vegetais/farmacologia , Infecções por HIV/tratamento farmacológico , Antivirais
18.
Viruses ; 14(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36366570

RESUMO

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.


Assuntos
Coinfecção , Infecções por HIV , Soropositividade para HIV , HIV-1 , Infecções por HTLV-II , Hepatite C , Humanos , Vírus Linfotrópico T Tipo 2 Humano , HIV-1/fisiologia , Provírus , Linfócitos T CD8-Positivos/patologia , Carga Viral , Hepatite C/complicações
19.
BMC Womens Health ; 22(1): 462, 2022 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-36404309

RESUMO

BACKGROUND: Cervical cancer is a global public health problem & is the fourth leading cause of cancer morbidity and mortality. Abnormal cervical lesion is common in commercial sex workers and is at a higher risk of developing cervical cancer due to multiple sexual partners besides other factors. Intention is an important predictor of behavior and is an initiative to transform their desire into action. Therefore, this study aimed to assess the predictors of intention to receive cervical cancer screening among commercial sex workers in Gondar city, northwest Ethiopia. METHODS: A community-based cross-sectional study was conducted from March 27 to May 25, 2021, in Gondar city, northwest Ethiopia. A total of 425 commercial sex workers selected using convenience sampling techniques were included in the study. Linear regression with robust standard errors was carried out to identify predictors of intention to receive cervical cancer screening. A 95% confidence interval and a p-value of less than 0.05 were used to declare statistical significance. RESULTS: A total of 393 commercial sex workers participated in the study with a response rate of 92.4%. The mean age of the participants was 27.68 ± 6.62. The median (interquartile range) of intention was 4 (3-4.25). The theory of planned behaviour variables explained 38.51% of the variance in intention to receive cervical cancer screening. Direct subjective norm (ß = 0.09), 95% CI (0.05, 0.13)), direct Attitude (ß = 0.09, 95% CI (0.04, 0.13)), past behaviour (ß = 0.27; 95% CI (0.09, 0.46), and positive HIV status (ß = 0.26; 95% CI (0.06, 0.46) were significant predictors of intention. CONCLUSIONS: Commercial sex workers' intention to undergo cervical cancer screening was high. The theory of planned behavior showed adequate utility in predicting commercial sex workers' intention to receive cervical cancer screening. Participant's attitudes, subjective norm, past behavior, and positive HIV status were important factors affecting their intention to receive cervical cancer screening. Thus, interventions aimed at enhancing commercial sex workers' cervical cancer screening behavior should target creating positive social pressure and attitudinal change towards cervical cancer screening.


Assuntos
Soropositividade para HIV , Profissionais do Sexo , Neoplasias do Colo do Útero , Feminino , Humanos , Detecção Precoce de Câncer , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Intenção , Estudos Transversais , Etiópia
20.
Viruses ; 14(11)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36366545

RESUMO

Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1-C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1-C3) regions differed between progressor groups. With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. Furthermore, diversity increased significantly with time in faster progressors, whereas no such change was observed in slower progressors. No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2-14.0) in either progressor groups. Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-2/genética , HIV-1/genética , Glicosilação , Progressão da Doença , Evolução Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...