RESUMEN

Human Herpesviruses (HHVs) play a significant role in neurological diseases such as encephalitis and meningitis, adding significant morbidity. This study aims to retrospectively analyze the effect of HHVs on patients with neurological symptoms, focusing on the Herpesviridae family's contributions to central nervous system (CNS) infections. METHODS: This retrospective cohort study included 895 patients suspected of viral CNS infections, utilizing molecular diagnosis via qPCR to identify HHVs in cerebrospinal fluid (CSF) samples. This was conducted at a reference tertiary care hospital for infectious diseases in the western Brazilian Amazon from January 2015 to December 2022, focusing on the Herpesviridae family's clinical repercussions and of Cytomegalovirus in CNS infections. RESULTS: The findings revealed that 7.5% of the analyzed samples tested positive for HHVs, with Human Cytomegalovirus (HCMV) and Epstein-Barr Virus (EBV) being the most prevalent. A significant association was found between HHVs and neurological diseases such as encephalitis and meningitis, especially among people living with HIV/AIDS (PLWHA), highlighting the opportunistic nature of these viruses. The study underscores the critical role of CSF analysis in diagnosing CNS infections and the complexity of managing these infections in HIV patients due to their immunocompromised status. CONCLUSIONS: The results emphasize the need for comprehensive diagnostic approaches and tailored treatment strategies for CNS infections in immunocompromised individuals. The study calls for ongoing research and advancements in clinical practice to improve patient outcomes facing CNS infections, particularly those caused by HHVs.

Asunto(s)

Infecciones por Herpesviridae , Herpesviridae , Humanos , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Herpesviridae/aislamiento & purificación , Herpesviridae/genética , Brasil/epidemiología , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/líquido cefalorraquídeo , Adulto Joven , Adolescente , Infecciones del Sistema Nervioso Central/virología , Infecciones del Sistema Nervioso Central/líquido cefalorraquídeo , Infecciones del Sistema Nervioso Central/epidemiología , Niño , Preescolar , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Anciano , Lactante , Enfermedades Virales del Sistema Nervioso Central/virología , Enfermedades Virales del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Infecciones por VIH/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/líquido cefalorraquídeo

RESUMEN

BACKGROUND: The human immunodeficiency virus 1 (HIV-1) infections in Brazil are predominantly caused by two subtypes, B and C. OBJECTIVES: Here we present the characterisation of a novel HIV-1 recombinant form, indicating a new Brazilian CRF_BC, named CRF146_BC. METHODS: RDP, JphMM and Simplot recombination tools were used to evaluate the mosaic pattern. FINDINGS: In this work, we identified three HIV-1 nucleotide sequences previously classified as unique recombinant forms (URFs), plus one new partial genome sharing the same BC recombination pattern. The mosaic genome is almost entirely represented by the subtype C sequence, with a small subtype B recombination region in the pol gene, at the Integrase level. The phylogenetic analyses strongly indicate a common origin between the strains, which were isolated in Rio Grande do Sul, Rio de Janeiro and Bahia states. MAIN CONCLUSIONS: Thus, the new HIV-1 CRF146_BC is circulating in three different Brazilian regions: South, Southeast and Northeast.

Asunto(s)

Infecciones por VIH , VIH-1 , Filogenia , Recombinación Genética , VIH-1/genética , VIH-1/clasificación , Humanos , Brasil/epidemiología , Infecciones por VIH/virología , Genotipo , ARN Viral/genética , Genoma Viral/genética

RESUMEN

BACKGROUND: Human immunodeficiency virus (HIV)-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWHs) who naturally control HIV-1 replication and overexpress some cellular restriction factors that negatively regulate the LTR-driven transcription of HIV-1 proviruses. OBJECTIVES: To understand the ability of HICs to control the expression of endogenous retroviruses. METHODS: We measured endogenous retrovirus type K6 (ERVK-6) RNA expression in peripheral blood mononuclear cells (PBMCs) of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 cellular restriction factors. FINDINGS: Our study revealed that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with that in both the ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1, two cellular restriction factors that limit the activation of macrophages and T cells by downregulating the activity of NF-kB. MAIN CONCLUSIONS: These findings support the hypothesis that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both exogenous (HIV-1) and endogenous (ERVK-6) retroviruses. Future studies with larger cohorts should be performed to confirm this hypothesis and to explore the role of p21 and MCPIP1 in regulating HERV-K expression in physiological and pathological conditions.

Asunto(s)

Retrovirus Endógenos , Infecciones por VIH , VIH-1 , ARN Viral , Ribonucleasas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Retrovirus Endógenos/genética , Retrovirus Endógenos/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Infecciones por VIH/genética , VIH-1/genética , VIH-1/inmunología , Inmunidad Innata/genética , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Ribonucleasas/genética , Ribonucleasas/metabolismo , ARN Viral/genética , Factores de Transcripción/genética , Replicación Viral/genética

RESUMEN

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.

Asunto(s)

Coinfección , Infecciones por VIH , Herpesvirus Humano 8 , Sarcoma de Kaposi , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Humanos , Sarcoma de Kaposi/virología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Herpesvirus Humano 8/genética , Femenino , Adulto , Persona de Mediana Edad , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Coinfección/virología , Coinfección/tratamiento farmacológico , VIH-1/genética , VIH-1/efectos de los fármacos , Variación Genética , Carga Viral , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4

RESUMEN

INTRODUCTION: Therapeutic measures have been successful in increasing survival rates and quality of life of HIV/AIDS-infected people. However, some people fail to respond to antiretroviral therapy (HAART) because of viral resistance-associated mutations. OBJECTIVE: To identify virus genotype and the presence of mutations that alter the susceptibility to HAART, and factors associated with the occurrence of these mutations. METHODS: A cross-sectional study was conducted on adults living with HIV attending a specialized outpatient clinic in southern Santa Catarina, Brazil. The participants were interviewed and had blood samples collected for analysis. Those with detectable viral load were genotyped. RESULTS: Out of the 629 patients recruited, 127 subjects were included due to having a detectable viral load. The most common mutations were M184V and K103N. HIV-1 subtype C was the most prevalent strain. Resistance to HAART was associated with modification in the treatment regimen (p <0.001). CONCLUSION: This study concluded that the circulating subtype virus was subtype C and that the mutations K103N and M184V were the most prevalent strains in southern Santa Catarina, Brazil.

Asunto(s)

Farmacorresistencia Viral , Genotipo , Infecciones por VIH , VIH-1 , Humanos , Brasil/epidemiología , Masculino , Femenino , Estudios Transversales , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Adulto , VIH-1/genética , VIH-1/efectos de los fármacos , Persona de Mediana Edad , Terapia Antirretroviral Altamente Activa , Carga Viral , Mutación , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Adulto Joven

RESUMEN

Coronavirus disease 2019 (COVID-19) might impact disease progression in people living with HIV (PLWH), including those on effective combination antiretroviral therapy (cART). These individuals often experience chronic conditions characterized by proviral latency or low-level viral replication in CD4+ memory T cells and tissue macrophages. Pro-inflammatory cytokines, such as TNF-α, IL-1ß, IL-6, and IFN-γ, can reactivate provirus expression in both primary cells and cell lines. These cytokines are often elevated in individuals infected with SARS-CoV-2, the virus causing COVID-19. However, it is still unknown whether SARS-CoV-2 can modulate HIV reactivation in infected cells. Here, we report that exposure of the chronically HIV-1-infected myeloid cell line U1 to two different SARS-CoV-2 viral isolates (ancestral and BA.5) reversed its latent state after 24 h. We also observed that SARS-CoV-2 exposure of human primary monocyte-derived macrophages (MDM) initially drove their polarization towards an M1 phenotype, which shifted towards M2 over time. This effect was associated with soluble factors released during the initial M1 polarization phase that reactivated HIV production in U1 cells, like MDM stimulated with the TLR agonist resiquimod. Our study suggests that SARS-CoV-2-induced systemic inflammation and interaction with macrophages could influence proviral HIV-1 latency in myeloid cells in PLWH.

Asunto(s)

COVID-19 , Citocinas , Infecciones por VIH , VIH-1 , Macrófagos , Células Mieloides , SARS-CoV-2 , Latencia del Virus , Humanos , SARS-CoV-2/fisiología , VIH-1/fisiología , COVID-19/virología , COVID-19/inmunología , Macrófagos/virología , Macrófagos/inmunología , Células Mieloides/virología , Citocinas/metabolismo , Infecciones por VIH/virología , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Línea Celular , Efecto Espectador , Activación Viral , Replicación Viral/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Linfocitos T CD4-Positivos/inmunología

RESUMEN

BACKGROUND: The incidence of comorbidities is higher in HIV-positive patients than in the general population due to factors, such as HIV-related chronic inflammation. There is no consensus on whether a low CD4 lymphocyte count after virological suppression at long-term follow-up increases the risk of comorbidities. This study evaluates the association between CD4 lymphocyte count and the incidence of comorbidities during the first 5 years of virological suppression after highly active antiretroviral treatment. METHODS: We conducted a cohort study of HIV-positive adults who achieved virological suppression in an HIV program between 2002 and 2016 in Colombia. A generalized equation estimation model was used to estimate the association between CD4 lymphocyte count and the incidence of comorbidities. RESULTS: A follow-up period of at least 1 year was completed in 921 HIV-positive patients with virological suppression. We found 71 comorbidities during a maximum of 5 years of follow-up; 41 (59%) were AIDS-defining comorbidities and 19 (46%) of them occurred during the first semester. Thirty cases of non-AIDS- defining comorbidities were diagnosed.We did not find any association between CD4 lymphocyte count and the incidence of comorbidities (OR 0.92, CI 95% 0.45 -1.91 for CD4 201-499 cells/µL vs CD4 ≤200 cells/µL, and OR 0.55, 95% CI 0.21-1.44 for CD4 ≥500 cells/µL vs CD4 ≤200 cells/µL). CONCLUSION: No association was found between CD4 lymphocyte count and the incidence of AIDS-defining or non-AIDS-defining comorbidities in patients with virological suppression. Further studies are needed to assess the risk of comorbidities in this population to design interventions aimed at improving their prognosis.

Asunto(s)

Terapia Antirretroviral Altamente Activa , Comorbilidad , Infecciones por VIH , Carga Viral , Humanos , Masculino , Femenino , Recuento de Linfocito CD4 , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Adulto , Incidencia , Persona de Mediana Edad , Colombia/epidemiología , Fármacos Anti-VIH/uso terapéutico , Estudios de Cohortes , Respuesta Virológica Sostenida , Estudios de Seguimiento

RESUMEN

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. SETTING: Referral tertiary care hospital for adult patients with cancer. METHODS: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. RESULTS: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. CONCLUSIONS: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

Asunto(s)

Canal Anal , Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Humanos , Masculino , Adulto , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Persona de Mediana Edad , Prevalencia , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Femenino , Canal Anal/virología , Canal Anal/patología , Neoplasias del Ano/virología , Neoplasias del Ano/epidemiología , Papillomaviridae/aislamiento & purificación , Papillomaviridae/genética , Homosexualidad Masculina/estadística & datos numéricos , Centros de Atención Terciaria , Virus del Papiloma Humano

RESUMEN

The presence of genetic mutations in HIV poses a significant challenge, potentially leading to antiretroviral resistance and hampering therapeutic development. The Brazilian population has presented variations in the HIV envelope V3 loop gene, especially the GWGR motif. This motif has been linked to reduced transmission potential and slower CD4+ T cell decline. This study aimed to assess clinical outcomes in patients with HIV-1 infected with strains containing the GWGR motif compared with those without it during long-term cART. A cohort of 295 patients with HIV was examined for the GWGR motif presence in the V3 loop. A total of 58 samples showed the GWGR signature, while 237 had other signatures. Multifactorial analyses showed no significant differences in demographic characteristics, CD4+ cell count, AIDS progression, or mortality between GWGR carriers and others. However, the mean interval between the first positive HIV test and the initial AIDS-defining event was more than two times longer for women carrying the GWGR signature (p = 0.0231). We emphasize the positive impact of cART on HIV/AIDS treatment, including viral suppression, CD4+ cell preservation, and immune function maintenance. Although no significant differences were found during cART, residual outcomes reflecting adherence challenges were observed between diagnosis and the first AIDS-defining event. The previously described outcomes, highlighting statistically significant differences between individuals carrying the GPGR motif compared with those with the Brazilian GWGR motif, may be directly linked to the natural progression of infection before advancements in cART. Presently, these physicochemical aspects may no longer hold the same relevance.

Asunto(s)

Infecciones por VIH , VIH-1 , Humanos , Femenino , VIH-1/genética , VIH-1/efectos de los fármacos , Masculino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Adulto , Recuento de Linfocito CD4 , Fármacos Anti-VIH/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Secuencias de Aminoácidos , Carga Viral , Proteína gp120 de Envoltorio del VIH/genética , Estudios de Cohortes , Brasil , Terapia Antirretroviral Altamente Activa , Progresión de la Enfermedad , Mutación

Asunto(s)

Infecciones por VIH , VIH-1 , Latencia del Virus , Humanos , Infecciones por VIH/virología , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , VIH-1/genética , Fármacos Anti-VIH/uso terapéutico

RESUMEN

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-É£, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties.

Asunto(s)

Coinfección , Citocinas , Infecciones por Virus de Epstein-Barr , Infecciones por VIH , VIH-1 , Herpesvirus Humano 4 , Polimorfismo de Nucleótido Simple , Humanos , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Infecciones por VIH/complicaciones , Brasil/epidemiología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Masculino , Adulto , Femenino , VIH-1/inmunología , VIH-1/genética , Citocinas/genética , Citocinas/sangre , Persona de Mediana Edad , Coinfección/virología , Coinfección/inmunología , Coinfección/genética , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/genética , Genotipo , Linfocitos T CD8-positivos/inmunología , Adulto Joven , Recuento de Linfocito CD4 , Inmunogenética

RESUMEN

HIV-1, Hepatitis B and HTLV-1 have similar risk factors and shared routes of transmission and MSM are disproportionately affected by HIV. The aim of the study was to determine the prevalence of HTLV-1 and HBsAg positivity at initial enrolment among MSM attending a large HIV Clinic in Trinidad. Chart reviews were conducted between 2 and 15 January 2024, among self-identified MSM and a comparative group of randomly selected self-identified heterosexual males where sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002-31 October 2023, in total there were 10,424 patients registered at the clinic, of whom 1255 (12.0%) were self-identified MSM, with an age range of 19-85 years and a median age of 40 years. There were 1822 randomly selected heterosexual males, with an age range of 18-94 years old and a median age of 52 years. Among the MSM, there were 21 (1.67%) patients who were HIV-1/HTLV-1-coinfected, 64 (5.10%) who were HIV-1/HBsAg-coinfected and two (0.16%) who were coinfected with all three viruses (HIV-1/HTLV-1/HBsAg) as compared to 47 ((2.58%) HIV-1/HTLV-1-coinfected (p = 0.12), 69 (3.79%) HIV-1/HBsAg-coinfected (p = 0.10) and three (0.16%) patients coinfected with all three viruses among the heterosexual males. There were no patients with HTLV-1-related diseases among the HIV-1/HTLV-1-coinfected patients and there were no deaths from chronic liver disease in patients coinfected with HIV-1/HBsAg. Despite the availability of an efficacious vaccine, there is a prevalence of hepatitis B of 5.1% among MSM attending the HIV Clinic in Trinidad; therefore, programmes to increase health literacy, screening and immunization are urgently needed.

Asunto(s)

Infecciones por VIH , Infecciones por HTLV-I , Antígenos de Superficie de la Hepatitis B , Hepatitis B , Homosexualidad Masculina , Humanos , Masculino , Adulto , Persona de Mediana Edad , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Trinidad y Tobago/epidemiología , Antígenos de Superficie de la Hepatitis B/sangre , Homosexualidad Masculina/estadística & datos numéricos , Anciano , Adulto Joven , Prevalencia , Hepatitis B/epidemiología , Anciano de 80 o más Años , Infecciones por HTLV-I/epidemiología , Coinfección/epidemiología , Coinfección/virología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Adolescente , VIH-1 , Factores de Riesgo

RESUMEN

Women living with human immunodeficiency virus are at an increased risk of developing cancers related to human papillomavirus (HPV). Thus, it is important to combine clinical assessments, serological screening, and HPV data for planning prevention policies. This study aimed to identify HPV and its specific types in the cervical, anal, and oral mucosa of HIV-seropositive women, associating it with viral load and lymphocyte count. Sociodemographic characteristics, health data (CD4+ and CD8+ T cell counts and viral load), and biological samples (cervical, anal, and oral) were collected from 86 HIV-positive women undergoing antiretroviral therapy. Data were classified according to the presence or absence of HPV-DNA, HPV-DNA presence at one or more anatomic sites, and level of oncogenic risk, considering low- and high-risk oncogenic HPV-DNA groups. The presence of HPV in the cervicovaginal site was 65.9%, 63.8% in anal canal, and 4.2% in oral mucosa. A viral load ≥75 HIV copies/mL was associated with the presence of HPV-DNA. There was an association between viral load and the low-risk HPV or high-risk HPV groups. We found a high prevalence of HPV infection in HIV-seropositive women, particularly in the cervical and anal mucosa, with viral load ≥75 HIV copies/mL being associated with HPV-DNA presence.

Asunto(s)

Cuello del Útero , ADN Viral , Infecciones por VIH , Infecciones por Papillomavirus , Carga Viral , Humanos , Femenino , Infecciones por Papillomavirus/complicaciones , Adulto , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , ADN Viral/análisis , Cuello del Útero/virología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Persona de Mediana Edad , Recuento de Linfocitos , Mucosa Bucal/virología , Canal Anal/virología , Prevalencia , Estudios Transversales , Factores Socioeconómicos , Recuento de Linfocito CD4 , Factores de Riesgo , Virus del Papiloma Humano

RESUMEN

The group-specific antigen (gag) plays a crucial role in the assembly, release, and maturation of HIV. This study aimed to analyze the partial sequence of the HIV gag gene to classify HIV subtypes, identify recombination sites, and detect protease inhibitor (PI) resistance-associated mutations (RAMs). The cohort included 100 people living with HIV (PLH) who had experienced antiretroviral treatment failure with reverse transcriptase/protease inhibitors. Proviral HIV-DNA was successfully sequenced in 96 out of 100 samples for gag regions, specifically matrix (p17) and capsid (p24). Moreover, from these 96 sequences, 82 (85.42%) were classified as subtype B, six (6.25%) as subtype F1, one (1.04%) as subtype C, and seven (7.29%) exhibited a mosaic pattern between subtypes B and F1 (B/F1), with breakpoints at p24 protein. Insertions and deletions of amino acid at p17 were observed in 51 samples (53.13%). The prevalence of PI RAM in the partial gag gene was observed in 78 out of 96 PLH (81.25%). Among these cases, the most common mutations were R76K (53.13%), Y79F (31.25%), and H219Q (14.58%) at non-cleavage sites, as well as V128I (10.42%) and Y132F (11.46%) at cleavage sites. While B/F1 recombination was identified in the p24, the p17 coding region showed higher diversity, where insertions, deletions, and PI RAM, were observed at high prevalence. In PLH with virological failure, the analysis of the partial gag gene could contribute to more accurate predictions in genotypic resistance to PIs. This can aid guide more effective HIV treatment strategies.

Asunto(s)

Variación Genética , Infecciones por VIH , VIH-1 , Productos del Gen gag del Virus de la Inmunodeficiencia Humana , Humanos , VIH-1/genética , VIH-1/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Variación Genética/genética , Masculino , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Femenino , Adulto , Farmacorresistencia Viral Múltiple/genética , Mutación , Genotipo , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Persona de Mediana Edad , Filogenia , ADN Viral/genética

RESUMEN

This study aims to explore the influence of coinfection with HCV and HIV on hepatic fibrosis. A coculture system was set up to actively replicate both viruses, incorporating CD4 T lymphocytes (Jurkat), hepatic stellate cells (LX-2), and hepatocytes (Huh7.5). LX-2 cells' susceptibility to HIV infection was assessed through measurements of HIV receptor expression, exposure to cell-free virus, and cell-to-cell contact with HIV-infected Jurkat cells. The study evaluated profibrotic parameters, including programed cell death, ROS imbalance, cytokines (IL-6, TGF-ß, and TNF-α), and extracellular matrix components (collagen, α-SMA, and MMP-9). The impact of HCV infection on LX-2/HIV-Jurkat was examined using soluble factors released from HCV-infected hepatocytes. Despite LX-2 cells being nonsusceptible to direct HIV infection, bystander effects were observed, leading to increased oxidative stress and dysregulated profibrotic cytokine release. Coculture with HIV-infected Jurkat cells intensified hepatic fibrosis, redox imbalance, expression of profibrotic cytokines, and extracellular matrix production. Conversely, HCV-infected Huh7.5 cells exhibited elevated profibrotic gene transcriptions but without measurable effects on the LX-2/HIV-Jurkat coculture. This study highlights how HIV-infected lymphocytes worsen hepatic fibrosis during HCV/HIV coinfection. They increase oxidative stress, profibrotic cytokine levels, and extracellular matrix production in hepatic stellate cells through direct contact and soluble factors. These insights offer valuable potential therapies for coinfected individuals.

Asunto(s)

Efecto Espectador , Técnicas de Cocultivo , Coinfección , Citocinas , Infecciones por VIH , Hepacivirus , Células Estrelladas Hepáticas , Hepatitis C , Cirrosis Hepática , Humanos , Células Estrelladas Hepáticas/metabolismo , Infecciones por VIH/complicaciones , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , Infecciones por VIH/inmunología , Hepacivirus/fisiología , Hepatitis C/metabolismo , Hepatitis C/virología , Hepatitis C/complicaciones , Hepatitis C/inmunología , Células Jurkat , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Cirrosis Hepática/etiología , Citocinas/metabolismo , Hepatocitos/metabolismo , Hepatocitos/virología , VIH/fisiología , Estrés Oxidativo , Comunicación Celular , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Matriz Extracelular/metabolismo

RESUMEN

Cryptococcus neoformans is primarily responsible for cases of cryptococcal meningitis in individuals with HIV/AIDS. This study evaluated the susceptibility of C. neoformans obtained from individuals with cryptococcal meningitis associated with HIV/AIDS in Manaus, Amazonas, Brazil, against the action of the antifungals amphotericin B, flucytosine, fluconazole, itraconazole and posaconazole and analyzed it using Multilocus Sequence Typing (MLST) in order to identify the Sequence Types (STs). We analyzed 30 isolates of C. neoformans, from 24 HIV/AIDS patients diagnosed with cryptococcosis from 2017 to 2019 in a reference hospital, in addition to 3 environmental isolates: 1 isolate obtained in the home of a patient and 2 isolates obtained from neighboring homes of patients. 86.6% (n = 26/30) of the clinical isolates were identified as C. neoformans VNI ST93, 6.6% (n = 2/30) as C. neoformans VNI ST5, 3.3% (n = 1/30) as C. neoformans VNI ST32 and 3.3% (n = 1/30) as C. neoformans VNB ST232. The environmental isolates were identified as C. neoformans VNI ST93 (n = 3/3). 96.6% (n = 29/30) isolates were sensitive to amphotericin B, though there was variation in the MIC. 60% (n = 18/30) presented a MIC above the proposed epidemiological cutoff values for one or more antifungals. All environmental isolates were sensitive to the tested antifungals. The MLST showed that there is an important relationship between C. neoformans VNI ST93 and individuals with HIV/AIDS, including in the environmental isolates analyzed. C. neoformans VNB ST232 was observed for the first time in Amazonas. Amphotericin B was proven to be the best drug, but fluconazole and posaconazole also showed relevant action.

Asunto(s)

Antifúngicos , Cryptococcus neoformans , Infecciones por VIH , Meningitis Criptocócica , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Humanos , Cryptococcus neoformans/genética , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/clasificación , Cryptococcus neoformans/aislamiento & purificación , Meningitis Criptocócica/microbiología , Brasil , Antifúngicos/farmacología , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Técnicas de Tipificación Micológica , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Masculino , Adulto , Femenino , Anfotericina B/farmacología

RESUMEN

MicroRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in regulating gene expression at the post-transcriptional level. These regulatory molecules are integral to many biological processes and have been implicated in the pathogenesis of various diseases, including Human Immunodeficiency Virus (HIV) infection. This review aims to cover the current understanding of the multifaceted roles miRNAs assume in the context of HIV infection and pathogenesis. The discourse is structured around three primary focal points: (i) elucidation of the mechanisms through which miRNAs regulate HIV replication, encompassing both direct targeting of viral transcripts and indirect modulation of host factors critical for viral replication; (ii) examination of the modulation of miRNA expression by HIV, mediated through either viral proteins or the activation of cellular pathways consequent to viral infection; and (iii) assessment of the impact of miRNAs on the immune response and the progression of disease in HIV-infected individuals. Further, this review delves into the potential utility of miRNAs as biomarkers and therapeutic agents in HIV infection, underscoring the challenges and prospects inherent to this line of inquiry. The synthesis of current evidence positions miRNAs as significant modulators of the host-virus interplay, offering promising avenues for enhancing the diagnosis, treatment, and prevention of HIV infection.

Asunto(s)

Infecciones por VIH , MicroARNs , Replicación Viral , Humanos , MicroARNs/genética , Infecciones por VIH/genética , Infecciones por VIH/virología , Replicación Viral/genética , VIH-1/genética , Interacciones Huésped-Patógeno/genética , Biomarcadores , Regulación de la Expresión Génica

RESUMEN

In the context of infectious diseases, the dynamic interplay between ever-changing host populations and viral biology demands a more flexible modeling approach than common fixed correlations. Embracing random-effects regression models allows for a nuanced understanding of the intricate ecological and evolutionary dynamics underlying complex phenomena, offering valuable insights into disease progression and transmission patterns. In this article, we employed a random-effects regression to model an observed decreasing median plasma viral load (pVL) among individuals with HIV in Mexico City during 2019-2021. We identified how these functional slope changes (i.e. random slopes by year) improved predictions of the observed pVL median changes between 2019 and 2021, leading us to hypothesize underlying ecological and evolutionary factors. Our analysis involved a dataset of pVL values from 7325 ART-naïve individuals living with HIV, accompanied by their associated clinical and viral molecular predictors. A conventional fixed-effects linear model revealed significant correlations between pVL and predictors that evolved over time. However, this fixed-effects model could not fully explain the reduction in median pVL; thus, prompting us to adopt random-effects models. After applying a random effects regression model-with random slopes and intercepts by year-, we observed potential "functional changes" within the local HIV viral population, highlighting the importance of ecological and evolutionary considerations in HIV dynamics: A notably stronger negative correlation emerged between HIV pVL and the CpG content in the pol gene, suggesting a changing immune landscape influenced by CpG-induced innate immune responses that could impact viral load dynamics. Our study underscores the significance of random effects models in capturing dynamic correlations and the crucial role of molecular characteristics like CpG content. By enriching our understanding of changing host-virus interactions and HIV progression, our findings contribute to the broader relevance of such models in infectious disease research. They shed light on the changing interplay between host and pathogen, driving us closer to more effective strategies for managing infectious diseases. SIGNIFICANCE OF THE STUDY: This study highlights a decreasing trend in median plasma viral loads among ART-naïve individuals living with HIV in Mexico City between 2019 and 2021. It uncovers various predictors significantly correlated with pVL, shedding light on the complex interplay between host-virus interactions and disease progression. By employing a random-slopes model, the researchers move beyond traditional fixed-effects models to better capture dynamic correlations and evolutionary changes in HIV dynamics. The discovery of a stronger negative correlation between pVL and CpG content in HIV-pol sequences suggests potential changes in the immune landscape and innate immune responses, opening avenues for further research into adaptive changes and responses to environmental shifts in the context of HIV infection. The study's emphasis on molecular characteristics as predictors of pVL adds valuable insights to epidemiological and evolutionary studies of viruses, providing new avenues for understanding and managing HIV infection at the population level.

Asunto(s)

Infecciones por VIH , Carga Viral , Humanos , Infecciones por VIH/inmunología , Infecciones por VIH/virología , México/epidemiología , Femenino , Masculino , VIH-1/fisiología , VIH-1/inmunología , VIH-1/genética , Adulto , Islas de CpG/genética

RESUMEN

The role of the oral microbiota in the overall health and in systemic diseases has gained more importance in the recent years, mainly due to the systemic effects that are mediated by the chronic inflammation caused by oral diseases, such as periodontitis, through the microbial communities of the mouth. The chronic infection by the human immunodeficiency virus (HIV) interacts at the tissue level (e.g. gut, genital tract, brain) to create reservoirs; the modulation of the gut microbiota by HIV infection is a good example of these interactions. The purpose of the present review is to assess the state of knowledge on the oral microbiota (microbiome, mycobiome and virome) of HIV-infected patients in comparison to that of HIV-negative individuals and to discuss the reciprocal influence of HIV infection and oral microbiota in patients with periodontitis on the potential establishment of a viral gingival reservoir. The influence of different clinical and biological parameters are reviewed including age, immune and viral status, potent antiretroviral therapies, smoking, infection of the airway and viral coinfections, all factors that can modulate the oral microbiota during HIV infection. The analysis of the literature proposed in this review indicates that the comparisons of the available studies are difficult due to their great heterogeneity. However, some important findings emerge: (i) the oral microbiota is less influenced than that of the gut during HIV infection, although some recurrent changes in the microbiome are identified in many studies; (ii) severe immunosuppression is correlated with altered microbiota and potent antiretroviral therapies correct partially these modifications; (iii) periodontitis constitutes a major factor of dysbiosis, which is exacerbated in HIV-infected patients; its pathogenesis can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances an inflammatory environment that perpetuates the periodontitis cycle. With the objective of curing viral reservoirs of HIV-infected patients in the future years, it appears important to develop further researches aimed at defining whether the inflamed gingiva can serve of viral reservoir in HIV-infected patients with periodontitis.

Asunto(s)

Encía , Infecciones por VIH , Microbiota , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/microbiología , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Encía/microbiología , Encía/virología , Boca/microbiología , Boca/virología , Reservorios de Enfermedades/microbiología , Reservorios de Enfermedades/virología , Periodontitis/microbiología , Periodontitis/virología , Viroma , Disbiosis/microbiología , Antirretrovirales/uso terapéutico , VIH

RESUMEN

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

Asunto(s)

Brotes de Enfermedades , Humanos , Brasil/epidemiología , Masculino , Femenino , Adulto , Adulto Joven , Adolescente , Persona de Mediana Edad , Animales , Zoonosis/epidemiología , Zoonosis/virología , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/aislamiento & purificación , Niño , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Anticuerpos Antivirales/sangre , Anciano , Inmunoglobulina G/sangre