RESUMEN
OBJECTIVE: This study examined the prevalence, severity and risk factors of anaemia among adult people living with HIV attending an antiretroviral therapy centre in Woreta Primary Hospital, Woreta town, Ethiopia. DESIGN: Hospital-based retrospective cross-sectional study. SETTING: Public health facility that provides HIV care in Woreta town. PARTICIPANTS: A total of 289 medical records of adults living with HIV/AIDS on highly active antiretroviral therapy from February 2019 to September 2023 at government hospital were reviewed using a systematic sampling method. The data were entered using Epi-info V.7 and exported to SPSS V.23 for data analysis. The data were analysed using bivariate and then multivariate logistic regression models in order to identify variables associated with anaemia. At the 95% CI level, variables having a p value of <0.05 were deemed to be statistically significant predictors. PRIMARY OUTCOME: Prevalence and severity of anaemia and its predictors among adult patients living with HIV on antiretroviral therapy in Woreta Primary Hospital. RESULTS: The total prevalence of anaemia was 31.5% (95% CI 28.9 to 33.8). The prevalence of mild, moderate and severe anaemia was 20.42%, 10.38% and 0.70%, respectively. Predictors independently linked with anaemia were female sex (adjusted OR (AOR) 1.08), age ≥40 years (AOR 1.21), lived with HIV >10 years (AOR 2.31), CD4 counts <200 cells/µL (AOR 3.81), non-suppressed viral load (AOR 1.28), history of opportunistic infections (AOR 1.54), WHO clinical stages III and IV (AOR 1.37 and 2.23, respectively) and history of parasitic infestation (AOR 2.81). CONCLUSIONS: A sizeable proportion of participants were found anaemic. Female sex, older age, longer periods lived with the virus, lower CD4 count, non-suppressed viral load, history of opportunistic infections, WHO clinical stages III and IV and history of parasitic infestation were the contributing factors. Therefore, to improve the anaemic status and living circumstances of patients living with HIV, immediate action on the linked factors is needed, such as monitoring for maintenance of CD4 counts >200 cells/µL and avoiding progression of HIV to the advanced WHO clinical stages, suppressed viral load, preventing opportunistic infections and parasitic infestation.
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Anemia , Terapia Antirretroviral Altamente Activa , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Oxazinas , Piridonas , Humanos , Femenino , Masculino , Adulto , Estudios Transversales , Estudios Retrospectivos , Anemia/epidemiología , Etiopía/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Prevalencia , Persona de Mediana Edad , Factores de Riesgo , Piridonas/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Recuento de Linfocito CD4 , Adulto Joven , Inhibidores de Integrasa VIH/uso terapéutico , Índice de Severidad de la Enfermedad , PiperazinasRESUMEN
BACKGROUND: From 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS. METHODS: The data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution. RESULTS: A final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets. CONCLUSIONS: Compared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility.
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Terapia Antirretroviral Altamente Activa , Medicamentos Herbarios Chinos , Infecciones por VIH , Puntaje de Propensión , Humanos , Masculino , Femenino , Medicamentos Herbarios Chinos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Adulto , China/epidemiología , Persona de Mediana Edad , Recuento de Linfocito CD4 , Estudios ProspectivosRESUMEN
Despite effective antiretroviral therapy (ART), 15-30% of people with HIV experience poor CD4+ T-cell recovery, termed immunologic non-responders (INR). This study aims to evaluate whether pre-ART plasma levels of interleukin-6 (IL-6), interferon gamma-induced protein-10 (IP-10), macrophage inflammatory protein-1-ß (MIP-1ß), and/or pentraxin-3 (PTX-3) could predict subsequent immunologic recovery. Seventy-four participants were enrolled and classified as INR and immunologic responders (IR) based on CD4+/CD8+ ratio increase over 24 months after starting ART. The results showed no significant differences in cytokine levels between INR and IR. Therefore, IL-6, IP-10, MIP-1ß, and PTX-3 were unsuitable as predictive markers of poor immune recovery.
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Biomarcadores , Proteína C-Reactiva , Quimiocina CCL4 , Quimiocina CXCL10 , Infecciones por VIH , Interleucina-6 , Componente Amiloide P Sérico , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/sangre , Componente Amiloide P Sérico/metabolismo , Masculino , Femenino , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Adulto , Quimiocina CCL4/sangre , Interleucina-6/sangre , Persona de Mediana Edad , Biomarcadores/sangre , Quimiocina CXCL10/sangre , Terapia Antirretroviral Altamente Activa , Resultado del Tratamiento , Antirretrovirales/uso terapéutico , Relación CD4-CD8 , Fármacos Anti-VIH/uso terapéuticoRESUMEN
BACKGROUND: Anaemia is one of the most common problems in HIV-infected patients associated with increased HIV progression, decreased functional capacity, survival and quality of life. For better interventions, up-to-date information concerning anaemia among HIV-infected children less than 5 years of age on antiretroviral therapy (ART) is vital. Thus, this study aims to determine the predictors of anaemia among HIV-infected children less than 5 years of age receiving ART in North-West Ethiopia. DESIGN: An institution-based retrospective follow-up study was conducted. STUDY SETTING: Amhara region Comprehensive Specialized Hospitals, North-West Ethiopia. PARTICIPANTS: In total, we examined 460 HIV-infected children less than 5 years of age who had followed highly active antiretroviral treatment from 2010 to 2020. OUTCOME MEASURES: The outcome measures were median time to detection of anaemia, the incidence and the effects of cotrimoxazole preventive therapy (CPT), ART adherence, tuberculosis (TB), WHO clinical stage and wasting on anaemia. RESULTS: The overall follow-up time was 9234 person-months of observation. The incidence density of anaemia was 8.34 per 1000 person-months of observation (95% CI 6.67 to 10.43). The cumulative survival probability of children after the last months of follow-up was 0.54. The independent predictors of anaemia were not receiving CPT (adjusted HR (AHR)=4.44; 95% CI 2.48 to 7.93), poor adherence to ART (AHR=2.46; 95% CI 1.37 to 4.42), TB (AHR=3.40; 95% CI 1.72 to 6.72), severe WHO clinical stage (AHR=3.03; 95% CI 1.40 to 6.58) and severe wasting (AHR=1.98; 95% CI 1.08 to 3.64). CONCLUSION AND RECOMMENDATION: The incidence rate of anaemia was high and it was provoked by predictors like CPT, ART adherence, TB, WHO clinical stage and wasting. Therefore, it is necessary to emphasise for these predictors.
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Anemia , Terapia Antirretroviral Altamente Activa , Infecciones por VIH , Humanos , Etiopía/epidemiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Masculino , Estudios Retrospectivos , Anemia/epidemiología , Preescolar , Terapia Antirretroviral Altamente Activa/efectos adversos , Incidencia , Lactante , Estudios de Seguimiento , Cumplimiento de la Medicación/estadística & datos numéricos , Factores de Riesgo , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Tuberculosis/epidemiologíaRESUMEN
Human immunodeficiency virus 1 (HIV-1) infection is characterized by a dynamic and persistent state of viral replication that overwhelms the host immune system in the absence of antiretroviral therapy (ART). The impact of prolonged treatment on the antiviral efficacy of HIV-1-specific CD8+ T cells has nonetheless remained unknown. Here, we used single-cell technologies to address this issue in a cohort of aging individuals infected early during the pandemic and subsequently treated with continuous ART. Our data showed that long-term ART was associated with a process of clonal succession, which effectively rejuvenated HIV-1-specific CD8+ T cell populations in the face of immune senescence. Tracking individual transcriptomes further revealed that initially dominant CD8+ T cell clonotypes displayed signatures of exhaustion and terminal differentiation, whereas newly dominant CD8+ T cell clonotypes displayed signatures of early differentiation and stemness associated with natural control of viral replication. These findings reveal a degree of immune resilience that could inform adjunctive treatments for HIV-1.
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Linfocitos T CD8-positivos , Infecciones por VIH , VIH-1 , Replicación Viral , Linfocitos T CD8-positivos/inmunología , VIH-1/inmunología , VIH-1/fisiología , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Replicación Viral/efectos de los fármacos , Masculino , Persona de Mediana Edad , Femenino , Terapia Antirretroviral Altamente Activa , Antirretrovirales/uso terapéutico , Análisis de la Célula Individual , Diferenciación Celular/inmunologíaRESUMEN
INTRODUCTION: The present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil. MATERIAL AND METHODS: Sixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months. RESULTS: Sixty-eight patients used itraconazole 200-400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115-355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01). DISCUSSION: The regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary.
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Infecciones Oportunistas Relacionadas con el SIDA , Síndrome de Inmunodeficiencia Adquirida , Anfotericina B , Antifúngicos , Ácido Desoxicólico , Histoplasmosis , Humanos , Histoplasmosis/tratamiento farmacológico , Histoplasmosis/inmunología , Masculino , Femenino , Antifúngicos/uso terapéutico , Antifúngicos/administración & dosificación , Adulto , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Persona de Mediana Edad , Ácido Desoxicólico/uso terapéutico , Ácido Desoxicólico/administración & dosificación , Anfotericina B/uso terapéutico , Anfotericina B/administración & dosificación , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Recuento de Linfocito CD4 , Brasil/epidemiología , Itraconazol/uso terapéutico , Itraconazol/administración & dosificación , Reconstitución Inmune , Combinación de Medicamentos , Quimioterapia de Consolidación , Estudios Retrospectivos , Cumplimiento de la Medicación/estadística & datos numéricos , Recurrencia , Duración de la Terapia , Resultado del Tratamiento , Estudios de Seguimiento , Terapia Antirretroviral Altamente ActivaRESUMEN
AIDS is a serious disease with impaired immune function caused by human immunodeficiency virus (HIV) infection. The treatment of AIDS has always been the focus of global scientific research, and Tat protein is a key regulatory protein in the process of HIV infection. Its high expression is closely related to virus replication, disease progression, etc. The aim of this study is to explore the molecular mechanism of regulating Tat protein expression by using network pharmacology based traditional Chinese medicine for calming the liver and detoxifying. 129 AIDS patients were enrolled in the study and randomly divided into HAART combined with PGJDP treatment and HAART alone treatment groups. The virological response rate, immunological response status (CD4 + T cell level, CD4/CD8) and incidence of abnormal liver function were observed before and 48 weeks after treatment. Using the TCMSP database to obtain the chemical components and targets of the main traditional Chinese medicine components in PGJDP, clinical results indicate that the combination of HAART and PGJDP treatment can improve the virological response rate (P > 0.05); Increase the number of CD4 + T lymphocytes (P > 0.05); Significantly increased CD4/CD8 ratio (P < 0.01); Simultaneously, it significantly reduced the incidence of liver dysfunction (P < 0.01). After screening and analysis, the Chinese herbal medicine for calming liver and detoxifying has the potential to significantly regulate the expression of Tat protein. These Chinese herbal compounds can reduce the expression of Tat protein by affecting key pathways and regulating the expression of related genes, which has potential therapeutic effects on the treatment of AIDS.
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Síndrome de Inmunodeficiencia Adquirida , Terapia Antirretroviral Altamente Activa , Medicamentos Herbarios Chinos , Medicina Tradicional China , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Humanos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Masculino , Medicamentos Herbarios Chinos/farmacología , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética , Medicina Tradicional China/métodos , Femenino , Adulto , Farmacología en Red , Persona de Mediana Edad , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacosRESUMEN
BACKGROUND: Despite successful antiretroviral therapy (ART), frequencies and immunological functions of memory CCR6+ Th17-polarised CD4+ T-cells are not fully restored in people with HIV (PWH). Moreover, long-lived Th17 cells contribute to HIV persistence under ART. However, the molecular mechanisms underlying these observations remain understudied. METHODS: mRNA-sequencing was performed using Illumina technology on freshly FACS-sorted memory CCR6+CD4+ T-cells from successfully ART-treated (ST), elite controllers (EC), and uninfected donors (HD). Gene expression validation was performed by RT-PCR, flow cytometry, and in vitro functional assays. FINDINGS: Decreased Th17 cell frequencies in STs and ECs versus HDs coincided with reduced Th17-lineage cytokine production in vitro. Accordingly, the RORγt/RORC2 repressor NR1D1 was upregulated, while the RORγt/RORC2 inducer Semaphorin 4D was decreased in memory CCR6+ T-cells of STs and ECs versus HDs. The presence of HIV-DNA in memory CCR6+ T-cells of ST and EC corresponded with the downregulation of HIV restriction factors (SERINC3, KLF3, and RNF125) and HIV inhibitors (tetraspanins), along with increased expression of the HIV-dependency factor MRE11, indicative of higher susceptibility/permissiveness to HIV-1 infection. Furthermore, markers of DNA damage/modification were elevated in memory CCR6+ T-cells of STs and ECs versus HDs, in line with their increased activation (CD38/HLA-DR), senescence/exhaustion phenotype (CTLA-4/PD-1/CD57) and their decreased expression of proliferation marker Ki-67. INTERPRETATION: These results reveal new molecular mechanisms of Th17 cell deficit in ST and EC PWH despite a successful control of HIV-1 replication. This knowledge points to potential therapeutic interventions to limit HIV-1 infection and restore frequencies, effector functions, and senescence/exhaustion in Th17 cells. FUNDING: This study was funded by the Canadian Institutes of Health Research (CIHR, operating grant MOP 142294, and the Canadian HIV Cure Enterprise [CanCURE 2.0] Team Grant HB2 164064), and in part, by the Réseau SIDA et maladies infectieuses du Fonds de recherche du Québec-Santé (FRQ-S).
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Infecciones por VIH , VIH-1 , Memoria Inmunológica , Receptores CCR6 , Células Th17 , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Receptores CCR6/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , VIH-1/efectos de los fármacos , Masculino , Adulto , Femenino , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Persona de Mediana Edad , Terapia Antirretroviral Altamente Activa , Citocinas/metabolismo , Biomarcadores , Carga Viral , Perfilación de la Expresión GénicaRESUMEN
The increased life expectancy of PLHIV (People Living with HIV) and the successful highly combined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection "accelerates" aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterized by inflammation and immune activation that persists despite cART, and that may contribute to the development of co-morbid conditions. In this regard, we aimed to compare current cART regimens in light of premature aging to evaluate differences in their ability to reduce immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1ß, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and affordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show a less favorable regimen profile containing a protease inhibitor. Our data suggest an incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the interest in various biomarkers related to immune activation and inflammation as predictors of clinical outcomes among PLHIV will increase in the future.
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Terapia Antirretroviral Altamente Activa , Biomarcadores , Infecciones por VIH , Inmunosenescencia , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Biomarcadores/sangre , Masculino , Femenino , Adulto , Persona de Mediana Edad , Citocinas/sangre , VIH-1/inmunología , Fármacos Anti-VIH/uso terapéutico , Inflamación/inmunologíaRESUMEN
Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH.
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Terapia Antirretroviral Altamente Activa , Biomarcadores , Infecciones por VIH , Inflamación , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Biomarcadores/sangre , Femenino , Adulto , Masculino , Persona de Mediana Edad , Enfermedades Renales , Fármacos Anti-VIH/uso terapéutico , Riñón/fisiopatologíaRESUMEN
Limited therapeutic options are available for patients with multidrug-resistant HIV. This report describes a 38-year-old female who was perinatally infected with HIV-1 and treated with 14 different antiretroviral regimens over 27 years, gradually leading to 4-class drug resistance. Despite various attempts to obtain sustained viral suppression, including the off-label administration of intravenous foscarnet and enfuvirtide, and thorough follow-up with 16 viral genotyping/phenotyping from 1999 to 2021, viral control was not maintained. Recently, the introduction of a regimen with fostemsavir and lenacapavir resulted in long-term viral suppression.
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Fármacos Anti-VIH , Farmacorresistencia Viral Múltiple , Infecciones por VIH , VIH-1 , Humanos , Femenino , Adulto , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Cumplimiento de la Medicación , Terapia Antirretroviral Altamente Activa , Carga Viral/efectos de los fármacosRESUMEN
Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption.
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Infecciones por VIH , VIH-1 , Carga Viral , Humanos , VIH-1/efectos de los fármacos , VIH-1/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Infecciones por VIH/inmunología , Carga Viral/efectos de los fármacos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD4-Positivos/inmunología , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , MasculinoRESUMEN
BACKGROUND: The incidence of Hodgkin's lymphoma (HL) in people living with HIV (PLWHA) and on HAART is approximately 20-30 times higher than in HIV-negative individuals. Most patients with HIV-HL present at an advanced stage (III-IV) have 'B' symptoms and extranodal involvement. The natural history and risk stratification of HIV-HL has undergone a significant change as a result of HAART's rollout. This study investigated the differences in clinicopathological and survival patterns of HL among individuals with and without HIV disease in Tanzania during the HAART era. METHODOLOGY: This hospital-based retrospective cohort study was conducted at the ORCI, Dar-Es-Salaam, Tanzania. Chi-square and Fisher's exact tests were used to compare proportions. The student t-test was used to compare means. To determine factors that predict survival, we used the log-rank test to analyze the variables in univariate analysis. A Cox regression model was used to analyze the significant factors from univariate analysis in multivariate analysis. RESULTS: Eighty-three patients with HL were recruited, and the prevalence of HIV-positive status was 27.7%. Most of the patients with HIV-HL had an age of > 30 years (73.9%), while most of the non-HIV-HL patients had an age of ≤ 30 years (63.3%) (P = 0.02). The 2-year OS rate for HIV-HL was 34%, while that for non-HIV-HL was 67%. Among the HIV-HL patients, predictors of a poorer outcome were a CD4 count ≤ 200 cells/mm3 (P = 0.05), lack of HAART use (P = 0.00), and the use of HAART for ≤ 10 months (P = 0.00). CONCLUSION: The prevalence of HIV-HL was 27.7% among HL patients. HIV positivity is still a poor prognostic factor in our setting, especially for patients not on HAART, on HAART for ≤ 10 months, or with a low CD4 count below 200 cells/mm3. Patients with HIV-HL were older and had higher LDH levels, whereas patients with non-HIV-HL were younger and had low LDH levels.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Tanzanía/epidemiología , Masculino , Femenino , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , AdolescenteRESUMEN
HIV infection is one of the most acute problems of our time, characterized by slow development, prolonged course, and numerous clinical manifestations. Currently, there is a large number of drugs acting on different processes of human immunodeficiency virus replication, which constitute the group of highly active antiretroviral therapy (HAART). This article shows a theoretical review of modern HAART and analyzes the prescribed treatment regimens for patients with HIV infection. The study revealed two most common combinations: nucleoside reverse transcriptase inhibitors + protease inhibitors; nucleoside + non-nucleoside reverse transcriptase inhibitors.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Fármacos Anti-VIH/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Inhibidores de la Proteasa del VIH/uso terapéuticoRESUMEN
Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.
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Linfocitos T CD4-Positivos , Infecciones por VIH , Reconstitución Inmune , Carga Viral , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Femenino , Masculino , Recuento de Linfocito CD4 , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Linfocitos T CD4-Positivos/inmunología , Fármacos Anti-VIH/uso terapéutico , Apoptosis/efectos de los fármacos , Resultado del Tratamiento , Terapia Antirretroviral Altamente Activa , Subgrupos de Linfocitos T/inmunología , Autofagia/efectos de los fármacos , VIH-1RESUMEN
BACKGROUND: To clarify whether next-generation sequencing (NGS) can be useful for resistance assessment in virologically suppressed highly treatment-experienced (HTE) individuals with MDR HIV. METHODS: Ninety-one participants from the PRESTIGIO Registry were included. NGS was performed on HIV-DNA at 1%, 5% and 20% cut-offs; major drug resistance mutations (DRMs) were evaluated and compared with those detected in historical plasma genotypic resistance testing (h-GRT). APOBEC editing was also characterized. RESULTS: Participants had a complex and long treatment history [median 23 (IQR 21-25) years of ART exposure) and had been virologically suppressed since a median of 3 (IQR 2-5) years. Among all major DRMs detected by HIV-DNA NGS and/or h-GRT, 30% were exclusively found through NGS. The highest detection rate of historical major DRMs was reached with NGS set at 1%, but unusual substitutions and extensive APOBEC hypermutations suggest technical issues and poor clinical relevance in the 1%-5% interval. At NGS set at 5%, 67.2% of historical major DRMs were detected. The number of major DRMs detected exclusively by DNA-NGS as minority variants (frequency 5%-20%) was significantly higher in individuals who later experienced virological rebound compared with those who maintained virological control [median 2 (IQR 1-3) versus 1 (0-2), Pâ=â0.030] and positively correlated with viraemia levels at rebound (rhoâ=â0.474, Pâ=â0.030). CONCLUSIONS: In non-viraemic people with an MDR virus, HIV-1 DNA NGS set at 5% is an acceptable technical cut-off that might help to reveal mutations with a potential clinical relevance. Moreover, the number of minority resistance mutations additionally detected by NGS might be associated with loss of virological control.
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ADN Viral , Farmacorresistencia Viral Múltiple , Infecciones por VIH , VIH-1 , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/genética , VIH-1/efectos de los fármacos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Farmacorresistencia Viral Múltiple/genética , ADN Viral/genética , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacología , Genotipo , Sistema de Registros , Terapia Antirretroviral Altamente ActivaRESUMEN
ABSTRACTSerious adverse drug reactions (sADRs) have a serious impact on the progress being made in providing antiretroviral therapy. The presence of HIV/AIDS and its complications associated with sADRs, has a negative effect on the quality of life (QoL) of people living with HIV/AIDS (PLWHA). This was a descriptive retrospective cohort study of 400 adult HIV patients in which the QoL of PLWHA with sADRs was compared to patients that did not experience ADR who had been on antiretroviral therapy (ART) was followed up for 48 months using the WHOQOL-HIV BREF to measure QoL. Out of 400 patients, 373 (93.25%) respondents completed the study with an overall mean age was 40.8 years (SD ± 8.64). One hundred and ninety-nine patients (53.4%) reported to have experiencing sADR. The response consistently showed significantly higher mean scores in the QoL of patients who had no ADRs in the psychological, social and environments state of health domains compared to those who had ADRs with mean scores (P = 0.000, 0.037 and 0.028), respectively. This study revealed significantly higher scores in patients who had no ADRs compared to those who had ADRs. Low QoL due to serious ADR may add additional burden to HIV disease and complications, and the related discrimination often faced by PLWHA. This study would help clinicians pay serious attention to identifying and promptly managing ADR.
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Terapia Antirretroviral Altamente Activa , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por VIH , Calidad de Vida , Humanos , Masculino , Estudios Retrospectivos , Femenino , Adulto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Nigeria/epidemiología , Terapia Antirretroviral Altamente Activa/efectos adversos , Persona de Mediana Edad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Encuestas y CuestionariosRESUMEN
Antiretroviral therapy (ART) is an effective treatment for people living with HIV (PLHIVs), requiring an extended period to achieve immune reconstitution. Metabolic alterations induced by ART are crucial for predicting long-term therapeutic responses, yet comprehensive investigation through large-scale clinical studies is still lacking. Here, we collected plasma samples from 108 PLHIVs to the untargeted plasma metabolomics study, based on the longitudinal metabolomics design. Cross-sectional analyzes were performed at pre- and post-ART to explore the metabolic transformation induced by the therapy. Subsequently, delta values between pre- and post-ART measurements were calculated to quantify metabolic alterations. Then, the optimal set of metabolic traits and clinical signatures were further identified and applied to construct random forest model for predicting the future therapeutic responses to ART. We found distinct ART-induced metabolic transformation among PLHIVs. After confounder-adjustments, five metabolites exhibited significant associations with future immune response: tetracosatetraenoic acid (24:4n-6) (pre-ART) (odds ratio [OR]: 0.978, 95% confidence interval [CI]: 0.955~0.997), 1-(3,4-dihydroxyphenyl)-5-hydroxy-3-decanone (pre-ART) (OR: 1.298, 95% CI: 1.061~1.727), beta-PC-M6 (change) (OR: 0.967, 95% CI: 0.938~0.993), d-Galactaro-1,4-lactone (change) (OR: 1.032, 95% CI: 1.007~1.063), Annuionone C (change) (OR: 1.100, 95% CI: 1.030~1.190). The addition of plasma metabolites to clinical markers accurately predicted immune response to ART with an area under curve of 0.91. Notably, most disrupted metabolites were significantly correlated with blood lipids, suggesting that metabolic transformation might contribute to dyslipidemia among PLHIVs. This study highlights the distinct metabolic transformation post-ART among PLHIVs and reveals the potential role of metabolic transformation as key determinants of ART efficacy.
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Infecciones por VIH , Metabolómica , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/sangre , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Metaboloma/efectos de los fármacos , Fármacos Anti-VIH/uso terapéutico , Estudios Longitudinales , Plasma/química , Antirretrovirales/uso terapéutico , Biomarcadores/sangre , Terapia Antirretroviral Altamente ActivaRESUMEN
OBJECTIVE: To investigate how antiretroviral therapy (ART) regimens and body mass index (BMI) interact to affect triglyceride (TG) levels in people living with HIV (PLWH). METHODS: This research involved 451 men living with HIV for cross-sectional analysis, and 132 underwent follow-up assessments in 2021 and 2023. Multivariate logistic regression identified key factors, while covariance regression models assessed interactions between ART regimens and BMI on TG levels. RESULTS: The result of this cross-sectional study indicated that advanced AIDS (acquired immune deficiency syndrome) stage (OR = 2.756, P = 0.003), higher BMI (OR = 1.131, P = 0.003), and waist-hip ratio (WHR, OR = 44.684, P = 0.019) are closely associated with high triglyceride levels. Additionally, regimens containing zidovudine (AZT) (OR = 3.927, P < 0.001) or protease inhibitors/integrase strand transfer inhibitors (PI/INSTI) (OR = 5.167, P < 0.001) were significantly linked to hypertriglyceridemia. Cross-sectional and longitudinal analyses from 2021 to 2023 emphasized that changes in BMI interact with antiretroviral treatment regimens to affect TG levels in PLWH (Pinteraction < 0.05). Especially in the AZT-based drug regimen, the correlation between BMI and TG is more prominent. CONCLUSION: The interaction between ART regimens and BMI influences TG levels in PLWH, indicating that weight management is crucial for reducing the risk of hypertriglyceridemia in this population.