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Santiago Moreno - One of the best experts on this subject based on the ideXlab platform.
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Effects of Maraviroc versus Efavirenz in Combination with Zidovudine-Lamivudine on the CD4/CD8 Ratio in Treatment-Naive HIV-Infected Individuals.
Antimicrobial agents and chemotherapy, 2017Co-Authors: Sergio Serrano-villar, G Caruana, Alexander Zlotnik, José A. Pérez-molina, Santiago MorenoAbstract:A low CD4/CD8 Ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 Ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 Ratio normalization with efavirenz, which was driven by a greater CD8+ T-cell decline.
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effects of maraviroc versus efavirenz in combination with zidovudine lamivudine on the CD4 CD8 Ratio in treatment naive hiv infected individuals
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Sergio Serranovillar, G Caruana, Alexander Zlotnik, Jose A Perezmolina, Santiago MorenoAbstract:A low CD4/CD8 Ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 Ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 Ratio normalization with efavirenz, which was driven by a greater CD8+ T-cell decline.
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different impact of raltegravir versus efavirenz on CD4 CD8 Ratio recovery in hiv infected patients
Journal of Antimicrobial Chemotherapy, 2017Co-Authors: Sergio Serranovillar, Yan Zhou, Anthony Rodgers, Santiago MorenoAbstract:OBJECTIVES A low CD4/CD8 Ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 Ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 Ratio. METHODS We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duRation of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm. RESULTS A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 Ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 Ratio normalization (HR = 1.23; P = 0.02). CONCLUSIONS We herein show that normalization of the CD4/CD8 Ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 Ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
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Different impact of raltegravir versus efavirenz on CD4/CD8 Ratio recovery in HIV-infected patients.
The Journal of antimicrobial chemotherapy, 2016Co-Authors: Sergio Serrano-villar, Yan Zhou, Anthony Rodgers, Santiago MorenoAbstract:OBJECTIVES A low CD4/CD8 Ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 Ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 Ratio. METHODS We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duRation of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm. RESULTS A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 Ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 Ratio normalization (HR = 1.23; P = 0.02). CONCLUSIONS We herein show that normalization of the CD4/CD8 Ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 Ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
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The CD4/CD8 Ratio as a marker T-cell activation, senescence and activation/exhaustion in treated HIV-infected children and young adults.
AIDS (London England), 2013Co-Authors: Talía Sainz, Sergio Serrano-villar, Laura Díaz, María Isabel González Tomé, María Dolores Gurbindo, María Isabel De José, María José Mellado, José Tomás Ramos, Javier Zamora, Santiago MorenoAbstract:We explored the associations of the CD4/CD8 Ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 Ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4+ and CD8+ T-cells, and a skewed T-cell phenotype from naive toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 Ratio may identify patients with higher immunoactivation despite ART.
Sergio Serranovillar - One of the best experts on this subject based on the ideXlab platform.
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effects of maraviroc versus efavirenz in combination with zidovudine lamivudine on the CD4 CD8 Ratio in treatment naive hiv infected individuals
Antimicrobial Agents and Chemotherapy, 2017Co-Authors: Sergio Serranovillar, G Caruana, Alexander Zlotnik, Jose A Perezmolina, Santiago MorenoAbstract:A low CD4/CD8 Ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 Ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 Ratio normalization with efavirenz, which was driven by a greater CD8+ T-cell decline.
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different impact of raltegravir versus efavirenz on CD4 CD8 Ratio recovery in hiv infected patients
Journal of Antimicrobial Chemotherapy, 2017Co-Authors: Sergio Serranovillar, Yan Zhou, Anthony Rodgers, Santiago MorenoAbstract:OBJECTIVES A low CD4/CD8 Ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 Ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 Ratio. METHODS We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duRation of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm. RESULTS A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 Ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 Ratio normalization (HR = 1.23; P = 0.02). CONCLUSIONS We herein show that normalization of the CD4/CD8 Ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 Ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
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increased risk of serious non aids related events in hiv infected subjects on antiretroviral therapy associated with a low CD4 CD8 Ratio
PLOS ONE, 2014Co-Authors: Sergio Serranovillar, José L. Casado, Talía Sainz, Jose A Perezmolina, Maria J Perezelias, Fernando Dronda, Ana Moreno, Ana Royuela, Enrique Navas, Jose HermidaAbstract:Background A low CD4/CD8 Ratio has been identified in the general population as a hallmark of inmmunosenescence and a surrogate of all-cause mortality. We aimed to investigate in treated HIV-infected individuals the relationship between the CD4/CD8 Ratio and serious non-AIDS events. Methods Case-control study within a prospective hospital-based cohort of HIV-infected subjects during at least one year of ART-mediated viral suppression. Cases were patients with serious non-AIDS events (non-AIDS malignancies, cardiovascular disease, and end-stage kidney disease), and controls individuals who did not developed non-AIDS events during follow-up. Data were analyzed using ROC analysis and multivariate logistic regression. Conditional logistic regression was performed in 200 cases/controls matched by age, sex, nadir CD4 and proximal CD4 counts. Results We analyzed 407 subjects (109 cases, 298 controls). The CD4/CD8 Ratio was lower in cases (0.44 vs. 0.70, P<0.0001), with higher discriminatory ability for the detection of non-AIDS events than the CD4 count, CD8 count and nadir CD4. Multivariate analyses (adjusted for age, sex, nadir CD4, proximal CD4 count, year of ART initiation and ART duRation) confirmed the independent association of a low CD4/CD8 Ratio with the risk of non-AIDS morbidity (per CD4/CD8 Ratio quartile decrease, OR, 2.9; 95% CI, 1.3–6.2) and non-AIDS mortality (OR, 2.8; 95% CI, 1.5–5.3). Conclusions The CD4/CD8 Ratio provides additional information to the CD4 counts and nadir CD4 in treated HIV-infected individuals, since it is independently associated with the risk of non-AIDS-related morbidity and mortality. This association is robust and maintained within different subgroups of patients.
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the CD4 CD8 Ratio is associated with markers of age associated disease in virally suppressed hiv infected patients with immunological recovery
Hiv Medicine, 2014Co-Authors: Sergio Serranovillar, S Moreno, Manuel Fuentesferrer, C Sanchezmarcos, M Avila, T Sainz, Ngp De Villar, Arturo Fernandezcruz, Vicente EstradaAbstract:Objectives Inversion of the CD4:CD8 Ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 Ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response. Methods A cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA 350 cells/μL and age < 65 years. We analysed the associations between the CD4:CD8 Ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtRation rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height2 (ALM) measured by dual-energy X-ray absorptiometry (DEXA)]. Results CD4:CD8 Ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P 200 cells/μL and those with CD4 counts > 500 cells/μL. Conclusions The CD4:CD8 Ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions.
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the CD4 CD8 Ratio as a marker t cell activation senescence and activation exhaustion in treated hiv infected children and young adults
AIDS, 2013Co-Authors: Talía Sainz, Sergio Serranovillar, Laura Díaz, María Isabel González Tomé, María Dolores Gurbindo, María Isabel De José, María José Mellado, José Tomás Ramos, Javier Zamora, Santiago MorenoAbstract:We explored the associations of the CD4/CD8 Ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 Ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4+ and CD8+ T-cells, and a skewed T-cell phenotype from naive toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 Ratio may identify patients with higher immunoactivation despite ART.
Marisa A. Hong - One of the best experts on this subject based on the ideXlab platform.
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CD4 CD8 Ratio and kt Ratio predict yellow fever vaccine immunogenicity in hiv infected patients
PLOS Neglected Tropical Diseases, 2016Co-Authors: Vivian Iida Avelinosilva, Peter W. Hunt, Karina Takesaki Miyaji, Sheila Maria Barbosa De Lima, Marisol Simões, Marcos Da Silva Freire, Marisa A. Hong, Helio H Caiaffafilho, Yong HuangAbstract:Author(s): Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G | Abstract: BackgroundHIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 Ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population.MethodsWe prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4g350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 Ratio, IDO activity (plasma kynurenine/tryptophan [KT] Ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.Results12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 Ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT Ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.ConclusionsHIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 Ratio or higher KT Ratio.
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CD4/CD8 Ratio Predicts Yellow Fever Vaccine-Induced Antibody Titers in Virologically Suppressed HIV-Infected Patients.
Journal of acquired immune deficiency syndromes (1999), 2016Co-Authors: Vivian Iida Avelino-silva, Karina Takesaki Miyaji, Augusto Mathias, Dayane Alves Costa, Juliana Zanatta De Carvalho Dias, Sheila Maria Barbosa De Lima, Marisol Simões, Marcos Da Silva Freire, Helio H. Caiaffa-filho, Marisa A. HongAbstract:BACKGROUND: Yellow fever vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. METHODS: We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) Ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. RESULTS: Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) Ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. CONCLUSIONS: ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4(+)/CD8(+) Ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) Ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART.
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CD4 CD8 Ratio predicts yellow fever vaccine induced antibody titers in virologically suppressed hiv infected patients
Journal of Acquired Immune Deficiency Syndromes, 2016Co-Authors: Vivian Iida Avelinosilva, Karina Takesaki Miyaji, Augusto Mathias, Dayane Alves Costa, Juliana Zanatta De Carvalho Dias, Sheila Maria Barbosa De Lima, Marisol Simões, Marcos Da Silva Freire, Helio H Caiaffafilho, Marisa A. HongAbstract:BACKGROUND: Yellow fever vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. METHODS: We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) Ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. RESULTS: Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) Ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. CONCLUSIONS: ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4(+)/CD8(+) Ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) Ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART.
Sergio Serrano-villar - One of the best experts on this subject based on the ideXlab platform.
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Effects of Maraviroc versus Efavirenz in Combination with Zidovudine-Lamivudine on the CD4/CD8 Ratio in Treatment-Naive HIV-Infected Individuals.
Antimicrobial agents and chemotherapy, 2017Co-Authors: Sergio Serrano-villar, G Caruana, Alexander Zlotnik, José A. Pérez-molina, Santiago MorenoAbstract:A low CD4/CD8 Ratio during treated HIV infection reflects heightened immune activation and predicts death. The effects of different antiretroviral therapy regimens on CD4/CD8 Ratio recovery remains unclear. We performed a post hoc analysis of the MERIT study, a randomized, double-blind trial of maraviroc versus efavirenz in combination with zidovudine-lamivudine in treatment-naive HIV-infected individuals. We found higher rates of CD4/CD8 Ratio normalization with efavirenz, which was driven by a greater CD8+ T-cell decline.
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Different impact of raltegravir versus efavirenz on CD4/CD8 Ratio recovery in HIV-infected patients.
The Journal of antimicrobial chemotherapy, 2016Co-Authors: Sergio Serrano-villar, Yan Zhou, Anthony Rodgers, Santiago MorenoAbstract:OBJECTIVES A low CD4/CD8 Ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 Ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 Ratio. METHODS We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duRation of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm. RESULTS A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 Ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 Ratio normalization (HR = 1.23; P = 0.02). CONCLUSIONS We herein show that normalization of the CD4/CD8 Ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 Ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
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The CD4/CD8 Ratio as a marker T-cell activation, senescence and activation/exhaustion in treated HIV-infected children and young adults.
AIDS (London England), 2013Co-Authors: Talía Sainz, Sergio Serrano-villar, Laura Díaz, María Isabel González Tomé, María Dolores Gurbindo, María Isabel De José, María José Mellado, José Tomás Ramos, Javier Zamora, Santiago MorenoAbstract:We explored the associations of the CD4/CD8 Ratio with markers of immunoactivation, immunosenescence and T-cell subsets, in 37 vertically HIV-infected children and adolescents. CD4/CD8 Ratio inversion was associated with higher frequencies of activated, senescent and activated/exhausted CD4+ and CD8+ T-cells, and a skewed T-cell phenotype from naive toward effector memory which persisted after the multivariate analysis. Thus, the CD4/CD8 Ratio may identify patients with higher immunoactivation despite ART.
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The CD4/CD8 Ratio in HIV-infected subjects is independently associated with T-cell activation despite long-term viral suppression.
The Journal of infection, 2012Co-Authors: Sergio Serrano-villar, Alejandro Vallejo, Laura Díaz, Javier Zamora, Fernando Dronda, Carolina Gutierrez, Beatriz Hernández-novoa, María Abad Fernández, Nadia Madrid, María Ángeles Muñoz-fernándezAbstract:Summary Objectives HIV-infected subjects on antiretroviral therapy often fail to normalize the CD4/CD8 Ratio despite CD4 count normalization. We aimed to analyze the biological significance of this finding. Methods Cross-sectional analysis in 20 HIV-infected subjects on stable triple-ART, plasma HIV RNA 350 cells/mm 3 . Laboratory measurements included T-cell activation (HLADR + , CD38 + ) and senescence (CD57 + ), lipopolysaccharide (LPS), sCD14 and the HIV latent reservoir (number of latently infected memory CD4 cells carrying replication-competent virus). Results CD4/CD8 Ratio was positively correlated with CD4 nadir ( r = 0.468, p = 0.038) and accumulated ART exposure ( r = 0.554, p = 0.0011), and negatively with viral load before ART initiation ( r = −0.547, p = 0.013), CD4 + HLADR + CD38 + T-cells ( r = −0.428, p = 0.086) and CD8 + CD57 + T-cells ( r = −0.431, p = 0.084). No associations with LPS, sCD14 or HIV latent reservoir were found. After the multivariate analyses, the CD4/CD8 Ratio remained independently associated with CD4 + HLADR + CD38 + T-cells and CD8 + HLADR + T-cells. Conclusions In our study in subjects on suppressive ART the CD4/CD8 Ratio was independently associated with T-cell activation. Our results must be confirmed in larger studies, as this parameter might be a useful clinical tool to identify subjects with ongoing immune activation despite long-term viral suppression.
Laura Monno - One of the best experts on this subject based on the ideXlab platform.
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HIV-1 coreceptor tropism: A syllogistic connection with The Veterans Aging Cohort Study Index and the CD4/CD8 Ratio.
PloS one, 2019Co-Authors: Armando Leone, Annalisa Saracino, Gioacchino Angarano, Nicolò De Gennaro, Claudia Fabrizio, Luigia Scudeller, Luciana Lepore, Antonella Lagioia, Grazia Punzi, Laura MonnoAbstract:BACKGROUND The association between X4 virus and an increased risk of non-AIDS-events has been reported. Morbidity/mortality due to non-AIDS events, which are properly predicted by the CD4/CD8 Ratio and VACS index, have become particularly remarkable in HIV-infected patients receiving effective combined antiretroviral therapy (cART). METHODS We verified the validity of the syllogism: as HIV-tropism (CRT) contributes to the onset of non-AIDS events which are successfully predicted by the CD4/CD8 Ratio and VACS index, then CRT correlates with these two variables. The CD4/CD8 Ratio and VACS index at baseline and overtime were analyzed according to CRT tested before the first successful cART regimen in newly-diagnosed patients. RESULTS Patients with R5 variants had a significantly lower baseline VACS percentage risk [mean (95%CI):18.2%(16.1-20.3) vs 24.3%(18.2-22.5), p = 0.002] and higher baseline CD4/CD8 Ratio [mean (95%CI):0.43 (0.38-0.47) vs 0.28 (0.19-0.36), p = 0.002] than non-R5 patients. After an initial drop, VACS increased again in R5 and non-R5 patients and the two trend curves almost overlapped. The CD4/CD8 Ratio had an increasing trend in both R5 and non-R5 patients; however, even though non-R5 patients had a greater gain of CD4+, they maintained a lower CD4/CD8 Ratio at any time point. CONCLUSION Our study confirms an association between pre-therapy CRT, CD4/CD8 Ratio and VACS. A successful cART regimen positively affects the CD4/CD8 Ratio; however, the disadvantage conferred by a non-R5 CRT is maintained overtime. The restoRation of VACS in all patients could be directly due to variables included in the VACS calculation and to factors that adversely influence these variables.
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hiv 1 coreceptor tropism a syllogistic connection with the veterans aging cohort study index and the CD4 CD8 Ratio
PLOS ONE, 2019Co-Authors: Armando Leone, Annalisa Saracino, Gioacchino Angarano, Nicolò De Gennaro, Claudia Fabrizio, Luigia Scudeller, Luciana Lepore, Antonella Lagioia, Grazia Punzi, Laura MonnoAbstract:BACKGROUND The association between X4 virus and an increased risk of non-AIDS-events has been reported. Morbidity/mortality due to non-AIDS events, which are properly predicted by the CD4/CD8 Ratio and VACS index, have become particularly remarkable in HIV-infected patients receiving effective combined antiretroviral therapy (cART). METHODS We verified the validity of the syllogism: as HIV-tropism (CRT) contributes to the onset of non-AIDS events which are successfully predicted by the CD4/CD8 Ratio and VACS index, then CRT correlates with these two variables. The CD4/CD8 Ratio and VACS index at baseline and overtime were analyzed according to CRT tested before the first successful cART regimen in newly-diagnosed patients. RESULTS Patients with R5 variants had a significantly lower baseline VACS percentage risk [mean (95%CI):18.2%(16.1-20.3) vs 24.3%(18.2-22.5), p = 0.002] and higher baseline CD4/CD8 Ratio [mean (95%CI):0.43 (0.38-0.47) vs 0.28 (0.19-0.36), p = 0.002] than non-R5 patients. After an initial drop, VACS increased again in R5 and non-R5 patients and the two trend curves almost overlapped. The CD4/CD8 Ratio had an increasing trend in both R5 and non-R5 patients; however, even though non-R5 patients had a greater gain of CD4+, they maintained a lower CD4/CD8 Ratio at any time point. CONCLUSION Our study confirms an association between pre-therapy CRT, CD4/CD8 Ratio and VACS. A successful cART regimen positively affects the CD4/CD8 Ratio; however, the disadvantage conferred by a non-R5 CRT is maintained overtime. The restoRation of VACS in all patients could be directly due to variables included in the VACS calculation and to factors that adversely influence these variables.
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The Revival of an "Old" Marker: CD4/CD8 Ratio.
AIDS reviews, 2017Co-Authors: Giuseppe Bruno, Annalisa Saracino, Laura Monno, Gioacchino AngaranoAbstract:The effectiveness of modern antiretroviral therapies (ART) transformed HIV infection into a chronic disease characterized by a persistent condition of inflammation and immune activation. For this reason, even thought AIDS-related mortality has been reduced with an increased life expectancy, patients living with HIV infection are more likely to develop non-AIDS events despite the achievement of a complete suppression of HIV replication. Hence, the scientific community feels the need to find new biomarkers which would be suitable in clinical practice for identifying patients who require a close monitoring because of an increased risk of developing comorbidities. A renewed interest has emerged about the usefulness of CD4/CD8 Ratio as a strong marker of immune activation and immune senescence. Recently, many studies have underlined that CD4/CD8 Ratio might represent a good predictor of AIDS and non-AIDS events. Herein, the potential role of the CD4/CD8 Ratio for the monitoring of HIV patients in different clinical settings is reviewed.
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the revival of an old marker CD4 CD8 Ratio
Aids Reviews, 2017Co-Authors: G E Bruno, Annalisa Saracino, Laura Monno, Gioacchino AngaranoAbstract:The effectiveness of modern antiretroviral therapies (ART) transformed HIV infection into a chronic disease characterized by a persistent condition of inflammation and immune activation. For this reason, even thought AIDS-related mortality has been reduced with an increased life expectancy, patients living with HIV infection are more likely to develop non-AIDS events despite the achievement of a complete suppression of HIV replication. Hence, the scientific community feels the need to find new biomarkers which would be suitable in clinical practice for identifying patients who require a close monitoring because of an increased risk of developing comorbidities. A renewed interest has emerged about the usefulness of CD4/CD8 Ratio as a strong marker of immune activation and immune senescence. Recently, many studies have underlined that CD4/CD8 Ratio might represent a good predictor of AIDS and non-AIDS events. Herein, the potential role of the CD4/CD8 Ratio for the monitoring of HIV patients in different clinical settings is reviewed.
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CD4 and CD4/CD8 Ratio progression in HIV-HCV infected patients after achievement of SVR.
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2016Co-Authors: Annalisa Saracino, Giuseppe Bruno, Laura Monno, Luigia Scudeller, Nicoletta Ladisa, N. De Gennaro, M. Allegrini, G. AngaranoAbstract:Abstract Background In HIV-HCV co-infected patients, the long-term effects of HCV eradication on HIV disease progression are still unclear. Objectives This study aims to determine if CD4 and CD4/CD8 Ratio slopes improved after anti-HCV treatment in patients achieving a sustained virological response (SVR). Study design A total of 116 HIV-HCV co-infected patients, previously treated with Peg-IFN/RBV, were divided into two groups: SVR (55 patients who had achieved SVR), and non-SVR (61 patients). Retrospective data before and after anti-HCV therapy were obtained for all patients, with a median 8 year-follow-up. Multilevel mixed models were fitted to assess the trends over time of FIB-4 score, APRI score, CD4, CD8 cell count and CD4/CD8 Ratio. Results Median HIV-infection duRation, HCV-RNA and GGT baseline levels were higher in non-SVR compared to the SVR group. A significantly decreased FIB-4 (p Conclusions Achievement of SVR determines an important beneficial impact in terms of liver-related mortality and fibrosis regression, but does not seem to alter neither the slope of long term CD4 gain nor the CD4/CD8 Ratio evolution in ART-treated HIV-HCV co-infected patients.