HIV Gag p24 specific responses secreting IFN-γ and/or IL-2 in treatment-naïve individuals in acute infection early disease (AIED) are associated with low viral load

Background: Viral and host immune kinetics during acute COVID-19 and after remission of acute symptoms need better characterization. Methods: SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and pro-inflammatory cytokines were measured in sequential samples among hospitalized COVID-19 patients during acute infection and 6 months following diagnosis. Results: 24 laboratory-confirmed COVID-19 patients with mild/moderate and severe COVID-19 were included. Most were males 83%, median age of 61 years. 21% were admitted to the ICU and 8 of them (33.3%) met criteria for severe COVID-19 disease. A delay in SARS-CoV-2 levels decline during the first 6 days of follow-up and viral load persistence until month 3 were related with severe COVID-19, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6, IL-8 and MIP-1β at the diagnosis time were related with severe COVID-19 outcome. Higher levels of MIP-1β, IL-1β, MIP-1α and IFN-γ were observed at month 1-3 during mild/moderate disease compared to severe COVID-19. IgG persisted at low levels after 6 months of diagnosis. Conclusions: Higher concentrations of IgA, IgM, and IgG, and IL-6, IL-8 and MIP-1β are identified as early predictors of COVID-19 severity, but not SARS-CoV-2 RNA levels at diagnosis.

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Elevated Anti-SARS-CoV-2 Antibodies and IL-6, IL-8, MIP-1β, Early Predictors of Severe COVID-19

Microorganisms ◽

10.3390/microorganisms9112259 ◽

2021 ◽

Vol 9 (11) ◽

pp. 2259

Author(s):

Helena Codina ◽

Irene Vieitez ◽

Alicia Gutierrez-Valencia ◽

Vasso Skouridou ◽

Cristina Martínez ◽

...

Keyword(s):

Intensive Care Unit ◽

Viral Load ◽

Acute Infection ◽

Igg Antibodies ◽

Early Predictors ◽

Moderate Disease ◽

Sequential Samples ◽

Ifn Γ ◽

Low Levels

Viral and host immune kinetics during acute COVID-19 and after remission of acute symptoms need better characterization. SARS-CoV-2 RNA, anti-SARS-CoV-2 IgA, IgM, and IgG antibodies, and proinflammatory cytokines were measured in sequential samples from hospitalized COVID-19 patients during acute infection and six months following diagnosis. Twenty four laboratory confirmed COVID-19 patients with mild/moderate and severe COVID-19 were included. Most were males (83%) with a median age of 61 years. Twenty one percent were admitted to the intensive care unit (ICU) and eight of them (33.3%) met the criteria for severe COVID-19 disease. A delay in SARS-CoV-2 levels’ decline during the first six days of follow up, and viral load persistence until month 3 were related to severe COVID-19, but not viral load levels at the diagnosis. Higher levels of anti-SARS-CoV-2 IgA, IgM, IgG and the cytokines IL-6, IL-8 and MIP-1β at the diagnosis time were related to the severe COVID-19 outcome. Higher levels of MIP-1β, IL-1β, MIP-1α and IFN-γ were observed at month 1 and 3 during mild/moderate disease, compared to severe COVID-19. IgG persisted at low levels after six months of diagnosis. In conclusion, higher concentrations of IgA, IgM, and IgG, and IL-6, IL-8 and MIP-1β are identified as early predictors of COVID-19 severity, whereas no significant association is found between baseline SARS-COV-2 viral load and COVID-19 severity.

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Effectiveness, Durability, and Safety of Dolutegravir and Lamivudine Versus Dolutegravir, Lamivudine, and Abacavir in a Real-Life Cohort of HIV-Infected Adults

Annals of Pharmacotherapy ◽

10.1177/10600280211034176 ◽

2021 ◽

pp. 106002802110341

Author(s):

Inés Mendoza ◽

Alicia Lázaro ◽

Miguel Torralba

Keyword(s):

Viral Load ◽

Safety Profile ◽

Real Life ◽

Hazard Ratio ◽

Treatment Discontinuation ◽

Treatment Naïve ◽

Tn 4 ◽

Risk Of Treatment ◽

Hiv 1 ◽

All Treatment

Background: Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. Objective: To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR). Methods: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VL<50 and 200 copies/mL in TE (margin 12%). Durability of response, and safety were also measured. Results: 242 patients were included (53 TN and 189 TE). Two TN patients on 2-DR had VL≥50 copies/mL and 1 had VL≥200 copies/mL at week 24. In TE patients on 2-DR, 90.2% achieved VL<200 copies/mL at week 24 (difference: 3.8%; 95% CI = −6.3% to 14%) and 91.8% at week 48 (difference: 0.06%; 95% CI = −9% to 10%), meeting noninferiority criteria. Among the 53 TN patients, only 1 VF was observed in 2-DR. In TN patients, the risk of treatment discontinuation was similar between groups (hazard ratio [HR] = 0.37; P = 0.15); similar rates were also found in TE patients (HR = 0.94; P = 0.85). TE patients on 2-DR showed a better safety profile compared with 3-DR patients ( P<0.001). Conclusion and Relevance: Our results did not show noninferiority in terms of virological effectiveness. Nevertheless, all effectiveness measures support the use of 2-DR in a real-life cohort of TN and TE. Additionally, durability and safety of 2-DR were confirmed to be similar to that of 3-DR.

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Rates and Correlates of Short Term Virologic Response among Treatment-Naïve HIV-Infected Children Initiating Antiretroviral Therapy in Ethiopia: A Multi-Center Prospective Cohort Study

Pathogens ◽

10.3390/pathogens8040161 ◽

2019 ◽

Vol 8 (4) ◽

pp. 161

Author(s):

Birkneh Tilahun Tadesse ◽

Adugna Chala ◽

Jackson Mukonzo ◽

Tolosssa Eticha Chaka ◽

Sintayehu Tadesse ◽

...

Keyword(s):

Drug Resistance ◽

Viral Load ◽

Plasma Viral Load ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Virological Suppression ◽

Virologic Suppression ◽

Hiv Drug Resistance ◽

Treatment Naïve ◽

The Impact

There is limited data on virologic outcome and its correlates among HIV-infected children in resource-limited settings. We investigated rate and correlates of virologic outcome among treatment naïve HIV-infected Ethiopian children initiating cART, and were followed prospectively at baseline, 8, 12, 24 and 48 weeks using plasma viral load, clinical examination, laboratory tests and pretreatment HIV drug resistance (PDR) screening. Virologic outcome was assessed using two endpoints–virological suppression defined as having “undetectable” plasma viral load < 150 RNA copies/mL, and rebound defined as viral load ≥150 copies/mL after achieving suppression. Cox Proportional Hazards Regression was employed to assess correlates of outcome. At the end of follow up, virologic outcome was measured for 110 participants. Overall, 94(85.5%) achieved virological suppression, of which 36(38.3%) experienced virologic rebound. At 48 weeks, 9(8.2%) children developed WHO-defined virological treatment failure. Taking tenofovir-containing regimen (Hazard Ratio (HR) 3.1-[95% confidence interval (95%CI) 1.0–9.6], p = 0.049) and absence of pretreatment HIV drug resistance (HR 11.7-[95%CI 1.3–104.2], p = 0.028) were independently associated with earlier virologic suppression. In conclusion, PDR and cART regimen type correlate with rate of virologic suppression which was prominent during the first year of cART initiation. However, the impact of viral rebound in 38.3% of the children needs evaluation.

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Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus

Journal of Experimental Medicine ◽

10.1084/jem.191.9.1499 ◽

2000 ◽

Vol 191 (9) ◽

pp. 1499-1512 ◽

Cited By ~ 937

Author(s):

Franziska Lechner ◽

David K.H. Wong ◽

P. Rod Dunbar ◽

Roger Chapman ◽

Raymond T. Chung ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Acute Infection ◽

Hcv Infection ◽

Ctl Response ◽

Acute Hcv ◽

Ifn Γ ◽

Acute Hcv Infection

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.

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Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A

Infection International ◽

10.1515/ii-2017-0021 ◽

2012 ◽

Vol 1 (3) ◽

pp. 137-145

Author(s):

Gui-lin Yang ◽

Ying-xia Liu ◽

Mu-tong Fang ◽

Wei-long Liu ◽

Xin-chun Chen ◽

...

Keyword(s):

T Cells ◽

Viral Load ◽

Cell Response ◽

Th17 Cell ◽

Influenza A ◽

H1n1 Influenza ◽

Cell Frequency ◽

Viral Loads ◽

Viral Shedding ◽

Ifn Γ

Abstract Objective To explore whether age, disease severity, cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance. Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study. Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients, respectively (P < 0.05). Moreover, the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients (P < 0.01). The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells. Additionally, the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells. Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods, which may partially be attributed to the impaired Th17 cell response.

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The Value of Detecting Pathological Changes During Clot Formation in Early Disease Treatment-Naïve Breast Cancer Patients

Microscopy and Microanalysis ◽

10.1017/s1431927621000015 ◽

2021 ◽

Vol 27 (2) ◽

pp. 425-436

Author(s):

Julien Paul Nunes Goncalves ◽

Greta Marie de Waal ◽

Martin Justin Page ◽

Chantelle Venter ◽

Timothy Roberts ◽

...

Keyword(s):

Breast Cancer ◽

Laser Scanning ◽

Laser Scanning Microscopy ◽

Coagulation System ◽

Confocal Laser ◽

Early Disease ◽

Specific Patient ◽

Ample Evidence ◽

Increased Risk ◽

Treatment Naïve

AbstractBreast cancer (BC) is one of the most prevalent forms of cancer in women worldwide. Clinical research indicates that BC patients are at an increased risk for thrombotic events, drastically decreasing their quality-of-life and treatment outcomes. There is ample evidence of this in the literature, but it is mainly focused on metastatic BC. Therefore, coagulopathies of nonmetastatic BC are understudied and require in-depth investigation. In this study, clot kinetics and ultrastructure were used to investigate treatment-naïve, nonmetastatic BC patients using scanning electron microscopy, Thromboelastography®, and confocal laser scanning microscopy. It was demonstrated that nonmetastatic BC patients exhibit minimal ultrastructural alterations of the clot components and no changes in the clot kinetics. However, BC patients presented changes to fibrinogen protein structure, compared to matched controls, using an amyloid-selective stain. Together, these findings suggest that coagulation dysfunction(s) in BC patients with early disease manifest at the microlevel, rather than the macrolevel. This study presents novel insights to a method that are more sensitive to coagulation changes in this specific patient group, emphasizing that the coagulation system may react in different forms to the disease, depending on the progression of the disease itself.

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Frequencies of circulating Th1-biased T follicular helper cells in acute HIV-1 infection correlate with the development of HIV-specific antibody responses and lower set point viral load

10.1101/304329 ◽

2018 ◽

Cited By ~ 1

Author(s):

Omolara Baiyegunhi ◽

Bongiwe Ndlovu ◽

Funsho Ogunshola ◽

Nasreen Ismail ◽

Bruce D. Walker ◽

...

Keyword(s):

Viral Load ◽

Neutralizing Antibodies ◽

Acute Infection ◽

Antibody Responses ◽

Set Point ◽

Follicular Helper ◽

Clade C ◽

Acute Hiv ◽

Anti Hiv ◽

Hiv 1

AbstractDespite decades of focused research, the field has yet to develop a prophylactic vaccine. In the RV144 vaccine trial, non-neutralizing antibody responses were identified as a correlate for prevention of HIV acquisition. However, factors that predict the development of such antibodies are not fully elucidated. We sought to define the contribution of circulating T follicular helper (cTfh) cell subsets to the development of non-neutralizing antibodies in HIV-1 clade C infection. Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-gp41, -gp120, -p24 and -p17 antibodies were screened using a customized multivariate Luminex assay. Phenotypic and functional characterization of cTfh were performed using HLA class II tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C infection skewed differentiation of functional cTfh subsets towards increased Tfh1 (p=0.02) and Tfh2 (p<0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (that shares both Tfh1 and Tfh17 properties) (p=0.01) and Tfh17 subsets (p<0.0001) compared to HIV negative subjects. Interestingly, the frequencies of Tfh1 during acute infection (5.0-8.0 weeks post-infection) correlated negatively with set point viral load (p=0.03, r=-60) and were predictive of p24-specific plasma IgG titers at one year of infection (p=0.003, r=0.85). Taken together, our results suggest that circulating the Tfh1 subset plays an important role in the development of anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. These results have implications for vaccine studies aimed at inducing long lasting anti-HIV antibody responses.ImportanceThe HIV epidemic in southern Africa accounts for almost half of the global HIV burden with HIV-1 clade C being the predominant strain. It is therefore important to define immune correlates of clade C HIV control that might have implications for vaccine design in this region. T follicular helper (Tfh) cells are critical for the development of HIV-specific antibody responses and could play a role in viral control. Here we showed that the early induction of circulating Tfh1 cells during acute infection correlated positively with the magnitude of p24-specific IgG and was associated with lower set point viral load. This study highlights a key Tfh cell subset that could limit HIV replication by enhancing antibody generation. This study underscores the importance of circulating Tfh cells in promoting non-neutralizing antibodies during HIV-1 infection.

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Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment

Sexual Health ◽

10.1071/sh07082 ◽

2008 ◽

Vol 5 (2) ◽

pp. 141 ◽

Cited By ~ 23

Author(s):

Kathleen Falster ◽

Linda Gelgor ◽

Ansari Shaik ◽

Iryna Zablotska ◽

Garrett Prestage ◽

...

Keyword(s):

Viral Load ◽

Antiretroviral Treatment ◽

Undetectable Viral Load ◽

Lower Proportion ◽

The Other ◽

Early Disease ◽

Community Based ◽

Disease Research ◽

Sex With Men ◽

Living With Hiv

Objectives: To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006. Methods: We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts. Results: We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81–92%) and two large, community-based surveys in Australia (69–85% and 49–83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria; however, the sample size was very small. Conclusions: For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.

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Naturally Occurring Resistance-Associated Variants of Hepatitis C Virus Protease Inhibitors in Poor Responders to Pegylated Interferon-Ribavirin

Journal of Clinical Microbiology ◽

10.1128/jcm.03633-14 ◽

2015 ◽

Vol 53 (7) ◽

pp. 2195-2202 ◽

Cited By ~ 15

Author(s):

Sylvie Larrat ◽

Sophie Vallet ◽

Sandra David-Tchouda ◽

Alban Caporossi ◽

Jennifer Margier ◽

...

Keyword(s):

Hepatitis C Virus ◽

Viral Load ◽

Hepatitis C ◽

Triple Therapy ◽

Pegylated Interferon ◽

Poor Responders ◽

Obvious Effect ◽

Treatment Naïve ◽

Detection Of Mutations ◽

The Impact

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of <1 log IU/ml during the pegIFN-RBV lead-in phase). The impact of the presence of these RAVs on the outcome of triple therapy was studied. Among 282 patients, the prevalances (95% confidence intervals) of baseline RAVs ranged from 5.7% (3.3% to 9.0%) to 22.0% (17.3% to 27.3%), depending to the algorithm used. Among mutations conferring a >3-fold shift in 50% inhibitory concentration (IC50) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (P= 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.

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