Virological Evolution Research Articles

Torque teno virus: a potential marker of immune reconstitution in youths with vertically acquired HIV

Torque teno virus (TTV) viral load (VL), a component of the human virome, increases during immune suppression or dysregulation. This study aimed to explore TTV VL in youths living with vertically acquired HIV (YWVH) and its potential as an immunovirological marker. We performed an observational, retrospective study involving YWVH under antiretroviral treatment (ART) from the Spanish Cohort of HIV-infected children, adolescents, and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO), compared to HIV-negative healthy donors (HD). Plasma TTV VL was assessed by qPCR. T-cell phenotype was analysed on cryopreserved peripheral blood mononuclear cells by flow cytometry. Correlations with baseline CD4 and CD8 and long-term virological evolution were examined. A total of 57 YWVH were compared with 23 HD. YWVH had a median CD4 T-cells of 736 cells/mm3 [IQR: 574–906], a median of 17 years [IQR: 14–20.5] since ART initiation, and 65 months [IQR: 39–116] under HIV-RNA virological control. TTV VL was higher among YWVH and in males compared with females (p < 0.05). Among YWVH, TTV VL correlated with CD4 and CD8 counts and the CD4/CD8 ratio (p = 0.002; r = − 0.39, p = 0.037; r = 0.277, p = 0.005; r = − 0.37 respectively). TTV VL correlated with activation expression markers (HLA-DR+/CD38+) on CD4 (p = 0.007, r = 0.39) and the soluble proinflammatory cytokine IL-6 (p = 0.006, r = 0.38).

Zanamivir and baloxavir combination to cure persistent influenza and coronavirus infections after hematopoietic stem cell transplant

ObjectivesImmunocompromised patients may experience prolonged shedding of influenza virus potentially leading to severe infections. Alternatives to monotherapy with neuraminidase inhibitors should be evaluated to entirely suppress viral replication and prevent drug-resistant mutations. MethodsWe investigated the clinical and virological evolution in a case of persistent influenza A and human coronavirus OC43 (HCoV-OC43) coinfection in a hematopoietic stem cell transplant recipient after different therapeutic strategies. ResultsSuccessive oseltamivir and zanamivir monotherapies failed to control both infections, with positive results persisting for over 110 days each. This led to the emergence of highly resistant oseltamivir strains due to neuraminidase mutations (E119V and R292K) followed by a deletion (del245-248), while maintaining sensitivity to zanamivir. The intra-host viral diversity data showed that the treatments impacted viral diversity of influenza virus, but not of HCoV-OC43. Considering the patient's underlying condition and the impact of prolonged viral shedding on pulmonary function, eradicating the influenza virus was necessary. A 10-day regimen combining zanamivir and baloxavir-marboxil effectively controlled influenza virus replication and was associated with the clearance of HCoV-OC43, finally resulting in comprehensive respiratory recovery. ConclusionThese observations underscore the importance of further investigating combination treatments as the primary approach to achieve influenza eradication in immunocompromised patients.

Epidemiological characteristics of acute hepatitis A, 2013–2016: a cross-sectional study in Morocco

Background Hepatitis A virus (HAV) is the common cause of acute hepatitis worldwide. Indeed, hepatitis A is endemic in developing countries such in Morocco and most residents are exposed in childhood. The characterisation of circulating strains of HAV remains crucial to understand the virological evolution and geo-temporal characteristics, which are essential for controlling infections and outbreaks. The purpose of the current study was the detection and characterisation of HAV strains circulating in Morocco by performing serological test, RT-PCR, sequencing and phylogenetic analysis. Methods In this cross-sectional study, 618 suspected acute hepatitis cases were examined by Architect HAV abIgM. Of the 162 positives, 64 underwent RNA extraction. None of the suspected cases was immune to HAV and none of them had received a blood transfusion. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and the VP1/VP3 capsid region of HAV were subjected to sequencing and phylogenetic analyses. Results HAV Acute infection rate was 26.2% [95% CI, 22.8–29.9], while viraemia reached 45% (29/64) after amplification of the VP3/VP1 region. Phylogenetic analysis of the VP1/2A segment revealed the presence of sub-genotypes IA and IB. Eighty-seven percent of the strains belonged to the subgenotype IA, while twelve percent to IB subgenotype. Conclusion This first molecular study of acute hepatitis A in Morocco provided information about genetic diversity of HAV, revealing the co-circulating of only two subgenotypes (IA and IB). Notably, subgenotype IA was found to be the predominant subgenotype in Morocco.

The combined effect of oseltamivir and favipiravir on influenza A virus evolution in patients hospitalized with severe influenza

Our previous study shows favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, but its effect on virological evolution and resistance mutation against oseltamivir is still unknown. In this study, we collected longitudinal respiratory samples from influenza patients who underwent combination therapy and applied them to next generation sequencing of the whole genome of the influenza A virus (IAV). We also included a cohort untreated with any antivirals to serve as the control. In total, 62 samples from 19 patients treated with combination therapy and 20 samples from 20 patients untreated were successfully sequenced. The nucleotide diversity in the whole genome of IAV in the combination group showed no difference compared to that in the control group (P > 0.05). Moreover, we observed 174 kinds of nonsynonymous nucleotide substitutions in patients with combination therapy, mostly in NA (n = 44) and HA (n = 43). Of them, the G→A transition was the dominant variant type (27%) and 46/174 (26%) was reported to have biological effects, such as increased pathogenicity and polymerase activity. Among the 29 mutations conferring reduction in oseltamivir sensitivity we investigated, H275Y was the only mutation detected in the 4 samples from 1 of 19 patients and demonstrated increasing frequency during the treatment. Mutations conferring favipiravir resistance were not observed. Our studies showed combination therapy of favipiravir and oseltamivir has little effect on virus nucleotide diversity, nor prevents the increase of oseltamivir-resistant variants.

Role and Limits of COVID-19 Vaccines in the Delicate Transition from Pandemic Mitigation to Endemic Control

The recent surge of COVID-19 related to the Omicron variant emergence has thrown a harsh light upon epidemic control in the near future. This should lead the scientific and medical community to question the long-term vaccine strategy for SARS-CoV-2 control. We provide here a critical point of view regarding the virological evolution, epidemiological aspects, and immunological drivers for COVID-19 control, including a vaccination strategy. Overall, we need more innovations in vaccine development to reduce the COVID-19 burden long term. The most adequate answer might be better cooperation between universities, biotech and pharmaceutical companies

Virological evolution of patients with HIV infection that start antiretroviral therapy with a very high baseline viral load

The degree of viral suppression in HIV patients who start antiretroviral therapy (ART) with very high viral loads (CV) is unknown. To know the percentage of viral suppression in HIV patients who start ART with CV ≥ 500,000 copies/mL at 96 weeks. Retrospective study. Patients who started ART with a CV ≥ 500,000 copies/mL between 2008 and 2018 were included, stratifying on the basis of a logarithmic scale. The percentage of viral suppression and the variables associated with this outcome were determined. 221 patients were included. The median age and CV were 43 years and 6.0 log, respectively, with the majority (37%) being in stage C3 at the start of ART. 48.8 and 87.7% of the patients achieved viral suppression at one year and two years of follow-up, respectively. It was observed that the older the immunosuppression, and the higher CV, the longer the time to achieve undetectability. Virological failure was only demonstrated in three patients. Patients with HIV infection who start ART with very high CVs take longer to achieve viral suppression, which is proportional to the magnitude of this and the degree of immunosuppression, without this entailing a greater risk of virological failure.

Pre-Existing HBV and HCV Infections Do Not Affect COVID-19-Related Outcomes: An Observational Retrospective Study

Background: A better understanding of the interaction between SARS-CoV-2 infection and HBV or HCV hepatitis is very important. Objectives: We aimed to determine the prevalence and the impact of pre-existing HBV and HCV infections in patients with COVID-19. Methods: We conducted a retrospective study and included all the subjects positive for SARS-CoV-2 from March to May 2020. We evaluated the prevalence of chronic HBV and HCV infections and performed a matched cohort analysis to compare COVID-19-related outcomes between patients with and without infections due to HBV or HCV. Results: Among 606 subjects, 12 cases (2%) had positive HBsAg, and 6 cases (0.99%) presented detectable HCV RNA. We recognized 80 individuals positive for SARS-CoV-2 with negative markers for HBV and HCV suitable for the matched analysis. No statistical differences in mechanical ventilation support and mortality rates were found (P = 0.27 and P = 0.80, respectively). Moreover, although not statistically different, individuals with viral hepatitis were more likely to be admitted to the Intensive Care Unit in comparison to those without HBV or HCV infections (29% vs. 15%). The median time of virus clearance was 27.5 days, with no difference between the two groups. Conclusions: In our cohort, the pre-existing viral liver infection did not have any impact on the clinical and virological evolution of COVID-19.

Efficacité de l’éducation thérapeutique du patient (ETP) sur l’évolution virologique des patients vivant avec le VIH/SIDA : cas de cinq centres de santé en Côte d’Ivoire

BackgroundThe objective of this work was to present the methodological approach to therapeutic education in five health centers in Côte d’Ivoire and its impact on the virological evolution of patients enrolled in this process. MethodsThis study involved a cohort of 739 adult patients with unsuppressed viral load over the period from January to March 2019. The variables studied were the sex of the patients, the number of therapeutic education sessions performed, the viral status and the virological evolution that whether or not it is favorable based on the 1 log decrease in the last viral load after therapeutic education. ResultsThe results obtained presented therapeutic education on these sites as an elaborate process in which the patient himself is a major player in the management of his disease and its adaptation to it; his way of life and that of his loved ones. However, only 136 patients or 18 % of this cohort actually benefited from therapeutic education. 51 % of them experienced a difference in viral status from patients with non-suppressed viral load to patients with suppressed viral load. Based on the 1-log decrease in the last viral load, these results showed that 60 % of patients who participate in therapeutic education experience a positive significant virological evolution. The Chi-square independence test showed no dependence on the sex of the patients, the number of sessions with viral status. ConclusionThis study has shown the importance of therapeutic education in the care of patients living with HIV and its necessary and essential consideration for achieving the UNAIDS 90-90-90 goals.

High quality of life, treatment tolerability, safety and efficacy in HIV patients switching from triple therapy to lopinavir/ritonavir monotherapy: A randomized clinical trial.

Trial designThe QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT).MethodsThis was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts.ResultsBaseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT.ConclusionsIn a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.

Opportunistic infections and immune reconstitution inflammatory syndrome (IRIS) in HIV infected patient – late presenter in cART era: case report

HIV-infected individuals are at high risk of developing numerous opportunistic infections. The severity of these infections may increase proportional to the immunosuppression degree. We must pay special attention to immune reconstitution inflammatory syndrome (IRIS) in order to prevent worsening symptoms and death. HIV coinfection is associated with high mortality rate despite effective antiretroviral therapy. We present the case of a 42 male patient who was diagnosed with AIDS and pulmonary tuberculosis in 2011 in our clinic. Our theme includes clinical, biological, immunological, virological evolution and therapeutics of this patient. He was a late-presenter patient with advanced immunodepression at baseline: low CD4 count, increased viral load in blood and cerebrospinal fluid. After a month of tuberculosis treatment, antiretroviral therapy was instituted according to guidelines. During one year the patient subsequently developed IRIS and, one by one, several opportunistic infections, including CNS involvement. Thus he presented: Cryptococcus neoformans meningoencephalitis resistant to fluconazole with multiple relapses, TB meningoencephalitis, severe form of CMV disease with encephalitis, demyelinating lesions, necrotic ulcerative stomatitis and esophagitis with HSV, systemic candidiasis, severe bacterial infections with multidrug-resistant germs. Diagnoses were based on the usual investigations, including molecular biology techniques (RT-PCR: Mycobacterium tuberculosis, JC virus, Cryptococcus neoformans), viral resistance testing, PLEX-ID, MRI. Viral PLEX-ID identified the presence of Epstein Barr virus in CSF at a high level. Opportunistic infections occurred imposed specific therapy and reconsideration of antiretroviral therapy with CNS penetration ARV (score Letendre). The patient was adherent to ARV therapy. The evolution was initially favorable under specific therapy with clinical, immunological and virological improvement. Unfortunately, about 10 months after diagnosis, the patient developed CNS lymphoma possibly in relationship with increased levels of Epstein Barr virus in CSF, having fatal outcome. The evolution of this case pointed out once again that in a patient with AIDS at the time of initiating ART, it should be considered the possibility of IRIS and future opportunistic infections, associated with a poor prognosis. Therefore it is important to detect persons with HIV infection in the early stages of the disease in order to obtain a favorable evolution.

New cases of HIV/AIDS in adults during 2007-2012

Methods We performed a retrospective, compared study, in the Regional Monitoring and Evaluation of HIV/AIDS from Craiova, between 01 January 2007 – 31 December 2012, in two groups of patients with HIV/AIDS, as follows: group A-59 patients diagnosed with HIV/AIDS in the period 01 January 2010 – 31 December 2012 and group B-113 patients diagnosed with HIV/AIDS in the period 01 January 2007 – 31 December 2009, the results analyzed were: clinical, epidemiological, immunological and virological evolution in the first 12 months of screening. For statistical analysis we used the Epi Info program, threshold (p) values are statistically significant at ≤0.05.

The Persistent Circulation of Enterovirus 71 in People's Republic of China: Causing Emerging Nationwide Epidemics Since 2008

Emerging epidemics of hand-foot-and-mouth disease (HFMD) associated with enterovirus 71 (EV71) has become a serious concern in mainland China. It caused 126 and 353 fatalities in 2008 and 2009, respectively. The epidemiologic and pathogenic data of the outbreak collected from national laboratory network and notifiable disease surveillance system. To understand the virological evolution of this emerging outbreak, 326 VP1 gene sequences of EV71 detected in China from 1987 to 2009 were collected for genetic analyses. Evidence from both traditional and molecular epidemiology confirmed that the recent HFMD outbreak was an emerging one caused by EV71 of subgenotype C4. This emerging HFMD outbreak is associated with EV71 of subgenotype C4, circulating persistently in mainland China since 1998, but not attributed to the importation of new genotype. Originating from 1992, subgenotype C4 has been the predominant genotype since 1998 in mainland China, with an evolutionary rate of 4.6∼4.8×10−3 nucleotide substitutions/site/year. The phylogenetic analysis revealed that the majority of the virus during this epidemic was the most recent descendant of subgenotype C4 (clade C4a). It suggests that the evolution might be one of the potential reasons for this native virus to cause the emerging outbreak in China. However, strong negative selective pressure on VP1 protein of EV71 suggested that immune escape might not be the evolving strategy of EV71, predicting a light future for vaccine development. Nonetheless, long-term antigenic and genetic surveillance is still necessary for further understanding.

Identificación de las diferentes variantes geneticas del VIH-1 en niños de procedencia no española

Introduction The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in Europe, beause of emigration from countries where genetic variants are endemic. Although HIV-NBS could have a different clinical evolution and could respond differently to antiretrovirals (AR) than B-subtypes, these variant's response remain undocumented. Aims To identify HIV-1 genetic variants and to determine clinical evolution in a non-Spaniard children infected with HIV-1. Patients and method Children with HIV-1 infection from endemic countries were tested for HIV-1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years old and born abroad were selected. Results HIV-NBS were isolated in 5 children (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtyoe C in one (Equatorial Guinea) and CRF13_cpx in last one (India). Discussion Because of the increasing frequency of patients with HIV-NBS and their unknown long-term evolution, all children from endemic countries should be tested for HIV subtypes. We believe new studies with more patients during longer times could reveal differences in these patient's clinical, immunological and virological evolution.

P1896 Relationship between virological evolution and acute exacerbation of chronic hepatitis C (A–E–CHC) and during the natural history of infection

P1896 Relationship between virological evolution and acute exacerbation of chronic hepatitis C (A–E–CHC) and during the natural history of infection

Utilización en la práctica clínica de los tests de resistencia genotípica al VIH-1. Factores predictivos de mala evolución virológica en tratamientos de rescate

To describe the use of genotype resistance testing (GRT) for virological failure in clinical practice, and the long-term clinical and virological evolution in patients for whom it is requested. To identify the predictive factors of virological failure in patients with antiretroviral (ARV) salvage therapy. Observational study in HIV-infected patients for whom GRT was requested for virological failure (VF) in the period of 1 October 1999 to 31 December 2001. Logistic regression analysis was used to determine the predictive factors of virological progression. Over the period studied, 196 patients required GRT for VF (15%) among those monitored in specific units. GRT was mainly requested for patients who had been extensively pretreated for a mean of 5 years and with a median of 5 ARV combinations. Half the patients presented 3 or more mutations associated with thymidine analogs (TAMs), mutations associated with non-nucleoside analogs (NNRTIs), and 5 or more mutations associated with protease inhibitors (PIs). In 143 (74%) patients, the RTV regimen was changed on the basis of GRT results. In the intent-to-treat analysis, the percentage of patients with plasma VL < 400 cop/mL at 6, 12 and 18 months was 41%, 29% and 17%, respectively. In the on-treatment analysis, the results were 50%, 48% and 46%, respectively. Mean CD4 lymphocyte increase was 59.74 and 94 cells/mm 3. The variables predicting virological failure (plasma VL > 400 cop/mL) at 12 months were plasma VL > 30,000 cop/mL (OR 6, 1.8-19.5) and accumulation of 3 or more TAMs (OR 4.4, 1.3-15) at the start of ARV salvage therapy. Even though in clinical practice GRT is requested for patients with various treatment failures, when ART salvage treatment was started, plasma VL was undetectable and immunological response persisted in 40% of patients followed-up for 18 months. The factors best predicting virological evolution were VL and the number of baseline TAMs.

P0312 HBV GENOTYPES AND CLINICAL AND VIROLOGICAL EVOLUTION IN BRAZILIAN CHILDREN WITH HBV CHRONIC INFECTION

Introduction: There are few reports about the relationship between HBV genotypes and clinical, laboratorial, virological and histological evolution in children with chronic HBV infection. The aims of this study are: a) to determine the genotypes of Brazilian children with HBV chronic infection; b) to evaluate clinical and virological evolution according to the genotype. Methods: 29 pt with HBV chronic infection (HBsAg+ve > 6 months) were evaluated; 15M:14F; 1 pt had Japanese origin and 1 mixed (Japanese and mulatto); age at diagnosis of HBV infection: 1.9–13.2 years-old (median: 4.7 years-old). Liver biopsy was performed in 24 pt: cirrhosis (n=1); chronic hepatitis (n=17); normal (n=6) The mean follow-up period was 5,4 years (0.4–11.8 years). Results: The only patient with genotype C had Japanese origin and histologically normal liver. None of the patients cleared HBsAg. All the patients have normal liver function.Table 1Conclusion: Genotypes A and D are the most prevalent in children with HBV chronic infection in Brazil. There was no correlation between the genotypes A and D and clinical and virological evolution. This data needs to be confirmed due to small sample size

Clinical, immunological and virological evolution in patients with CD4 T-cell count above 500/mm3: is there a benefit to treat with highly active antiretroviral therapy (HAART)?

To assess the clinical, immunological and virological evolution in HIV-1 infected patients with CD4 T-cell count above 500/mm3, a historical cohort of 202 untreated and 96 patients treated with HAART was longitudinally studied (median follow-up 36 months). Fourteen untreated and 2 treated patients experienced clinical progression (p = 0.09). The difference between baseline CD4 T-cell count and after 3 years, was -240/mm3 in the untreated group +19/mm3 in the HAART group (p < 10(-3)). A better immunological outcome was significantly associated with a HIV sexual contamination (p = 0.01), HAART (p = 0.01), high baseline CD4 T-cell count (p < 10(-3)) and low baseline HIV viral load (p = 0.01). In the HAART group, the incidence rate of antiretroviral modification due to tolerance difficulties was 0.23+/-0.36/patient year. A sustained undetectable HIV viral load was correlated with a low baseline HIV viral load (p = 0.003) and to be antiretroviral naive (p < 10(-3)). Thus, HAART provide a better immunological outcome in patients with high CD4 T-cell count. However, the CD4 decay slope after 3 years, the risk of therapeutic side-effects and the low risk of clinical progression do not support systematic treatment of those patients.

Successful combination therapy of polyarteritis nodosa associated with a pre-core promoter mutant hepatitis B virus infection

Background/Aims : To describe the clinical and virological evolution of a polyarteritis nodosa (PAN) case associated with a hepatitis B virus (HBV) pre-core promoter mutant infection that was successfully treated with plasma exchanges, corticosteroids, and interferon alpha (IFN- α). Methods : Viral markers were used, including HBV DNA quantified by the branched DNA assay and detected by PCR, the HBV genome sequence, pre-S1Ag and anti-HBC IgM which were studied throughout the treatment period and the entire follow-up in the serum, while the presence of virus in extrahepatic sites was detected by immuno-staining. Results : The patient was infected with a typical pre-core promoter mutant harboring four point mutations. Pre-S1Ag was cleared rapidly from serum, most likely via the formation of immune complexes since HBV DNA declined more progressively. Viral infection was then cleared after a second episode of hepatocyte lysis. This was accompanied by a recovery from all clinical manifestations. Conclusions : The favorable treatment outcome observed in this first case of pre-core promoter HBV mutant associated PAN underlines that combination therapy based on IFN- α can clear pre-core promoter HBV infection and cure PAN. It also provides new insight in the pathogenesis of HBV associated PAN.

Histological and virological evolution of long term response after ribavirin and interferon-α combination

Histological and virological evolution of long term response after ribavirin and interferon-α combination