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Clinical Relevance of Torque Teno Virus (TTV) in HIV/HCV Coinfected and HCV Monoinfected Patients Treated with Direct-Acting Antiviral Therapy.

ABSTRACT: Torque Teno virus (TTV) is a ubiquitous virus that causes chronic infection in humans with unknown clinical consequences. Here, we investigated the influence of TTV infection on HCV direct-acting antiviral (DAA) efficacy in HIV/HCV coinfected and HCV monoinfected patients as controls. Of 92 study patients, 79.3% were TTV DNA positive; untreated patients exhibited a significantly higher proportion of TTV DNA-positivity vs. sustained virological response (SVR) patients (100.0% vs. 65.2%, p < 0.001), while TTV positivity was not significant in DAA failure patients vs. SVR patients despite HIV/HCV coinfection. TTV DNA viral load was higher among HCV monoinfected patients vs. HIV/HCV coinfected, although marginally significant (p = 0.074) and no significant viral load difference was detected between DAA failures and SVR patients, while untreated vs. SVR patients had a significantly higher viral load (19,884, IQR 5977-333,534, vs. 469, IQR 10-4124, p = 0.004). Alpha-genogroup 3 TTV was the most prevalent genetic group, and no specific strain or genogroup was observed in relapser patients. Among HIV/HCV patients with HCV RNA detectable at end of treatment (EOT), TTV DNA was detected in 9/17 treatment responder patients and 3/5 relapser patients, thus, TTV infection does not appear to influence the control HCV viremia after EOT. Levels of IL-6 IL-4, and CD14 were not significantly different between TTV PCR-positive and -negative patients. These results suggest no association between TTV DNA positivity or viral load and HCV DAA failure whether patients were HIV/HCV coinfected or HCV monoinfected.

SUBMITTER: Lapa D

PROVIDER: S-EPMC8152458 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Structural Bone Deficits in HIV/HCV-Coinfected, HCV-Monoinfected, and HIV-Monoinfected Women.

Project description:BackgroundCoinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is associated with reduced bone mineral density (BMD) and increased fracture rates, particularly in women. The structural underpinnings for skeletal fragility in coinfected women have not been characterized. We used tibial peripheral quantitative computed tomography to evaluate skeletal parameters in women, by HIV/HCV status.MethodsWe conducted a cross-sectional study among 50 HIV/HCV-coinfected, 51 HCV-monoinfected, and 50 HIV-monoinfected women. Tibial volumetric BMD and cortical dimensions were determined with peripheral quantitative computed tomography. Race-specific z scores for age were generated using 263 female reference participants without HIV infection or liver disease.ResultsCoinfected participants had lower mean z scores for trabecular volumetric BMD (-0.85), cortical volumetric BMD (-0.67), cortical area (-0.61), and cortical thickness (-0.77) than reference participants (all P < .001). The smaller cortical dimensions were due to greater mean z scores for endosteal circumference (+0.67; P < .001) and comparable z scores for periosteal circumference (+0.04; P = .87). Trabecular volumetric BMD was lower in coinfected than in HCV- or HIV-monoinfected participants. HCV-infected women with stage 3-4 liver fibrosis had lower mean z scores for trabecular volumetric BMD, cortical thickness, and total hip BMD those with stage 0-2 fibrosis.ConclusionsCompared with healthy reference patients, HIV/HCV-coinfected women had decreased tibial trabecular volumetric BMD, diminished cortical dimensions, and significant endocortical bone loss.

| S-EPMC4548465 | biostudies-literature

Baseline Plasma Metabotype Correlates With Direct-Acting Antiviral Therapy Nonresponse for HCV in HIV-HCV Coinfected Patients.

Project description:Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV-HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV-HCV patients. Methods: Non-cirrhotic HIV-HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders). Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = -0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = -0.713) significantly differentiated between nonresponders from responders in HIV-HCV coinfected patients and was able to predict the failure of treatment response. Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV-HCV coinfected patients.

| S-EPMC8784690 | biostudies-literature

The Molecular Epidemiology and Phylogeny of Torque Teno Virus (TTV) in Jordan.

Project description:Torque teno virus (TTV) is the most common component of the human blood virobiota. Little is known, however, about the prevalence of TTV in humans and the most common farm domesticates in Jordan, or the history and modality of TTV transmission across species lines. We therefore tested sera from 396 Jordanians and 171 farm animals for the presence of TTV DNA using nested 5'-UTR-PCR. We then performed phylogenetic, ordination and evolutionary diversity analyses on detected DNA sequences. We detected a very high prevalence of TTV in Jordanians (~96%); much higher than in farm animal domesticates (~29% pooled over species). TTV prevalence in the human participants is not associated with geography, demography or physical attributes. Phylogenetic, ordination and evolutionary diversity analyses indicated that TTV is transmitted readily between humans across the geography of the country and between various species of animal domesticates. However, the majority of animal TTV isolates seem to derive from a single human-to-animal transmission event in the past, and current human-animal transmission in either direction is relatively rare. In conclusion, animal TTV in Jordan is historically derived from human variants; however, ongoing human-animal TTV exchange is minimal and zoonotic infection seems to be of limited importance.

| S-EPMC7077251 | biostudies-literature

Detection of torque teno virus (TTV) in domestic village chickens in Iran.

Project description:Torque teno virus (TTV) is prevalent worldwide and has been extensively studied in human and some wild and domestic animals. As the studies on TTV in chickens was rare and there was no information about the infection of domestic village chickens with TTV and also structural resemblance of this virus to chicken anemia virus, the frequency of the infection in domestic village chickens in different villages in Isfahan (Iran) was investigated. Sera were collected from 50 chickens. Viral DNA was extracted and subjected to polymerase chain reaction (PCR) using the previously described T801 and T935 primers that were used for amplification of a highly conserved non-coding region (UTR) of the viral genome in a single round of PCR and Set B primers of conserved region in a nested PCR reaction. Using T801 and T835 primers TTV or viruses of TTV family were detected in 16 out of 50 sera tested (32%). Fourteen out of the same 50 sera (28%) were positive for TTV using Set B primers. Totally 20 sera were positive using both primers (40%). Ten sera were detected with both sets of primers, six sera with T801 and T935 primers and only four sera were positive using Set B primers for TTV. Different patterns of the detection of the virus with the two different sets of primers suggests the possibility of the presence of different genotypes of TTV in domestic village chickens and the possibility of the transmission of the virus from human to village chickens and vice versa. This necessitates further investigations.

| S-EPMC4293898 | biostudies-literature

Detection of Torque Teno Virus (TTV) and TTV-Like Minivirus in patients with presumed infectious endophthalmitis in India.

Project description:Human anelloviruses (Torque Teno Virus (TTV) and TTV Like Mini Virus (TLMV)) are now being reported at a high prevalence across the world, with a controversial disease-inducing potential. The aim of this study was to investigate the role of these anellovirus in vitreous of patients with presumed infectious endophthalmitis. After informed consent, vitreous fluid from patients with endophthalmitis (n = 103) and non-infectious pathologies (n = 102) were analyzed for the presence of TTV and TLMV DNA by qPCR with the limit of quantification defined as 100 copies per reaction. Among the patients clinically diagnosed with endophthalmitis, 29 of the 40 culture proven samples (72.5%) and 42 out of 63 (66.6%) of culture-negative samples were positive for presence of TTV/TLMV. Interestingly, 51 of the 102 (50%) samples in the control group were also positive for TTV/TLMV. Comparing the clinical outcome among patients diagnosed with endophthalmitis, we observed no significant association in the final visual acuity of patients who were positive for presence of TTV/TLMV, however, these patients had significantly higher repeat antibiotic injections (p = 0.03). Further evidence is however needed to correlate TTV / TLMV with a particular pathology or group of pathologies in the eye.

| S-EPMC6946165 | biostudies-literature

Direct-Acting Antiviral Agents for HCV Infection.

Project description: Not available

| S-EPMC5938327 | biostudies-literature

Retreatment Options Following HCV Direct Acting Antiviral Failure.

Project description:Despite the excellent efficacy of direct acting antivirals (DAA) for hepatitis C virus (HCV), treatment failures do occur. Until recently, retreatment decisions after DAA failure were influenced by the number of available agents, concerns about HCV drug resistance, and lack of data regarding retreatment. Recommended treatment approaches previously depended on limited clinical trials and expert opinion. In this article, we review the current state of the evidence for HCV retreatment after DAA failure. Based on recent clinical trial data, most patients who fail HCV treatment with DAA agents now have excellent retreatment options. While some patients may benefit from resistance testing after DAA therapy failure to select the optimal treatment and duration, newly approved salvage therapies are not significantly impacted by common mutations and have been approved by the Food and Drug Administration for HCV retreatment without regard for the presence of resistance associated substitutions. While prior retreatment efforts were limited to longer courses of therapy, the addition of ribavirin, or novel combinations of approved therapies based on expert guidance, current DAA options make HCV retreatment in the DAA era more streamlined and evidence-based.

| S-EPMC5726279 | biostudies-literature

The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients.

Project description:Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All patients completed treatment and follow-up to the 12th-week post-DAA treatment (P12). Blood samples were measured for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and HBV pregenomic RNA (HBV pgRNA). The predictive factors for HBVr after DAA treatment were analyzed. Among 31 patients without nucleot(s)ide analogue (NA) treatment, seven (22.5%, 7/31) developed HBVr without hepatitis flare-up. Patients with HBVr had higher HBsAg titers than those without HBVr from baseline to P12 (p = 0.008, 0.009, 0.004, and 0.006 at baseline, week 4, end of treatment, and P12, respectively). The baseline HBsAg level was the only predictive factor associated with HBVr (HR, 2.303; 95% CI, 1.086-4.882; p = 0.030). In predicting HBVr, a baseline HBsAg titer > 20 IU/mL had a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 75.0%, 50%, and 94.7%, respectively. No patient had HBVr if the baseline HBsAg titer was <8 IU/mL. Serum HBcrAg and HBV pgRNA levels had no role in predicting HBVr. In conclusion, HBV/HCV coinfected patients are at risk of HBVr after DAA treatment. The baseline HBsAg level was the predictive factor associated with HBVr. Patients with a baseline HBsAg titer < 8 IU/mL can be considered as not having HBVr.

| S-EPMC9414824 | biostudies-literature

HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients.

Project description:Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways ("cytokine-cytokine receptor interaction", "viral protein interaction with cytokine and cytokine receptor", "chemokine signaling pathway", and "hepatitis C"). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.

| S-EPMC8419228 | biostudies-literature

Rates of HCV treatment eligibility among HCV-monoinfected and HCV/HIV-coinfected patients in tertiary care referral centers.

Project description:BackgroundTreatment eligibility rates in patients with HCV monoinfection have not been directly compared with patients with HCV/HIV coinfection. These data are important for planning interventions to optimize HCV management.MethodWe enrolled consecutive HCV-monoinfected and HCV/HIV-coinfected subjects presenting to hepatology and HIV clinics at three academic medical centers. Data were obtained through structured subject and provider interviews and a review of medical records.ResultsOf the 399 subjects enrolled, 241 (60%) were HCV monoinfected and 158 (40%) were HCV/HIV coinfected. HCV/HIV-coinfected subjects were less likely to have indications for treatment based on HCV RNA positivity (70.9% vs. 81.3%, p = .04) but were more likely to have at least one contraindication to treatment (81.6% vs. 64.9%, p < .004). Depression and ongoing alcohol and injection drug abuse were more common in the HCV/HIV-coinfected persons. HCV/HIV-coinfected persons were less likely to undergo liver biopsy or to ever get treatment for HCV.ConclusionsHCV/HIV-coinfected persons are less likely to undergo a liver biopsy or be eligible for HCV therapy and are more likely to have treatment contraindications compared with HCV-monoinfected subjects. Strategies to address modifiable factors (e.g., depression, substance abuse) may enhance treatment eligibility in HCV-infected populations.

| S-EPMC2845454 | biostudies-literature

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