Antonsson, Annika; Knight, Lani; Panizza, Benedict J; Porceddu, Sandro V; Emmett, Sarah; Whiteman, David C
We did not identify any strong associations between HPV-16 viral load and any of the clinical or lifestyle factors. The epidemiology of oropharyngeal SCC is changing, with an increasing proportion of HPV-positive cases seen in the last decade. It is known that a high viral load is linked to the development of cervical cancer, the relation between viral load and oropharyngeal SCC is less clear. We sought to determine HPV-16 viral load in HPV-positive oropharyngeal SCCs using highly sensitive digital PCR and to identify clinical and lifestyle factors associated with viral load. We analysed 45 HPV-16 positive oropharyngeal SCCs diagnosed between 2013 and 2015. All patients completed a lifestyle questionnaire and clinical data were extracted from medical charts. Viral load was determined using digital PCR assays for HPV-L1 and RNAseP. We found large variations in HPV-16 viral load from 1 to 930 copies per cell (median 34 copies per cell).
Кристина Владимировна Марочко
Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.
Hu, Zhili; Liu, Lishi; Zhang, Wenjing; Liu, Hui; Li, Junpeng; Jiang, Lifen; Zeng, Kang
Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV. Copyright © 2017 Elsevier B.V. All rights reserved.
Kim, Byoung Gie; Lee, Eui Don; Zin, Yong Jae
This study was performed to determine the frequency of viral integration and viral load in women with positive HPV type 16 infection, and showing normal findings, CIN, and cervical cancer. Total 75 (normal, 15; CIN I, 20; CIN III, 20; cervical cancer, 20) cervical swab specimens were used. HPV detection, typing, and viral load was determined by PCR method. Seventy of 75 (93.3%) of cervical swab specimens showed same results with hybrid capture assay and PCR method for detecting HPV DNA. HPV type 16 DNA was identified more frequently with progression from normal to cervical cancer (normal, 13 %; CIN I, 15%; CIN III, 40 %; cervical cancer, 55 %). The frequency of HPV type 16 DNA integration also increased with grade of the lesion (normal, 0 %; CIN I, 33 %; CIN III, 87 %; cervical cancer, 91 %) suggesting most of HPV type 16 present as integration forms in the cells. In addition, high-level of HPV 16 viral load also was found more frequently in CIN III and cervical cancer (normal, 0 %; CIN I, 0 %; CIN III, 87 %; cervical cancer, 100 %). These results suggest that viral integration and high-level of viral load may play an important role in cervical carcinogenesis. (author). 13 refs., 5 figs
Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6\\/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205\\/299) of the cases were positive by hc2 and 38% (112\\/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.
Rousseau, Marie-Noelle Didelot; Costes, Valérie; Konate, Issouf; Nagot, Nicolas; Foulongne, Vincent; Ouedraogo, Abdoulaye; Van de Perre, Philippe; Mayaud, Philippe; Segondy, Michel
The relationships between human papillomavirus type 16 (HPV 16) viral load, HPV 16 integration status, human immunodeficiency virus type 1 (HIV-1) status, and cervical cytology were studied among women enrolled in a cohort of female sex workers in Burkina Faso. The study focused on 24 HPV 16-infected women. The HPV 16 viral load in cervical samples was determined by real-time PCR. Integration ratio was estimated as the ratio between E2 and E6 genes DNA copy numbers. Integrated HPV16 viral load was defined as the product of HPV 16 viral load by the integration ratio. High HPV 16 viral load and high integration ratio were more frequent among women with squamous intraepithelial lesions compared with women with normal cytology (33% vs. 11%, and 33% vs. 0%, respectively), and among women with high-grade squamous intraepithelial lesions compared with women without high-grade squamous intraepithelial lesions (50% vs. 17%, and 50% vs. 11%, respectively). High HPV 16 DNA load, but not high integration ratio, was also more frequent among HIV-1-positive women (39% vs. 9%; and 23% vs. 18%, respectively). The absence of statistical significance of these differences might be explained by the small study sample size. High-integrated HPV 16 DNA load was significantly associated with the presence of high-grade squamous intraepithelial lesions (50% vs. 5%, P = 0.03) in univariate and multivariate analysis (adjusted odds-ratio: 19.05; 95% confidence interval (CI), 1.11-328.3, P = 0.03), but not with HIV-1 or other high-risk HPV types (HR-HPV). Integrated HPV 16 DNA load may be considered as a useful marker of high-grade cervical lesions in HPV 16-infected women. (c) 2007 Wiley-Liss, Inc.
... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...
Camacho-Aguilar, S; Ramírez-Amador, V; Rosendo-Chalma, P; Guido-Jiménez, M; García-Carrancá, A; Anaya-Saavedra, G
Although HPV emerged as a crucial carcinogenic and prognostic biomarker in head and neck cancer, and considering the increase in HPV-associated oral lesions (HPV-OLs) in HIV individuals, molecular information about HPV-OLs is scarce; thus, our aim was to determine viral loads in HPV-OLs from HIV/AIDS individuals. HIV/AIDS subjects with HPV-OL were included in this cross-sectional study. Following informed consent, biopsies were obtained. HPV detection and typing were carried out by PCR and sequencing (MY09/11, GP5+/6+). HPV-13 and HPV-32 loads were determined by a high-resolution melting assay. For statistical analysis, X 2 , Fisher's exact, and Mann-Whitney U tests were applied, using SPSS software (v.23). Twenty-nine HIV subjects (median age 38 years, 93% males) were included. Most were AIDS individuals (72.4%) under HAART (89.7%). Twenty-two (75.9%) participants had more than one HPV-OL (four with florid presentations), mostly multifocal epithelial hyperplasia (62%), being HPV-13 (26%) and HPV-32 (31%) the most frequent types. HPV load was higher in individuals with multiple HPV-OLs than in solitary lesions (4.9 vs. 3.2 Log 10 copies/ml, p = .090) and in HPV-32 + than in HPV-13 + (8.3 vs. 6.4 Log 10 copies/ml, p = .014). Multiple HPV-OLs showed high HPV loads, possibly indicating transcriptional activity of the virus; however, in the HIV setting, the individual and local immunological response could be the key process. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.
José E. Levi
Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.
Levi José E.
Full Text Available HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV and cervical intraepithelial neoplasia (CIN prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%. Twenty (7.5% women were infected by one or more low-risk viruses, 89 (33% by one or more high-risk viruses, and 64 (24% harbored at least one HPV type from each risk group. Abnormal smears were observed in 19% of the patients, though there were no invasive carcinomas. Severely immunosuppressed patients (CD4/µL <100 were at the greatest risk of having a cytological abnormality and a high high-risk HPV viral load.
Marongiu, Luigi; Godi, Anna; Parry, John V; Beddows, Simon
Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45. Samples singly infected with HPV16 (n = 226), HPV18 (n = 32), HPV31 (n = 75) or HPV45 (n = 29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3’L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample. Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2–26.1; p < 0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0–6.8; p = 0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8–18.0; p < 0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31. This
Full Text Available Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n = 270 from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63% followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT assay in a subset of samples positive for HPV16 and/or HPV18 (n = 86 and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal could be an important prognostic marker for cervical cancer.
Human papillomaviruses (HPV) are a group of related viruses. They can cause warts on different parts of your body. There are ... cancer. There are two categories of sexually-transmitted HPV. Low-risk HPV can cause genital warts. High- ...
Depuydt, Christophe E; Jonckheere, Jef; Berth, Mario; Salembier, Geert M; Vereecken, Annie J; Bogers, Johannes J
Persistent high-risk human papillomavirus (HPV) infection is strongly associated with the development of high-grade cervical intraepithelial neoplasia (CIN) or cancer. Not all persistent infections lead to cancer. Viral load measured at a single time-point is a poor predictor of the natural history of HPV infections. However the profile of viral load evolution over time could distinguish nonprogressive from progressive (carcinogenic) infections. A retrospective natural history study was set up using a Belgian laboratory database including more than 800,000 liquid cytology specimens. All samples were submitted to qPCR identifying E6/E7 genes of 18 HPV types. Viral load changes over time were assessed by the linear regression slope. Database search identified 261 untreated women with persistent type-specific HPV DNA detected (270 infections) in at least three of the last smears for a average period of 3.2 years. Using the coefficient of determination (R²) infections could be subdivided in a latency group (n = 143; R² < 0.85) and a regressing group (n = 127; R² ≥ 0.85). In (≥3) serial viral load measurements, serial transient infections with latency is characterized by a nonlinear limited difference in decrease or increase of type-specific viral load (R² < 0.85 and slopes between 2 measurements 0.0010 and −0.0010 HPV copies/cell per day) over a longer period of time (1553 days), whereas regression of a clonal cell population is characterized by a linear (R² ≥ 0.85) decrease (−0.0033 HPV copies/cell per day) over a shorter period of time (708 days; P < 0.001). Using serial HPV type-specific viral load measurements we could for the first time identify regressing CIN2 and CIN3 lesions. Evolution of the viral load is an objective measurable indicator of the natural history of HPV infections and could be used for future triage in HPV-based cervical screening programs
Full Text Available Abstract Background HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper. Methods A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit. Results HPV loads were consistently higher among women Conclusions The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.
Zhang, Donghong; Zhang, Qingying; Zhou, Li; Huo, Leijun; Zhang, Yi; Shen, Zhongying; Zhu, Yi
Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain. Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining. The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027). High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC
Redmond, Catherine J.; Dooley, Katharine E.; Fu, Haiqing; Gillison, Maura L.; Akagi, Keiko; Symer, David E.; Aladjem, Mirit I.
Integration of human papillomavirus (HPV) genomes into cellular chromatin is common in HPV-associated cancers. Integration is random, and each site is unique depending on how and where the virus integrates. We recently showed that tandemly integrated HPV16 could result in the formation of a super-enhancer-like element that drives transcription of the viral oncogenes. Here, we characterize the chromatin landscape and genomic architecture of this integration locus to elucidate the mechanisms that promoted de novo super-enhancer formation. Using next-generation sequencing and molecular combing/fiber-FISH, we show that ~26 copies of HPV16 are integrated into an intergenic region of chromosome 2p23.2, interspersed with 25 kb of amplified, flanking cellular DNA. This interspersed, co-amplified viral-host pattern is frequent in HPV-associated cancers and here we designate it as Type III integration. An abundant viral-cellular fusion transcript encoding the viral E6/E7 oncogenes is expressed from the integration locus and the chromatin encompassing both the viral enhancer and a region in the adjacent amplified cellular sequences is strongly enriched in the super-enhancer markers H3K27ac and Brd4. Notably, the peak in the amplified cellular sequence corresponds to an epithelial-cell-type specific enhancer. Thus, HPV16 integration generated a super-enhancer-like element composed of tandem interspersed copies of the viral upstream regulatory region and a cellular enhancer, to drive high levels of oncogene expression. PMID:29364907
Tamarozzi, Elvira Regina; Giuliatti, Silvana
Intrinsic disorder is very important in the biological function of several proteins, and is directly linked to their foldability during interaction with their targets. There is a close relationship between the intrinsically disordered proteins and the process of carcinogenesis involving viral pathogens. Among these pathogens, we have highlighted the human papillomavirus (HPV) in this study. HPV is currently among the most common sexually transmitted infections, besides being the cause of several types of cancer. HPVs are divided into two groups, called high- and low-risk, based on their oncogenic potential. The high-risk HPV E6 protein has been the target of much research, in seeking treatments against HPV, due to its direct involvement in the process of cell cycle control. To understand the role of intrinsic disorder of the viral proteins in the oncogenic potential of different HPV types, the structural characteristics of intrinsically disordered regions of high and low-risk HPV E6 proteins were analyzed. In silico analyses of primary sequences, prediction of tertiary structures, and analyses of molecular dynamics allowed the observation of the behavior of such disordered regions in these proteins, thereby proving a direct relationship of structural variation with the degree of oncogenicity of HPVs. The results obtained may contribute to the development of new therapies, targeting the E6 oncoprotein, for the treatment of HPV-associated diseases.
Challenges with targeted viral load testing 179. Malawi Medical ... targeted viral load (VL) testing for patients who have been on ART for at least .... Tuberculosis. 32. Community-acquired pneumonia. 17. Non-typhoidal Salmonella sepsis. 5. Bacterial meningitis. 5. Disseminated Kaposi sarcoma. 4. Cryptococcal meningitis. 4.
Background: Quantification of the viral burden is an important laboratory tool in the management of hepatitis B virus (HBV)-infected patients. However, widespread use of assays is still hampered by the high cost. Treatment reduces viral load to undetectable levels. HBV infected patients tend to have high HBV DNA levels, ...
ABSTRACT. Background: Quantification of the viral burden is an important laboratory tool in the management of hepatitis B virus. (HBV)-infected patients. However, widespread use of assays is still hampered by the high cost. Treatment reduces viral load to undetectable levels. HBV infected patients tend to have high HBV ...
Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas
In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral
OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis\\/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.
Crum, C.P.; Friedman, D.; Nuovo, G.; Silverstein, S.J.
Current studies indicate a strong correlation between specific morphological changes and the presence of certain HPV strains in precancerous squamous epithelium of the cervix, vulva and vagina. HPV type 16 is the most commonly detected HPV type in cervical lesions in our experience, and 85% of these lesions exhibit some morphological features associated with aneuploid epithelium (CIN). However, over 50% of these lesions containing HPV 16 DNA exhibit, in addition, foci of epithelium indistinguishable from condyloma, although in our experience, only one HPV type(16) is detected in the majority of these lesions. DNA-DNA in situ hybridization analysis of these lesions containing HPV 16 DNA has demonstrated nucleic acids in areas resembling both condyloma and CIN, with the greatest concentration in mature cells containing cytoplasmic maturation. Ten percent of lesions containing HPV 16 produce detectable capsid antigens, and we have confirmed the presence of these antigens in the same areas which hybridize in-situ for HPV DNA. Recent studies using biotin and S-35 labeled RNa probes constructed in GEM-1 vectors indicate that early HPV genes are expressed primarily in the upper (more mature) regions of the neoplastic epithelium. Thus maturation appears to exert a positive influence on a variety of HPV functions in neoplastic epithelium, including DNA replication, early and late gene expression. It is possible that patterns of gene expression may vary between lesions associated with different HPV types or different morphologies. This possibility is being explored
Salma Ghulam Nabi
Full Text Available Background and Aim: The basic aim of this study was to find out the association of genotypes with host age, gender and viral load. Material and Methods: The present study was conducted at Social Security Hospital, Pakistan. This study included 320 patients with chronic hepatitis C virus (HCV infection who were referred to the hospital between November 2011 and July 2012. HCV viral detection and genotyping was performed and the association was seen between genotypes and host age, gender and viral load. Results : The analysis revealed the presence of genotypes 1 and 3 with further subtypes 1a, 1b, 3a, 3b and mixed genotypes 1b + 3a, 1b + 3b and 3a + 3b. Viral load quantification was carried out in all 151 HCV ribonucleic acid (RNA positive patients. The genotype 3a was observed in 124 (82.12% patients, 3b was found in 21 (13.91%, 1a was seen in 2 (1.32%, 1b in 1 (0.66%, mixed infection with 1b + 3a in 1 (0.66%, 1b + 3b in 1 (0.66% and 3a + 3b was also found in 1 (0.66% patient. Viral load quantification was carried out in all 151 HCV RNA positive patients and was compared between the various genotypes. The mean viral load in patients infected with genotype 1a was 2.75 × 10 6 , 1b 3.9 × 10 6 , 3a 2.65 × 10 6 , 3b 2.51 × 10 6 , 1b + 3a 3.4 × 106, 1b + 3b 2.7 × 106 and 3a + 3b 3.5 × 10 6 . An association between different types of genotypes and viral load was observed. Conclusion : Further studies should be carried out to determine the association of viral load with different genotypes so that sufficient data is available and can be used to determine the type and duration of therapy needed and predict disease outcome.
Nov 9, 2010 ... treatment i.e. mean difference (signed-rank test) in viral load “before” and .... We used Abbott Determine and Unigold as the rapid HIV test kits. The ..... N: Number of patients, *: Wilcoxon signed ranks test for Median difference ...
Zheng, Zi-Zheng; Sun, Yuan-Yuan; Zhao, Min; Huang, Hui [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhang, Jun; Xia, Ning-Shao [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China); Miao, Ji, E-mail: email@example.com [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Zhao, Qinjian, E-mail: firstname.lastname@example.org [National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, Fujian 361005 (China); School of Public Health, Xiamen University, Xiamen, Fujian 361005 (China)
Highlights: ► The RNA-binding hnRNP H regulates late viral gene expression. ► hnRNP H activity was inhibited by a late viral protein. ► Specific interaction between HPV L1 and hnRNP H was demonstrated. ► Co-localization of HPV L1 and hnRNP H inside cells was observed. ► Viral capsid protein production, enabling rapid capsid assembly, was implicated. -- Abstract: Heterogeneous nuclear ribonucleoproteins (hnRNPs), including hnRNP H, are RNA-binding proteins that function as splicing factors and are involved in downstream gene regulation. hnRNP H, which binds to G triplet regions in RNA, has been shown to play an important role in regulating the staged expression of late proteins in viral systems. Here, we report that the specific association between hnRNP H and a late viral capsid protein, human papillomavirus (HPV) L1 protein, leads to the suppressed function of hnRNP H in the presence of the L1 protein. The direct interaction between the L1 protein and hnRNP H was demonstrated by complex formation in solution and intracellularly using a variety of biochemical and immunochemical methods, including peptide mapping, specific co-immunoprecipitation and confocal fluorescence microscopy. These results support a working hypothesis that a late viral protein HPV16 L1, which is down regulated by hnRNP H early in the viral life cycle may provide an auto-regulatory positive feedback loop that allows the rapid production of HPV capsid proteins through suppression of the function of hnRNP H at the late stage of the viral life cycle. In this positive feedback loop, the late viral gene products that were down regulated earlier themselves disable their suppressors, and this feedback mechanism could facilitate the rapid production of capsid proteins, allowing staged and efficient viral capsid assembly.
Myer, Landon; Essajee, Shaffiq; Broyles, Laura N; Watts, D Heather; Lesosky, Maia; El-Sadr, Wafaa M; Abrams, Elaine J
Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.
Dreilich, Martin; Bergqvist, Michael; Moberg, Martin; Brattström, Daniel; Gustavsson, Inger; Bergström, Stefan; Wanders, Alkwin; Hesselius, Patrik; Wagenius, Gunnar; Gyllensten, Ulf
Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma
Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.
Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel
Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael
Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.
Full Text Available The constitutive expression of the high-risk HPV E6 and E7 viral oncogenes is the major cause of cervical cancer. To comprehensively explore the composition of HPV16 early transcripts and their genomic annotation, cervical squamous epithelial tissues from 40 HPV16-infected patients were collected for analysis of papillomavirus oncogene transcripts (APOT. We observed different transcription patterns of HPV16 oncogenes in progression of cervical lesions to cervical cancer and identified one novel transcript. Multiple-integration events in the tissues of cervical carcinoma (CxCa are significantly more often than those of low-grade squamous intraepithelial lesions (LSIL and high-grade squamous intraepithelial lesions (HSIL. Moreover, most cellular genes within or near these integration sites are cancer-associated genes. Taken together, this study suggests that the multiple-integrations of HPV genome during persistent viral infection, which thereby alters the expression patterns of viral oncogenes and integration-related cellular genes, play a crucial role in progression of cervical lesions to cervix cancer.
Tam Clarence C
Full Text Available Abstract Background Reverse transcription-polymerase chain reaction (RT-PCR is the main method for laboratory diagnosis of norovirus-associated infectious intestinal disease (IID. However, up to 16% of healthy individuals in the community, with no recent history of IID, may be RT-PCR positive; so it is unclear whether norovirus is actually the cause of illness in an IID case when they are RT-PCR positive. It is important to identify the pathogen causing illness in sporadic IID cases, for clinical management and for community based incidence studies. The aim of this study was to investigate how faecal viral load can be used to determine when norovirus is the most likely cause of illness in an IID case. Methods Real-time RT-PCR was used to determine the viral load in faecal specimens collected from 589 IID cases and 159 healthy controls, who were infected with genogroup II noroviruses. Cycle threshold (Ct values from the real-time RT-PCR were used as a proxy measure of viral load. Receiver-operating characteristic (ROC analysis was used to identify a cut-off in viral load for attributing illness to norovirus in IID cases. Results One hundred and sixty-nine IID cases and 159 controls met the inclusion criteria for the ROC analysis. The optimal Ct value cut-off for attributing IID to norovirus was 31. The same cut-off was selected when using healthy controls, or IID cases who were positive by culture for bacterial pathogens, as the reference negative group. This alternative reference negative group can be identified amongst specimens routinely received in clinical virology laboratories. Conclusion We demonstrated that ROC analysis can be used to select a cut-off for a norovirus real time RT-PCR assay, to aid clinical interpretation and diagnose when norovirus is the cause of IID. Specimens routinely received for diagnosis in clinical virology laboratories can be used to select an appropriate cut-off. Individual laboratories can use this method to
Full Text Available Post-translational modification can modulate protein conformation and alter binding partner recruitment within gene regulatory regions. Here, we report that bromodomain-containing protein 4 (BRD4, a transcription co-factor and chromatin regulator, uses a phosphorylation-induced switch mechanism to recruit E2 protein encoded by cancer-associated human papillomavirus (HPV to viral early gene and cellular matrix metalloproteinase-9 (MMP-9 promoters. Enhanced MMP-9 expression, induced upon keratinocyte differentiation, occurs via BRD4-dependent recruitment of active AP-1 and NF-κB to their target sequences. This is triggered by replacement of AP-1 family members JunB and JunD by c-Jun and by re-localization of NF-κB from the cytoplasm to the nucleus. In addition, BRD4 phosphorylation is critical for E2- and origin-dependent HPV DNA replication. A class of phospho-BRD4-targeting compounds, distinct from the BET bromodomain inhibitors, effectively blocks BRD4 phosphorylation-specific functions in transcription and factor recruitment.
Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology
Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian
with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8-year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0-25.6%). The corresponding risks for HPV18......In this prospective cohort study, we estimated the long-term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high-risk human papillomavirus (hrHPV) genotype and semi-quantitative viral load at baseline among 33,288 women aged 14-90 years with normal baseline cytology. During...... 2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women...
Zhang, Lahong; Dai, Yibei; Chen, Jiahuan; Hong, Liquan; Liu, Yuhua; Ke, Qiang; Chen, Yiwen; Cai, Chengsong; Liu, Xia; Chen, Zhaojun
A new multiplex real-time PCR assay, the high-risk HPV genotyping real time PCR assay (HR HPV RT-PCR), has been developed to detect 15 high-risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT-PCR and the PCR reaction and reverse dot blot (PCR-RDB) assays, using a PCR-sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR-RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR-sequencing, while the PCR-RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR-sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high-risk HPV types in women diagnosed with vaginitis were HPV-52, HPV-16, and HPV-58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR-RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections. © 2017 Wiley Periodicals, Inc.
Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in a tertiary health facility in Maiduguri, Northeastern Nigeria. ... This study aims to estimate the HIV-1 RNA viral load and impact of anti TB therapy (ATT) ... HOW TO USE AJOL.
de Haan, Timo R.; Beersma, Matthijs F. C.; Oepkes, Dick; de Jong, Eveline P.; Kroes, Aloys C. M.; Walther, Frans J.
To correlate quantitative maternal and fetal parvovirus B19 (B19V) viral loads and antibody levels at intrauterine transfusion (IUT) as a predictor of fetal morbidity. Prospectively collected clinical data and quantitative B19V viral load and specific IgM and IgG values in fetal and maternal blood
M. G. Galitskaya
Full Text Available HPV is the most widespread sexually transmitted infection. HPV affects men and women regardless of age and leads to the development of various anogenital area diseases. International studies proved a wide clinical range of the tetravalent HPV vaccine protection and allowed recommending it for the prevention of not only cervical cancer, but also of vulvar, vaginal and anal cancer and anogenital condylomae in patients of both sexes. 42 countries have already introduced national HPV-vaccination programs in compliance with WHO recommendations. Anogenital area cancer morbidity reduction in these countries is expected in 10-15 years. However, a reduction or even complete disappearance of anogenital condylomae among the population has already been noted in a range of countries because the incubation period of this disease is short; this is the first marker of vaccination efficacy in a population.
Killingo, Bactrin M; Taro, Trisa B; Mosime, Wame N
HIV treatment outcomes are dependent on the use of viral load measurement. Despite global and national guidelines recommending the use of routine viral load testing, these policies alone have not translated into widespread implementation or sufficiently increased access for people living with HIV (PLHIV). Civil society and communities of PLHIV recognize the need to close this gap and to enable the scale up of routine viral load testing. The International Treatment Preparedness Coalition (ITPC) developed an approach to community-led demand creation for the use of routine viral load testing. Using this Community Demand Creation Model, implementers follow a step-wise process to capacitate and empower communities to address their most pressing needs. This includes utlizing a specific toolkit that includes conducting a baseline assessment, developing a treatment education toolkit, organizing mobilization workshops for knowledge building, provision of small grants to support advocacy work and conducting benchmark evaluations. The Community Demand Creation Model to increase demand for routine viral load testing services by PLHIV has been delivered in diverse contexts including in the sub-Saharan African, Asian, Latin American and the Caribbean regions. Between December 2015 and December 2016, ITPC trained more than 240 PLHIV activists, and disbursed US$90,000 to network partners in support of their national advocacy work. The latter efforts informed a regional, community-driven campaign calling for domestic investment in the expeditious implementation of national viral load testing guidelines. HIV treatment education and community mobilization are critical components of demand creation for access to optimal HIV treatment, especially for the use of routine viral load testing. ITPC's Community Demand Creation Model offers a novel approach to achieving this goal. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of
T Déirdre Hollingsworth
Full Text Available It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'. Individuals with suspected intra-couple transmission (97 couples had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted and the couple effect explained 16% of variance in viral loads (23% adjusted. The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted and the size of the effect was 27% (37% adjusted. Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.
Alemnji, George; Onyebujoh, Philip; Nkengasong, John N
Viral load measurement is a key indicator that determines patients' response to treatment and risk for disease progression. Efforts are ongoing in different countries to scale-up access to viral load testing to meet the Joint United Nations Programme on HIV and AIDS target of achieving 90% viral suppression among HIV-infected patients receiving antiretroviral therapy. However, the impact of these initiatives may be challenged by increased inefficiencies along the viral load testing spectrum. This will translate to increased costs and ineffectiveness of scale-up approaches. This review describes different parameters that could be addressed across the viral load testing spectrum aimed at improving efficiencies and utilizing test results for patient management. Though progress is being made in some countries to scale-up viral load, many others still face numerous challenges that may affect scale-up efficiencies: weak demand creation, ineffective supply chain management systems; poor specimen referral systems; inadequate data and quality management systems; and weak laboratory-clinical interface leading to diminished uptake of test results. In scaling up access to viral load testing, there should be a renewed focus to address efficiencies across the entire spectrum, including factors related to access, uptake, and impact of test results.
Katzenstein, T.; Ullum, H.; Røge, B.T.
OBJECTIVE: To quantify HIV-RNA in plasma, in lymphoid tissue and proviral DNA in peripheral blood mononuclear cells and to relate these to immunological markers among patients with plasma viral load counts of
Watanabe, Hideki; Nagayama, Kazuyoshi; Enomoto, Nobuyuki; Itakura, Jun; Tanabe, Yoko; Hamano, Kosei; Izumi, Namiki; Sato, Chifumi; Watanabe, Mamoru
The correlation between hepatitis C virus (HCV) genomic sequences and circulating HCV RNA levels was assessed to investigate the genetic elements affecting viral load. The interferon sensitivity-determining region (ISDR) sequence and the serum viral load were strongly correlated in 226 patients examined. Analysis of the entire HCV genome from six patients (three with a high and the others with a low viral load) with similar ISDR sequences identified several candidate residues associated with viral load. The amino acid (aa) sequences of these candidate residues and flanking regions in 67 additional patients revealed that only the residue at aa 962 varied significantly between the HCV patients with low and high serum loads (P 0.042). At this position, alanine was observed more frequently in the patients with a high viral load. In conclusion, our results strongly suggest that serum HCV RNA loads are inversely correlated with amino acid substitutions in the ISDR, and aa 962 was identified as a possible second determinant of serum HCV RNA load
Full Text Available Gammapapillomavirus (Gamma-PV is a diverse and rapidly expanding PV-genus, currently consisting of 76 fully characterized human papillomavirus (HPV types. In this study, DNA genomes of two novel HPV types, HPV179 and HPV184, obtained from two distinct facial verrucae vulgares specimens of a 64 year-old renal-transplant recipient, were fully cloned, sequenced and characterized. HPV179 and HPV184 genomes comprise 7,228-bp and 7,324-bp, respectively, and contain four early (E1, E2, E6 and E7 and two late genes (L1 and L2; the non-coding region is typically positioned between L1 and E6 genes. Phylogenetic analysis of the L1 nucleotide sequence placed both novel types within the Gamma-PV genus: HPV179 was classified as a novel member of species Gamma-15, additionally containing HPV135 and HPV146, while HPV184 was classified as a single member of a novel species Gamma-25. HPV179 and HPV184 type-specific quantitative real-time PCRs were further developed and used in combination with human beta-globin gene quantitative real-time PCR to determine the prevalence and viral load of the novel types in the patient's facial warts and several follow-up skin specimens, and in a representative collection, a total of 569 samples, of HPV-associated benign and malignant neoplasms, hair follicles and anal and oral mucosa specimens obtained from immunocompetent individuals. HPV179 and HPV184 viral loads in patients' facial warts were estimated to be 2,463 and 3,200 genome copies per single cell, respectively, suggesting their active role in the development of common warts in organ-transplant recipients. In addition, in this particular patient, both novel types had established a persistent infection of the skin for more than four years. Among immunocompetent individuals, HPV179 was further detected in low-copy numbers in a few skin specimens, indicating its cutaneous tissue tropism, while HPV184 was further detected in low-copy numbers in one mucosal and a few skin
Shakibazad, Nader; Honar, Naser; Dehghani, Seyed Mohsen; Alborzi, Abdolvahab
Many children with chronic liver disease require a liver transplant. These patients are prone to various infections, including Epstein-Barr virus infection. This study sought to measure the Epstein-Barr viral load by polymerase chain reaction before a liver transplant. This cross-sectional study was done at the Shiraz University of Medical Sciences, Shiraz, Iran, in 2011. All patients were aged younger than 18 years with chronic liver disease and were candidates for a liver transplant at the Shiraz Nemazee Hospital Organ Transplant Center. They had been investigated regarding their demographic characteristics, underlying disease, laboratory findings, and Epstein-Barr viral load by real-time TaqMan polymerase chain reaction. Ninety-eight patients were studied and the mean age was 6.5 ± 5.9 years. Cryptogenic cirrhosis was the most-prevalent reason for liver transplant, and the death rate before a transplant was 15%. Among the study subjects, 6 had measurable Epstein-Barr viral load by polymerase chain reaction before the transplant, and 4 of them had considerably higher Epstein-Barr viral loads (more than 1000 copies/mL). With respect to the close prevalence of posttransplant lymphoproliferative disease (6%) and the high Epstein-Barr viral load in the patients before a transplant (4%), high pretransplant Epstein-Barr viral load can be considered a risk factor for posttransplant lymphoproliferative disorder.
Mar 13, 2015 ... Abstract. Background: Hepatitis B viral infection is an old medical problem with worldwide distribution. It is usually diagnosed using serologic methods. However, the decision as to which patient to treat or not remains challenging due to the poor sensitivity of serologic markers as prognostic or severity ...
Cervical screening with cytology has been the basis for substantial reductions in cervical cancer incidence and mortality in most high-income countries over the last few decades. More recently, there have been two key, parallel developments which have prompted a major re-consideration of cervical screening. The first is the emergence of evidence on the improved sensitivity of human papillomavirus (HPV) DNA testing compared to cytology, and the second is the large-scale deployment of prophylactic vaccination against HPV. A key challenge to be overcome before HPV screening could be introduced into national cervical screening programs was the specificity of an infection, for detection of precancerous lesions. This has been done in three ways: (1) by considering the appropriate age for starting HPV screening (30 years in unvaccinated populations and 25 years in populations with mature vaccination programs and high vaccine uptake) and the appropriate screening interval; (2) via development of clinical HPV tests, which are (by design) not as sensitive to low viral loads; and (3) by introducing effective triaging for HPV-positive women, which further risk-stratifies women before referral for diagnostic evaluation. This review discusses these major developments and describes how the benefits of HPV screening are being optimized in both unvaccinated and vaccinated populations.
Swati P Ahir
Full Text Available Background & objectives: Mother-to-child transmission (MTCT is the most significant route of HIV transmission in children below the age of 15 yr. In India, perinatal HIV transmission, even after treatment, accounts for 5.4 per cent of HIV cases. The present study was conducted to evaluate the efficacy of anti-retro viral therapy (ART or prophylactic treatment (PT to control maternal viral load in HIV positive women, and its effect on vertical HIV transmission to their infants. Methods: A total of 58 HIV positive women were enrolled at the time of delivery and their plasma samples were obtained within 24 h of delivery for estimation of viral load. Viral load analysis was completed in 38 women. Infants received single dose nevirapine within 2 h of birth and zidovudine for 6 wk. At the end of 18 month follow up, HIV positive or negative status was available in 28 infants. Results: Results revealed undetectable levels of viral load in 58.3 per cent of women with ART compared to 30.7 per cent of women with PT. No women on ART had viral load more than 10,000 copies/ml, whereas seven (26.9%, P=0.07 women receiving PT had this viral load. Median CD4 count of women on PT (483 cells/μl was high compared to the women on ART (289 cells/ μl. At the end of 18 months follow up, only two children were HIV positive, whose mothers were on PT. One had in utero transmission; infection detected within 48 h of delivery, while the other child was infected post partum as HIV was detected at six months follow up. Interpretation & conclusions: Women who received a single dose of nevirapine during delivery had higher levels of viral load than women on ART. Combination drug therapy for pregnant women is now a standard of care in most of the western countries; use of nevirapine monotherapy at the time of delivery in our settings is not effective in controlling viral load. This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit
Picconi, Maria Alejandra; Gronda, Jorge; Alonio, Lidia V; Villa, Luisa L; Sichero, Laura; Miranda, Sergio; Barcena, Martin; Teyssie, Angelica
Human Papillomaviruses (HPVs) are etiologically associated to cervical carcinoma. In order to evaluate HPV infection and its relationship with the high frequency of this neoplasia in Quechua women from Jujuy (Argentina), 271 cervical samples from preneoplastic and neoplastic lesions (biopsies) and normal controls (cytologies) were studied. Detection and typing were performed using PCR-RFLP or PCR-hybridization and the HPV-16 variability in L1 and E6 genes (by PCR-hybridization) was analysed. HPV was detected in 52% of controls, 91% of low-grade lesions, 97% of high-grade lesions and 100% of invasive carcinomas, corresponding 55% to HPV-16. HPV-16 European variants were predominant, most of them being non-prototypic strains. The high frequency of high risk infection types and the raised proportion of HPV-16 non-prototypic variants related to a greater oncogenic potential could explain, in part, the high cervical cancer frequency of this native population. These data may contribute to disease control and vaccinal formulation.
Snijder, J.; Ivanovska, I.L.; Baclayon, M.; Roos, W.H.; Wuite, G.J.L.
The effects of changes in the loading rate during the forced dissociation of single bonds have been studied for a wide variety of interactions. Less is known on the loading rate dependent behaviour of more complex systems that consist of multiple bonds. Here we focus on viral nanoparticles, in
Tian, Yongjun; Chen, Wen-ling; Ou, Jing-hsiung James
Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low. PMID:21829354
Brendan J W Osborne
Full Text Available The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load.Semen was collected by masturbation from HIV-infected, therapy-naïve men who have sex with men (MSM either undiluted (Visit 1 or directly into transport medium (Visit 2. Seminal plasma was then isolated, and the HIV RNA concentration obtained with each collection technique was measured and corrected for dilution if necessary. Collection of semen directly into transport medium resulted in a median HIV RNA viral load that was 0.4 log10 higher than undiluted samples.The method of semen collection is an important consideration when quantifying the HIV RNA viral load in this compartment.
Wentzensen, Nicolas; Wilson, Lauren E.; Wheeler, Cosette M.; Carreon, Joseph D.; Gravitt, Patti E.; Schiffman, Mark; Castle, Philip E.
Anogenital cancers are associated with about 13 carcinogenic HPV types in a broader group that cause cervical intraepithelial neoplasia (CIN). Multiple concurrent cervical HPV infections are common which complicate the attribution of HPV types to different grades of CIN. Here we report the analysis of HPV genotype patterns in the ASCUS-LSIL triage study using unsupervised hierarchical clustering. Women who underwent colposcopy at baseline (n = 2780) were grouped into 20 disease categories based on histology and cytology. Disease groups and HPV genotypes were clustered using complete linkage. Risk of 2-year cumulative CIN3+, viral load, colposcopic impression, and age were compared between disease groups and major clusters. Hierarchical clustering yielded four major disease clusters: Cluster 1 included all CIN3 histology with abnormal cytology; Cluster 2 included CIN3 histology with normal cytology and combinations with either CIN2 or high-grade squamous intraepithelial lesion (HSIL) cytology; Cluster 3 included older women with normal or low grade histology/cytology and low viral load; Cluster 4 included younger women with low grade histology/cytology, multiple infections, and the highest viral load. Three major groups of HPV genotypes were identified: Group 1 included only HPV16; Group 2 included nine carcinogenic types plus non-carcinogenic HPV53 and HPV66; and Group 3 included non-carcinogenic types plus carcinogenic HPV33 and HPV45. Clustering results suggested that colposcopy missed a prevalent precancer in many women with no biopsy/normal histology and HSIL. This result was confirmed by an elevated 2-year risk of CIN3+ in these groups. Our novel approach to study multiple genotype infections in cervical disease using unsupervised hierarchical clustering can address complex genotype distributions on a population level. PMID:20959485
Hernandez, Alexandra L; Karthik, Rajiv; Sivasubramanian, Murugesan; Raghavendran, Anantharam; Gnanamony, Manu; Lensing, Shelly; Lee, Jeannette Y; Kannangai, Rajesh; Abraham, Priya; Mathai, Dilip; Palefsky, Joel M
India has a large population of HIV-positive individuals, including men who have sex with men (MSM), and the incidence of human papillomavirus (HPV)-related cancers is high. In developed countries, HIV-positive MSM exhibit the highest prevalence of anal HPV infection and incidence of anal cancer. Little is known about anal HPV infection in HIV-positive Indian MSM. We evaluated 300 HIV-positive MSM from 2 cities in India. Men were tested for anal HPV infection using L1-HPV DNA polymerase chain reaction with probes specific for 29 types and a mixture of 10 additional types. CD4 level and plasma HIV viral load were measured. Participants completed an interviewer-administered questionnaire including a sexual history. The prevalence of anal HPV was 95% (95% confidence interval: 91% to 97%). The 3 most common types were HPV 35 (20%), HPV 16 (13%), and HPV 6/11 (13%). History of taking antiretroviral medications decreased risk of anal HPV 16 infection [relative risk (RR): 0.6 (0.4-1.0)]. Having an increased number of vaginal sex partners lowered risk of any anal HPV infection. Ever having receptive sex increased risk of any anal HPV [RR: 1.2 (1.1-1.4)] and anal HPV 16 [RR: 6.5 (1.8-107)]. Almost all Indian HIV-positive MSM had anal HPV infection. The prevalence of HPV 16 was lower and the prevalence of other oncogenic HPV types was higher than in similar populations in North America and Europe. Vaccine-based prevention strategies for HPV infection in India should consider potential differences in HPV type distribution among HIV-infected MSM when designing interventions.
Belopolskaya, Maria; Avrutin, Viktor; Firsov, Sergey; Yakovlev, Alexey
Background Viral load measurement is necessary to estimate mother-to-child transmission risk for women with chronic hepatitis B (CHB), however, it is expensive. The present study aimed to investigate the relationship between HBsAg and hepatitis B virus (HBV) DNA levels, and to determine potential applications of HBsAg level monitoring for estimating viral load. Methods 85 patients with CHB (31 pregnant women, 26 non-pregnant women, 28 men) were included in the study. HBV DNA level was measured by real-time PCR, and HBsAg level by chemiluminescent immunoassay method. Dependency between viral load and HBsAg level was determined by Spearman correlation coefficient ρ. Results The correlation between HBsAg and HBV DNA levels was significant for all patients [ρ=0.3762 (P<0.0005; n=85)]. In the group of pregnant women, a low (unmeasurable) HBV DNA level led to a decrease in the Spearman coefficient ρ. In almost all cases a low level of the HBsAg corresponded to a low HBV DNA level. Only 2 patients had a low level of HBsAg and a relatively high viral load. By contrast, a high HBsAg level was observed in patients both with high and low viral load. Conclusions Correlation between HBsAg and HBV DNA levels is significant. In most cases, a low level of HBsAg indicates a low HBV DNA level, whereas a high HBsAg level does not always correspond to a high viral load. The measurement of HBV DNA level is necessary for pregnant women with a high HBsAg level. PMID:26127004
Wu, Liang; Zhang, Xiaolong; Zhao, Zhikun; Wang, Ling; Li, Bo; Li, Guibo; Dean, Michael; Yu, Qichao; Wang, Yanhui; Lin, Xinxin; Rao, Weijian; Mei, Zhanlong; Li, Yang; Jiang, Runze; Yang, Huan; Li, Fuqiang; Xie, Guoyun; Xu, Liqin; Wu, Kui; Zhang, Jie; Chen, Jianghao; Wang, Ting; Kristiansen, Karsten; Zhang, Xiuqing; Li, Yingrui; Yang, Huanming; Wang, Jian; Hou, Yong; Xu, Xun
Viral infection causes multiple forms of human cancer, and HPV infection is the primary factor in cervical carcinomas. Recent single-cell RNA-seq studies highlight the tumor heterogeneity present in most cancers, but virally induced tumors have not been studied. HeLa is a well characterized HPV+ cervical cancer cell line. We developed a new high throughput platform to prepare single-cell RNA on a nanoliter scale based on a customized microwell chip. Using this method, we successfully amplified full-length transcripts of 669 single HeLa S3 cells and 40 of them were randomly selected to perform single-cell RNA sequencing. Based on these data, we obtained a comprehensive understanding of the heterogeneity of HeLa S3 cells in gene expression, alternative splicing and fusions. Furthermore, we identified a high diversity of HPV-18 expression and splicing at the single-cell level. By co-expression analysis we identified 283 E6, E7 co-regulated genes, including CDC25, PCNA, PLK4, BUB1B and IRF1 known to interact with HPV viral proteins. Our results reveal the heterogeneity of a virus-infected cell line. It not only provides a transcriptome characterization of HeLa S3 cells at the single cell level, but is a demonstration of the power of single cell RNA-seq analysis of virally infected cells and cancers.
Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 infected untreated children in Kenya; implication for immunodeficiency and AIDS progression. Washingtone Ochieng, Dorington Ogoyi, Francis J Mulaa, Simon Ogola, Rachel Musoke, Moses G Otsyula ...
Laar, J.A. van; Buysse, C.M.; Vossen, A.C.; Hjalmarsson, B.; Berg, B. van de; Lom, K. van; Deinum, J.
We describe 2 immunocompetent adolescents with fulminant infectious mononucleosis and virus-associated hemophagocytosis. A new quantitative polymerase chain reaction revealed high serum Epstein-Barr virus DNA levels in these patients. One patient died with an increasing viral load not responding to
Procop, Gary W; Taege, Alan J; Starkey, Colleen; Tungsiripat, Marisa; Warner, Diane; Schold, Jesse D; Yen-Lieberman, Belinda
The processing of specimens often occurs in a central processing area within laboratories. We demonstrated that plasma centrifuged in the central laboratory but allowed to remain within the primary tube following centrifugation was associated with spuriously elevated HIV viral loads compared with recentrifugation of the plasma just prior to testing. Copyright © 2016 Elsevier Inc. All rights reserved.
1-infected patients. However, the virus persists ... chronological changes in HIV viral load and CD4+ T-cell count, and treatment outcomes of multiple combinations of .... Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the ...
Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik
BACKGROUND: The diagnostic yield for cytomegalovirus (CMV) PCR viral load in Bronchoalveolar Lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain, and was investigated in a large cohort of consecutive lung transplant recipients. METHODS: Bronchoscopi...
Estell, K E; Dawson, D R; Magdesian, K G; Swain, E; Laing, S T; Siso, S; Mapes, S; Pusterla, N
Data associating quantitative viral load with severity, clinical signs and survival in equine herpesvirus-1 myeloencephalopathy (EHM) have not been reported. To report the clinical signs, treatment, and temporal progression of viral loads in 7 horses with naturally occurring EHM and to examine the association of these factors with survival. Retrospective case series. The population included 7 horses with EHM presented to the University of California, Davis William R. Pritchard Veterinary Medical Teaching Hospital from May to September 2011. Horses were graded using a neurological grading scale. Daily quantitative PCR was performed on nasal secretions and whole blood. Treatment, survival, outcome and histopathology were reported. At presentation, one horse was neurological grade 5/5, 3 were grade 4/5 and 3 were grade 3/5. All were treated with anti-inflammatory drugs, valacyclovir and management in a sling if necessary. All were infected with equine herpesvirus-1 of DNA polymerase D752 genotype. Peak viral load in nasal secretions and blood of 5 survivors ranged from 6.9 × 10(3) to 2.81 × 10(5) (median 5.11 × 10(4) ) and from 143 to 4340 gB gene copies/million eukaryotic cells (median 3146), respectively. The 2 nonsurvivors presented with grade 3/5 neurological signs and progressed to encephalopathy. Peak viral load was higher in nonsurvivors, with levels in nasal secretions of 1.9 × 10(9) and 2.2 × 10(9) and in blood of 2.05 × 10(4) and 1.02 × 10(5) gB gene copies/million eukaryotic cells. Case fatality was 2/7. Nonsurvivors had viral loads 1000-fold higher in nasal secretions and 10-fold higher in blood than survivors. There was no relationship between severity of clinical signs at presentation and survival. Thus, encephalopathy and high viral load were negatively associated with survival in this population. Further research should be performed to determine whether high viral loads are associated with encephalopathy and poor prognosis. The Summary is
Vu, Huong Thi Thu; Yoshida, Lay Myint; Suzuki, Motoi; Nguyen, Hien Anh Thi; Nguyen, Cat Dinh Lien; Nguyen, Ai Thi Thuy; Oishi, Kengo; Yamamoto, Takeshi; Watanabe, Kiwao; Vu, Thiem Dinh
The interplay between nasopharyngeal bacterial carriage, viral coinfection, and lower respiratory tract infections (LRTIs) is poorly understood. We explored this association in Vietnamese children aged less than 5 years. A hospital-based case-control study of pediatric LRTIs was conducted in Nha Trang, Vietnam. A total of 550 hospitalized children (274 radiologically confirmed pneumonia [RCP] and 276 other LRTIs) were enrolled and 350 healthy controls were randomly selected from the community. Polymerase chain reaction-based methods were used to measure bacterial loads of Streptococcus pneumoniae (SP), Haemophilus influenzae, and Moraxella catarrhalis and to detect 13 respiratory viruses and bacterial serotypes in nasopharyngeal samples of study participants. The median nasopharyngeal bacterial load of SP was substantially higher in children with RCP compared with healthy controls or children with other LRTIs (P RCP or other LRTIs groups. An increased load of SP in the nasopharynx was associated with RCP, viral coinfection, and presence of pneumococcal capsule.
Fujiwara, Keiichi; Kojima, Hiroshige; Yasui, Shin; Okitsu, Koichiro; Yonemitsu, Yutaka; Omata, Masao; Yokosuka, Osamu
A correlation between hepatitis A virus (HAV) genomes and the clinical severity of hepatitis A has not been established. The viral load in sera of hepatitis A patients was examined to determine the possible association between hepatitis A severity and HAV replication. One hundred sixty-four serum samples from 91 Japanese patients with sporadic hepatitis A, comprising 11 patients with fulminant hepatitis, 10 with severe acute hepatitis, and 70 with self-limited acute hepatitis, were tested for HAV RNA. The sera included 83 serial samples from 20 patients. Viral load was measured by real-time RT-PCR. The detection rates of HAV RNA from fulminant, severe acute, and acute hepatitis were 10/11 (91%), 10/10 (100%), and 55/70 (79%), respectively. Mean values of HAV RNA at admission were 3.48 ± 1.30 logcopies/ml in fulminant, 4.19 ± 1.03 in severe acute, and 2.65 ± 1.64 in acute hepatitis. Patients with severe infection such as fulminant hepatitis and severe acute hepatitis had higher initial viral load than patients with less severe infection (P hepatitis after clinical onset (P = 0.19). HAV RNA was detectable quantitatively in the majority of the sera of hepatitis A cases during the early convalescent phase by real-time PCR. Higher initial viral replication was found in severely infected patients. An excessive host immune response might follow, reducing the viral load rapidly as a result of the destruction of large numbers of HAV-infected hepatocytes, and in turn severe disease might be induced. 2010 Wiley-Liss, Inc.
Lythgoe, Katrina A.; Blanquart, François
The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models. We study the dynamics of virus replication and cytotoxic T lymphocytes (CTLs) within a metapopulation of spatially segregated patches, representing T cell areas connected by circulating blood and lymph. The dynamics of the system depend critically on the interaction between CTLs and infected cells at the within-patch level. We show that for a wide range of parameters, the system admits an unexpected outcome called the shifting-mosaic steady state. In this state, the whole body’s viral population is stable over time, but the equilibrium results from an underlying, highly dynamic process of local infection and clearance within T-cell centers. Notably, and in contrast to previous models, this new model can explain the large differences in set-point viral load (SPVL) observed between patients and their distribution, as well as the relatively low proportion of cells infected at any one time, and alters the predicted determinants of viral load variation. PMID:27706164
Krentz, Hartmut B; Gill, M John
The concept of community viral load (CVL) was introduced to quantify the pool of transmissible HIV within a community and to monitor the potential impact of highly active antiretroviral therapy (HAART) on reducing new infections. The implications of churn (patient movement in/out of care in a community) on CVL have not been studied. The annual CVL was determined in the entire geographic HIV population receiving care in southern Alberta from 2001 to 2010; the CVL for specific subpopulations was analyzed for 2009. CVL was determined for patients under continuous care, newly diagnosed, new to the region, moved away, returned, and lost to follow-up (LTFU). Viral loads (VLs) churn significantly limited CVL use as a measure for evaluating the impact of HAART in reducing HIV transmissions in our population.
Paul L Sacamano
Full Text Available Persons living with HIV (PLWH who are engaged in care, yet not virally suppressed, represent a risk for transmission and opportunity for risk reduction interventions. This study describes characteristics of an outpatient clinic cohort of PLWH by laboratory confirmed viral suppression status and examines associations with demographics and sexual and drug use behaviors gathered through questionnaire. From a sample of 500 clinic patients, 438 were prescribed antiretroviral treatment (ART and 62 were not. Among the 438 on ART, 72 (16.4% were not virally suppressed at the most recent lab draw. Compared to individuals with a suppressed viral load, those that were unsuppressed were more likely to: be black (79.2% vs. 64.2%; p = 0.014; earn below $25,000/year (88.9% vs. 65.0%; p < 0.001; be of a younger age (47.8 vs. 50.0 mean years; p = 0.009; be on opiate substitution (14.1% vs. 6.3%; p = 0.023; and acknowledge poly-substance (38.9% vs. 24.4%; p = 0.012 and excessive alcohol use (13.9% vs. 6.0%; p = 0.019. Conversely, a smaller proportion of those with an unsuppressed viral load had multiple sex partners in the previous 30 days (39.8% vs. 58.5%; p = 0.003. In multivariable regression of those on ART, the prevalence of an unsuppressed viral load was 3% lower with each increasing year of age (aPR: 0.97; 95% CI: 0.95, 0.99 and 47% lower with income over $25,000/year (aPR: 0.33; 95% CI: 0.16, 0.70. In a separate analysis of all 500 subjects, ART was less frequently prescribed to blacks compared to whites, heterosexuals, those with lower education and income, and persons with active substance use. Findings confirm that a large proportion of PLWH and engaged in care were not virally suppressed and continued behaviors that risk transmission, indicating the need for screening, prevention counseling and access to ancillary services to lower the incidence of HIV infections.
Leonora Maciel de Souza Vianna
Full Text Available Background The number of oropharyngeal lesions caused by HPV (Human papillomavirus has been increasing worldwide in the past years. In spite of the clinical relevance of HPV infection in the anogenital tract of HIV-positive patients, the relevance of oropharynx HPV infection in these patients is not clear. The aim of the present study was to detect HPV infection, and clinical and cytological changes in the oropharynx of HIV-positive patients. Methods Samples collected from the oropharynx of 100 HIV-positive patients were subjected to hybrid capture (HC, conventional and liquid-based cytology. Clinical data were also collected to investigate the relation with HPV status. Results High and low-risk types of HPV were present in 8% and 16.7% of the total sample. The mean ± sd (maximum-minimum of the relative ratio light unit (RLU/cutoff (CO was 2.94 ± 2.58 (1.09–7.87 and 1.61 ± 0.65 (1.07–2.8 for high- and low-risk-HPV, respectively. By cytology, dysplasia was not detected, but atypical squamous cells of undetermined significance (ASC-US were diagnosed in two samples. No clinical change, suggestive of dysplasia/cancer, was detected. Conclusion Our study was able to detect and characterize HPV infection by hybrid capture, which may represent a good tool for screening and follow-up of HPV in the studied population. The frequency and viral load of HPV were low. Neither clinical nor cytological changes suggestive of dysplasia/neoplasia were observed in oropharynx of HIV-positive patients.
The prevalence of the HPV 16 genome, integrated viral status and p53 genotype in cervical cancer population of north-eastern Hungary, the correlation with the established markers of tumour progression.
Hernádi, Zoltán; Sápy, Tamás; Krasznai, Zoárd T
To evaluate the prevalence of the HPV 16 integrated status and the p53 genotype in cervical cancer in north-eastern Hungary and their correlation with the established prognostic factors. Parallel with the routine histological examination, Southern blot hybridisation and multiplex PCRs were used to detect type/physical state of HPV DNA in primary tumours and in regional lymph nodes combined with p53 genotyping of 83 patients. 46.9% (39/83) prevalence rate of HPV 16 genome was found. The frequency of viral integration (76.9% in primary tumours and 95.2% in regional lymph nodes) and that of the p53Arg homozygous genotype (64.1%) proved to be higher than reported from other parts of the world. The HPV 16 integration and the p53 genotype, failed to correlate with the FIGO stage and lymphatic spread. The prevalence of the integrated status of the HPV 16 genome combined with homozygous p53Arg genotype is relatively high in Hungary. These factors however failed to show a strong correlation with the established markers of tumour progression.
Full Text Available Infection by human papillomavirus (HPV can cause cervical intraepithelial neoplasia (CIN and cancer. Down-regulation of E6 and E7 expression may be responsible for the positive clinical outcomes observed with IFN treatment, but the molecular basis has not been well determined. As miRNAs play an important role in HPV induced cervical carcinogenesis, we hypothesize that IFN-β can regulate the expressions of specific miRNAs in cervical cancer cells, and that these miRNAs can mediate E6 and E7 expression, thus modulate their oncogenic potential. In this study, we found that miR-129-5p to be a candidate IFN-β inducible miRNA. MiR-129-5p levels gradually decrease with the development of cervical intraepithelial lesions. Manipulation of miR-129-5p expression in Hela cells modulates HPV-18 E6 and E7 viral gene expression. Exogenous miR-129-5p inhibits cell proliferation in Hela cells, promotes apoptosis and blocks cell cycle progression in Hela cells. SP1 is a direct target of miR-129-5p in Hela cells. This study is the first report of a cellular miRNA with anti-HPV activity and provides new insights into regulatory mechanisms between the HPV and the IFN system in host cells at the miRNA level.
Full Text Available Abstract Background The human papillomavirus (HPV E2 protein is a multifunctional DNA-binding protein. The transcriptional activity of HPV E2 is mediated by binding to its specific binding sites in the upstream regulatory region of the HPV genomes. Previously we reported a HPV-2 variant from a verrucae vulgaris patient with huge extensive clustered cutaneous, which have five point mutations in its E2 ORF, L118S, S235P, Y287H, S293R and A338V. Under the control of HPV-2 LCR, co-expression of the mutated HPV E2 induced an increased activity on the viral early promoter. In the present study, a series of mammalian expression plasmids encoding E2 proteins with one to five amino acid (aa substitutions for these mutations were constructed and transfected into HeLa, C33A and SiHa cells. Results CAT expression assays indicated that the enhanced promoter activity was due to the co-expressions of the E2 constructs containing A338V mutation within the DNA-binding domain. Western blots analysis demonstrated that the transiently transfected E2 expressing plasmids, regardless of prototype or the A338V mutant, were continuously expressed in the cells. To study the effect of E2 mutations on its DNA-binding activity, a serial of recombinant E2 proteins with various lengths were expressed and purified. Electrophoresis mobility shift assays (EMSA showed that the binding affinity of E2 protein with A338V mutation to both an artificial probe with two E2 binding sites or HPV-2 and HPV-16 promoter-proximal LCR sequences were significantly stronger than that of the HPV-2 prototype E2. Furthermore, co-expression of the construct containing A338V mutant exhibited increased activities on heterologous HPV-16 early promoter P97 than that of prototype E2. Conclusions These results suggest that the mutation from Ala to Val at aa 338 is critical for E2 DNA-binding and its transcriptional regulation.
Wu, Hsiu; Cohen, Stephanie E; Westheimer, Emily; Gay, Cynthia L; Hall, Laura; Rose, Charles; Hightow-Weidman, Lisa B; Gose, Severin; Fu, Jie; Peters, Philip J
New recommendations for laboratory diagnosis of HIV infection in the United States were published in 2014. The updated testing algorithm includes a qualitative HIV-1 RNA assay to resolve discordant immunoassay results and to identify acute HIV-1 infection (AHI). The qualitative HIV-1 RNA assay is not widely available; therefore, we evaluated the performance of a more widely available quantitative HIV-1 RNA assay, viral load, for diagnosing AHI. We determined that quantitative viral loads consistently distinguished AHI from a false-positive immunoassay result. Among 100 study participants with AHI and a viral load result, the estimated geometric mean viral load was 1,377,793copies/mL. Copyright © 2017 Elsevier B.V. All rights reserved.
Jakovljevic, A; Knezevic, A; Nikolic, N; Soldatovic, I; Jovanovic, T; Milasin, J; Andric, M
This study aimed to analyse Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) viral loads in symptomatic and asymptomatic apical periodontitis lesions, to determine levels of TNF-α, IL-1β and IL-6 in these lesions and to investigate a possible correlation between herpesviral copy numbers and levels of proinflammatory cytokines. A total of 100 samples of apical periodontitis were subjected to HCMV and EBV copy numbers analysis by nested polymerase chain reaction (PCR) and TaqMan real-time PCR. The concentrations of TNF-α, IL-1β and IL-6 were determined by ELISA method. SPSS software was used for statistical analysis. There were no significant differences in the occurrence of EBV and HCMV between symptomatic and asymptomatic periapical lesions (p = .686, p = .879, respectively). Only 12 of 74 EBV (16.2%) and four of 54 HCMV (13.5%) nested PCR-positive samples showed increased viral copy numbers above the limit of 125 copies/ml. There was no significant correlation between the levels of analysed proinflammatory cytokines and herpesviral copy numbers in our sample. The observed low viral loads point to a relatively rare occurrence of active EBV and HCMV infection in our sample. Latent herpesviral infection does not enhance the production of investigated proinflammatory cytokines. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.
Krarup, Henrik; Andersen, Stig; Madsen, Poul Henning
To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....
Krarup, Henrik Bygum; Andersen, Stig; Madsen, Poul Henning
To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....
Friedman, M Reuel; Coulter, Robert W S; Silvestre, Anthony J; Stall, Ron; Teplin, Linda; Shoptaw, Steve; Surkan, Pamela J; Plankey, Michael W
Though functional social support has been shown to serve as a protective factor for HIV viral load suppression in other populations, scant research has examined this relationship among men who have sex with men (MSM) in the United States. We assessed characteristics of social support, effects of social support on HIV viral load, and moderation by social support of the relationship between psychosocial indicators of a synergistic epidemic (syndemic) and HIV viral load. We analyzed longitudinal data from HIV-positive MSM using antiretroviral therapy who were enrolled in the Multicenter AIDS Cohort Study between 2002 and 2009 (n = 712). First, we conducted reliability assessments of a one-item social support measure. Then, we conducted a series of generalized longitudinal mixed models to assess our research questions. Moderation was assessed using an interaction term. A three-level (low/medium/high) social support variable demonstrated high reliability (intraclass correlation coefficients = 0.72; 95% CI: 0.70, 0.75). Black and Hispanic MSM reported lower social support than their White counterparts (p social support (p social support (p social support levels were associated with greater viral load suppression and lower viral load means (p Social support moderated the relationships between syndemic and HIV viral load (p social support. Creating strengths-based interventions may also have particularly high impact among HIV-positive MSM with the highest psychosocial burdens.
Jordan E. Cates
Full Text Available Background. To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss among HIV-infected women enrolled in the Women’s Interagency HIV Study between 1994 and 2013. Methods. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART to conception, and log10 copy-years viremia in the two years before conception. Results. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI: 0.99, 2.56 times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs: 0.80 (95% CI: 0.69, 0.92 and 1.00 (95% CI: 0.90, 1.11, resp.. Conclusions. Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.
Cates, Jordan E; Westreich, Daniel; Edmonds, Andrew; Wright, Rodney L; Minkoff, Howard; Colie, Christine; Greenblatt, Ruth M; Cejtin, Helen E; Karim, Roksana; Haddad, Lisa B; Kempf, Mirjam-Colette; Golub, Elizabeth T; Adimora, Adaora A
To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss) among HIV-infected women enrolled in the Women's Interagency HIV Study between 1994 and 2013. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART) to conception, and log10 copy-years viremia in the two years before conception. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI): 0.99, 2.56) times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs): 0.80 (95% CI: 0.69, 0.92) and 1.00 (95% CI: 0.90, 1.11), resp.). Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.
Guigayoma, John; Chen, Yea-Hung; Snowden, Jonathan M; Santos, Glenn-Milo; Hecht, Jennifer; Raymond, H Fisher
Self-perceived viral suppression status among men who have sex with men (MSM) may impact HIV risk transmission behaviors. We conducted a 2014 cross-sectional survey of MSM in San Francisco and assessed differences in sexual risk behavior among known HIV-positive MSM based on viral suppression of HIV. We collected demographics, self-perceived viral load status, and sexual risk behavior and tested for viral load levels through laboratory assays. Men were categorized in a hierarchical schema of sexual risk behavior categories based on responses to questions regarding recent partners' HIV status, condom use, and sexual positioning. We used Fisher exact tests to assess for differences based on self-perceived viral load status. Out of a sample of 96 known HIV-positive men, 59 men self-reported an undetectable HIV viral load and 9 men self-reported a detectable viral load consented to confirmatory laboratory testing. The sample of self-reported undetectable men had gradually larger proportions of higher-risk sexual practices, whereas the sample of detectable men was evenly distributed across sexual practices. This association was not statistically significant (P = 0.91). Self-perceived viral suppression may influence sexual practices of known HIV-positive MSM, but small sample size, especially within the detectable category, hinders our ability to determine statistical significance. More research is necessary to assess how HIV-positive men account for viral load in sexual decision-making practices, and this research may inform resource allocation and clinical recommendations to maintain the health of MSM populations.
Herrera-Goepfert, Roberto; Vela-Chávez, Teresa; Carrillo-García, Adela; Lizano-Soberón, Marcela; Amador-Molina, Alfredo; Oñate-Ocaña, Luis F; Hallmann, Rita Sotelo-Regil
, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas
Amaro-Filho, Sérgio Menezes; Pereira Chaves, Cláudia Bessa; Felix, Shayany Pinto; Basto, Diogo Lisbôa; de Almeida, Liz Maria; Moreira, Miguel Angelo Martins
To compare and describe type-specific characteristics of HPV16, HPV18 and HPV45 in cervical cancer with respect to 3'LCR methylation and disruption of E1/E2. The methylation level of 137 cervical cancer samples (70 with HPV16, 37 with HPV18, and 30 with HPV45) of Brazilian patients was analyzed by pyrosequencing. PCR amplifications were performed to characterize E1 and E2 disruption as an episomal surrogate. The 3'LCR of HPV16 showed a higher methylation at all CpG sites (7%, 9%, 11%, 10% and 10%) than homologous HPV18 regions (4%, 5%. 6%, 9% and 5%) and HPV45 regions (7%, 7% and 5%). Presence of intact E1/E2 was associated with higher HPV16 and HPV18 methylation levels at all CpG sites (p < 0.05). Disruption of E1/E2 was more frequently found in HPV45 (97%) and HPV18 (84%) than in HPV16 DNA (30%). HPV16 disruption was more frequently found in E1 (48%) unlike HPV18, where it was found in E2 (61%). Concomitant disruption of E1/E2 was most frequent in HPV45 (72%). The findings showed a higher methylation associated with intact E1/E2 for HPV16 and HPV18. The closely phylogenetic related HPV18 and HPV45 share a similar methylation level and the frequency of viral genome disruption. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
... Against HPV Print en español Vacuna contra el virus del papiloma humano (VPH) What Is HPV and Why Is It a Problem? Human papillomavirus (HPV) is one of the most common sexually transmitted diseases (STDs) . HPV is the virus that causes genital warts . Besides genital warts, an ...
Full Text Available In the patients with end-stage renal disease (ESRD with hepatitis B virus (HBV infection who underwent hemodialysis, the viral load of HBV DNA is relatively low and stable. For this phenomenon, some studies suggest that hemodialysis can reduce the HBV DNA load. The mechanism, which remains unclear, may be as follows: when HBV DNA enters the dialysate through the dialysis membrane, it was adsorbed onto the dialysis membrane; some virus particles were destroyed, and antiviral substances were produced in the course of hemodialysis. At present, there is no consensus on the mechanism responsible for the influence of maintained hemodialysis on the viral load of HBV DNA. This article reviews the factors involved in the influence of maintained hemodialysis on the viral load in ESRD patients with HBV infection and the recent progress.
The SIV plasma viral load assay performed by the Quantitative Molecular Diagnostics Core (QMDC) utilizes reagents specifically designed to detect and accurately quantify the full range of SIV/SHIV viral variants and clones in common usage in the rese
Mortier, Virginie; Vancoillie, Leen; Dauwe, Kenny; Staelens, Delfien; Demecheleer, Els; Schauvliege, Marlies; Dinakis, Sylvie; Van Maerken, Tom; Dessilly, Géraldine; Ruelle, Jean; Verhofstede, Chris
Pre-analytical sample processing is often overlooked as a potential cause of inaccurate assay results. Here we demonstrate how plasma, extracted from standard EDTA-containing blood collection tubes, may contain traces of blood cells consequently resulting in a false low-level HIV-1 viral load when using Roche Cobas HIV-1 assays. The presence of human DNA in Roche Cobas 4800 RNA extracts and in RNA extracts from the Abbott HIV-1 RealTime assay was assessed by quantifying the human albumin gene by means of quantitative PCR. RNA was extracted from plasma samples before and after an additional centrifugation and tested for viral load and DNA contamination. The relation between total DNA content and viral load was defined. Elevated concentrations of genomic DNA were detected in 28 out of 100 Cobas 4800 extracts and were significantly more frequent in samples processed outside of the AIDS Reference Laboratory. An association between genomic DNA presence and spurious low-level viraemia results was demonstrated. Supplementary centrifugation of plasma before RNA extraction eliminated the contamination and the false viraemia. Plasma isolated from standard EDTA-containing blood collection tubes may contain traces of HIV DNA leading to false viral load results above the clinical cutoff. Supplementary centrifugation of plasma before viral load analysis may eliminate the occurrence of this spurious low-level viraemia.
Anne F Rositch
Full Text Available Most data on HPV and antiretroviral therapy (ART come from high-resource countries with infrequent sampling for HPV pre- and post-ART initiation. Therefore, we examined the frequency of cervical HPV DNA detection among HIV/HSV-2 co-infected women followed monthly for 6 months both before and after initiation of ART in Rakai, Uganda.Linear Array was used to detect 37 HPV genotypes in self-collected cervicovaginal swabs from 96 women who initiated ART. Random-effects log-binomial regression was used to compare the prevalence of HPV detection in the pre- and post-ART periods and determine other potential risk factors, including CD4 counts and HIV viral load.Nearly all women had detectable HPV in the 6 months preceding ART initiation (92% and the cumulative prevalence remained high following initiation of therapy (90%. We found no effect of ART on monthly HPV DNA detection (prevalence ratio: 1.0; 95% confidence interval: 0.96, 1.08, regardless of immune reconstitution or HIV viral suppression. Older age and higher pre-ART CD4 counts were associated with a significantly lower risk of HPV DNA detection.ART did not impact HPV detection within 6 months of therapy initiation, highlighting the importance of continued and consistent screening, even after ART-initiation and immune reconstitution.
Liu, Cindy M.; Osborne, Brendan J. W.; Hungate, Bruce A.; Shahabi, Kamnoosh; Huibner, Sanja; Lester, Richard; Dwan, Michael G.; Kovacs, Colin; Contente-Cuomo, Tania L.; Benko, Erika; Aziz, Maliha
Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r2 = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r2 = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission. PMID:25058515
Cindy M Liu
Full Text Available Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM, including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024, TNF-α (p = 0.009, and IL-1b (p = 0.002. IL-1b in particular was associated with semen VL (r(2 = 0.18, p = 0.02. Semen bacterial load was also directly linked to the semen HIV VL (r(2 = 0.15, p = 0.02. HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.
Liu, Ying; Lu, Zheming; Xu, Ruiping; Ke, Yang
Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.
Hoffmann, Christopher J; Maritz, Jean; van Zyl, Gert U
CD4 count decline often triggers antiretroviral regimen switches in resource-limited settings, even when viral load testing is available. We therefore compared CD4 failure and CD4 trends in patients with viraemia with or without antiretroviral resistance. Retrospective cohort study investigating the association of HIV drug resistance with CD4 failure or CD4 trends in patients on first-line antiretroviral regimens during viraemia. Patients with viraemia (HIV RNA >1000 copies/ml) from two HIV treatment programmes in South Africa (n = 350) were included. We investigated the association of M184V and NNRTI resistance with WHO immunological failure criteria and CD4 count trends, using chi-square tests and linear mixed models. Fewer patients with the M184V mutation reached immunologic failure criteria than those without: 51 of 151(34%) vs. 90 of 199 (45%) (P = 0.03). Similarly, 79 of 220 (36%) patients, who had major NNRTI resistance, had immunological failure, whereas 62 of 130 (48%) without (chi-square P = 0.03) did. The CD4 count decline among patients with the M184V mutation was 2.5 cells/mm(3) /year, whereas in those without M184V it was 14 cells/mm(3) /year (P = 0.1), but the difference in CD4 count decline with and without NNRTI resistance was marginal. Our data suggest that CD4 count monitoring may lead to inappropriate delayed therapy switches for patients with HIV drug resistance. Conversely, patients with viraemia but no drug resistance are more likely to have a CD4 count decline and thus may be more likely to be switched to a second-line regimen. © 2015 John Wiley & Sons Ltd.
Finkler, Fabrine; de Lima, Diane Alves; Cerva, Cristine; Cibulski, Samuel Paulo; Teixeira, Thais Fumaco; Dos Santos, Helton Fernandes; de Almeida, Laura Lopes; Roehe, Paulo Michel; Franco, Ana Cláudia
Chicken parvovirus (ChPV) has been associated with malabsorption syndrome (MAS) in broilers. However, the participation of this virus in such syndrome is unclear, since it may be detected in diseased and healthy chickens. In the course of these studies, it was argued whether ChPV genome loads might be correlated to the occurrence of MAS. To check such a hypothesis, a SYBR green-based quantitative polymerase chain reaction was developed to detect and quantify ChPV genomes. Cloacal swabs from 68 broilers with MAS and 59 from healthy animals were collected from different poultry farms. Genomes of ChPV were detected in all samples, regardless of their health status. However, viral genome loads in MAS-affected broilers were significantly higher (1 × 10 5 genome copies per 100 ng DNA) than in healthy animals (1.3 × 10 3 GC/100 ng DNA). These findings indicate that there is an association between high ChPV genome loads and the occurrence of MAS in broilers.
Volle, Romain; Bailly, Jean-Luc; Mirand, Audrey; Pereira, Bruno; Marque-Juillet, Stéphanie; Chambon, Martine; Regagnon, Christel; Brebion, Amélie; Henquell, Cécile; Peigue-Lafeuille, Hélène; Archimbaud, Christine
Acute enterovirus (EV) meningitis is a major cause of hospitalization among adults and children. It is caused by multiple EV genotypes assigned to 4 species (EV-A, EV-B, EV-C, and EV-D). We determined viral loads in the cerebrospinal fluid (CSF) of 156 patients of all ages with EV meningitis during a 5-year observational prospective study. The virus strains were genotyped, and their time origin was determined with Bayesian phylogenetic methods. The CSF viral loads ranged between 3.4 and 7.5 log10 copies/mL (median, 4.9 log10 copies/mL). They were higher in neonates than in infants and children (P = .02) but were comparable in adults. Viral loads were associated with EV genotypes (P < .001). The EV strains were identified in 152 of 156 patients and assigned to 23 genotypes within the EV-A and EV-B species. The most frequent genotypes, echoviruses 6 and 30, were associated with different viral loads (P < .001). The highest viral loads were in meningitis cases caused by coxsackievirus A9, B4, and B5 genotypes. Most patients infected by a same genotype were infected by a major virus variant of recent emergence. The variations in CSF viral loads in patients at the onset of EV meningitis are related to genotypic differences in the virus strains involved. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: email@example.com.
Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang
To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (Pacute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.
Full Text Available Background and aim: BK virus, a member of human polyomavirus family, is a worldwide distributed virus characterized by a seroprevalence rate of 70-90% in adult population. Monitoring of viral replication is made by evaluation of BK DNA by quantitative polymerase chain reaction. Many different methods can be applied for extraction of nucleic acid from several specimens. The aim of this study was to assess the impact of two different DNA extraction procedure on BK viral load. Materials and methods: DNA extraction procedure including the Nuclisens easyMAG platform (bioMerieux, Marcy l’Etoile, France and manual QIAGEN extraction (QIAGEN Hilden, Germany. BK DNA quantification was performed by Real Time TaqMan PCR using a commercial kit. Result and discussion: The samples capacity, cost and time spent were compared for both systems. In conclusion our results demonstrate that automated nucleic acid extraction method using Nuclisense easyMAG was superior to manual protocol (QIAGEN Blood Mini kit, for the extraction of BK virus from serum and urine specimens.
Mekuria, Legese A; Prins, Jan M; Yalew, Alemayehu W; Sprangers, Mirjam A G; Nieuwkerk, Pythia T
Combination antiretroviral therapy (cART) suppresses viral replication to an undetectable level if a sufficiently high level of adherence is achieved. We investigated which adherence measurement best distinguishes between patients with and without detectable viral load in a public ART programme without routine plasma viral load monitoring. We randomly selected 870 patients who started cART between May 2009 and April 2012 in 10 healthcare facilities in Addis Ababa, Ethiopia. Six hundred and sixty-four (76.3%) patients who were retained in HIV care and were receiving cART for at least 6 months were included and 642 had their plasma HIV-1 RNA concentration measured. Patients' adherence to cART was assessed according to self-report, clinician recorded and pharmacy refill measures. Multivariate logistic regression model was fitted to identify the predictors of detectable viremia. Model accuracy was evaluated by computing the area under the receiver operating characteristic (ROC) curve. A total of 9.2% and 5.5% of the 642 patients had a detectable viral load of ≥40 and ≥400 RNA copies/ml, respectively. In the multivariate analyses, younger age, lower CD4 cell count at cART initiation, being illiterate and widowed, and each of the adherence measures were significantly and independently predictive of having ≥400 RNA copies/ml. The ROC curve showed that these variables altogether had a likelihood of more than 80% to distinguish patients with a plasma viral load of ≥400 RNA copies/ml from those without. Adherence to cART was remarkably high. Self-report, clinician recorded and pharmacy refill non-adherence were all significantly predictive of detectable viremia. The choice for one of these methods to detect non-adherence and predict a detectable viral load can therefore be based on what is most practical in a particular setting. © 2016 John Wiley & Sons Ltd.
Raizes, Elliot; Hader, Shannon; Birx, Deborah
The US President's Emergency Plan for AIDS Relief (PEPFAR) supports aggressive scale-up of antiretroviral therapy (ART) in high-burden countries and across all genders and populations at risk toward global human immunodeficiency virus (HIV) epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a consequence of aggressive ART scale-up and is actively promoting 3 key steps to mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring in all settings; (2) optimization of ART regimens; and (3) routine collection and analysis of HIVDR data to monitor the success of mitigation strategies. The transition to dolutegravir-based regimens in PEPFAR-supported countries and the continuous evolution of HIVDR surveillance strategies are essential elements of PEPFAR implementation. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Diana Pereira Anjos
Full Text Available Kaposi’s sarcoma is considered an acquired immunodeficiency syndrome-defining illness and is caused by human herpesvirus 8. It has been associated with patients infected with human immunodeficiency virus (HIV who have CD4 T lymphocytes <200 cells/uL and high viral loads. We report a case of a 23-year old woman infected with HIV-1 and receiving antiretroviral treatment since diagnosis, with high CD4 cell count and low viral load that presented with disseminated Kaposi’s sarcoma. Clinicians should be aware of the occurrence of Kaposi’s sarcoma despite robust CD4 cell counts.
V. B. Musatov
Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central
Full Text Available Expansion of HIV viral load (VL testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert's random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites. Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS and whole blood, was investigated.Precision, accuracy (agreement and clinical misclassification (1000cp/ml of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155 and Abbott HIV-1 RT (n = 145. Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145 and whole blood (n = 147.Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42 and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32-0.37logcp/ml and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh and Abbott HIV-1 RT (frozen, respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument.The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services.
Kadji, Francois Marie Ngako; Okamoto, Michiko; Furuse, Yuki; Tamaki, Raita; Suzuki, Akira; Lirio, Irene; Dapat, Clyde; Malasao, Rungnapa; Saito, Mariko; Pedrera-Rico, Gay Anne Granada; Tallo, Veronica; Lupisan, Socorro; Saito, Mayuko; Oshitani, Hitoshi
Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.
Kann, Rebecca K C; Seddon, Jennifer M; Kyaw-Tanner, Myat T; Henning, Joerg; Meers, Joanne
Veterinarians have few tools to predict the rate of disease progression in FIV-infected cats. In contrast, in HIV infection, plasma viral RNA load and acute phase protein concentrations are commonly used as predictors of disease progression. This study evaluated these predictors in cats naturally infected with FIV. In older cats (>5 years), log10 FIV RNA load was higher in the terminal stages of disease compared to the asymptomatic stage. There was a significant association between log10 FIV RNA load and both log10 serum amyloid A concentration and age in unwell FIV-infected cats. This study suggests that viral RNA load and serum amyloid A warrant further investigation as predictors of disease status and prognosis in FIV-infected cats. Copyright © 2014 Elsevier Ltd. All rights reserved.
Bertels, Frederic; Marzel, Alex; Leventhal, Gabriel; Mitov, Venelin; Fellay, Jacques; Günthard, Huldrych F; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Battegay, Manuel; Rauch, Andri; Cavassini, Matthias; Calmy, Alexandra; Bernasconi, Enos; Schmid, Patrick; Scherrer, Alexandra U; Müller, Viktor; Bonhoeffer, Sebastian; Kouyos, Roger; Regoes, Roland R
Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as "per-parasite pathogenicity". Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence-measured as the rate of decline of CD4+ T cells-and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5-30%), and that of the per-parasite pathogenicity is 17% (4-29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12-46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Rathore, M. A.; Hussain, A. B.; Ghani, E.
Objective: To determine the End-of-Treatment-Response (ETR) to standard interferon and ribavirin based regimen in patients of chronic hepatitis C and to compare the ETR response in low and high viral load groups. Study Design: Descriptive study. Place and Duration of Study: Virology Department, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from March 2012 to May 2013. Methodology: Patients with chronic hepatitis C virus infection were included in the study. Pre-treatment viral load was determined by RoboGene Quantification kit. Based on viral load, the 400 patients were divided into two equal groups of low viral load (< 800,000 IU/ml) and high viral load (> 800,000 IU/ml). The patients were treated with standard interferon alpha (3 million units subcutaneously thrice weekly) and ribavirin (10.6 mg/kg body weight) for 6 months. ETR was measured using Sacace Biotechnologies Qualitative kit. Chi-square test was used to compare the ETR in the two viral load groups. P-value < 0.05 was considered as significant. Results: Out of 400 patients, 206 (51.5%) were males and 194 (48.5%) were females. Two hundred seventy (67.5%) patients achieved ETR and 130 (35.5%) failed to do so. In low viral load group, 145 (72.5%) patients achieved and 55 (27.5%) patients did not achieve ETR. In high viral load group, 123 (61.5%) patients achieved and 77 (38.5%) did not achieve ETR. The difference in ETR between low and high viral load groups was statistically significant (p=0.019). Conclusion: End-of-treatment-response in patients treated for hepatitis C virus with standard interferon and ribavirin was greater in patients with low viral load as compared to patients with high viral load. (author)
Prach, Lisa M; Puren, Adrian; Lippman, Sheri A; Carmona, Sergio; Stephenson, Sophie; Cutler, Ewalde; Barnhart, Scott; Liegler, Teri
An external quality assurance program was developed for HIV-1 RNA viral load measurements taken from dried blood spots using a reference panel and field-collected specimens. The program demonstrated that accurate and reproducible quantitation can be obtained from field-collected specimens. Residual proviral DNA may confound interpretation in virologically suppressed subjects. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm
AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determ...
Arnaiz, J.A.; Mallolas, J.; Podzamczer, D.; Gerstoft, J.; Lundgren, J.D.; Cahn, P.; Fatkenheuer, G.; D'Arminio-Monforte, A.; Casiro, A.; Reiss, P.; Burger, D.M.; Stek Jr, M.; Gatell, J.M.
OBJECTIVE: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). DESIGN: Multicentre, international,
Arnaiz, Juan A.; Mallolas, Josep; Podzamczer, Daniel; Gerstoft, Jan; Lundgren, Jens D.; Cahn, Pedro; Fätkenheuer, Gerd; D'Arminio-Monforte, Antonella; Casiró, Arnaldo; Reiss, Peter; Burger, David M.; Stek, Michael; Gatell, José M.
Objective: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). Design: Multicentre, international,
Full Text Available Abstract Background There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects. Methods 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load. Results Median age (interquartile range [IQR] of HIV-2 infected subjects at time of enrollment was 47 (36, 60 years, similar to that of HIV-uninfected control subjects, 49 (38, 62 (p = 0.4. Median (IQR plasma viral load and CD4 percentage were 347 (50, 4,300 copies/ml and 29 (22, 35 respectively. Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8% and 16 (10.1% of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI was 4.5 (3.6, 5.8 among HIV-2 infected subjects compared to 2.1 (1.6, 2.9 among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml (IQR did not change significantly over time, being 150 (50, 1,554; n = 77 in 1996, 203 (50, 2,837; n = 47 in 2003 and 171 (50, 497; n = 31 in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia ( Conclusions A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37% at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given
Sanner, Karin; Wikström, Ingrid; Gustavsson, Inger; Wilander, Erik; Lindberg, Julia Hedlund; Gyllensten, Ulf; Olovsson, Matts
Self-sampling for HPV as part of primary screening is a well-tolerated method for women not attending organized Pap smear screening and could increase coverage of cervical cancer screening. To investigate if the prevalence of HR-HPV varies from day to day in infected women and if one single sample is reliable for detecting an ongoing infection. This is a prospective cohort study on 12 premenopausal and 13 postmenopausal women performing daily self-sampling for HR-HPV testing. They were all HR-HPV-positive 1-3 months ago. Postmenopausal women were sampled for 28 days and premenopausal women sampled during bleeding-free days in one menstrual cycle. A possible difference in viral load between the estrogen-dominated proliferative phase and the progesterone-dominated secretory phase was analyzed. Consistent results throughout the sampling period were observed for 19 women, with either a daily presence of HPV (14 women) or no HPV at all during the sampling period (5 women). Of 607 samples from 25 women, 596 were consistently positive or negative for HPV during the sampling period and 11 were inconsistent (2%). There was no difference in HPV copy number between the estrogen dominated proliferative or progesterone dominated secretory menstrual cycle phases. The major finding was a high degree of consistency concerning HR-HPV positivity and negativity of HR-HPV in vaginal fluid during a sustained period of daily self-sampling. It does not appear to matter whether the sample is collected in the proliferative or secretory phase. Copyright © 2015 Elsevier B.V. All rights reserved.
Jennings, Jacky M.; Schumacher, Christina; Perin, Jamie; Myers, Tanya; Fields, Nathan; Greiner Safi, Amelia; Chaulk, Patrick
Background Eliminating HIV transmission in a population necessitates identifying population reservoirs of HIV infection and subgroups most likely to transmit. HIV viral load is the single most important predictor of HIV transmission. The objective of this analysis was to evaluate whether a public health practice pilot project based on community viral load resulted in increases in the proportion of time spent testing in high viral load areas (process measure) and 3 outcome measures—the number and percent of overall HIV diagnoses, new diagnoses, and high viral load positives—in one mid-Atlantic US city with a severe HIV epidemic. Methods The evaluation was conducted during three, 3-month periods for 3 years and included the use of community viral load, global positioning system tracking data, and statistical testing to evaluate the effectiveness of the pilot project. Results The proportion of time spent outreach testing in high viral load areas (69%–84%, P the overall number and percent of HIV positives ((60 (3%) to 127 (6%), P The number and percent of new diagnoses (3 (0.1%) to 6 (0.2%)) and high viral load positives (5 (0.2%) to 9 (0.4%)) increased, but the numbers were too small for statistical testing. Discussion These results suggest that using community viral load to increase the efficiency of HIV outreach testing is feasible and may be effective in identifying more HIV positives. The pilot project provides a model for other public health practice demonstration projects. PMID:29420450
Cao, Pengfei; Zhang, Meili; Wang, Wei; Dai, Yafei; Sai, Buqing; Sun, Jun; Wang, Lujuan; Wang, Fan; Li, Guiyuan; Xiang, Juanjuan
DNA detected using real-time PCR was observed in 89.5% of these IM patients. The EBV genome was detected by the FISH assay in 97.4% of the IM patients. The EB viral loads detected by FISH and real-time PCR increased with the severity of IM. The EBV genome was detected in almost all the PBMC of IM with haemophagocytic lymphohistiocytosis and chronic active EBV infection patients. Molecular tests, including FISH and EBV real-time PCR, are more sensitive than serological assays for the detection of EBV infection. The FISH assay detecting EBV copies in unfractionated whole blood is preferable and superior to plasma real-time PCR in its reflection of the absolute viral burden circulating in the patients.
DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Hilbig, Lydia; Sapp, Martin
The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels. - Highlights: • mNLS mutant HPV16 L2 protein traffics pseudogenome to the TGN but fails to egress. • Cyclophilin activity is required for trafficking of the L2/DNA complex to the TGN. • Majority of L1 protein is shed from the L2/DNA complex prior to reaching the TGN
DiGiuseppe, Stephen; Bienkowska-Haba, Malgorzata; Hilbig, Lydia; Sapp, Martin, E-mail: firstname.lastname@example.org
The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels. - Highlights: • mNLS mutant HPV16 L2 protein traffics pseudogenome to the TGN but fails to egress. • Cyclophilin activity is required for trafficking of the L2/DNA complex to the TGN. • Majority of L1 protein is shed from the L2/DNA complex prior to reaching the TGN.
Carrillo, Carolina; Suñé, Josep Maria; Pérez-Lozano, Pilar; García-Montoya, Encarna; Sarrate, Rocío; Fàbregas, Anna; Miñarro, Montserrat; Ticó, Josep Ramon
Chitosan has been studied for use in particle delivery systems for therapeutic purposes, since one of its most important applications is as a non-viral vector in gene therapy. Due to its positive charge, it is capable of forming DNA complexes (polyplexes) obtained through several methods and with the property of protecting nucleic acids. Two methods for obtaining the nanoparticles of chitosan-nucleic acids are reported in this study: simple complexation (of depolymerized chitosan or of different chitosan salts with plasmid) and ionic gelation (by adsorption of plasmid in the nanoparticles or by encapsulation of plasmid into nanoparticles). The determination of the loading efficiency of chitosan nanoparticles with the plasmid is carried out by electrophoretic mobility of the samples on agarose gel. Furthermore, the nanoparticles have been characterized according to their morphology, size and surface charge using AFM, TEM, laser diffraction and dynamic light scattering techniques. The polyplexes obtained have been found to be spherical and nanometric in size (between 100-230nm) with a zeta potential between 37 and 48mV. Positive results have been obtained by agarose gel electrophoresis for all studied cases: a concentration of between 20 and 30μg/mL of chitosan salts is required while for the remaining chitosan samples studied, 100% loading efficiency does not occur until a concentration equal to 100μg/mL (regardless of previous depolymerisation and the method performed). Chitosan-plasmid nanocapsules have been obtained at the polymer concentrations worked with (between 0.025 and 0.2%). Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Dolezal, Adam G.; Hendrix, Stephen D.; Scavo, Nicole A.; Carrillo-Tripp, Jimena; Harris, Mary A.; Wheelock, M. Joseph; O’Neal, Matthew E.; Toth, Amy L.
Evidence of inter-species pathogen transmission from managed to wild bees has sparked concern that emerging diseases could be causing or exacerbating wild bee declines. While some pathogens, like RNA viruses, have been found in pollen and wild bees, the threat these viruses pose to wild bees is largely unknown. Here, we tested 169 bees, representing 4 families and 8 genera, for five common honey bee (Apis mellifera) viruses, finding that more than 80% of wild bees harbored at least one virus. We also quantified virus titers in these bees, providing, for the first time, an assessment of viral load in a broad spectrum of wild bees. Although virus detection was very common, virus levels in the wild bees were minimal—similar to or lower than foraging honey bees and substantially lower than honey bees collected from hives. Furthermore, when we experimentally inoculated adults of two different bee species (Megachile rotundata and Colletes inaequalis) with a mixture of common viruses that is lethal to honey bees, we saw no effect on short term survival. Overall, we found that honey bee RNA viruses can be commonly detected at low levels in many wild bee species, but we found no evidence that these pathogens cause elevated short-term mortality effects. However, more work on these viruses is greatly needed to assess effects on additional bee species and life stages. PMID:27832169
Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon
Background and Aims Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). Methods We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. Results In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, Phepatitis A. PMID:26090677
Lee, Hyun Woong; Chang, Dong-Yeop; Moon, Hong Ju; Chang, Hye Young; Shin, Eui-Cheol; Lee, June Sung; Kim, Kyung-Ah; Kim, Hyung Joon
Clinical manifestations of hepatitis A virus (HAV) infection vary from mild to fulminant hepatic failure (FHF) in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA) and evaluated predictive factors for severe acute hepatitis (s-AH). We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT) of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128). Other patients were defined as mild acute hepatitis (m-AH) (n = 642). Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer. In a multivariate analysis, age (HR = 1.042, P = 0.041), peak creatinine (HR = 4.014, P = 0.001), bilirubin (HR = 1.153, P = 0.003), alanine aminotransferase (ALT) (HR = 1.001, P hepatitis A.
Nash, Madlen; Huddart, Sophie; Badar, Sayema; Baliga, Shrikala; Saravu, Kavitha; Pai, Madhukar
Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation ( n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation ( n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics ( n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed. Copyright © 2018 Nash et al.
Full Text Available The aim of the study was to determine the hepatropic viruses load on the natural sources of wastewater use of the industrial region. Methods. We investigated open water samples from places of water intake, which is later purified and used in consumer’s drinking purposes; river water samples in resting places and samples of sewage from discharge to the environment places. We used EUSA method using sets of reagents for the detection of antigen of hepatitis A virus (HAV HAV-antigen ELISA-Best (Russia, devices for the automatic washing of microplates and automatic record of the results using the immunoassay analyzer StatFax303 (Awareness Technology Inc., USA. Results. During 2000–2015 three peaks of the indication of HAV antigens’ rise in river water and sewage samples were noted. In 2002–2003 in average 34.4 and 32.3 % of the sewage and river water samples were positive, in 2008 26.7 and 27.1 %, respectively. The third peak of HAV antigen detection in open water was observed in 2012, only 17.8 %. Wastewater has been losing viral antigens since 2008, in fact to 0 % in 2013–2014. Conclusions. Aquatic ecosystem pollution by biological components occurs despite of primary treatment of wastewater. Drinking water contamination, which is used in everyday life, probably can be linked to an unsatisfactory condition of pipelines and laying of sewage supply.
Dolezal, Adam G; Hendrix, Stephen D; Scavo, Nicole A; Carrillo-Tripp, Jimena; Harris, Mary A; Wheelock, M Joseph; O'Neal, Matthew E; Toth, Amy L
Evidence of inter-species pathogen transmission from managed to wild bees has sparked concern that emerging diseases could be causing or exacerbating wild bee declines. While some pathogens, like RNA viruses, have been found in pollen and wild bees, the threat these viruses pose to wild bees is largely unknown. Here, we tested 169 bees, representing 4 families and 8 genera, for five common honey bee (Apis mellifera) viruses, finding that more than 80% of wild bees harbored at least one virus. We also quantified virus titers in these bees, providing, for the first time, an assessment of viral load in a broad spectrum of wild bees. Although virus detection was very common, virus levels in the wild bees were minimal-similar to or lower than foraging honey bees and substantially lower than honey bees collected from hives. Furthermore, when we experimentally inoculated adults of two different bee species (Megachile rotundata and Colletes inaequalis) with a mixture of common viruses that is lethal to honey bees, we saw no effect on short term survival. Overall, we found that honey bee RNA viruses can be commonly detected at low levels in many wild bee species, but we found no evidence that these pathogens cause elevated short-term mortality effects. However, more work on these viruses is greatly needed to assess effects on additional bee species and life stages.
Attonito, Jennifer; Dévieux, Jessy G; Lerner, Brenda D G; Hospital, Michelle M; Rosenberg, Rhonda
Psychosocial factors may directly impact HIV health measures such as viral load (VL) whether or not patients are taking antiretroviral treatment (ART) consistently. Structural equation modeling plus Baron and Kenny's (1986) four-step approach were used to test a mediated model predicting VL among 246 HIV-infected adults who were on ART. Exogenous variables were social support, barriers to adherence, and stress. Moderators were alcohol use, marijuana use, and neurocognitive impairment. A small positive association between marijuana use and ART adherence approached significance. Only barriers to adherence predicted a decrease in adherence rates and an increase in VL. No other factors were significantly associated with either VL or adherence, and no interaction effects between exogenous variables and moderators were identified. The association between barriers to adherence and VL was partially mediated by ART adherence. Findings provide modest support for a direct link between psychosocial variables and a virologic response to ART. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.
Correa, C; Kourí, V; Pérez, L; Soto, Y; Limia, C
Cytomegalovirus (CMV) is the leading cause of viral congenital infection. Some viral factors have been proposed to be CMV pathogenicity markers. The objective of this study was to investigate the frequency of congenital CMV infection in symptomatic patients and the possible association with the CMV glycoprotein B (gB) genotype and viral load. A total of 361 newborns (NB) and 158 pregnant women (PW) with clinically suspected CMV infection were enrolled. Studied samples included urine, saliva, serum, vaginal swabs and amniotic fluid. CMV infection was diagnosed by multiplex nested PCR. CMV gB genotyping was performed on infected samples, followed by viral load determination. Overall, 18.7% of the tested patients were positive for CMV infection, 19.7% of NB were congenitally infected and 16.5% of PW showed active CMV infection. gB-2 was the most prevalent genotype detected (39/97 patients). gB CMV mixed infections were detected in 12 patients. gB-2 was associated with mono-infections (PCMV load was statistically significant among patients presenting different clinical signs (P=0.04). This study showed that CMV is a frequent cause of congenital infection in symptomatic Cuban patients. Despite gB2 being the most frequently detected, gB-4 was the only genotype associated with clinical features (sepsis-like syndrome in NB). No other associations among specific genotypes and clinical characteristics were found. Further studies are needed to clarify the role that viral load and genotype play in the outcome of congenital infection.
Mirabello, Lisa; Clarke, Megan A; Nelson, Chase W; Dean, Michael; Wentzensen, Nicolas; Yeager, Meredith; Cullen, Michael; Boland, Joseph F; Schiffman, Mark; Burk, Robert D
Of the ~60 human papillomavirus (HPV) genotypes that infect the cervicovaginal epithelium, only 12-13 "high-risk" types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral-host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.
... Videos for Educators Search English Español Genital Warts (HPV) KidsHealth / For Teens / Genital Warts (HPV) What's in ... HPV infection. How Do People Know They Have HPV? Most HPV infections have no signs or symptoms. ...
Pártlová, S.; Bouček, Jan; Kloudová, K.; Lukešová, E.; Zábrodský, M.; Grega, M.; Fučíková, J.; Truxová, I.; Tachezy, R.; Spíšek, R.; Fialová, A.
Roč. 4, č. 1 (2015), e965570 ISSN 2162-402X R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA MZd(CZ) NT11542 Institutional support: RVO:61388971 Keywords : CD8(+) T lymphocytes * HNSCC * HPV Subject RIV: EC - Immunology Impact factor: 7.644, year: 2015
Luciana Cristina Fagundes Gequelin
Full Text Available The Epstein-Barr virus is responsible for infectious mononucleosis syndrome and is also closely associated to several types of cancer. The main complication involving Epstein-Barr virus infection, both in recipients of hematopoietic stem cells and solid organs, is post-transplant lymphoproliferative disease. The importance of this disease has increased interest in the development of laboratory tools to improve post-transplant monitoring and to detect the disease before clinical evolution. Viral load analysis for Epstein-Barr virus through real-time polymerase chain reaction is, at present, the best tool to measure viral load. However, there is not a consensus on which sample type is the best for the test and what is its predictive value for therapeutic interventions.
Full Text Available The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103. The most common oromucosal lesion was erythematous candidiasis (EC (38.8% followed by melanotic hyperpigmentation (35.9%. Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio 20,000 copies/mL (20,000 copies/mL.
A membrane bioreactor (MBR)-based wastewater treatment plant in Saudi Arabia was assessed over a nine-month period for virus removal efficiency. Viral diversity was detected using omics-based approaches. Log reduction values (LRV) of Adenoviruses (AdV) and Enteroviruses (EV) were enumerated using digital polymerase chain reaction (dPCR) and assessed for infectivity using fluorescence-based infection assays. MBR treatment was successful in reducing viral diversity. Plant viruses remained abundant in the treated effluent. Human enteric viruses were present in lower abundance than plant viruses, and were reduced by MBR at varying LRV. AdV copy numbers were reduced by 3.7-log. Infectious AdV was not detected in the effluent. EV copy numbers were reduced by 1.7-log post MBR and infectious EV decreased by an average of 2.0-log. Infectious EV was detected in the chlorinated effluent, occasionally in concentrations that approximate to its 50% infectious dose. Overall, results indicated that a MBR-based wastewater treatment plant (WWTP) effectively reduces viral diversity, viral load, and infectious capacity by up to 4-logs. These findings suggest potential concerns associated with plant and human enteric viruses for reuse events in this country. Local guidelines for assessment of treated water quality should take into consideration both infectious viral concentration and LRV.
Sarah E Rutstein
Full Text Available To evaluate the feasibility and effectiveness of dried blood spots (DBS use for viral load (VL monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa.We recruited adult antiretroviral therapy (ART patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt and effectiveness (second-line therapy initiation.We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8% of participants with elevated baseline VL had suppressed (4 years were more likely to be failing than participants on therapy 1-4 years (RR 1.7, 95% CI 1.0-2.8; older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98. There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11.DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy.
Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien
Abstract The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS. Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined. A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was 25% of the specimens differed by >0.5 log cps/mL. All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1). The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens. PMID:27902602
Stanton, Jeffrey J.; Zong, Jian-Chao; Eng, Crystal; Howard, Lauren; Flanagan, Joe; Stevens, Martina; Schmitt, Dennis; Wiedner, Ellen; Graham, Danielle; Junge, Randall E.; Weber, Martha A.; Fischer, Martha; Mejia, Alicia; Tan, Jie; Latimer, Erin; Herron, Alan; Hayward, Gary S.; Ling, Paul D.
Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elephas maximus); however, sporadic shedding of virus in trunk washes collected from healthy elephants also has been detected. Data regarding the relationship of viral loads in blood compared with trunk washes are lacking, and questions about whether elephants can undergo multiple infections with EEHVs have not been addressed previously. Real-time quantitative polymerase chain reaction was used to determine the kinetics of EEHV1 loads, and genotypic analysis was performed on EEHV1 DNA detected in various fluid samples obtained from five Asian elephants that survived detectable EEHV1 DNAemia on at least two separate occasions. In three elephants displaying clinical signs of illness, preclinical EEHV1 DNAemia was detectable, and peak whole-blood viral loads occurred 3–8 days after the onset of clinical signs. In two elephants with EEHV1 DNAemia that persisted for 7–21 days, no clinical signs of illness were observed. Detection of EEHV1 DNA in trunk washes peaked approximately 21 days after DNAemia, and viral genotypes detected during DNAemia matched those detected in subsequent trunk washes from the same elephant. In each of the five elephants, two distinct EEHV1 genotypes were identified in whole blood and trunk washes at different time points. In each case, these genotypes represented both an EEHV1A and an EEHV1B subtype. These data suggest that knowledge of viral loads could be useful for the management of elephants before or during clinical illness. Furthermore, sequential infection with both EEHV1 subtypes occurs in Asian elephants, suggesting that they do not elicit cross-protective sterilizing immunity. These data will be useful to individuals involved in the husbandry and clinical care of Asian elephants. PMID:23505702
Karlsson, Ulf; Antonsson, Liselotte; Ljungberg, Bengt; Medstrand, Patrik; Esbjörnsson, Joakim; Jansson, Marianne; Gisslen, Magnus
To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4 T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1). All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4 T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4 T-cell counts. The use of other alternative coreceptors was less pronounced. Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4 T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS.
Marysabel Pinto Telis Silveira
Full Text Available Factors associated with undetectable viral load ( or = 95% of adherence (CI 95% 1,80-13,28; CI 95% 1,73-9,53, compared with less than 60% adherence; it was greater for less than 6 months in treatment (OR = 3.37; CI 95% 1.09-10.46; and smaller for viral load previous to adherence measurement > or = 5.2 log10 (OR = 0.19; CI95% 0.06-0.58, adjusted for these variables and sex, age, clinical status, current immune status, group of drugs and interval between the two measurements of viral load. The crude odds were lower for age 16-24 years and use of Nucleoside Analog Reverse Transcriptase Inhibitors only, but these effects were not significant in the multivariate model. There was no evidence of effect of sex, clinical status, current immune status, and changes in treatment regimen. Treatment adherence gave the largest effect. Motivational interventions directed at adherence may improve treatment effectiveness.
Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.
Aziz, N; Sokoloff, A; Kornak, J; Leva, N V; Mendiola, M L; Levison, J; Feakins, C; Shannon, M; Cohan, D
To compare time to achieve viral load HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). Retrospective cohort study. Three university medical centers, USA. HIV-infected pregnant women initiated or restarted on HAART during pregnancy. We calculated time to viral load HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. Time to HIV viral load HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load HIV log10 viral load was associated with a later time of achieving viral load HIV log10 viral load was associated with a longer time of achieving viral load Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.
Leroux-Kozal, Valérie; Lévêque, Nicolas; Brodard, Véronique; Lesage, Candice; Dudez, Oriane; Makeieff, Marc; Kanagaratnam, Lukshe; Diebold, Marie-Danièle
Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis. Copyright © 2015 Elsevier Inc. All rights reserved.
Paul D Griffiths
Full Text Available To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml of whole blood.Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A. A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml or less than 3000 genomes/ml were obtained (Part B. For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml.In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56% in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37% in the immediate treatment arm (p = 0.193. However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022. In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35% in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45% among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322. However, the duration of antiviral treatment was significantly shorter (p = 0.0012 in those randomized to stop treatment when viraemia was less than 3000 genomes/ml.The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy.
Neogi, Ujjwal; Gupta, Soham; Rodridges, Rashmi; Sahoo, Pravat Nalini; Rao, Shwetha D.; Rewari, Bharat B.; Shastri, Suresh; De Costa, Ayesha; Shet, Anita
Background & objectives: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. Methods: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. Results: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (−0.21 to +0.8 log10 copies/ml). The mean difference was 0.29 log10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting Interpretation & conclusions: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally. PMID:23391790
The synergistic transactivation of the hepatitis B viral (HBV) pregenomic promoter by the E6 protein of human papillomavirus type 16 (HPV-16 E6) with HBV X protein was mediated through the AP1 site of E element in the enhancer I (EnI) in human liver cell.
Lee, D H; Choi, B H; Rho, H M
Infection by HBV of a cell already infected with other viral species or vice versa has been suggested as being involved in hepatocellular carcinoma. Using the CAT assay method, we investigated the interactive roles of HBx and potentially oncogenic and transactivating viral early proteins such as Ad5 E1A, HPV-16 E6, and SV40 T ag. In the presence of HBx, only HPV-16 E6 showed significant synergistic transactivation of EnI. We further investigated the function of the HPV-16 E6 using deletion, heterologous promoter, and mutation analyses on the EnI promoter. The results showed that the synergistic effect was mediated through the AP1 site of the E element in EnI by the direct activation of AP1 and support the idea that the infection by HBV of the cell with other viral species such as HPV-16 could increase the transcription activity of the HBV and other oncogenes containing an AP1 site in the promoter. Copyright 1999 Academic Press.
Kurth, Ann E; Spielberg, Freya; Cleland, Charles M; Lambdin, Barrot; Bangsberg, David R; Frick, Pamela A; Severynen, Anneleen O; Clausen, Marc; Norman, Robert G; Lockhart, David; Simoni, Jane M; Holmes, King K
Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Longitudinal randomized controlled trial. An academic HIV clinic and a community-based organization in Seattle. In a total of 240 HIV-positive adults on ART, 209 completed 9-month follow-up (87% retention). Randomization to computerized counseling or assessment only, 4 sessions over 9 months. HIV-1 viral suppression, and self-reported ART adherence and transmission risks, compared using generalized estimating equations. Overall, intervention participants had reduced viral load: mean 0.17 log10 decline, versus 0.13 increase in controls, P = 0.053, and significant difference in ART adherence baseline to 9 months (P = 0.046). Their sexual transmission risk behaviors decreased (odds ratio = 0.55, P = 0.020), a reduction not seen among controls (odds ratio = 1.1, P = 0.664), and a significant difference in change (P = 0.040). Intervention effect was driven by those most in need; among those with detectable virus at baseline (>30 copies/mL, n = 89), intervention effect was mean 0.60 log10 viral load decline versus 0.15 increase in controls, P = 0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, P = 0.038. Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior.
Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...
Sigaloff, Kim C E; Hamers, Raph L; Wallis, Carole L; Kityo, Cissy; Siwale, Margaret; Ive, Prudence; Botes, Mariette E; Mandaliya, Kishor; Wellington, Maureen; Osibogun, Akin; Stevens, Wendy S; van Vugt, Michèle; de Wit, Tobias F Rinke
This study aimed to investigate the consequences of using clinicoimmunological criteria to detect antiretroviral treatment (ART) failure and guide regimen switches in HIV-infected adults in sub-Saharan Africa. Frequencies of unnecessary switches, patterns of HIV drug resistance, and risk factors for the accumulation of nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were evaluated. Cross-sectional analysis of adults switching ART regimens at 13 clinical sites in 6 African countries was performed. Two types of failure identification were compared: diagnosis of clinicoimmunological failure without viral load testing (CIF only) or CIF with local targeted viral load testing (targeted VL). After study enrollment, reference HIV RNA and genotype were determined retrospectively. Logistic regression assessed factors associated with multiple thymidine analogue mutations (TAMs) and NRTI cross-resistance (≥2 TAMs or Q151M or K65R/K70E). Of 250 patients with CIF switching to second-line ART, targeted VL was performed in 186. Unnecessary switch at reference HIV RNA <1000 copies per milliliter occurred in 46.9% of CIF only patients versus 12.4% of patients with targeted VL (P < 0.001). NRTI cross-resistance was observed in 48.0% of 183 specimens available for genotypic analysis, comprising ≥2 TAMs (37.7%), K65R (7.1%), K70E (3.3%), or Q151M (3.3%). The presence of NRTI cross-resistance was associated with the duration of ART exposure and zidovudine use. Clinicoimmunological monitoring without viral load testing resulted in frequent unnecessary regimen switches. Prolonged treatment failure was indicated by extensive NRTI cross-resistance. Access to virological monitoring should be expanded to prevent inappropriate switches, enable early failure detection and preserve second-line treatment options in Africa.
Castle, Philip E; Schiffman, Mark; Wheeler, Cosette M
The purpose of this study was to determine the clinical value of a semiquantitative measure of human papillomavirus viral load by the hybrid capture 2 assay for stratification of the risk of histologic cervical intraepithelial neoplasia grade 3 or carcinoma. The Atypical Cells of Unknown Significance and Low-Grade Squamous Intraepithelial Lesions Triage Study was a randomized clinical trial of 5060 women with 2 years of follow-up to evaluate treatment strategies for women with equivocal or mildly abnormal cervical cytologic condition. The usefulness of the continuous hybrid capture 2 output relative light units/positive controls that were above the positive threshold (1.0 relative light units/positive controls), which was a surrogate for human papillomavirus viral load, for distinguishing between hybrid capture 2 positive women who were diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma during the study from those who were not diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma was examined with the use of receiver-operator characteristic analyses. Relative light units/positive controls values did not further discriminate between hybrid capture 2 positive women with cervical intraepithelial neoplasia grade 3 or carcinoma from those with less than cervical intraepithelial neoplasia grade 3 or carcinoma. The use of a cervical intraepithelial neoplasia grade 2 or more severe or carcinoma case definition did not alter our findings. Among women with atypical cells of unknown significance or low-grade squamous intraepithelial lesion cervical cytologic findings, the hybrid capture 2 viral load measurement did not improve the detection of 2-year cumulative cases of cervical intraepithelial neoplasia grade 3 or carcinoma significantly.
Farquhar, Carey; Nduati, Ruth; Haigwood, Nancy; Sutton, William; Mbori-Ngacha, Dorothy; Richardson, Barbra; John-Stewart, Grace
Background Studies among HIV-1–infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. Methods To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1–infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1–specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. Results Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks’ gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1–specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). Conclusions This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1–exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1–exposed infants. PMID:16280707
Guido van Marle
Full Text Available Human immunodeficiency virus type 1 (HIV-1 infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS. The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM enrolled pre-HAART (Highly Active Antiretroviral Therapy. We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum and somatostatin (duodenum and colon immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.
Mealey, Robert H.; Zhang Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.
Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined
Makadzange, A Tariro; Boyd, F Kathryn; Chimukangara, Benjamin; Masimirembwa, Collen; Katzenstein, David; Ndhlovu, Chiratidzo E
Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system. Copyright © 2017 Makadzange et al.
Ciccocioppo, Rachele; Racca, Francesca; Paolucci, Stefania; Campanini, Giulia; Pozzi, Lodovica; Betti, Elena; Riboni, Roberta; Vanoli, Alessandro; Baldanti, Fausto; Corazza, Gino Roberto
To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.
Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.
Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.
Yan, Xiao-Li; Li, Yu-Ning; Tang, Yi-Jie; Xie, Zhi-Ping; Gao, Han-Chun; Yang, Xue-Mei; Li, Yu-Mei; Liu, Li-Jun; Duan, Zhao-Jun
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Chemaly, Roy F; Yen-Lieberman, Belinda; Castilla, Elias A; Reilly, Amy; Arrigain, Susana; Farver, Carol; Avery, Robin K; Gordon, Steven M; Procop, Gary W
Cytomegalovirus (CMV) is an important pathogen in lung transplant recipients. Early detection of CMV end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.
Claudia Patricia Consuegra Mayor
Full Text Available Una de las patologías más frecuentes con la que el hombre ha tenido que luchar en las últimas décadas es el cáncer. Los países industrializados y aun aquellos en vía de desarrollo se han dado a la tarea de combatir el cáncer, han hecho grandes esfuerzos e invertido cantidades de dinero con el propósito de conocer el origen y seguimiento de esta enfermedad y buscar alternativas que ayuden a erradicarla o a limitarla. Son impresionantes los datos recientes respecto al origen del cáncer a nivel molecular y se conocen con más precisión los procesos de progresión, invasión y metástasis tumoral (1. Todos estos experimentos han podido dilucidar algunos factores potenciadores o estimuladores para la aparición de esta enfermedad. El cáncer de cuello uterino es el segundo cáncer más común en la mujer después del cáncer de mama, y existe un desproporcionado aumento del cáncer cervical en mujeres jóvenes (2. Como el cáncer de cuello uterino se desarrolla en mujeres más jóvenes que el de mama, es una de las neoplasias malignas más devastadoras y es el principal cáncer genital femenino en los países en desarrollo (3,4. En Colombia es la segunda causa de mortalidad femenina (5. Desde hace más de 100 años se ha considerado que el cáncer cervical tiene una causa infecciosa (1. Posteriormente se demostró que los virus del papiloma humano (HPV, por su sigla en inglés human papillomavirus contribuyen directamente en la carcinogénesis. Es de anotar que el HPV es causa necesaria para el desarrollo del cáncer de cérvix, pero no es suficiente, ya que otros factores están involucrados en la progresión de infección a cáncer (6
Full Text Available Human Papillomavirus type 16 (HPV16 causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs determine oncogenicity.A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica.HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5±1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution.Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable resource for future studies of HPV16
KURTH, Ann E.; SPIELBERG, Freya; CLELAND, Charles M.; LAMBDIN, Barrot; BANGSBERG, David R.; FRICK, Pamela A.; SEVERYNEN, Anneleen O.; CLAUSEN, Marc; NORMAN, Robert G.; LOCKHART, David; SIMONI, Jane M.; HOLMES, King K.
Objective Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Design Longitudinal RCT. Settings An academic HIV clinic and a community-based organization in Seattle. Subjects 240 HIV-positive adults on ART; 209 completed nine-month follow-up (87% retention). Intervention Randomization to computerized counseling or assessment-only, 4 sessions over 9 months. Main Outcome Measures HIV-1 viral suppression, and self-reported ART adherence, and transmission risks, compared using generalized estimating equations. Results Overall, intervention participants had reduced viral load (VL): mean 0.17 log10 decline, versus 0.13 increase in controls, p = 0.053, and significant difference in ART adherence baseline to 9 months (p = 0.046). Their sexual transmission risk behaviors decreased (OR = 0.55, p = 0.020), a reduction not seen among controls (OR = 1.1, p = 0.664), and a significant difference in change (p = 0.040). Intervention effect was driven by those most in need: among those with detectable virus at baseline (>30 copies/milliliter, n=89), intervention effect was mean 0.60 log10 VL decline versus 0.15 increase in controls, p=0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, p = 0.038. Conclusions Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior. PMID:24384803
Stenmark, Matthew H., E-mail: email@example.com [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); McHugh, Jonathan B. [Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Walline, Heather M.; Komarck, Christine [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Worden, Francis P. [Department of Medical Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Mukherji, Suresh K. [Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Carey, Thomas E. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States)
Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.
Stenmark, Matthew H.; McHugh, Jonathan B.; Schipper, Matthew; Walline, Heather M.; Komarck, Christine; Feng, Felix Y.; Worden, Francis P.; Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R.; Mukherji, Suresh K.; Eisbruch, Avraham; Carey, Thomas E.
Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings
Kim, John E; Beckthold, Brenda; Chen, Zhaoxia; Mihowich, Jennifer; Malloch, Laurie; Gill, Michael John
The presence of HIV-1 non-B subtypes is increasing worldwide. This poses challenges to commercial diagnostic and viral load (RNA) monitoring tests that are predominantly based on HIV-1 subtype B strains. Based on phylogenetic analysis of the gag, pol, and env gene regions, we describe the first HIV-1 H/J recombinant in Canada that presented divergent viral load values. DNA sequence analysis of the gag gene region further revealed that genetic diversity between this H/J recombinant and the primers and probes used in the bio-Merieux Nuclisens HIV-1 QT (Nuclisens) and Roche Amplicor Monitor HIV-1, v1.5 (Monitor) viral RNA assays can erroneously lead to undetectable viral load values. This observation appears to be more problematic in the Nuclisens assay. In light of increasing genetic diversity in HIV worldwide we recommend that DNA sequencing of HIV, especially in the gag gene region targeted by primers and probes used in molecular diagnostic and viral load tests, be incorporated into clinical monitoring practices.
Nguyen, Quyen Le Thi; Nguyen, Long Hoang; Tran, Bach Xuan; Phan, Huong Thi Thu; Le, Huong Thi; Nguyen, Hinh Duc; Tran, Tho Dinh; Do, Cuong Duy; Nguyen, Cuong Manh; Thuc, Vu Thi Minh; Latkin, Carl; Zhang, Melvyn W B; Ho, Roger C M
Viral load testing is considered the gold standard for monitoring HIV treatment; however, given its high cost, some patients cannot afford viral load testing if this testing is not subsidized. Since foreign aid for HIV/AIDS in Vietnam is rapidly decreasing, we sought to assess willingness to pay (WTP) for viral load and CD4 cell count tests among HIV-positive patients, and identified factors that might inform future co-payment schemes. A multi-site cross-sectional survey was conducted with 1133 HIV-positive patients on antiretroviral therapy (ART) in Hanoi and Nam Dinh. Patients' health insurance coverage, quality of life, and history of illicit drug use were assessed. A contingent valuation approach was employed to measure patients' WTP for CD4 cell count and viral load testing. HIV-positive patients receiving ART at provincial sites reported more difficulty obtaining health insurance (HI) and had the overall the poorest quality of life. Most patients (90.9%) were willing to pay for CD4 cell count testing; here, the mean WTP was valued at US$8.2 (95%CI = 7.6-8.8 US$) per test. Most patients (87.3%) were also willing to pay for viral load testing; here, mean WTP was valued at US$18.6 (95%CI = 16.3-20.9 US$) per test. High income, high education level, and hospitalization were positively associated with WTP, while co-morbidity with psychiatric symptoms and trouble paying for health insurance were both negatively related to WTP. These findings raise concerns that HIV-positive patients in Vietnam might have low WTP for CD4 cell count and viral load testing. This means that without foreign financial subsidies, many of these patients would likely go without these important tests. Treating psychiatric co-morbidities, promoting healthcare services utilization, and removing barriers to accessing health insurance may increase WTP for monitoring of HIV/AIDS treatment among HIV+-positive Vietnamese patients.
Daniel O. Griffin
Full Text Available Despite much focus on moving toward a cure to end the epidemic human immunodeficiency virus (HIV epidemic there are still thousands of new infections occurring every year in the United States. Although there is ongoing transmission of HIV in the United States and a growing population of people living with HIV, the acute presentation of HIV infection can be challenging to diagnose and is often not considered when patients present to healthcare providers. Although in certain states there are HIV testing laws that require that all persons between the ages of 13 and 64 be offered HIV testing in an opt-out approach, many patient presenting with an acute illness, that would warrant diagnostic testing for HIV, leave without having an HIV test performed for either diagnostic or screening purposes.We describe the case of a woman who presented to medical attention with symptoms later confirmed to be due to acute HIV infection. She was initially discharged from the hospital and only underwent HIV testing with confirmation of her diagnosis after readmission. We describe the algorithm where fourth generation testing combined with HIV viral load testing allowed for the diagnosis of acute HIV prior to the development of a specific immunoglobulin response. Consideration of this diagnosis, improved HIV screening, and understanding of the use of antigen/antibody screening tests, combined with Multispot and HIV viral RNA detection, when appropriate, can allow for early diagnosis of HIV before progression of disease and before undiagnosed patient spread the infection to new contacts.
T. A. Daminov
Full Text Available This article presents the analysis of indicators of CD4 lymphocyte count and viral load in the natural history (in the absence of ART in perinatally HIV-infected children. It was revealed that perinatal way of transmission is characterized by a higher rate of immunodeficiency progression. It may be associated with intrauterine infection, as well as an early defeat HIV immature immune system of the child. The concentration of virus in perinatally infected children since the beginning of the observation and in 30 months after infection is more than in parenterally infected children in 5 and 2 times, respectively, which determines a infavourable version of the disease in perinatally infected children.
Praveen Kumar Balne
Full Text Available The data presented in this article shows the longitudinal analysis of tear fluid cytokine profiles, blood CD4 and CD8 counts and HIV viral load in 34 dry eye patients with HIV infection during the HAART therapy. Clinical samples were collected from HIV patients with dry eye disease at the time of presentation to the clinic (visit 1, three months (visit 2 and 6 months (visit 3 after the presentation. At each time point tear samples were evaluated for 41 cytokines using Luminex bead based multiplex assay and blood samples were tested for HIV viral load and CD4 and CD8 counts.
Full Text Available BACKGROUND: Lethal mutagenesis is a transition towards virus extinction mediated by enhanced mutation rates during viral genome replication, and it is currently under investigation as a potential new antiviral strategy. Viral load and virus fitness are known to influence virus extinction. Here we examine the effect or the multiplicity of infection (MOI on progeny production of several RNA viruses under enhanced mutagenesis. RESULTS: The effect of the mutagenic base analogue 5-fluorouracil (FU on the replication of the arenavirus lymphocytic choriomeningitis virus (LCMV can result either in inhibition of progeny production and virus extinction in infections carried out at low multiplicity of infection (MOI, or in a moderate titer decrease without extinction at high MOI. The effect of the MOI is similar for LCMV and vesicular stomatitis virus (VSV, but minimal or absent for the picornaviruses foot-and-mouth disease virus (FMDV and encephalomyocarditis virus (EMCV. The increase in mutation frequency and Shannon entropy (mutant spectrum complexity as a result of virus passage in the presence of FU was more accentuated at low MOI for LCMV and VSV, and at high MOI for FMDV and EMCV. We present an extension of the lethal defection model that agrees with the experimental results. CONCLUSIONS: (i Low infecting load favoured the extinction of negative strand viruses, LCMV or VSV, with an increase of mutant spectrum complexity. (ii This behaviour is not observed in RNA positive strand viruses, FMDV or EMCV. (iii The accumulation of defector genomes may underlie the MOI-dependent behaviour. (iv LCMV coinfections are allowed but superinfection is strongly restricted in BHK-21 cells. (v The dissimilar effects of the MOI on the efficiency of mutagenic-based extinction of different RNA viruses can have implications for the design of antiviral protocols based on lethal mutagenesis, presently under development.
Full Text Available Abstract Background Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL and tegumentary leishmaniasis (ATL have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. Methods To address this issue we analyzed CD4+ T absolute counts and the proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. Results We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4+ T cell counts under 200 cells/mm3, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm3. Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4+ T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8+ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. Conclusions Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4+ T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.
Full Text Available Hepatitis B virus (HBV quantification is essential in the management of chronic hepatitis B, both to determine treatment eligibility and in the monitoring of treatment effect. This test, however, is rarely available in resource-limited settings due to high costs and stringent requirements for shipment and storage of plasma. Dried Blood Spots (DBS can be a convenient alternative to plasma, but its use for HBV monitoring has not been investigated under real-life conditions in Africa.The performance of DBS in HBV quantification was investigated using a modified commercial test (Abbott RealTime HBV assay. Paired DBS and plasma samples were collected from an HBV positive cohort in Addis Ababa, Ethiopia. DBS were stored at ambient temperature for 4-39 days before shipment to the laboratory.Twenty-six paired samples were selected covering the total range of quantification, from 2.14 log IU/ml to >7 log IU/ml. HBV was detected in 21 of 21 (100% DBS from patients with a corresponding plasma viral load above 2.70 log IU/ml. The mean difference between plasma and DBS was 0.59 log IU/ml, and the correlation was strong (R2 = 0.92. In stability studies there was no significant change in DBS viral load after storage at room temperature for up to 12 weeks.This study suggests that DBS can be a feasible and reliable alternative to plasma for quantification of HBV in resource-limited settings. DBS can expand access to antiviral treatment for patients in low- and middle-income countries.
Wood, N H; Khammissa, R A G; Chikte, U M E; Meyerov, R; Lemmer, J; Feller, L
There are more than 120 types of low-risk and high-risk human papillomaviruses, all of which are epitheliotropic. HPV infection may be latent, or active in a subclinical form or a symptomatic form, the latter manifesting as benign or malignant neoplasms. In basal cells with non-productive HPV infection some early HPV proteins are expressed independently of cell maturation: the productive cycle of HPV replication depends upon specific cellular factors of the maturation of the infected keratinocytes. In HPV-mediated oncogenesis, the combined pathobiological effects of E6 and E7 oncoproteins of high-risk HPV culminate in cellular genomic instability and transformation of persistently infected cells, that progress to the development of a malignant phenotype. In this article we provide insights into the stages of HPV infection, and into the viral genomic organization and replicative cycle.
Kawada, Jun-ichi; Torii, Yuka; Kawano, Yoshihiko; Suzuki, Michio; Kamiya, Yasuko; Kotani, Tomomi; Kikkawa, Fumitaka; Kimura, Hiroshi; Ito, Yoshinori
Congenital cytomegalovirus (CMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL) in children. However, congenital SNHL without other clinical abnormalities is rarely diagnosed as CMV-related in early infancy. The aim of this study was to identify and treat patients with congenital CMV-related SNHL or CMV-related clinical abnormalities other than SNHL. The association between CMV load and SNHL was also evaluated. Newborns who had abnormal hearing screening results or other clinical abnormalities were screened for congenital CMV infection by PCR of saliva or urine specimens, and identified infected patients were treated with valganciclovir (VGCV) for 6 weeks. The CMV load of patients with or without SNHL was compared at regular intervals during as well as after VGCV treatment. Of 127 infants with abnormal hearing screening results, and 31 infants with other clinical abnormalities, CMV infection was identified in 6 and 3 infants, respectively. After VGCV treatment, 1 case had improved hearing but the other 5 SNHL cases had little or no improvement. Among these 9 patients with or without SNHL at 1 year of age, there was no significant difference in CMV blood or urine load at diagnosis, but both were significantly higher in patients with SNHL during VGCV treatment. Selective CMV screening of newborns having an abnormal hearing screening result would be a reasonable strategy for identification of symptomatic congenital CMV infection. Prolonged detection of CMV in blood could be a risk factor for SNHL. Copyright © 2015 Elsevier B.V. All rights reserved.
Sichero, Laura; Pierce Campbell, Christine M; Ferreira, Silvaneide; Sobrinho, João S; Luiza Baggio, Maria; Galan, Lenice; Silva, Roberto C; Lazcano-Ponce, Eduardo; Giuliano, Anna R; Villa, Luisa L
The HPV infection in men (HIM) study examines the natural history of genital HPV infection in men. Genotyping methods used in this study identify 37 α-HPV types; however, the viral type could not be identified in approximately 22% of male genital specimens that were HPV PCR positive. Our aim was to genotype HPV-unclassified specimens by sequencing PGMY09/11, GP5+/6+ or FAP59/64 PCR products. Using this approach we were able to detect 86 unique HPV types among 508 of 931 specimens analyzed. We report for the first time the presence of a broad range of α-, β- and γ-HPV at the male genitals. Copyright © 2013 Elsevier Inc. All rights reserved.
Tubiana, Roland; Le Chenadec, Jerome; Rouzioux, Christine; Mandelbrot, Laurent; Hamrene, Karima; Dollfus, Catherine; Faye, Albert; Delaugerre, Constance; Blanche, Stephane; Warszawski, Josiane
The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 is as low as 0.5% in non-breast-feeding mothers who delivered at term while receiving antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20% of the infected children born during the period 1997-2006 in the French Perinatal Cohort. We aimed to identify factors associated with such residual transmission risk. We performed a case-control study nested in the aforementioned subpopulation of the French Perinatal Cohort. Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included. Case patients and control subjects did not differ by geographical origin, gestational age at HIV diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients were less often receiving treatment at the time that they conceived pregnancy than control subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500 copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7% vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a multivariate analysis at 30+/-4 weeks adjusted for viral load, CD4(+) T cell count, and time at antiretroviral therapy initiation, viral load was the only factor independently associated with MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5-553; P<.001). Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV-1. Guidelines should take into account not only CD4(+) T cell count and risk of preterm delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during pregnancy.
Bingler, M A; Feingold, B; Miller, S A; Quivers, E; Michaels, M G; Green, M; Wadowsky, R M; Rowe, D T; Webber, S A
Increased use of serial EBV-PCR monitoring after pediatric transplantation has led to the identification of asymptomatic patients who carry very high viral loads over prolonged periods. The significance of this high-load state is unknown. We speculated that this state may identify patients at high risk for development of late PTLD/lymphoma. We reviewed data on 71 pediatric heart recipients who had serial viral load monitoring since 1997. Chronic high-load state was defined as the presence of >16,000 genome copies/mL whole blood on > or =50% of samples over at least 6 months. Among 20 high-load carriers (eight following prior PTLD, seven with prior symptomatic EBV infection, five without previous EBV disease), 9 (45%) developed late-onset PTLD 2.5-8.4 years posttransplant (including with four Burkitt's lymphoma). Among 51 controls with low (n = 39) or absent (n = 12) loads, only 2 (4%; p < 0.001 absent/low vs. high load) developed late PTLD/lymphoma. By multivariable analysis, high-load carrier state (OR = 12.4, 95% CI 2.1-74.4) and prior history of PTLD (OR = 10.7, 95% CI 1.9-60.6) independently predicted late PTLD. A chronic high EBV-load state is not benign and is a predictor of de novo or recurrent PTLD.
de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B.; Kuiken, Sjoerd D.; Weijer, Sebastiaan; van Nieuwkerk, Carin M. J.; Zaaijer, Hans L.; Molenkamp, Richard; Takkenberg, R. Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W.
Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen
DeVange Panteleeff, Dana; Emery, Sandra; Richardson, Barbra A.; Rousseau, Christine; Benki, Sarah; Bodrug, Sharon; Kreiss, Joan K.; Overbaugh, Julie
Human immunodeficiency type 1 (HIV-1) continues to spread at an alarming rate. The virus may be transmitted through blood, genital secretions, and breast milk, and higher levels of systemic virus in the index case, as measured by plasma RNA viral load, have been shown to correlate with increased risk of transmitting HIV-1 both vertically and sexually. Less is known about the correlation between transmission and HIV-1 levels in breast milk or genital secretions, in part because reliable quantitative assays to detect HIV-1 in these fluids are not available. Here we show that the Gen-Probe HIV-1 viral load assay can be used to accurately quantify viral load in expressed breast milk and in cervical and vaginal samples collected on swabs. Virus could be quantified from breast milk and swab samples spiked with known amounts of virus, including HIV-1 subtypes A, C, and D. As few as 10 copies of HIV-1 RNA could be detected above background threshold levels in ≥77% of assays performed with spiked breast milk supernatants and mock swabs. In genital swab samples from HIV-1-infected women, similar levels of HIV-1 RNA were consistently detected in duplicate swabs taken from the same woman on the same clinic visit, suggesting that the RNA values from a single swab sample can be used to measure genital viral load. PMID:12409354
Phillips, Andrew N; Pillay, Deenan; Miners, Alec H
BACKGROUND: In lower-income countries, WHO recommends a population-based approach to antiretroviral treatment with standardised regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Our aim was to study the potential consequenc...... laboratory monitoring-is currently the highest priority....
Mocroft, Amanda; Phillips, Andrew N; Gatell, Jose
CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study...
Farid Suleimani Mohammadi
Full Text Available Background: Schizophrenia (SC and bipolar disorder (BD are two chronic psychiatric illnesses with worldwide distribution. People could be involved at any age, particularly in early adolescence. Main symptoms of SC are non- affective symptoms such as auditory hallucination and illogical thinking. In contrast, BD represents affective symptoms such as depression and mania. Although the main cause of these mood disorders has been remained elusive, there are some potential contributing factors that could be considered in the pathogenesis of mentioned illnesses including, genetic and environmental factors. Cytomegalovirus (CMV is one of the probable contributing factors in SC and BD. CMV is a prototype of herpesviridae family which may infect different cell types such as endothelial and differentiated hematopoietic cells. CMV infections in immunocompromised patients as well as congenitally infected children represent CNS complication such as microcephaly and hearing loss. This virus has capability to impair the limbic structures in brain. Methods: This descriptive study was designed to evaluate the role of CMV in these illnesses. We investigated the level of serum IgG antibody and the presence of CMV DNA in serum and peripheral blood mononuclear cells (PBMCs samples of 46 SC and BD patients admitted to Iran Psychiatry Hospital Tehran, Iran from 2014 to 2015 as well as 46 healthy control groups at Tehran University of Medical Sciences. First, the level of CMV IgG antibody was evaluated in serum samples, by enzyme-linked immunosorbent assay (ELISA. Then, DNA extraction conducted by using the high pure viral nucleic acid kit (Roche, Germany. Serologically positive sera along with PBMC samples were tested by Real-time PCR, to investigate the presence of CMV DNA. Results: Results indicated higher levels of CMV IgG antibody in psychiatric patients, compared with a healthy control group. Afterward, we did not observe the presence of CMV DNA in either case
Rahangdale, Lisa; Cates, Jordan; Potter, JoNell; Badell, Martina L; Seidman, Dominika; Miller, Emilly S; Coleman, Jenell S; Lazenby, Gweneth B; Levison, Judy; Short, William R; Yawetz, Sigal; Ciaranello, Andrea; Livingston, Elizabeth; Duthely, Lunthita; Rimawi, Bassam H; Anderson, Jean R; Stringer, Elizabeth M
Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women. We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options. We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA >40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach. Copyright © 2016 Elsevier Inc. All rights reserved.
Horacio A. Duarte
Full Text Available Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable’ viral load ( 0.3. Last time missed any antiretroviral therapy dose was reported as “never” for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p < 0.001 for test of trend. The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p ≤ 0.005, but not at the 6-month visit (p = 0.2. While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.
Full Text Available BACKGROUND: The combination of transaminases (ALT, biopsy, HBeAg and viral load have classically defined the inactive status of carriers of chronic hepatitis B. The use of FibroTest (FT and ActiTest (AT, biomarkers of fibrosis and necroinflammatory activity, has been previously validated as alternatives to biopsy. We compared the 4-year prognostic value of combining FT-AT and viral load for a better definition of the inactive carrier status. METHODS AND FINDINGS: 1,300 consecutive CHB patients who had been prospectively followed since 2001 were pre-included. The main endpoint was the absence of liver-related complications, transplantation or death. We used the manufacturers' definitions of normal FT (< = 0.27, normal AT (< = 0.29 and 3 standard classes for viral load. The adjustment factors were age, sex, HBeAg, ethnic origin, alcohol consumption, HIV-Delta-HCV co-infections and treatment. RESULTS: 1,074 patients with baseline FT-AT and viral load were included: 41 years old, 47% African, 27% Asian, 26% Caucasian. At 4 years follow-up, 50 complications occurred (survival without complications 93.4%, 36 deaths occurred (survival 95.0%, including 27 related to HBV (survival 96.1%. The prognostic value of FT was higher than those of viral load or ALT when compared using area under the ROC curves [0.89 (95%CI 0.84-0.93 vs 0.64 (0.55-0.71 vs 0.53 (0.46-0.60 all P<0.001], survival curves and multivariate Cox model [regression coefficient 5.2 (3.5-6.9; P<0.001 vs 0.53 (0.15-0.92; P = 0.007 vs -0.001 (-0.003-0.000;P = 0.052] respectively. A new definition of inactive carriers was proposed with an algorithm combining "zero" scores for FT-AT (F0 and A0 and viral load classes. This new algorithm provides a 100% negative predictive value for the prediction of liver related complications or death. Among the 275 patients with the classic definition of inactive carrier, 62 (23% had fibrosis presumed with FT, and 3 died or had complications at 4 year
Soulie, Cathia; Grudé, Maxime; Descamps, Diane; Amiel, Corinne; Morand-Joubert, Laurence; Raymond, Stéphanie; Pallier, Coralie; Bellecave, Pantxika; Reigadas, Sandrine; Trabaud, Mary-Anne; Delaugerre, Constance; Montes, Brigitte; Barin, Francis; Ferré, Virginie; Jeulin, Hélène; Alloui, Chakib; Yerly, Sabine; Signori-Schmuck, Anne; Guigon, Aurélie; Fafi-Kremer, Samira; Haïm-Boukobza, Stéphanie; Mirand, Audrey; Maillard, Anne; Vallet, Sophie; Roussel, Catherine; Assoumou, Lambert; Calvez, Vincent; Flandre, Philippe; Marcelin, Anne-Geneviève
HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log 10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations. Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm. Among the 227 studied patients with VL > 1.7 log 10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log 10 copies/mL] and 32 had discordant VL in plasma (VL plasma compared with patients with plasma VL > 1.7 log 10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients. Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Petta, S; Di Marco, V; Di Stefano, R; Cabibi, D; Cammà, C; Marchesini, G; Craxì, A
The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load. © 2011 Blackwell Publishing Ltd.
Hyle, Emily P; Jani, Ilesh V; Rosettie, Katherine L; Wood, Robin; Osher, Benjamin; Resch, Stephen; Pei, Pamela P; Maggiore, Paolo; Freedberg, Kenneth A; Peter, Trevor; Parker, Robert A; Walensky, Rochelle P
To examine the clinical and economic value of point-of-care CD4 (POC-CD4) or viral load monitoring compared with current practices in Mozambique, a country representative of the diverse resource limitations encountered by HIV treatment programs in sub-Saharan Africa. We use the Cost-Effectiveness of Preventing AIDS Complications-International model to examine the clinical impact, cost (2014 US$), and incremental cost-effectiveness ratio [$/year of life saved (YLS)] of ART monitoring strategies in Mozambique. We compare: monitoring for clinical disease progression [clinical ART monitoring strategy (CLIN)] vs. annual POC-CD4 in rural settings without laboratory services and biannual laboratory CD4 (LAB-CD4), biannual POC-CD4, and annual viral load in urban settings with laboratory services. We examine the impact of a range of values in sensitivity analyses, using Mozambique's 2014 per capita gross domestic product ($620) as a benchmark cost-effectiveness threshold. In rural settings, annual POC-CD4 compared to CLIN improves life expectancy by 2.8 years, reduces time on failed ART by 0.6 years, and yields an incremental cost-effectiveness ratio of $480/YLS. In urban settings, biannual POC-CD4 is more expensive and less effective than viral load. Compared to biannual LAB-CD4, viral load improves life expectancy by 0.6 years, reduces time on failed ART by 1.0 year, and is cost-effective ($440/YLS). In rural settings, annual POC-CD4 improves clinical outcomes and is cost-effective compared to CLIN. In urban settings, viral load has the greatest clinical benefit and is cost-effective compared to biannual POC-CD4 or LAB-CD4. Tailoring ART monitoring strategies to specific settings with different available resources can improve clinical outcomes while remaining economically efficient.
DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén
The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions
Helfer-Hungerbuehler, A Katrin; Widmer, Stefan; Kessler, Yvonne; Riond, Barbara; Boretti, Felicitas S; Grest, Paula; Lutz, Hans; Hofmann-Lehmann, Regina
It is a remarkable feature for a retrovirus that an infection with feline leukemia virus (FeLV) can result in various outcomes. Whereas some cats contain the infection and show a regressive course, others stay viremic and succumb to the infection within a few years. We hypothesized, that differences in the infection outcome might be causally linked to the viral RNA and provirus loads within the host and these loads therefore may give additional insight into the pathogenesis of the virus. Thus, the goals of the present study were to follow-up on experimentally infected cats and investigate tissues from cats with different infection outcomes using sensitive, specific TaqMan real-time PCR and reverse transcriptase (RT)-PCR. Nineteen experimentally FeLV-A/Glasgow-1-infected cats were categorized into having regressive, progressive or reactivated FeLV infection according to follow-up of FeLV p27 antigen detection in the blood. Remarkably, regressively infected cats showed detectable provirus and viral RNA loads in almost all of the 27 tested tissues, even many years after virus exposure. Moreover, some regressively infected cats reactivated the infection, and these cats had intermediate to high viral RNA and provirus tissue loads. The highest loads were found in viremic cats, independent of their health status. Tissues that represented sites of virus replication and shedding revealed the highest viral RNA and provirus loads, while the lowest loads were present in muscle and nerve tissues. A supplementary analysis of 20 experimentally infected cats with progressive infection revealed a median survival time of 3.1 years (range from 0.6 to 6.5 years); ∼70% (n=14) of these cats developed lymphoma, while leukemia and non-regenerative anemia were observed less frequently. Our results demonstrate that the different infection outcomes are associated with differences in viral RNA and provirus tissue loads. Remarkably, no complete clearance of FeLV viral RNA or provirus was
Tang, Ning; Pahalawatta, Vihanga; Frank, Andrea; Bagley, Zowie; Viana, Raquel; Lampinen, John; Leckie, Gregor; Huang, Shihai; Abravaya, Klara; Wallis, Carole L
HIV RNA suppression is a key indicator for monitoring success of antiretroviral therapy. From a logistical perspective, viral load (VL) testing using Dried Blood Spots (DBS) is a promising alternative to plasma based VL testing in resource-limited settings. To evaluate the analytical and clinical performance of the Abbott RealTime HIV-1 assay using a fully automated one-spot DBS sample protocol. Limit of detection (LOD), linearity, lower limit of quantitation (LLQ), upper limit of quantitation (ULQ), and precision were determined using serial dilutions of HIV-1 Virology Quality Assurance stock (VQA Rush University), or HIV-1-containing armored RNA, made in venous blood. To evaluate correlation, bias, and agreement, 497 HIV-1 positive adult clinical samples were collected from Ivory Coast, Uganda and South Africa. For each HIV-1 participant, DBS-fingerprick, DBS-venous and plasma sample results were compared. Correlation and bias values were obtained. The sensitivity and specificity were analyzed at a threshold of 1000 HIV-1 copies/mL generated using the standard plasma protocol. The Abbott HIV-1 DBS protocol had an LOD of 839 copies/mL, a linear range from 500 to 1×10 7 copies/mL, an LLQ of 839 copies/mL, a ULQ of 1×10 7 copies/mL, and an inter-assay SD of ≤0.30 log copies/mL for all tested levels within this range. With clinical samples, the correlation coefficient (r value) was 0.896 between DBS-fingerprick and plasma and 0.901 between DBS-venous and plasma, and the bias was -0.07 log copies/mL between DBS-fingerprick and plasma and -0.02 log copies/mL between DBS-venous and plasma. The sensitivity of DBS-fingerprick and DBS-venous was 93%, while the specificity of both DBS methods was 95%. The results demonstrated that the Abbott RealTime HIV-1 assay with DBS sample protocol is highly sensitive, specific and precise across a wide dynamic range and correlates well with plasma values. The Abbott RealTime HIV-1 assay with DBS sample protocol provides an
Clausen, Louise Nygaard; Astvad, Karen; Ladelund, Steen
OBJECTIVE: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals. DESIGN AND METHODS: Observational prospective cohort study. Mortality rates were compared in a time-updated multivariate Poisson regression analysis....... RESULTS: We included 264 consecutive HIV-HCV-coinfected individuals. During 1143 person years at risk (PYR) 118 individuals died [overall mortality rate 10 (95% confidence interval; 8, 12)/100 PYR]. In multivariate analysis, a 1 log increase in HCV viral load was associated with a 30% higher mortality......) CC genotype was associated with 54% higher mortality risk [aMRR: 1.54 (0.89, 3.82] compared to TT genotype. CONCLUSION: High-HCV viral load, HCV genotype 3 and IL28B genotype CC had a significant influence on the risk of all-cause mortality among individuals coinfected with HIV-1. This may have...
Nomura, Takushi; Yamamoto, Hiroyuki; Takahashi, Naofumi; Naruse, Taeko K; Kimura, Akinori; Matano, Tetsuro
Virus-specific CD8(+) T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype, 90-120-Ia, associated with lower viral loads after SIVmac239 infection. Gag206-216 and Gag241-249 epitope-specific CD8(+) T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8(+) T-cell responses induced in all the 90-120-Ia(+) macaques on SIV replication remains unknown. Here, we identified three CD8(+) T-cell epitopes, Nef9-19, Nef89-97, and Nef193-203, associated with 90-120-Ia. Nef9-19 and Nef193-203 epitope-specific CD8(+) T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8(+) T cells, indicating that these CD8(+) T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with 90-120-Ia. Copyright © 2014 Elsevier Inc. All rights reserved.
Human papillomaviruses (HPVs) are a group of more than 200 related viruses that can cause several cancers including cervical cancer, anal cancer, and oropharyngeal cancer. Learn more about how HPV is transmitted, the different types of HPV, HPV vaccines, and HPV treatment.
Ito, Yoshinori; Suzuki, Michio; Kawada, Jun-ichi; Kimura, Hiroshi
Chronic active Epstein-Barr virus disease (CAEBV) is a distinct EBV-associated lymphoproliferative disease with a poor prognosis. Although the viral load in blood samples has been widely used for diagnosing CAEBV, well-defined viral load thresholds to guide clinicians are currently lacking. The aim of the present study was to determine standardized diagnostic values for EBV load in blood samples of CAEBV patients using the World Health Organization international standard for reporting. Levels of EBV DNA in 103 peripheral blood mononuclear cells (PBMCs) and 95 plasma/serum samples from 107 cases with CAEBV were quantified and expressed in international units. Receiver operating characteristic curves were analyzed to assess the most appropriate cut-off values for levels of EBV DNA to distinguish CAEBV from EBV-associated infectious mononucleosis (IM) and controls with past EBV infection. Levels of EBV DNA in PBMCs were significantly higher in the CAEBV group (median, 10(4.2) IU/μgDNA) compared to the IM (median, 10(2.1) IU/μgDNA) and control groups. An inconsistent qualitative result was seen in 13 of 86 CAEBV patients; in these, EBV-DNA was positive in PBMCs, but negative in plasma. Diagnostic cut-off values for viral load in PBMCs from CAEBV patients, as compared to those of healthy controls and IM patients, were 10(2.0) IU/μgDNA and 10(3.2) IU/μgDNA, respectively. For diagnostic purposes, the viral load of PBMCs was better than of plasma/serum. A diagnostic cut-off EBV load for CAEBV may be useful for the management of CAEBV patients. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Ohgitani, Eriko; Kita, Masakazu; Mazda, Osam; Imanishi, Jiro
To enhance the effect of anti-influenza-virus agent treatment, the effect of combined administration of oseltamivir phosphate and hochu-ekki-to (Japanese traditional herbal medicine, HET) on early viral clearance was examined. Senescence-accelerated mice were given HET in drinking water for 2 weeks, followed by intranasal infection with influenza A virus strain PR8. After 4 hours of infection, oseltamivir was administered orally for 5 days. The viral loads in the lungs of the group receiving combined treatment were dramatically lower when compared with the viral loads in the lungs of the group receiving oseltamivir alone. HET significantly increased the induction of IL-1β and TNF-α in the lungs of PR8-infected mice and stimulated alveolar macrophage phagocytosis. From these results, we conclude that these functions may be responsible the increased effect on viral load reduction. Here, we show that the combined administration of oseltamivir and HET is very useful for influenza treatment in senescence-accelerated mice.
Chikandiwa, Admire; Kelly, Helen; Sawadogo, Bernard; Ngou, Jean; Pisa, Pedro T; Gibson, Lorna; Didelot, Marie-Noelle; Meda, Nicolas; Weiss, Helen A; Segondy, Michel; Mayaud, Philippe; Delany-Moretlwe, Sinead
To report the prevalence and incidence of low-risk human papillomavirus infection (LR-HPV) and anogenital warts (AGW) among women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA), and to explore HIV-related factors associated with these outcomes. We enrolled 1238 WLHIV (BF = 615; SA = 623) aged 25-50 years and followed them at three time points (6, 12 and 16 months) after enrolment. Presence of AGW was assessed during gynaecological examination. Cervico-vaginal swabs for enrolment and month 16 follow-up visits were tested for HPV infection by Inno-LiPA® genotyping. Logistic regression was used to assess risk factors for prevalent infection or AGW. Cox regression was used to assess risk factors for incident AGW. Women in SA were more likely than those in BF to have prevalent LR-HPV infection (BF: 27.1% vs. SA: 40.9%; p500 cells/μL). Duration of ART and HIV plasma viral load were not associated with any LR-HPV infection or AGW outcomes. LR-HPV infection and AGW are common in WLHIV in sub-Saharan Africa. Type-specific HPV vaccines and effective ART with immunological reconstitution could reduce the burden of AGW in this population.
Full Text Available To report the prevalence and incidence of low-risk human papillomavirus infection (LR-HPV and anogenital warts (AGW among women living with HIV (WLHIV in Burkina Faso (BF and South Africa (SA, and to explore HIV-related factors associated with these outcomes.We enrolled 1238 WLHIV (BF = 615; SA = 623 aged 25-50 years and followed them at three time points (6, 12 and 16 months after enrolment. Presence of AGW was assessed during gynaecological examination. Cervico-vaginal swabs for enrolment and month 16 follow-up visits were tested for HPV infection by Inno-LiPA® genotyping. Logistic regression was used to assess risk factors for prevalent infection or AGW. Cox regression was used to assess risk factors for incident AGW.Women in SA were more likely than those in BF to have prevalent LR-HPV infection (BF: 27.1% vs. SA: 40.9%; p500 cells/μL. Duration of ART and HIV plasma viral load were not associated with any LR-HPV infection or AGW outcomes.LR-HPV infection and AGW are common in WLHIV in sub-Saharan Africa. Type-specific HPV vaccines and effective ART with immunological reconstitution could reduce the burden of AGW in this population.
Full Text Available Indirect transmission of influenza A virus (IAV in swine is poorly understood and information is lacking on levels of environmental exposure encountered by swine and people during outbreaks of IAV in swine barns. We characterized viral load, viability and persistence of IAV in air and on surfaces during outbreaks in swine barns. IAV was detected in pigs, air and surfaces from five confirmed outbreaks with 48% (47/98 of oral fluid, 38% (32/84 of pen railing and 43% (35/82 of indoor air samples testing positive by IAV RT-PCR. IAV was isolated from air and oral fluids yielding a mixture of subtypes (H1N1, H1N2 and H3N2. Detection of IAV RNA from air was sustained during the outbreaks with maximum levels estimated between 7 and 11 days from reported onset. Our results indicate that during outbreaks of IAV in swine, aerosols and surfaces in barns contain significant levels of IAV potentially representing an exposure hazard to both swine and people.
Hood, Iris V.; Berger, James M.
Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of the
Schiffman, Mark; Vaughan, Laurence M; Raine-Bennett, Tina R; Castle, Philip E; Katki, Hormuzd A; Gage, Julia C; Fetterman, Barbara; Befano, Brian; Wentzensen, Nicolas
In US cervical screening, immediate colposcopy is recommended for women with HPV-positive ASC-US (equivocal) cytology. We evaluated whether partial typing by Onclarity™ (BD) might identify HPV-positive women with low enough CIN3+ risk to permit 1-year follow-up instead. The NCI-Kaiser Permanente Northern California Persistence and Progression cohort includes a subset of 13,890 women aged 21+ with HC2 (Qiagen)-positive ASC-US at enrollment; current median follow-up is 3.0years. Using stratified random sampling, we typed 2079 archived enrollment specimens including 329 women subsequently diagnosed with CIN3+, 563 with CIN2, and 1187 with
Full Text Available Persistent viral infection with high-risk human papillomavirus (HPV genotypes causes virtually all cancer of the cervix. The same HPV genotypes (“types” also cause cases of anal cancer. Cervical cancer is the third most frequent cancer in women worldwide after breast and colorectal cancers. It ranks fourth of women’s cancers according to the mortality ratio. Two vaccines have been developed against HPV infection; one is a quadrivalent vaccine (Gardasil™ and the other is a bivalent vaccine (Cervarix™. This topic will cover issues related to HPV infections, routine HPV immunization recommendations, vaccination in special patient populations, the cost-effectiveness of HPV vaccination, and vaccine safety. [TAF Prev Med Bull 2013; 12(3.000: 327-334
Torres-Poveda, K.; Burguete-García, A. I.; Bahena-Román, M.; Méndez-Martínez, R.; Zurita-Díaz, M. A.; López-Estrada, G.; Delgado-Romero, K.; Peralta-Zaragoza, O.; Bermúdez-Morales, V. H.; Cantú, D.; García-Carrancá, A.; Madrid-Marina, V.
Alterations in the host cellular immune response allow persistent infections with High-Risk Human Papillomavirus (HR-HPV) and development of premalignant cervical lesions and cervical cancer (CC). Variations of immunosuppressive cytokine levels in cervix are associated with the natural history of CC. To assess the potential role of genetic host immunity and cytokines serum levels in the risk of developing CC, we conducted a case–control study paired by age. Peripheral blood samples from patients with CC (n = 200) and hospital controls (n = 200), were used to evaluate nine biallelic SNPs of six cytokine genes of the adaptive immune system by allelic discrimination and cytokines serum levels by ELISA. After analyzing the SNP association by multivariate logistic regression adjusted by age, CC history and smoking history, three Th2 cytokines (IL-4, IL-6 and IL-10) and one Th3 (TGFB1) cytokine were significantly associated with CC. Individuals with at least one copy of the following risk alleles: T of SNP (−590C > T IL-4), C of SNP (−573G > C IL-6), A of SNP (−592C > A IL-10), T of SNP (−819C > T IL-10) and T of SNP (−509C > T TGFB1), had an adjusted odds ratio (OR) of 2.08 (95 % CI 1.475–2.934, p = 0.0001), an OR of 1.70 (95 % CI 1.208–2.404, p = 0.002), an OR of 1.87 (95 % CI 1.332–2.630, p = 0.0001), an OR of 1.67 (95 % CI 1.192–2.353, p = 0.003) and an OR of 1.91 (95 % CI 1.354–2.701, p = 0.0001), respectively, for CC. The burden of carrying two or more of these risk alleles was found to have an additive effect on the risk of CC (p trend = 0.0001). Finally, the serum levels of Th2 and Th3 cytokines were higher in CC cases than the controls; whereas IFNG levels, a Th1 cytokine, were higher in controls than CC cases. The significant associations of five SNPs with CC indicate that these polymorphisms are potential candidates for predicting the risk of development of CC, representing a risk allelic load for CC and can be used as a biomarker of
Small, Will; Milloy, M J; McNeil, Ryan; Maher, Lisa; Kerr, Thomas
People who inject drugs (PWID) living with HIV often experience sub-optimal antiretroviral therapy (ART) treatment outcomes, including HIV plasma viral load (PVL) rebound. While previous studies have identified risk factors for PVL rebound among PWID, no study has examined the perspectives of PWID who have experienced PVL rebound episodes. We conducted an ethno-epidemiological study to investigate the circumstances surrounding the emergence of rebound episodes among PWID in Vancouver, BC, Canada. Comprehensive clinical records linked to a community-based prospective observational cohort of HIV-positive drug users were used to identify PWID who had recently experienced viral rebound. In-depth qualitative interviews with 16 male and 11 female participants explored participant perspectives regarding the emergence of viral rebound. A timeline depicting each participant's HIV viral load and adherence to ART was used to elicit discussion of circumstances surrounding viral rebound. Viral rebound episodes were shaped by interplay between various individual, social, and environmental factors that disrupted routines facilitating adherence. Structural-environmental influences resulting in non-adherence included housing transitions, changes in drug use patterns and intense drug scene involvement, and inadequate care for co-morbid health conditions. Social-environmental influences on ART adherence included poor interactions between care providers and patients producing non-adherence, and understandings of HIV treatment that fostered intentional treatment discontinuation. This study describes key pathways which led to rebound episodes among PWID receiving ART and illustrates how environmental forces may increase vulnerability for non-adherence leading to treatment failure. Our findings have potential to help inform interventions and supports that address social-structural forces that foster non-adherence among PWID.
Full Text Available Objective: To study the effect of hrHPV infection on anti-apoptotic gene and pro-apoptotic gene expression in cervical cancer tissue. Methods: A total of 56 patients with cervical cancer, 94 cases of patients with cervical intraepithelial neoplasia and 48 cases of patients with chronic cervicitis who were treated in our hospital from May 2013 to December 2015 were selected for study and included in malignant group, precancerous lesion group and benign group respectively. hrHPV infection as well as the expression of anti-apoptotic genes and proapoptotic genes in cervical tissue were detected. Results: hrHPV infection rate and viral load in cervical tissue of malignant group were significantly higher than those of precancerous lesion group and benign group; P27 and p16 levels in cervical tissue of malignant group were significantly lower than those of precancerous lesion group and benign group, and K-ras, c-myc, Prdx4 and TNFAIP8 levels were significantly higher than those of precancerous lesion group and benign group; the greater the HPV virus load, the lower the p27 and p16 levels and the higher the K-ras, c-myc, Prdx4 and TNFAIP8 levels in cervical tissue. Conclusions: hrHPV infection can result in tumor suppressor genes p27 and p16 expression deletion and increase the expression of proto-oncogene and apoptosis-inhibiting genes, and it is associated with the occurrence and development of cervical cancer.
Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P
-68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential...... of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...
Groenbaek, K.; Friis, H.; Hansen, Max
Objective To assess the effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status. Methods We performed a randomized, placebo-controlled, double-blind trial to assess the effect of antioxidant supplementation on serum alanine aminotransferase, plasma...... hepatitis C viral load as well as oxidative and antioxidant markers in patients with hepatitis C virus infection. The participants received a daily dose of ascorbic acid (500 mg), D-alpha-tocopherol (9451 U) and selenium (200 mu g) or placebo tablets for 6 months. Results Twenty-three patients were included...... aminotransferase and logo-transformed plasma hepatitis C virus-RNA between the groups or changes from the baseline at any time. No consistent differences between groups or changes from the baseline with respect to erythrocyte activities of antioxidative enzymes (glutathione reductase, superoxide dismutase...
Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien
The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS.Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined.A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was 25% of the specimens differed by >0.5 log cps/mL.All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1).The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens.
Murillo, Wendy; de Rivera, I L; Parham, L; Jovel, E; Palou, E; Karlsson, A C; Albert, J
The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93). The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.
Ana Júlia Luz
Full Text Available OBJECTIVE: To evaluate the factors associated with plasma concentrations of atazanavir (ATV in a cohort of well-controlled HIV infected subjects (undetectable viremia. Design: Cross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011. METHODS: Patients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm³, and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography. RESULTS AND DISCUSSION: Overall, 54 patients (mean age of 47 years and 50% women were included in the analysis. Those without ritonavir (unboosted atazanavir had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p = 0.001 and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r = 0.32 and r = 0.33 respectively; p < 0.05 in both cases. no statistical association was found among gender, ethnicity, age, weight, body mass index (BMI, lipid profile, and the plasma concentration of atazanavir. CONCLUSION: in summary, as expected, concomitant ritonavir use was the only factor associated with atazanavir plasma levels. prospective studies with a larger sample size might help to observe an association of atazanavir concentrations to other characteristics such as body weight, since the p-value showed to be close to significance (p = 0.068.
Ouedraogo, David Eric; Bollore, Karine; Viljoen, Johannes; Foulongne, Vincent; Reynes, Jacques; Cartron, Guillaume; Vendrell, Jean-Pierre; Van de Perre, Philippe; Tuaillon, Edouard
Epstein-Barr virus (EBV) genome quantitation in whole blood is used widely for therapeutic monitoring of EBV-associated disorders in immunosuppressed individuals and in patients with EBV-associated lymphoma. However, the most appropriate biological material to be used for EBV DNA quantitation remains a subject of debate. This study compare the detection rate and levels of EBV DNA from whole blood, plasma, enriched B-cells, and B-cell short-term culture supernatant using quantitative real-time PCR. Samples were collected from 33 subjects with either HIV infection or B-cell lymphoma. Overall, EBV DNA was detected in 100% of enriched B-cell samples, in 82% of B-cell culture supernatants, in 57% of plasma, and 42% of whole blood samples. A significant correlation for EBV viral load was found between enriched B-cell and B-cell culture supernatant material (ρ = 0.92; P cells (ρ = -0.02; P = 0.89), whole blood and plasma (ρ = 0.24; P = 0.24), or enriched B-cells and plasma (ρ = 0.08; P = 0.77). Testing of enriched B-cells appeared to be the most sensitive method for detection of EBV DNA as well as for exploration of the cellular reservoir. Quantitation of EBV DNA in plasma and B-cell culture supernatant may be of interest to assess EBV reactivation dynamics and response to treatment as well as to decipher EBV host-pathogen interactions in various clinical scenarios. © 2013 Wiley Periodicals, Inc.
Landis, R Clive; Carmichael-Simmons, Kelly; Hambleton, Ian R; Best, Anton
Since 2009, seven countries in the Organization of Eastern Caribbean States (OECS), Antigua & Barbuda, Dominica, Grenada, Montserrat, St. Kitts & Nevis, Saint Lucia, and St. Vincent & the Grenadines, have been utilizing a laboratory referral service for HIV-1 viral load (VL) offered by The Ladymeade Reference Unit (LRU) Laboratory, Barbados. The objective of this study was to evaluate 5 year VL trends in the six larger OECS countries participating in this regional referral service. Blood samples were collected in source countries and transported to Barbados as frozen plasma according to a standardized protocol. Plasma specimens were amplified by RT PCR on a Roche TaqMan 48 analyser (Roche Diagnostics, Panama City, Panama). VL was considered optimally suppressed below a threshold level of < 200 HIV-1 copies/mL of blood. The same threshold was used as a binary indicator in an analysis of the secular change in VL suppression. Montserrat was excluded due to insufficient number of samples. A steady rise in VL referrals from OECS countries was recorded, rising from 312 samples in 2009 to 1,060 samples in 2013. A total of 3,543 samples were tested, with a sample rejection rate (9.2%) mostly due to breaks in the cold chain. Aggregate VL data showed the odds of VL suppression in the Eastern Caribbean improved by 66% for each additional year after 2009 (Odds Ratio 1.66 [95% CI 1.46 to 1.88]; p<0.001). We demonstrate the feasibility of establishing a regional laboratory referral service for HIV VL monitoring in the Eastern Caribbean. Aggregate VL trends showed a significant year-on-year improvement in VL suppression, implying public health benefits through treatment as prevention in the OECS. VL provides a powerful monitoring & evaluation tool for strengthening HIV programs at country level among the small island states participating in this regional referral network.
R Clive Landis
Full Text Available Since 2009, seven countries in the Organization of Eastern Caribbean States (OECS, Antigua & Barbuda, Dominica, Grenada, Montserrat, St. Kitts & Nevis, Saint Lucia, and St. Vincent & the Grenadines, have been utilizing a laboratory referral service for HIV-1 viral load (VL offered by The Ladymeade Reference Unit (LRU Laboratory, Barbados. The objective of this study was to evaluate 5 year VL trends in the six larger OECS countries participating in this regional referral service.Blood samples were collected in source countries and transported to Barbados as frozen plasma according to a standardized protocol. Plasma specimens were amplified by RT PCR on a Roche TaqMan 48 analyser (Roche Diagnostics, Panama City, Panama. VL was considered optimally suppressed below a threshold level of < 200 HIV-1 copies/mL of blood. The same threshold was used as a binary indicator in an analysis of the secular change in VL suppression. Montserrat was excluded due to insufficient number of samples.A steady rise in VL referrals from OECS countries was recorded, rising from 312 samples in 2009 to 1,060 samples in 2013. A total of 3,543 samples were tested, with a sample rejection rate (9.2% mostly due to breaks in the cold chain. Aggregate VL data showed the odds of VL suppression in the Eastern Caribbean improved by 66% for each additional year after 2009 (Odds Ratio 1.66 [95% CI 1.46 to 1.88]; p<0.001.We demonstrate the feasibility of establishing a regional laboratory referral service for HIV VL monitoring in the Eastern Caribbean. Aggregate VL trends showed a significant year-on-year improvement in VL suppression, implying public health benefits through treatment as prevention in the OECS. VL provides a powerful monitoring & evaluation tool for strengthening HIV programs at country level among the small island states participating in this regional referral network.
Dorward, Jienchi; Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K
Introduction Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shift...
Fidler, Sarah; Lewis, Heather; Meyerowitz, Jodi; Kuldanek, Kristin; Thornhill, John; Muir, David; Bonnissent, Alice; Timson, Georgina; Frater, John
There is a global need for HIV viral load point-of-care (PoC) assays to monitor patients receiving antiretroviral therapy. UNICORN was the first study of an off-label protocol using whole blood finger-prick samples tested with and without a simple three minute spin using a clinic-room microcentrifuge. Two PoC assays were evaluated in 40 HIV-positive participants, 20 with detectable and 20 with undetectable plasma viral load (pVL) (<20 copies/ml). Using 100 µl finger-prick blood samples, the Cepheid Xpert HIV-1 Viral Load and HIV-1 Qual cartridges were compared with laboratory pVL assessment (TaqMan, Roche). For participants with undetectable viraemia by TaqMan, there was poor concordance without centrifugation with the TaqMan platform with only 40% 'undetectable' using Xpert VL and 25% 'not detected' using the Qual assay. After a 3 minute spin, 100% of samples were undetectable using either assay, showing full concordance with the TaqMan assay. Defining a lower limit of detection of 1000 copies/ml when including a spin, there was 100% concordance with the TaqMan platform with strong correlation (rho 0.95 and 0.94; p < 0.0001 for both assays). When including a simple microcentrifugation step, finger-prick PoC testing was a quick and accurate approach for assessing HIV viraemia, with excellent concordance with validated laboratory approaches.
Kulkarni, Smita; Jadhav, Sushama; Khopkar, Priyanka; Sane, Suvarna; Londhe, Rajkumar; Chimanpure, Vaishali; Dhilpe, Veronica; Ghate, Manisha; Yelagate, Rajendra; Panchal, Narayan; Rahane, Girish; Kadam, Dilip; Gaikwad, Nitin; Rewari, Bharat; Gangakhedkar, Raman
Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.
Hepatitis C seroprevalence and correlation between viral load and viral genotype among primary care clients in Mexico Seroprevalencia de hepatitis C y correlación entre la carga viral y el genotipo viral en asistentes al nivel primario de atención enMéxico
Ana I Burguete-Garcia
Full Text Available OBJECTIVE: To measure hepatitis C virus (HCV sero-prevalence, prevalence, hepatitis risk characteristics frequency, and genotype correlation with viral load among clients attending health care clinics. MATERIAL AND METHODS: Venous blood samples from l12 226 consecutive consenting adults were collected from January 2006 through December 2009. HCV antibodies were detected by immunoassay. HCV RNA was detected by qRT-PCR and viral genotype was performed by PCR and LIPA test. RESULTS: The HCV seroprevalence observed was l.5 % (C.I. 95% l.3-l.7, from seropositive individuals 60.9 % reported previous blood transfusion, 28.3% declared to have relatives with cirrhosis, 25.2% had tattoos or piercings, and 6.9% referred to have used drugs. Male gender and transfusion (pOBJETIVO: Medir la seroprevalencia y prevalencia del virus de hepatitis C (VHC, la frecuencia de caracteristicas de riesgo y la correlacion genotipica con la carga viral en sujetos asistentes a clinicas de medicina familiar. MATERIAL Y METODOS: muestras de sangre venosa se colectaron de l12 226 adultos, previo consentimiento informado, de enero 2006 hasta diciembre 2009, para la deteccion de anticuerpos contra VHC por ELISA. La deteccion de RNA-VHC y el genotipo viral se realizo mediante qRT-PCR. RESULTADOS: La seroprevalencia de VHC fue l.5 % (C.I. 95% l.3-l.7, 60.9% reportaron transfusion sanguinea previa, 28.3% dijo tener familiares cercanos con cirrosis, 25.2% tenian tatuajes o piercing y 6.9% refirio ser usuario de drogas intravenosas. El ser hombre, el antecedente de transfusiones y el uso de drogas (p<0.00l, fueron los factores con mayor frecuencia en el grupo VHC seropositivo. La prevalencia del RNA-VHC en seropositivos fue de 48.3%. El genotipo mas frecuente en todas las areas geograficas de Mexico fue el l (subtipo lA, 33%; subtipo lB, 21.4% seguido por el genotipo 2 (subtipo 2A, 8.50%. Se observó una correlación positiva de 51% con la carga viral más alta y el genotipo viral 1A
Pia Carmen Melillo
Full Text Available Cervical cancer is due to persistent genital infection with Human Papillomavirus (HPV.The purpose of this study was to evaluate prevalence of HPV in Irpinia (Campania region, Italy, distribution of different viral genotypes, correlating cytological results and virological investigations. In the period 2006-2011, were made 1080 cervical samples of women aged 18-65 years for HPV identification and genotyping. Detection of the virus was performed by Multiplex-PCR System (Seegene,Arrow and typing with INNO-LiPA HPV Genotyping Extra test (Innogenetics. Out of the 1080 tested samples, 330 (30.6% samples were positive for HPV DNA. The most frequently occurring High Risk (HR-HPV genotype in single infections was HPV16 (16.6%, followed by HPV51 (10.7%, in multiple infections HPV16 (15.7% and 31 (14.6%. The prevalence of infection, correlated with age of patients studied, is greater in the group aged 26-30 years (42.5%. HR-HPV were detected in different percent in patients with Pap test scores: 22.5% in normal Pap smear (20% HPV16, 14.5% ASCUS (47.6% HPV16, 24% LSIL (20% HPV16, 79.3% HSIL (72.7% HPV16; 9.1% HPV18 detected only in this type of cellular alteration. The high prevalence of HR-HPV in patients with ASCUS or normal Pap test, suggesting the real advantage of HPV screening test, more sensitive in selecting the actual population at risk. Based on the findings of our epidemiological study, HR-HPV screening and HPV genotyping test should be strongly advised also to the vaccinated population for the high incidence of genotypes which are not included in vaccines (67%.
Full Text Available Abstract Background Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression. Methods PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied. Results Declined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p Conclusion PD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.
Full Text Available It is important to distinguish among squamous intraepithelial lesions (SIL those associated with increased risk cervical cancer. Our aim was to evaluate if the expression level of gen E2 in women with SIL and evidence of viral integration is associated to the grade of lesion. Cervical scrapes HPV16 positive from 19 women with normal histology, 45 women with low-grade SIL (LSIL and 45 women with high-grade SIL (HSIL were analyzed. Real-time PCR was used to quantify the mRNA of E2 and E2 and E6 genes to calculate viral load (E6 and the ratio E2/E6 to assess viral integration. Similar frequencies of E2 expression were found in LSIL and HSIL15/45 (33 %, the frequency in women without SIL was lower 3/19 (15.8 %, and all cases with E2 gene expression had mixed episomal and integrated viral DNA. The viral load increased significantly with the grade of SIL (p= 0.049, while E2/E6 ratio decreased (p=0.049. The ROC analysis showed low capacity of the three viral parameters analyzed to distinguish between low and high grade SIL. In conclusion although SIL with mixed and integrated viral DNA with E2 expression could be at lower risk of progression, and viral load and integration were associated with higher severity of the lesion, its clinical value as biomarkers of HSIL is limited.
... Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More sharing ... Español In Chamorro In Urdu In Vietnamese HPV (human papillomavirus) is a sexually transmitted virus. It is ...
Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P; Holst, Peter J
Gammaherpesviruses establish life-long latent infections in their hosts. If the host becomes immunosuppressed, these viruses may reactivate and cause severe disease, and even in immunocompetent individuals the gammaherpesviruses are presumed to have an oncogenic potential. Murine gammaherpesvirus-68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond 14 days post-infection, and thus demonstrates that a non-replicating vaccine may successfully be employed to reduce the viral burden during chronic gammaherpesvirus infection.
Jumat, Muhammad; Hasan, Nur; Subramanian, Poorani; Heberling, Colin; Colwell, Rita; Hong, Pei-Ying
(AdV) and Enteroviruses (EV) were enumerated using digital polymerase chain reaction (dPCR) and assessed for infectivity using fluorescence-based infection assays. MBR treatment was successful in reducing viral diversity. Plant viruses remained
Kerschberger, Bernhard; Boulle, Andrew M; Kranzer, Katharina; Hilderbrand, Katherine; Schomaker, Michael; Coetzee, David; Goemaere, Eric; Van Cutsem, Gilles
Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001). A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.
Sripan, Patumrat; Le Coeur, Sophie; Ingsrisawang, Lily; Cressey, Tim R; Bouazza, Naïm; Foissac, Frantz; Ngo-Giang-Huong, Nicole; Traisathit, Patrinee; Srirompotong, Ussanee; Ayudhaya, Orada Patamasingh Na; Puangsombat, Achara; Jungpipun, Jantana; Jittayanun, Kanokwan; Tréluyer, Jean-Marc; Jourdain, Gonzague; Lallemant, Marc; Urien, Saïk
Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV have evolved over time. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV RNA viral load (VL) during pregnancy. A total of 1,833 VL measurements from ARV-naive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either zidovudine (ZDV) monotherapy, ZDV plus lopinavir/ritonavir (LPV/r), or ZDV plus lamivudine (3TC) plus LPV/r. VL time-course during pregnancy was described as a function of pretreatment VL and treatment duration using an Emax non-linear mixed-effect model. VL reduction and median time to achieve a VL<50 copies/ml were estimated for each regimen. Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/ml with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/ml and the higher the pretreatment VL, the larger the effect 3TC had on reducing the time to VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/ml was shorter. This beneficial effect of 3TC is crucial for prevention of mother-to-child transmission in women who receive ARVs late and with high pretreatment VL.
... and anus. If I have HPV, will that cause pregnancy problems? It is unclear. Even though HPV is ... HPV can be passed to a newborn during pregnancy or through the birth canal. Usually this causes no problems for the newborn. In rare cases, ...
Longuet, M; Beaudenon, S; Orth, G
The genomes of two novel human papillomavirus (HPV) types, HPV68 and HPV70, were cloned from a low-grade cervical intraepithelial neoplasia and a vulvar papilloma, respectively, and partially sequenced. Both types are related to HPV39, a potentially oncogenic virus. HPV68 and HPV70 were also detected in genital intraepithelial neoplasia from three patients and one patient, respectively. Comparison with sequence data in the literature indicates that the subgenomic ME180-HPV DNA fragment, clone...
The contribution of Ebola viral load at admission and other patient characteristics to mortality in a Médecins Sans Frontières (MSF) Ebola Case Management Centre (CMC), Kailahun, Sierra Leone, June -October, 2014.
This paper describes patient characteristics, including Ebola viral load, associated with mortality in an MSF Ebola case management centre. Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270\\/525). Ebola viral load (whole blood sample) data was available on 76% (397\\/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission and distance travelled to the CMC were associated with mortality (p value<0.05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per millilitre (p value<0.05, Odds Ratio>10), aged 50 years or more (p value=0.08, Odds Ratio=2) and symptom duration prior to admission less than 5 days (p value=0.14). The presence of confusion, diarrhoea and conjunctivitis were significantly higher (p value<0.05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.
Sun, Yun-Yan; Peng, Shiwen; Han, Liping; Qiu, Jin; Song, Liwen; Tsai, Yachea; Yang, Benjamin; Roden, Richard B.S.; Trimble, Cornelia L.; Hung, Chien-Fu; Wu, T-C
Purpose Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Experimental Design Here we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than IM delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc). Results We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Conclusions Our results support future clinical translation using cervicovaginal TA-HPV vaccination. PMID:26420854
Bosch, F Xavier; Robles, Claudia; Díaz, Mireia
protocol would represent an attractive approach for many health-care systems, in particular, countries in Central and Eastern Europe, Latin America, Asia, and some more-developed parts of Africa. The role of vaccination in women aged >30 years and the optimal number of HPV-screening tests required......Human papillomavirus (HPV)-related screening technologies and HPV vaccination offer enormous potential for cancer prevention, notably prevention of cervical cancer. The effectiveness of these approaches is, however, suboptimal owing to limited implementation of screening programmes and restricted...... indications for HPV vaccination. Trials of HPV vaccination in women aged up to 55 years have shown almost 90% protection from cervical precancer caused by HPV16/18 among HPV16/18-DNA-negative women. We propose extending routine vaccination programmes to women of up to 30 years of age (and to the 45-50-year...
Das, Bibhuti; Morrow, Robert; Huang, Rong; Fixler, David
To examine the risk of late-onset post-transplant lymphoproliferative disorder (PTLD) in the presence of persisting high Epstein-Barr virus (EBV) in EBV naïve pediatric heart transplant (HT) recipients. A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age. PTLD was diagnosed in 8 out of 145 patients (5.5%); 6/91 (6.5%) in those who were EBV seropositive and 2/54 (3.7%) in the EBV naïve group at the time of HT ( P = 0.71). We found 32/145 (22%) patients with persistently high EBV load during continuing follow-up; 20/91 (22%) in EBV seropositive group vs 12/54 (22%) in EBV naïve group ( P = 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant ( P > 0.05). In the EBV seropositive group, PTLD was diagnosed in 15% (3/20) of patients with high EBV vs 4.2% (3/71) of patients with low or undetectable EBV load ( P = 0.14) whereas in EBV naïve patients 8.3% (1/12) of those with high EBV load and 2.3% (1/42) with low or undetectable EBV load ( P = 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up (4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort ( P = 0.005). At least one episode of acute rejection occurred in 72% (23/32) of patients with high EBV vs 36% (41/113) patients with low or undetectable EBV after HT ( P < 0.05). There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in
Orem, Jackson; Sandin, Sven; Mbidde, Edward; Mangen, Fred Wabwire; Middeldorp, Jaap; Weiderpass, Elisabete
Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory conditions. In this study, EBV detection was compared in children with non-Hodgkin's lymphoma and children with chronic inflammatory conditions, using samples and data from a case-control study carried out at the Mulago National Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva, whole blood and white blood cells by real-time PCR. Serological values for IgG-VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non-Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Of the 127 children included (87 males and 40 females; median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory conditions, and only 10% were HIV-positive. The most common clinical presentations for all disease categories considered were fever, night sweats, and weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value = 0.04), but EBV viral loads in saliva and white blood cells were not different in any of the disease categories considered. A significant difference in EAd-IgG was observed when non-Hodgkin's lymphoma was compared with chronic inflammatory conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to chronic inflammatory conditions, EBV viral load was elevated in Burkitt's lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an association between virological and serological markers of EBV and childhood non-Hodgkin's lymphoma, irrespective of subtype, in Uganda. © 2014 Wiley Periodicals, Inc.
Revill, Paul; Walker, Simon; Cambiano, Valentina; Phillips, Andrew; Sculpher, Mark J
The WHO HIV Treatment Guidelines suggest routine viral-load monitoring can be used to differentiate antiretroviral therapy (ART) delivery and reduce the frequency of clinic visits for patients stable on ART. This recommendation was informed by economic analysis that showed the approach is very likely to be cost-effective, even in the most resource constrained of settings. The health benefits were shown to be modest but the costs of introducing and scaling up viral load monitoring can be offset by anticipated reductions in the costs of clinic visits, due to these being less frequent for many patients. The cost-effectiveness of introducing viral-load informed differentiated care depends upon whether cost reductions are possible if the number of clinic visits is reduced and/or how freed clinic capacity is used for alternative priorities. Where freed resources, either physical or financial, generate large health gains (e.g. if committed to patients failing ART or to other high value health care interventions), the benefits of differentiated care are expected to be high; if however these freed physical resources are already under-utilized or financial resources are used less efficiently and would not be put to as beneficial an alternative use, the policy may not be cost-effective. The implication is that the use of conventional unit costs to value resources may not well reflect the latter's value in contributing to health improvement. Analyses intended to inform resource allocated decisions in a number of settings may therefore have to be interpreted with due consideration to local context. In this paper we present methods of how economic analyses can reflect the real value of health care resources rather than simply applying their unit costs. The analyses informing the WHO Guidelines are re-estimated by implementing scenarios using this framework, informing how differentiated care can be prioritized to generate greatest gains in population health. The findings have
Pannus, Pieter; Fajardo, Emmanuel; Metcalf, Carol; Coulborn, Rebecca M; Durán, Laura T; Bygrave, Helen; Ellman, Tom; Garone, Daniela; Murowa, Michael; Mwenda, Reuben; Reid, Tony; Preiser, Wolfgang
Rollout of routine HIV-1 viral load monitoring is hampered by high costs and logistical difficulties associated with sample collection and transport. New strategies are needed to overcome these constraints. Dried blood spots from finger pricks have been shown to be more practical than the use of plasma specimens, and pooling strategies using plasma specimens have been demonstrated to be an efficient method to reduce costs. This study found that combination of finger-prick dried blood spots and a pooling strategy is a feasible and efficient option to reduce costs, while maintaining accuracy in the context of a district hospital in Malawi.
Full Text Available Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART. Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a HIV negative non-smokers, b HIV positive non-smokers, c HIV negative mild-to-moderate smokers, and d HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest
Walker, Simon; Cambiano, Valentina; Phillips, Andrew; Sculpher, Mark J.
Background The WHO HIV Treatment Guidelines suggest routine viral-load monitoring can be used to differentiate antiretroviral therapy (ART) delivery and reduce the frequency of clinic visits for patients stable on ART. This recommendation was informed by economic analysis that showed the approach is very likely to be cost-effective, even in the most resource constrained of settings. The health benefits were shown to be modest but the costs of introducing and scaling up viral load monitoring can be offset by anticipated reductions in the costs of clinic visits, due to these being less frequent for many patients. Key issues for economic evaluation The cost-effectiveness of introducing viral-load informed differentiated care depends upon whether cost reductions are possible if the number of clinic visits is reduced and/or how freed clinic capacity is used for alternative priorities. Where freed resources, either physical or financial, generate large health gains (e.g. if committed to patients failing ART or to other high value health care interventions), the benefits of differentiated care are expected to be high; if however these freed physical resources are already under-utilized or financial resources are used less efficiently and would not be put to as beneficial an alternative use, the policy may not be cost-effective. The implication is that the use of conventional unit costs to value resources may not well reflect the latter’s value in contributing to health improvement. Analyses intended to inform resource allocated decisions in a number of settings may therefore have to be interpreted with due consideration to local context. In this paper we present methods of how economic analyses can reflect the real value of health care resources rather than simply applying their unit costs. The analyses informing the WHO Guidelines are re-estimated by implementing scenarios using this framework, informing how differentiated care can be prioritized to generate greatest
Wang Yuanchi; Huang Jinwei
Objective: To investigate the relationship between changes of blood HBV DNA viral load and serum liver fibrosis markers levels in patients with chronic hepatitis B. Methods: In 2002, 20 patients with hepatitis B were divided into two groups: Group A treated with antiviral ageat (n=10), Group B not treated.Five years later (2007) the blood viral load (with FQ-PCR) and serum levels of hepatic fibrosis markers (with RIA) were determined in these patients. Results: The average log viral load in serum in the tow groups were 3.56 ± 1.12 (treated group) and 7.76 ± 1.23 respectively with significant difference (P<0.05). In 2002, serum liver fibrosis markers (HA, LN, IV-C, PCIII) levels were about the same in the two groups were (82.72 ± 30.62μg/ml, 71.18 ± 26.71μg/ml, 93.77 ± 69.87μg/ml, 91.4 ± 18.64μg/ml and 79.32 ± 31.34μg/ml, 70.25 ± 28.23)μg/ml, 90.35 ± 67.81μg/ml, 85.77 ± 20.56μg/ml respectively). In 2007, in the treated patients, serum liver fibrosis markers HA, LN, IV-C, PCIII levels were 85.72 ± 29.52μg/ml, 70.18 ± 25.4μg/ml, 94.2 ± 70.92μg/ml, 93.4 ± 19.32μg/ml respectively However, in the non-treated groups, the serum HA, LN, IV-C, PCIII levels were105.67 ± 28.54μg/ml, 97.75 ± 26.25μg/ml, 132 ± 72.13μg/ml, 120.72 ± 19.87μg/ml, being significantly higher than those in the treated group (P<0.05). Conclusion: Effective decrease of the viral load might control the progress of hepatic fibrosis in patients with chronic hepatitis B. (authors)
Full Text Available Objective To investigate the independent predictive factors for significant liver histological changes (SLHCs in patients with HBeAg-positive high-viral-load chronic hepatitis B virus (HBV infection and a normal alanine aminotransferase (ALT level. MethodsA retrospective analysis was performed on the clinical data of 116 previously untreated patients with HBeAg-positive high-viral-load (HBV DNA≥105 copies/ml chronic HBV infection and a normal ALT level (＜50 U/L who were hospitalized in Shanghai Public Health Clinical Center Affiliated to Fudan University from June 2013 to August 2015. The definition of SLHCs was inflammation ≥G2 and/or fibrosis≥S2. The t-test or Mann-Whitney U rank sum test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate regression analyses were used to determine independent predictive factors for SLHCs. ResultsOf all the 116 patients, 47(40.5% had SLHCs. The multivariate analysis showed that age (OR=2.828, P＜0.05, ALT (OR=1.011, P＜0.05, and gamma-glutamyl transpeptidase (GGT (OR=1.089, P＜0.05 were independent predictors for SLHCs in patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level. The patients aged ≤30 years had a significantly lower incidence rate of SLHCs than those aged＞30 years (21.6% vs 49.4%, χ2=6.42, P=0.015, the patients with ALT ≤30 U/L had a significantly lower incidence rate of SLHCs than those with 30 U/L＜ALT≤50 U/L (17.6% vs 50.0%, χ2=19.86, P＜0.001, and the patients with GGT≤40 U/L had a significantly lower incidence rate of SLHCs than those with GGT＞40 U/L (28.8% vs 66.7%, χ2=28.63, P＜0.001. ConclusionIn patients with HBeAg-positive high-viral-load chronic HBV infection and a normal ALT level, those with an age of＞30 years, ALT＞30 U/L, and GGT＞40 U/L tend to develop SLHCs and need liver biopsy.
Schäfer, Georgia; Kabanda, Siti; Rooyen, Beverly van; Marušič, Martina Bergant; Banks, Lawrence; Parker, M Iqbal
Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-α-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-α-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. This study showed that although the carcinogen benzo
Joel M. Palefsky
Full Text Available While much is known about the natural history of cervical human papillomavirus (HPV infection and its consequences, including cervical intraepithelial neoplasia and cervical cancer, relatively little is known about the natural history of anogenital HPV infection and diseases in men. In part this reflects difficulties in penile sampling and visual assessment of penile lesions. Anal HPV infection and disease also remain poorly understood. Although HPV is transmitted sexually and infects the genitals of both sexes, the cervix remains biologically more vulnerable to malignant transformation than does the penis or anus in men. An understanding of male HPV infection is therefore important in terms of reducing transmission of HPV to women and improving women's health. However, it is also important due to the burden of disease in men, who may develop both penile and anal cancer, particularly among HIV-positive men who have sex with men. Improved sampling techniques of the male genitalia and cohort studies in progress should provide important information on the natural history of anogenital HPV infection and disease in men, including risk factors for HPV acquisition and transmission. The impact of HPV vaccination in women on male anogenital HPV infection will also need to be assessed.
Wesley H Stepp
Full Text Available We have shown previously that Sp100 (a component of the ND10 nuclear body represses transcription, replication and establishment of incoming human papillomavirus (HPV DNA in the early stages of infection. In this follow up study, we show that Sp100 does not substantially regulate viral infection in the maintenance phase, however at late stages of infection Sp100 interacts with amplifying viral genomes to repress viral processes. We find that Sp100 localizes to HPV16 replication foci generated in primary keratinocytes, to HPV31 replication foci that form in differentiated cells, and to HPV16 replication foci in CIN 1 cervical biopsies. To analyze this further, Sp100 was down regulated by siRNA treatment of differentiating HPV31 containing cells and levels of viral transcription and replication were assessed. This revealed that Sp100 represses viral transcription and replication in differentiated cells. Analysis of Sp100 binding to viral chromatin showed that Sp100 bound across the viral genome, and that binding increased at late stages of infection. Therefore, Sp100 represses the HPV life cycle at both early and late stages of infection.
Thompson, Alexander J V; Nguyen, Tin; Iser, David; Ayres, Anna; Jackson, Kathy; Littlejohn, Margaret; Slavin, John; Bowden, Scott; Gane, Edward J; Abbott, William; Lau, George K K; Lewin, Sharon R; Visvanathan, Kumar; Desmond, Paul V; Locarnini, Stephen A
Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo. In all, 149 treatment-naïve CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (r = 0.69, 0.71, 0.76, P < 0.01). HBeAg correlated with serum HBV DNA (r = 0.60, P < 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker.
Full Text Available Epstein-Barr virus (EBV is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350 or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]. No comparative trials, however, have been performed. Rhesus lymphocryptovirus (LCV encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated rhesus monkeys at 0, 4 and 12 weeks with (a soluble rhesus LCV gp350, (b virus-like replicon particles (VRPs expressing rhesus LCV gp350, (c VRPs expressing rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with rhesus LCV, animals vaccinated with soluble rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with
Lesosky, Maia; Glass, Tracy; Mukonda, Elton; Hsiao, Nei-Yuan; Abrams, Elaine J; Myer, Landon
HIV viral load (VL) monitoring is a central tool to evaluate ART effectiveness and transmission risk. There is a global movement to expand VL monitoring following recent recommendations from the World Health Organization (WHO), but there has been little research into VL monitoring in pregnant women. We investigated one important question in this area: when and how frequently VL should be monitored in women initiating ART during pregnancy to predict VL at the time of delivery in a simulated South African population. We developed a mathematical model simulating VL from conception through delivery using VL data from the Maternal and Child Health - Antiretroviral Therapy (MCH-ART) cohort. VL was modelled based on three major compartments: pre-ART VL, viral decay immediately after ART initiation and viral maintenance (including viral suppression and viraemic episodes). Using this simulation, we examined the performance of various VL monitoring schema in predicting elevated VL at delivery. If WHO guidelines for non-pregnant adults were used, the majority of HIV-infected pregnant women (69%) would not receive a VL test during pregnancy. Most models that based VL monitoring in pregnancy on the time elapsed since ART initiation (regardless of gestation) performed poorly (sensitivity pregnancy on the woman's gestation (regardless of time on ART) appeared to perform better overall (sensitivity >60%). Across all permutations, inclusion of pre-ART VL values had a negligible impact on predictive performance (improving test sensitivity and specificity pregnancy, supporting better integration of maternal and HIV health services. Testing turnaround times require careful consideration, and point-of-care VL testing may be the best approach for measuring VL at delivery. Broadening the scope of this simulation model in the light of current scale up of VL monitoring in high burden countries is important. © 2017 The Authors. Journal of the International AIDS Society published by John
Medina González, Rafael; Orta Mira, Nieves; Guna Serrano, María Del Remedio; Latorre Martínez, José-Carlos; Gopegui, Enrique Ruiz de; Rosario Ovies, María; Poveda, Marta; Gimeno Cardona, Concepción
Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarizes the results obtained from the 2014 SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology) External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of 5 standards were sent. One standard consisted in seronegative human plasma, while the remaining 4 contained plasma from 3 different viremic patients, in the range of 2-5 log10 copies/mL; 2 of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (30.8% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 95.8% of laboratories reporting results within the limits (Δ quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Liu, Man-Qing; Tang, Li; Kong, Wen-Hua; Zhu, Ze-Rong; Peng, Jin-Song; Wang, Xia; Yao, Zhong-Zhao; Schilling, Robert; Zhou, Wang
In China, the rate of human immunodeficiency virus (HIV) testing is increasing among men who have sex with men. The purpose of the present study was to describe HIV-related biomarkers and selected demographic variables of persons with newly diagnosed HIV/AIDS, among men who have sex with men in particular, in Wuhan China. Demographic indicators, and CD4+ T cell counts and HIV-1 viral load were collected from individuals newly identified as HIV-1 antibody positive during 2011. Of 176 enrolled patients, 132 (75.0%) were men who have sex with men. This group was significantly younger and had higher CD4+ T cell counts than patients who were likely infected through heterosexual contact. Most men who have sex with men (56.6%) were discovered by initiative investigation. Among heterosexual patients CD4+ T cell counts and HIV-1 viral load were significantly correlated; among the group of men who have sex with men, no such association was found. Copyright © 2013 Wiley Periodicals, Inc.
Stacey X Xu
Full Text Available HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.
Xu, Stacey X; Leontyev, Danila; Kaul, Rupert; Gray-Owen, Scott D
HIV synergy with sexually transmitted co-infections is well-documented in the clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital HIV shedding and mucosal transmission. However, no animal model of co-infection currently exists to directly explore this relationship or to bridge the gap in understanding between clinical and in vitro studies of this interaction. This study aims to test the feasibility of using a humanized mouse model to overcome this barrier. Combining recent in vivo modelling advancements in both HIV and gonococcal research, we developed a co-infection model by engrafting immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae infection. Systemic plasma and vaginal lavage titres of HIV were measured in order to assess the impact of gonococcal challenge on viral plasma titres and genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels but higher viral shedding in the genital tract, which reflects published clinical observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an experimentally tractable animal model in which to study HIV shedding during gonococcal co-infection, allowing dissection of molecular and immunological interactions between these pathogens, and providing a platform to assess future therapeutics aimed at reducing HIV transmission.
Naegele, Klaudia; Lautenschlager, Irmeli; Gosert, Rainer; Loginov, Raisa; Bir, Katia; Helanterä, Ilkka; Schaub, Stefan; Khanna, Nina; Hirsch, Hans H
Cytomegalovirus (CMV) management post-transplantation relies on quantification in blood, but inter-laboratory and inter-assay variability impairs commutability. An international multicenter study demonstrated that variability is mitigated by standardizing plasma volumes, automating DNA extraction and amplification, and calibration to the 1st-CMV-WHO-International-Standard as in the FDA-approved Roche-CAP/CTM-CMV. However, Roche-CAP/CTM-CMV showed under-quantification and false-negative results in a quality assurance program (UK-NEQAS-2014). To evaluate factors contributing to quantification variability of CMV viral load and to develop optimized CMV-UL54-QNAT. The UL54 target of the UK-NEQAS-2014 variant was sequenced and compared to 329 available CMV GenBank sequences. Four Basel-CMV-UL54-QNAT assays of 361 bp, 254 bp, 151 bp, and 95 bp amplicons were developed that only differed in reverse primer positions. The assays were validated using plasmid dilutions, UK-NEQAS-2014 sample, as well as 107 frozen and 69 prospectively collected plasma samples from transplant patients submitted for CMV QNAT, with and without DNase-digestion prior to nucleic acid extraction. Eight of 43 mutations were identified as relevant in the UK-NEQAS-2014 target. All Basel-CMV-UL54 QNATs quantified the UK-NEQAS-2014 but revealed 10-fold increasing CMV loads as amplicon size decreased. The inverse correlation of amplicon size and viral loads was confirmed using 1st-WHO-International-Standard and patient samples. DNase pre-treatment reduced plasma CMV loads by >90% indicating the presence of unprotected CMV genomic DNA. Sequence variability, amplicon length, and non-encapsidated genomes obstruct standardization and commutability of CMV loads needed to develop thresholds for clinical research and management. Besides regular sequence surveys, matrix and extraction standardization, we propose developing reference calibrators using 100 bp amplicons. Copyright © 2018 Elsevier B.V. All
Pedro Brevis Azocar
Full Text Available La candidiasis bucal aparece con frecuencia en las personas infectadas por el virus de la inmunodeficiencia humana (VIH y puede causar diversas manifestaciones clínicas y complicaciones. En los pacientes VIH la carga viral es considerada uno de los principales predictores en la progresión de la enfermedad. Se realizó un estudio en 29 pacientes adultos VIH-positivos para evaluar los niveles de linfocitos T-CD4 y carga viral; se estableció una relación con las manifestaciones de la candidiasis bucal. El análisis estadístico mostró que hubo relación entre la manifestación de la candidiasis bucal y la carga viral, pues en pacientes con cargas virales superiores a 10 000 copias/mL, las lesiones fueron más frecuentes.Oral candidiasis is frequently appearing in persons infected by human immunodeficiency virus (HIV and may to cause many clinical and complications manifestations. In HIV patients the viral load is considered one of the main predictors in disease progression. A study was conducted in 29 HIV-positive adult patients to assess the T-CD4 lymphocyte levels and the viral load establishing a relationship with oral candidiasis manifestations. The statistical analysis showed that there was a relationship between the oral candidiasis manifestation and the viral load since in patients with viral load higher than 10 000 copies/mL, lesions were more frequent.
Laporta, Robert F.; Taichman, Lorne B.
Human papilloma virus (HPV) is poorly understood because systems for its growth in tissue culture have not been developed. We report here that cultured human epidermal keratinocytes could be infected with HPV from plantar warts and that the viral DNA persisted and replicated as a stable episome. There were 50-200 copies of viral DNA per cell and there was no evidence to indicate integration of viral DNA into the cellular genome. There was also no evidence to suggest that viral DNA underwent productive replication. We conclude that cultured human epidermal keratinocytes may be a model for the study of certain aspects of HPV biology.
Magaly M Blas
Full Text Available Human Papilloma Virus (HPV infection is the most common sexually transmitted viral infection worldwide. HPV is highly prevalent in sexually active men who have sex with men (MSM and has been associated with anal cancer, penile cancer, and oropharyngeal cancer.From March to September 2011, we conducted a cross-sectional study of HPV prevalence among MSM above age 18 years. Participants were recruited using respondent driven sampling at Clinica Cayetano Heredia. All participants provided anal, genital, and oral samples for HPV DNA testing, and blood for HIV and HPV antibody testing.A total of 200 MSM were recruited in the study. The mean age was 34 years (range 18-59 years, SD = 9.4 and101 participants were HIV negative (99 HIV positive. HPV 6/11/16/18 or quadrivalent HPV vaccine (HPV4 genotype seroprevalence among HIV negative and positive MSM was 64.3% (55%-75.9% and 93.8% (87.6%-99.2% respectively (p<0.001. HIV positivity was associated with a higher prevalence of HPV4 and HPV 16/18 DNA at external genital sites and the anal canal. HPV4 DNA prevalence at external genital sites among HIV negative and positive MSM was 14.9% and 28.7% (p = 0.02 respectively, at anal canal was 50.9% and 79.0% (p = 0.001, and at the oral cavity was 9.9% and 8.5% (p = 0.6.HPV4 seroprevalence was high in our study among both HIV positives and negatives, with HPV DNA prevalence much lower, and the anal canal being the anatomical site with the highest HPV DNA prevalence. HPV prevention interventions are needed among MSM at high-risk for HIV infection.
Mustanski, Brian; Ryan, Daniel T; Remble, Thomas A; D'Aquila, Richard T; Newcomb, Michael E; Morgan, Ethan
Suppressing HIV viral load through daily antiretroviral therapy (ART) substantially reduces the risk of HIV transmission, however, the potential population impact of treatment as prevention (TasP) is mitigated due to challenges with sustained care engagement and ART adherence. For an undetectable viral load (VL) to inform decision making about transmission risk, individuals must be able to accurately classify their VL as detectable or undetectable. Participants were 205 HIV-infected young men who have sex with men (YMSM) and transgender women (TGW) from a large cohort study in the Chicago area. Analyses examined correspondence among self-reported undetectable VL, study-specific VL, and most recent medical record VL. Among HIV-positive YMSM/TGW, 54% had an undetectable VL (suppression between medical visits may represent a particular risk for the TasP strategy among YMSM/TGW. Strategies for frequent viral load monitoring, that are not burdensome to patients, may be necessary to optimize TasP.
Clausen, L N; Weis, N; Astvad, K
Summary. Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are able to clear HCV spontaneously. Differences in host genetics are believed to affect the outcome of HCV infection. We analysed an exonic, a promoter and an intronic single nucleotide polymorphism (SNP) of the i......Summary. Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are able to clear HCV spontaneously. Differences in host genetics are believed to affect the outcome of HCV infection. We analysed an exonic, a promoter and an intronic single nucleotide polymorphism (SNP...... higher median HCV RNA levels than individuals with unfavourable haplotype blocks (P = 0.05). Our findings suggest that IL28B may account for some differences in HCV outcome but that other factors including the viral genotype, host genetics and the host-virus interaction are likely to influence...
Schabath, Matthew B; Thompson, Zachary J; Egan, Kathleen M; Torres, B Nelson; Nguyen, Anthony; Papenfuss, Mary R; Abrahamsen, Martha E; Giuliano, Anna R
Moderate alcohol consumption can impair host defence against viral infections. The objective of this cross-sectional analysis was to assess the association between alcohol intake and prevalent human papillomavirus (HPV) infection among US men enrolled in the HPV in Men (HIM) study using quantitative alcohol intake measured from a Food Frequency Questionnaire. The HIM study is a prospective, multinational study of the natural history of HPV infection. For this report, we restricted our analyses to men from the US cohort (N = 1313). Samples from the corona of glans penis, penile shaft and scrotum were combined for HPV DNA testing. Self-reported alcohol intake was quantified by grams of alcohol intake per day. Multivariable prevalence ratios (mPRs) were used to assess the association between alcohol intake and HPV infections. Prevalent infections were significantly higher among men in the highest quartile of alcohol intake and multivariable models revealed that the highest quartile of alcohol intake was associated with significantly increased risks for any (mPR = 1.13; 95% CI 1.00 to 1.27) HPV types and oncogenic (mPR = 1.35; 95% CI 1.08 to 1.68) HPV types. The fourth quartile of alcohol intake was associated with elevated risks for prevalent HPV infection across all strata of number of sexual partners and among never-smokers and current smokers, but not among former smokers. These results demonstrate that high intake of alcohol is associated with an increased risk for prevalent HPV infections among men. The biological role that alcohol plays in genital HPV infection remains understudied and limited epidemiological data exist, especially among men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Xu, Y; Li, Y F; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, M L; Grobler, J A; Lai, M-T; Gobburu, J; Ankrom, W
We applied model-based meta-analysis of viral suppression as a function of drug exposure and in vitro potency for short-term monotherapy in human immunodeficiency virus type 1 (HIV-1)-infected treatment-naïve patients to set pharmacokinetic targets for development of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs). We developed class-specific models relating viral load kinetics from monotherapy studies to potency normalized steady-state trough plasma concentrations. These models were integrated with a literature assessment of doses which demonstrated to have long-term efficacy in combination therapy, in order to set steady-state trough concentration targets of 6.17- and 2.15-fold above potency for NNRTIs and InSTIs, respectively. Both the models developed and the pharmacokinetic targets derived can be used to guide compound selection during preclinical development and to predict the dose-response of new antiretrovirals to inform early clinical trial design. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.
Xu, Y; Li, YF; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, ML; Grobler, JA; Lai, M‐T; Gobburu, J
We applied model‐based meta‐analysis of viral suppression as a function of drug exposure and in vitro potency for short‐term monotherapy in human immunodeficiency virus type 1 (HIV‐1)‐infected treatment‐naïve patients to set pharmacokinetic targets for development of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs). We developed class‐specific models relating viral load kinetics from monotherapy studies to potency normalized steady‐state trough plasma concentrations. These models were integrated with a literature assessment of doses which demonstrated to have long‐term efficacy in combination therapy, in order to set steady‐state trough concentration targets of 6.17‐ and 2.15‐fold above potency for NNRTIs and InSTIs, respectively. Both the models developed and the pharmacokinetic targets derived can be used to guide compound selection during preclinical development and to predict the dose–response of new antiretrovirals to inform early clinical trial design. PMID:27171172
Full Text Available Epstein Barr Virus (EBV and Human Herpes Virus 6 (HHV-6 are responsible for severe diseases, particularly in immunocompromised persons. There are poor data on the infection with these opportunistic viruses in Burkina Faso. The purpose of this study is to characterize EBV and HHV-6 subtypes and to assess their impact on CD4 T cell count, HIV-1 viral load and antiretroviral treatment in people living with HIV-1. The study population consisted of 238 HIV-positive patients with information on CD4 count, HIV-1 viral load and HAART. Venous blood samples collected on EDTA tubes were used for EBV and HHV-6 Real Time PCR subtyping. An infection rate of 6.7% (16/238 and 7.1% (17/238 were found respectively for EBV and HHV-6 in the present study. Among EBV infections, similar prevalences were noted for both subtypes (3.9% [9/238] for EBV-1 vs 4.6% [11/238] for EBV-2 with 2.1% (5/238 of co-infection. HHV-6A infection represented 6.3% (15/238 of the study population against 5.0% (12/238 for HHV-6B. . EBV-2 infection was significantly higher in patients with CD4 count ≥ 500 compared to those with CD4 count less than 500 cells (1.65% vs 8.56%, p = 0,011. The prevalence of EBV and HHV-6 infections were almost similar in HAART-naive and HAART-experienced patients. The present study provides information on the prevalence of EBV and HHV-6 subtypes in people living with HIV-1 in Burkina Faso. The study also suggests that HAART treatment has no effect on infection with these opportunistic viruses in people living with HIV-1.
Fernández-Rodríguez, Conrado M; Morillas, Rosa María; Masnou, Helena; Navarro, José María; Bárcena, Rafael; González, José Manuel; Martín-Martín, Leticia; Poyato, Antonio; Miquel-Planas, Mireia; Jorquera, Francisco; Casanovas, Teresa; Salmerón, Javier; Calleja, José Luis; Solà, Ricard; Alonso, Sonia; Planas, Ramón; Romero-Gomez, Manuel
Less than half of patients with chronic hepatitis C genotype 3 (G3) and high viral load (HVL) without a rapid virological response (RVR) achieve a sustained virological response (SVR) when treated with peginterferon plus ribavirin (RBV). To assess the impact of high doses of RBV on SVR in patients with G3 and HVL. Ninety-seven patients were randomized to receive peginterferon α-2a+RBV 800 mg/day (A; n=42) or peginterferon α-2a+RBV 1600 mg/day+epoetin β 400 IU/kg/week SC (B; n=55). Patients allocated to group B who achieved RVR continued on RBV (800mg/day) for a further 20 weeks (B1; n=42) while non-RVR patients received a higher dose of RBV (1600 mg/day)+epoetin β (B2; n=13). RVR was observed in 64.3% of patients in A and in 76.4% in B (p=0.259). Intention-to-treat (ITT) analysis showed SVR rates of 64.3% (A) and 61.8% (B), with a reduction of -2.5% (-21.8% to 16.9%) (p=0.835). The SVR rate was 61.9% in arm B1 and 61.5% in arm B2. No serious adverse events were reported, and the rate of moderate adverse events was < 5%. G3 patients with high viral load without RVR did not obtain a benefit from a higher dose of RBV. Higher doses of RBV plus epoetin β were safe and well tolerated (Clin Trials Gov NCT00830609). Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.
Full Text Available Dengue virus (DENV causes more human infections than any other mosquito-borne virus. The current lack of antiviral strategies has prompted genome-wide screens for host genes that are required for DENV infectivity. Earlier transcriptomic studies that identified DENV host factors in the primary vector Aedes aegypti used inbred laboratory colonies and/or pools of mosquitoes that erase individual variation. Here, we performed transcriptome sequencing on individual midguts in a field-derived Ae. aegypti population to identify new candidate host factors modulating DENV replication. We analyzed the transcriptomic data using an approach that accounts for individual co-variation between viral RNA load and gene expression. This approach generates a prediction about the agonist or antagonist effect of candidate genes on DENV replication based on the sign of the correlation between gene expression and viral RNA load. Using this method, we identified 39 candidate genes that went undetected by conventional pairwise comparison of gene expression levels between DENV-infected midguts and uninfected controls. Only four candidate genes were detected by both methods, emphasizing their complementarity. We demonstrated the value of our approach by functional validation of a candidate agonist gene encoding a sterol regulatory element-binding protein (SREBP, which was identified by correlation analysis but not by pairwise comparison. We confirmed that SREBP promotes DENV infection in the midgut by RNAi-mediated gene knockdown in vivo. We suggest that our approach for transcriptomic analysis can empower genome-wide screens for potential agonist or antagonist factors by leveraging inter-individual variation in gene expression. More generally, this method is applicable to a wide range of phenotypic traits displaying inter-individual variation.
Dou, Z; Chen, J; Jiang, Z; Song, W L; Xu, J; Wu, Z Y
Objective: To understand the distribution of population viral load (PVL) data in HIV infected men who have sex with men (MSM), fit distribution function and explore the appropriate estimating parameter of PVL. Methods: The detection limit of viral load (VL) was ≤ 50 copies/ml. Box-Cox transformation and normal distribution tests were used to describe the general distribution characteristics of the original and transformed data of PVL, then the stable distribution function was fitted with test of goodness of fit. Results: The original PVL data fitted a skewed distribution with the variation coefficient of 622.24%, and had a multimodal distribution after Box-Cox transformation with optimal parameter ( λ ) of-0.11. The distribution of PVL data over the detection limit was skewed and heavy tailed when transformed by Box-Cox with optimal λ =0. By fitting the distribution function of the transformed data over the detection limit, it matched the stable distribution (SD) function ( α =1.70, β =-1.00, γ =0.78, δ =4.03). Conclusions: The original PVL data had some censored data below the detection limit, and the data over the detection limit had abnormal distribution with large degree of variation. When proportion of the censored data was large, it was inappropriate to use half-value of detection limit to replace the censored ones. The log-transformed data over the detection limit fitted the SD. The median ( M ) and inter-quartile ranger ( IQR ) of log-transformed data can be used to describe the centralized tendency and dispersion tendency of the data over the detection limit.
Arpi S Terzian
Full Text Available Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA in New York City (NYC with sustained high VL (SHVL and durably suppressed VL (DSVL.Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and ≥12 years old by the end of 2005 and who had ≥2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs ≥100,000 copies/mL and PLWHA with all VLs ≤400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7% had SHVL and 38% had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average.Nearly 60% of PLWHA in 2005 had multiple VLs, of whom almost 40% had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based on longitudinal analyses of surveillance data in conjunction with cross-sectional measures such as community viral load represent more precise and powerful tools for monitoring ART effectiveness and potential impact on disease transmission than cross-sectional measures alone.
Saskia M. Wilting
Full Text Available Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV and develops via precursor stages, called cervical intraepithelial neoplasia (CIN. High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1 increase our understanding of cervical carcinogenesis, 2 yield biomarkers for early diagnosis, and 3 identify therapeutic targets for HPV-induced (pre cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.
Most human papillomavirus (HPV) antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR) and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies.
Parfenov, Michael; Pedamallu, Chandra Sekhar; Gehlenborg, Nils; Freeman, Samuel S.; Danilova, Ludmila; Bristow, Christopher A.; Lee, Semin; Hadjipanayis, Angela G.; Ivanova, Elena V.; Wilkerson, Matthew D.; Protopopov, Alexei; Yang, Lixing; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Ren, Xiaojia; Zhang, Jianhua; Pantazi, Angeliki; Santoso, Netty; Xu, Andrew W.; Mahadeshwar, Harshad; Wheeler, David A.; Haddad, Robert I.; Jung, Joonil; Ojesina, Akinyemi I.; Issaeva, Natalia; Yarbrough, Wendell G.; Hayes, D. Neil; Grandis, Jennifer R.; El-Naggar, Adel K.; Meyerson, Matthew; Park, Peter J.; Chin, Lynda; Seidman, J. G.; Hammerman, Peter S.; Kucherlapati, Raju; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Butterfield, Yaron S.N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Protopopov, Alexei; Santoso, Netty; Lee, Semin; Parfenov, Michael; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Haseley, Psalm; Zeng, Dong; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Bristow, Christopher; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Lu, Yiling; Mills, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Liu, Jinze; Wang, Kai; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Buda, Elizabeth; Hayes, D. Neil; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Marron, J.S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Mathew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Cherniack, Andrew D.; Hammerman, Peter S.; Tward, Aaron D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Chin, Lynda; Getz, Gad; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil; Lawrence, Michael S.; Sougnez, Carrie; Lichtenstein, Lee; Cibulskis, Kristian; Lander, Eric; Gabriel, Stacey B.; Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu; Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinha, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timothy; Morris, Luc; Stuart, Joshua; Benz, Stephen; Ng, Sam; Benz, Christopher; Yau, Christina; Baylin, Stephen B.; Cope, Leslie; Danilova, Ludmila; Herman, James G.; Bootwalla, Moiz; Maglinte, Dennis T.; Laird, Peter W.; Triche, Timothy; Weisenberger, Daniel J.; Van Den Berg, David J.; Agrawal, Nishant; Bishop, Justin; Boutros, Paul C.; Bruce, Jeff P; Byers, Lauren Averett; Califano, Joseph; Carey, Thomas E.; Chen, Zhong; Cheng, Hui; Chiosea, Simion I.; Cohen, Ezra; Diergaarde, Brenda; Egloff, Ann Marie; El-Naggar, Adel K.; Ferris, Robert L.; Frederick, Mitchell J.; Grandis, Jennifer R.; Guo, Yan; Haddad, Robert I.; Hammerman, Peter S.; Harris, Thomas; Hayes, D. Neil; Hui, Angela BY; Lee, J. Jack; Lippman, Scott M.; Liu, Fei-Fei; McHugh, Jonathan B.; Myers, Jeff; Ng, Patrick Kwok Shing; Perez-Ordonez, Bayardo; Pickering, Curtis R.; Prystowsky, Michael; Romkes, Marjorie; Saleh, Anthony D.; Sartor, Maureen A.; Seethala, Raja; Seiwert, Tanguy Y.; Si, Han; Tward, Aaron D.; Van Waes, Carter; Waggott, Daryl M.; Wiznerowicz, Maciej; Yarbrough, Wendell; Zhang, Jiexin; Zuo, Zhixiang; Burnett, Ken; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candance; Shelton, Troy; Sherman, Mark; Yena, Peggy; Black, Aaron D.; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M.; Harper, Hollie A.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Baboud, Julien; Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Walton, Jessica S.; Wan, Yunhu; Burton, Robert; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin L.; Shaw, Kenna R. Mills; Ozenberger, Bradley A.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Saller, Charles; Tarvin, Katherine; Chen, Chu; Bollag, Roni; Weinberger, Paul; Golusiński, Wojciech; Golusiński, Paweł; Ibbs, Matthiew; Korski, Konstanty; Mackiewicz, Andrzej; Suchorska, Wiktoria; Szybiak, Bartosz; Wiznerowicz, Maciej; Burnett, Ken; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert; Shelton, Troy; Yena, Peggy; Beard, Christina; Mitchell, Colleen; Sandusky, George; Agrawal, Nishant; Ahn, Julie; Bishop, Justin; Califano, Joseph; Khan, Zubair; Bruce, Jeff P; Hui, Angela BY; Irish, Jonathan; Liu, Fei-Fei; Perez-Ordonez, Bayardo; Waldron, John; Boutros, Paul C.; Waggott, Daryl M.; Myers, Jeff; Lippman, Scott M.; Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Bradford, Carol R.; Carey, Thomas E.; Chepeha, Douglas B.; Haddad, Andrea S.; Jones, Tamara R.; Komarck, Christine M.; Malakh, Mayya; McHugh, Jonathan B.; Moyer, Jeffrey S.; Nguyen, Ariane; Peterson, Lisa A.; Prince, Mark E.; Rozek, Laura S.; Sartor, Maureen A.; Taylor, Evan G.; Walline, Heather M.; Wolf, Gregory T.; Boice, Lori; Chera, Bhishamjit S.; Funkhouser, William K.; Gulley, Margaret L.; Hackman, Trevor G.; Hayes, D. Neil; Hayward, Michele C.; Huang, Mei; Rathmell, W. Kimryn; Salazar, Ashley H.; Shockley, William W.; Shores, Carol G.; Thorne, Leigh; Weissler, Mark C.; Wrenn, Sylvia; Zanation, Adam M.; Chiosea, Simion I.; Diergaarde, Brenda; Egloff, Ann Marie; Ferris, Robert L.; Romkes, Marjorie; Seethala, Raja; Brown, Brandee T.; Guo, Yan; Pham, Michelle; Yarbrough, Wendell G.
Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis. PMID:25313082
Full Text Available It is widely accepted that only persistent infection with high risk types of Human Papillomavirus (HPV HR is a significant risk factor for the development of an invasive squamous cervical cancer. The overexpression of viral oncogenes E6/E7 of HPV is considered a necessary process for incurring in a malignant phenotype.A HPV infection can be identified by detection of HPV DNA in biological samples, but the DNAbased tests cannot delineate between transient or persistent and potentially transforming infection. Instead there is many evidence to suggest that detection of HPV gene expression may constitute a more specific approach to highlight a clinically significant infection. Especially seems that the detection of E6/E7 transcripts can be usefully used for identify the women with a persistent HPV infection that will can induce a future cervical cancer. The aim of our study is to investigate if the detection of oncogenic viral gene activity by detecting transcripts of the E6 and E7 genes can be most usefull of HPV-DNA test in the triage of ASCUS or low grade cervical lesions. Our results confirm that HPV E6/E7 mRNA test can be considered a promising method to stratify HPV positive women for risk of future high-grade cervical lesions or cervical intaepithelial neoplasia.
... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...
Joeli A. Brinkman
Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.
Full Text Available Silvestro Ennio D’Anna,1 Bruno Balbi,2 Francesco Cappello,3,4 Mauro Carone,2 Antonino Di Stefano21Department of Rehabilitation, Cardiorespiratory Unit, Fondazione Istituto G. Giglio di Cefalù, 2Pneumology Unit and Laboratory of Cytoimmunopathology of Heart and Lung, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO and Cassano delle Murge (BA, 3Human Anatomy Section, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy; 4Euro-Mediterranean Institute of Science and Technology, Palermo, ItalyAbstract: Chronic obstructive pulmonary disease (COPD is characterized by persistent airflow limitation and an abnormal inflammatory response of the lung. Bacteria and viruses are a major cause of COPD exacerbations and may contribute to COPD progression by perpetuating the inflammatory response in the airways. Bacterial variety diminishes with increasing COPD severity. Respiratory viruses can colonize the lower respiratory tract in stable COPD, altering the respiratory microbiome and facilitating secondary bacterial infections. In this review, we present the most updated information about the role of bacteria and viruses in stable and exacerbated COPD. In our opinion, to optimize therapeutic strategies, the dynamic events involving bacterial–viral infections and related immune response in COPD phenotypes need to be better clarified. Our paper would address these points that we consider of great importance for the clinical management of COPD.Keywords: COPD phenotype, biomarkers, exacerbations, severity of COPD, microbiome
Gemigniani, Franco; Hernández-Losa, Javier; Ferrer, Berta; García-Patos, Vicente
Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine. © 2015 Japanese Dermatological Association.
Full Text Available Abstract Background The female lower genital tract is a gateway for pathogens entering the host through the mucous membrane. One of the prevalent human viruses is Torque teno virus (TTV. The major reported routes of TTV transmission are fecal-oral and parenteral. Furthermore, other modes of transmission, e.g. sexual contact, are suggested. To investigate the sexual route of TTV transmission, cervical smears of healthy women and those with cervical lesions were screened for the presence of TTV DNA. Methods TTV DNA was studied in cervical smears of 95 patients with cervical lesions and 55 healthy women. Paired serum samples were available from 55 and 42 women, respectively. All healthy women had normal cytology while 44 patients had histologically confirmed low-grade lesion (LGL and 51 high-grade lesion (HGL. TTV DNA was detected with primers specific for the non-coding region. In 40 paired cervical smears and serum samples, the phylogenetic group of TTV isolates was determined. The presence of HPV DNA in cervical smears was detected by means of PCR with MY09/11 primers. Results The prevalence of TTV DNA in cervical smears of healthy women was 52.7% and was comparable with that in paired serum samples (50%. Symptomatic women had significantly higher prevalence of TTV DNA in cervical smears (74.7% than healthy controls. The TTV DNA prevalence in patient serum samples was 51%. The phylogenetic groups of TTV serum isolates were concordant with those of TTV from cervical smears of the same subjects. In cervical smears, a wider variety of TTV isolates was found. The viral loads in cervical smears were 10 to 1000 times as high as in sera. The HPV-positive study subjects had significantly higher TTV DNA prevalence than HPV negatives. The prevalence of TTV was not associated with disease severity. Conclusion High prevalence of TTV in cervical smears suggests that sexual transmission is another mode of expansion of TTV infection among the population. The
Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.
... test; Cancer of cervix - HPV DNA test References Hacker NF. Cervical dysplasia and cancer. In: Hacker NF, Gambone JC, Hobel CJ, eds. Hacker and Moore's Essentials of Obstetrics and Gynecology . 6th ...
Ilardi, Gennaro; Russo, Daniela; Varricchio, Silvia; Salzano, Giovanni; Dell'Aversana Orabona, Giovanni; Napolitano, Virginia; Di Crescenzo, Rosa Maria; Borzillo, Alessandra; Martino, Francesco; Merolla, Francesco; Mascolo, Massimo; Staibano, Stefania
Human Papilloma Virus (HPV) can play a causative role in the development of sinonasal tract malignancies. In fact, HPV may be the most significant causative agent implicated in sinonasal tumorigenesis and is implicated in as many as 21% of sinonasal carcinomas. To date, there are no definitive, reliable and cost-effective, diagnostic tests approved by the FDA for the unequivocal determination of HPV status in head and neck cancers. We followed an exhaustive algorithm to correctly test HPV infection, including a sequential approach with p16INK4a IHC, viral DNA genotyping and in situ hybridization for E6/E7 mRNA. Here, we report a case of sinonasal carcinoma with discordant results using HPV test assays. The tumor we describe showed an irregular immunoreactivity for p16INK4a, and it tested positive for HPV DNA; nevertheless, it was negative for HR-HPV mRNA. We discuss the possible meaning of this discrepancy. It would be advisable to test HPV transcriptional status of sinonasal carcinoma on a diagnostic routine basis, not only by p16INK4a IHC assay, but also by HPV DNA genotyping and HR-HPV mRNA assessment.
Arpadi, Stephen M; Shiau, Stephanie; De Gusmao, Eduarda Pimentel; Violari, Avy
The objective of this commentary is to review considerations for implementing routine viral load (VL) monitoring programmes for HIV-infected infants and children living in low- and middle-income countries (LMIC). Since 2013, the World Health Organization (WHO) guidelines recommend VL testing as the preferred monitoring approach for all individuals treated with ART in order to assess treatment response, detect treatment failure and determine the need to switch to a second-line regimen in a timely manner. More recently, WHO guidelines from 2016 identify HIV-infected infants and children as a priority group for routine VL monitoring. There are a number of reasons why HIV-infected infants and children should be prioritized for routine VL monitoring. Data from national VL monitoring programmes as well as systematic reviews and meta-analyses from LMIC indicate rates of viral suppression are lower for infants and children compared to adults. The number of antiretroviral drugs and palatable formulations suitable for young children are limited. In addition, emotional and developmental issues particular to children can make daily medication administration difficult and pose a challenge to adherence and achievement of sustained viral suppression. VL monitoring can be instrumental for identifying those in need of additional adherence support, reducing regimen switches and preserving treatment options. The needs of infants and children warrant consideration in all aspects of VL monitoring services. If capacity for paediatric venipuncture is not assured, platforms that accept dried blood spot specimens are necessary in order for infants and children to have equitable access. Healthcare systems also need to prepare to manage the substantial number of infants and children identified with elevated VL, including adherence interventions that are appropriate for children. Establishing robust systems to evaluate processes and outcomes of routine VL monitoring services and to support
Joseph Davey, D; Abrahams, Z; Feinberg, M; Prins, M; Serrao, C; Medeossi, B; Darkoh, E
Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs when treatment fails to suppress a person's VL and is associated with decreased survival and increased HIV transmission. The objective of this study was to evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients currently in care on first-line ART for ≥ 6 months attending South African public healthcare facilities. We analysed electronic medical records of ART patients with a VL result on record who started ART between January 2004 and April 2016 from 271 public health facilities. We present descriptive and multivariable logistic regression for unsuppressed VL at last visit using a priori variables. We included 244,370 patients (69% female) on first-line ART in April 2016 for ≥ 6 months. Median age at ART start was 33 years (7% were < 15 years old). Median duration on ART was 3.7 years. Adjusting for other variables, factors associated with having an unsuppressed VL at the most recent visit among patients in care included: (1) < 15 years old at ART start (adjusted odds ratio [aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender (aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR = 1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95% CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI = 1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved viral suppression, though men, youth/adolescents, patients with prior ART exposure, those with short duration of ART, and patients on TB treatment had increased odds of not achieving viral suppression. There is a need to develop and evaluate targeted interventions for ART patients in care who are at high risk of unsuppressed VL.
Susta, Leonardo; Diel, Diego G; Courtney, Sean; Cardenas-Garcia, Stivalis; Sundick, Roy S; Miller, Patti J; Brown, Corrie C; Afonso, Claudio L
In mammals, interleukin 2 (IL-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens (herpes simplex virus, vaccinia virus, human respiratory syncytial virus, human immunodeficiency virus) by activating natural killer cells (NK), cytotoxic T lymphocytes and expanding subsets of memory cells. In chickens, IL-2 has been shown to activate T cells, and as such it might have the potential to affect replication and pathogenesis of Newcastle disease virus (NDV). To assess the effect of IL-2 during NDV infection in chickens, we produced a recombinant virulent NDV strain expressing chicken IL-2 (rZJ1-IL2). The effects of IL-2 expression were investigated in vivo using the intracerebral pathogenicity index (ICPI) in day-old chicks and pathogenesis experiments in 4-week-old chickens. In these studies, rZJ1-IL2 was compared to a control virus expressing the green fluorescent protein (rZJ1-GFP). Assessed parameters included survival curves, detailed histological and immunohistochemical grading of lesions in multiple organs, and virus isolation in blood, spleen and mucosal secretions of infected birds. At the site of infection (eyelid), expression of IL-2 was demonstrated in areas of rZJ-IL2 replication, confirming IL-2 production in vivo. Compared to rZJ1-GFP strain, rZJ1-IL2 caused milder lesions and displayed decreased viral load in blood, spleen and mucosal secretions of infected birds. In the rZJ1-IL2-infected group, virus level in the blood peaked at day 4 post-infection (pi) (10(3.46) EID50 /0.1 ml) and drastically decreased at day 5 pi (10(0.9) EID50/0.1 ml), while in the rZJ1-GFP-infected group virus levels in the blood reached 10(5.35) EID50/0.1 ml at day 5. However, rZJ1-IL2-infected groups presented survival curves similar to control birds infected with rZJ1-GFP, with comparable clinical signs and 100 % mortality. Further, expression of IL-2 did not significantly affect the ICPI scores, compared to rZJ1-GFP strain. Increased
de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B; Kuiken, Sjoerd D; Weijer, Sebastiaan; van Nieuwkerk, Carin M J; Zaaijer, Hans L; Molenkamp, Richard; Takkenberg, R Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W
Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen [anti-HBs]). We assessed HBsAg loss during peg-interferon-alfa-2a (peg-IFN) and nucleotide analogue combination therapy in patients with chronic hepatitis B with a low viral load. In this randomised controlled, open-label trial, patients were enrolled from the Academic Medical Center (AMC), Amsterdam, Netherlands. Eligible patients were HBsAg positive and hepatitis B e antigen (HBeAg) negative for more than 6 months, could be treatment naive or treatment experienced, and had alanine aminotransferase (ALT) concentrations less than 5 × upper limit of normal (ULN). Participants were randomly assigned (1:1:1) by a computerised randomisation programme (ALEA Randomisation Service) to receive peg-IFN 180 μg/week plus adefovir 10 mg/day, peg-IFN 180 μg/week plus tenofovir disoproxil fumarate 245 mg/day, or no treatment for 48 weeks. The primary endpoint was the proportion of patients with serum HBsAg loss among those who received at least one dose of study drug or had at least one study visit (modified intention-to-treat population [mITT]). All patients have finished the initial study of 72 weeks and will be observed for up to 5 years of follow-up. This study is registered with ClinicalTrials.gov, number NCT00973219. Between Aug 4, 2009, and Oct 17, 2013, 167 patients were screened for enrolment, of whom 151 were randomly assigned (52 to peg-IFN plus adefovir, 51 to peg-IFN plus tenofovir, and 48 to no treatment). 46 participants in the peg-IFN plus adefovir group, 45 in the peg-IFN plus tenofovir group, and 43 in the no treatment group began treatment or observation and were included in the mITT population. At week 72, two (4%) patients in the peg-IFN plus adefovir group and two (4
Brand, Toni M; Hartmann, Stefan; Bhola, Neil E; Peyser, Noah D; Li, Hua; Zeng, Yan; Isaacson Wechsler, Erin; Ranall, Max V; Bandyopadhyay, Sourav; Duvvuri, Umamaheswar; LaVallee, Theresa M; Jordan, Richard C K; Johnson, Daniel E; Grandis, Jennifer R
Purpose: Human papillomavirus (HPV) 16 plays an etiologic role in a growing subset of head and neck squamous cell carcinomas (HNSCC), where viral expression of the E6 and E7 oncoproteins is necessary for tumor growth and maintenance. Although patients with HPV + tumors have a more favorable prognosis, there are currently no HPV-selective therapies. Recent studies identified differential receptor tyrosine kinase (RTK) profiles in HPV + versus HPV - tumors. One such RTK, HER3, is overexpressed and interacts with phosphoinositide-3-kinase (PI3K) in HPV + tumors. Therefore, we investigated the role of HPV oncoproteins in regulating HER3-mediated signaling and determined whether HER3 could be a molecular target in HPV + HNSCC. Experimental Design: HER3 was investigated as a molecular target in HPV + HNSCC using established cell lines, patient-derived xenografts (PDX), and human tumor specimens. A mechanistic link between HPV and HER3 was examined by augmenting E6 and E7 expression levels in HNSCC cell lines. The dependency of HPV + and HPV - HNSCC models on HER3 was evaluated with anti-HER3 siRNAs and the clinical stage anti-HER3 monoclonal antibody KTN3379. Results: HER3 was overexpressed in HPV + HNSCC, where it was associated with worse overall survival in patients with pharyngeal cancer. Further investigation indicated that E6 and E7 regulated HER3 protein expression and downstream PI3K pathway signaling. Targeting HER3 with siRNAs or KTN3379 significantly inhibited the growth of HPV + cell lines and PDXs. Conclusions: This study uncovers a direct relationship between HPV infection and HER3 in HNSCC and provides a rationale for the clinical evaluation of targeted HER3 therapy for the treatment of HPV + patients. Clin Cancer Res; 23(12); 3072-83. ©2016 AACR . ©2016 American Association for Cancer Research.
Full Text Available PURPOSE: The aim of this study was to evaluate the comprehension and acceptance of HPV vaccination in parents of adolescent boys aged 11 to 15 years. METHODS: A cross-sectional survey was conducted by means of questionnaires sent directly to the homes of all families with young males aged between 11 and 15, residents of three municipalities of the Province of Brescia, Italy. The documentation also contained an informative leaflet summarizing the HPV-related disease characteristics, the burden of disease and the available strategies for prevention and treatment, illustrating the rationale of vaccination and describing the project and its phases. The questionnaire included questions on demographic data, acceptance and motivations for HPV vaccination. The collected data was analyzed using descriptive statistics. At the end of the study, parents who received the questionnaires were also offered the possibility of vaccinating their male sons for free. RESULTS: From a total of 1072 questionnaires sent, 161 where returned from the three selected municipalities (average response rate 15%; 97% of adolescent males involved in the study were Italian and 91% Catholic; 97% of parents declared themselves to be willing to vaccinate their sons: the principal motivation given (92% was prevention of the disease, cancerous or not, related to viral infection. Among the respondents not willing to vaccinate their sons, the motivation was lack of information about the vaccine and the disease. At the end of the study, around 71 boys were vaccinated. DISCUSSION: To our knowledge, this is the first survey in Italy exclusively conducted on parents of adolescent males about the acceptability and feasibility of vaccination against HPV: a very high percentage of respondents was favorable to accept the vaccination for their sons, the main motivation being the fact that parents considered protecting their sons from HPV-related diseases highly important. Of the 161 boys
de Freitas, Vera Lúcia Teixeira; da Silva, Sheila Cristina Vicente; Sartori, Ana Marli; Bezerra, Rita Cristina; Westphalen, Elizabeth Visone Nunes; Molina, Tatiane Decaris; Teixeira, Antonio R. L.; Ibrahim, Karim Yaqub; Shikanai-Yasuda, Maria Aparecida
Background Reactivation of chronic Chagas disease, which occurs in approximately 20% of patients coinfected with HIV/Trypanosoma cruzi (T. cruzi), is commonly characterized by severe meningoencephalitis and myocarditis. The use of quantitative molecular tests to monitor Chagas disease reactivation was analyzed. Methodology Polymerase chain reaction (PCR) of kDNA sequences, competitive (C-) PCR and real-time quantitative (q) PCR were compared with blood cultures and xenodiagnosis in samples from 91 patients (57 patients with chronic Chagas disease and 34 with HIV/T. cruzi coinfection), of whom 5 had reactivation of Chagas disease and 29 did not. Principal Findings qRT-PCR showed significant differences between groups; the highest parasitemia was observed in patients infected with HIV/T. cruzi with Chagas disease reactivation (median 1428.90 T. cruzi/mL), followed by patients with HIV/T. cruzi infection without reactivation (median 1.57 T. cruzi/mL) and patients with Chagas disease without HIV (median 0.00 T. cruzi/mL). Spearman's correlation coefficient showed that xenodiagnosis was correlated with blood culture, C-PCR and qRT-PCR. A stronger Spearman correlation index was found between C-PCR and qRT-PCR, the number of parasites and the HIV viral load, expressed as the number of CD4+ cells or the CD4+/CD8+ ratio. Conclusions qRT-PCR distinguished the groups of HIV/T. cruzi coinfected patients with and without reactivation. Therefore, this new method of qRT-PCR is proposed as a tool for prospective studies to analyze the importance of parasitemia (persistent and/or increased) as a criterion for recommending pre-emptive therapy in patients with chronic Chagas disease with HIV infection or immunosuppression. As seen in this study, an increase in HIV viral load and decreases in the number of CD4+ cells/mm3 and the CD4+/CD8+ ratio were identified as cofactors for increased parasitemia that can be used to target the introduction of early, pre-emptive therapy. PMID
Eliane Pedra Dias
Full Text Available The authors present a study of five cases of vulvar congenital papillomas and papillomatoses in stillborns and neonates dead upon birth. The studied material was collected from five necropsies. The histopathological evaluation showed hyperkeratosis, acanthosis, papillomatosis, perinuclear haloes, and nuclear abnormalities. In three of the cases, the electron microscopy identified nuclear and cytoplasmatic viral particles ranging from 40 to 60 nm in size, compatible with HPV. The immunohistochemical study of those lesions showed nuclear and cytoplasmatic positivity. The authors concluded that the presence of viral particles suggestive of HPV added to the immunopositivity indicated the possibility of viral infection.
Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.
Helen C Johnson
Full Text Available Quantifying rates governing the clearance of Human Papillomavirus (HPV and its progression to clinical disease, together with viral transmissibility and the duration of naturally-acquired immunity, is essential in estimating the impact of vaccination programmes and screening or testing regimes. However, the complex natural history of HPV makes this difficult. We infer the viral transmissibility, rate of waning natural immunity and rates of progression and clearance of infection of 13 high-risk and 2 non-oncogenic HPV types, making use of a number of rich datasets from Sweden. Estimates of viral transmissibility, clearance of initial infection and waning immunity were derived in a Bayesian framework by fitting a susceptible-infectious-recovered-susceptible (SIRS transmission model to age- and type-specific HPV prevalence data from both a cross-sectional study and a randomised controlled trial (RCT of primary HPV screening. The models fitted well, but over-estimated the prevalence of four high-risk types with respect to the data. Three of these types (HPV-33, -35 and -58 are among the most closely related phylogenetically to the most prevalent HPV-16. The fourth (HPV-45 is the most closely related to HPV-18; the second most prevalent type. We suggest that this may be an indicator of cross-immunity. Rates of progression and clearance of clinical lesions were additionally estimated from longitudinal data gathered as part of the same RCT. Our estimates of progression and clearance rates are consistent with the findings of survival analysis studies and we extend the literature by estimating progression and clearance rates for non-16 and non-18 high-risk types. We anticipate that such type-specific estimates will be useful in the parameterisation of further models and in developing our understanding of HPV natural history.
Lee, Sin Hang; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William
The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm
Lee, Sin Hang, E-mail: email@example.com; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William [Department of Pathology, Milford Hospital, 300 Seaside Ave., Milford, CT 06460 (United States)
The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm.
Full Text Available Human papillomavirus (HPV infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design.
Arucha L Ekeowa-Anderson
Full Text Available Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV, particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma-HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma- PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN and vulval squamous cell carcinoma (vSCC. We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy.
Full Text Available Background: In cervical cancer, the carcinogenic mechanism of human papillomavirus (HPV occurs through the integration of viral DNA into the host genome. This process initiates with a disruption in the E2 open reading frame (ORF of the viral genome. Disruption of E2 ORF results in an increased expression of the viral oncoproteins, E6 and E7, by removal of E2 suppression effect on their promoters. E6 and E7 interfere with the normal cell cycle by degrading the p53 and pRb tumor suppressor proteins, respectively. Objectives: The objective of this study was to determine the physical status (episomal/integral of HPV genome in esophageal squamous cell carcinoma (ESCC. Materials and Methods: The rate of copy numbers of E2 and E6 genes in HPV-18 and HPV-16 positive samples were analyzed by quantitative polymerase chain reaction (qPCR in order to assess the physical status (episomal/integral of HPV. DNA extracts from HeLa cell line were used as the positive control. Results: The E2 gene was detected in 1 sample, co-infected with HPV-16 and HPV-18. While, E6 gene was detected in all 11 HPV positive samples. The qPCR analysis showed the presence of integrated form of viral DNA in all HPV positive samples and only 1 mixed episomal-integrated form was detected. Conclusion: The presence of integrated forms of high risk HPV-16 and HPV-18 genomes might reflect a crucial process towards malignant transformation of ESCC.
Sun, Yun-Yan; Peng, Shiwen; Han, Liping; Qiu, Jin; Song, Liwen; Tsai, Yachea; Yang, Benjamin; Roden, Richard B S; Trimble, Cornelia L; Hung, Chien-Fu; Wu, T-C
Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high-grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Here, we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than intramuscular (IM) delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16(+) cervical cancer (TC-1 luc). We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8(+) T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8(+) T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8(+) T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8(+) T-cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Our results support future clinical translation using cervicovaginal TA-HPV vaccination. ©2015 American Association for Cancer Research.
Neil A Martinson
Full Text Available BACKGROUND: CD4 count is a proxy for the extent of immune deficiency and declines in CD4 count are a measure of disease progression. Decline in CD4 count is an important component: for estimating benefits of ARV treatment; for individual level counselling on the rapidity of untreated disease progression and prognosis; and can be used in planning demand for health services. Our objective is to report CD4 decline and changes in viral load (VL in a group of HIV-infected adults enrolled in a randomized trial of preventive treatment for TB in South Africa where clade C infection predominates. METHODS: HIV-infected, tuberculin skin test positive adults who were not eligible for antiretroviral (ARV treatment were randomized to a trial of preventive treatment from 2003-2005. VL and CD4 count were assessed at enrollment and CD4 counts repeated at least annually. During follow-up, individuals whose CD4 counts decreased to 100,000 (N = 122 copies/ml. CONCLUSIONS: Our data suggests that six and a half years will elapse for an individual's CD4 count to decline from 750 to 350 cells/mm3 in the absence of ART.
Brittain, Kirsty; Asafu-Agyei, Nana Akua; Hoare, Jacqueline; Bekker, Linda-Gail; Rabie, Helena; Nuttall, James; Roux, Paul; Stein, Dan J; Zar, Heather J; Myer, Landon
Accurate measurement of antiretroviral therapy (ART) adherence remains challenging and there are few data assessing the validity of self-reported adherence among perinatally HIV-infected adolescents. We examined adolescent and caregiver reports of adolescent adherence among perinatally-infected adolescents aged 9-14 years in Cape Town, South Africa, and explored factors that may modify associations between reported adherence and elevated viral load (VL). Among 474 adolescents (median age 12.0 years; median duration of ART use 7.5 years), elevated VL and caregiver- and adolescent-report of missed ART doses were common. Elevated VL was particularly prevalent among older, male adolescents. Low-moderate concordance was observed between caregiver and adolescent report. Among adolescents aged ≥ 12 years, caregiver- and adolescent-reported adherence was associated with elevated VL across most items assessed, but few significant associations were observed among adolescents adolescents who require adherence interventions are needed in this context.
Ostrowski, S R; Katzenstein, T L; Pedersen, B K
Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active......-count, CD4+HLA-DR+, CD8+HLA-DR+CD38+, CD4+CD45RA-CD45RO+, CD8+CD45RA-CD45RO+, CD4+CD45RA+CD62L+, CD8+CD45RA+CD62L+ T cells, IgG or IgM. In conclusion, RV was associated with increased blood levels of soluble immune activation markers in HAART-treated HIV-1-infected patients. The finding that RV...... antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2...
Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt
OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 year...... in HIV-infected patients in Copenhagen were included. HIV-RNA, CD4 cell counts, and RPR-serology were measured before, during, and after syphilis. RESULTS: Forty-one patients were included. CD4 cell count decreased significantly during infection in patients with primary and secondary stages of syphilis...... (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25...
Avaliação de ensaio molecular para determinação de carga viral em indivíduos sorologicamente negativos para o HIV-1 Evaluation of a molecular assay for determining viral load on HIV-1 antibody negative patients
José Moreira Pereira
Full Text Available O teste de carga viral foi concebido para acompanhar a evolução e o tratamento do paciente com diagnóstico confirmado de HIV-1. Contudo, sua especificidade diagnóstica não foi ainda avaliada em pessoas que apresentam um teste sorológico negativo. Mesmo assim, ele tem sido erroneamente utilizado para o diagnóstico da infecção primária pelo HIV-1. Este trabalho relata quatro pacientes em que a carga viral plasmática NucliSens (Organon Teknika foi repetidamente positiva na ausência de anticorpos para HIV e chama atenção para o fato de que a carga viral abaixo de 10 mil cópias/ml é de difícil interpretação, como tem sido assinalado em numerosos artigos, em que foram utilizadas outras metodologias.The plasma viral load test for HIV-1,a exquisitely high sensitive assay, were neither developed nor evaluated for the diagnosis of primary HIV infection; therefore, their diagnostic specificity is not well delineated when applied to persons who are negative for HIV antibody. This article reported four cases of false positive results obtained by using NucliSens viral load assay (Organon Teknika and emphasize the importance that low positive plasma viral load (< 10 000 copies/ml may be difficult to interpret how has been assinalated in numerous articles in the medical literature, using other methodologies.
... better from treatment such as an antiviral medicine. Antibiotics do not help viral infections, so they are not useful in the treatment of viral meningitis. However, antibiotics do fight bacteria, so they are very important ...
... throat is due to a viral infection. The antibiotics will not help. Using them to treat viral infections helps bacteria become resistant to antibiotics. With some sore throats (such as those caused ...
Kuo, Yung-Bin; Li, Yi-Shuan; Chan, Err-Cheng
Human papillomavirus (HPV) types 16 and 18 are known to be high-risk viruses that cause cervical cancer. An HPV rapid testing kit that could help physicians to make early and more informed decisions regarding patient care is needed urgently but not yet available. This study aimed to develop a multiplex nested polymerase chain reaction-immunochromatographic test (PCR-ICT) for the rapid identification of HPV 16 and 18. A multiplex nested PCR was constructed to amplify the HPV 16 and 18 genotype-specific L1 gene fragments and followed by ICT which coated with antibodies to identify rapidly the different PCR products. The type-specific gene regions of high-risk HPV 16 and 18 could be amplified successfully by multiplex nested PCR at molecular sizes of approximately 99 and 101bp, respectively. The capture antibodies raised specifically against the moleculars labeled on the PCR products could be detected simultaneously both HPV 16 and 18 in one strip. Under optimal conditions, this PCR-ICT assay had the capability to detect HPV in a sample with as low as 100 copies of HPV viral DNA. The PCR-ICT system has the advantage of direct and simultaneous detection of two high-risk HPV 16 and 18 DNA targets in one sample, which suggested a significant potential of this assay for clinical application. Copyright © 2014. Published by Elsevier B.V.
Purpose: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising in contrast to the decreasing incidence of carcinomas in other subsides of the head and neck, in spite of the reduced prevalence of smoking in developed countries. Human papilloma virus (HPV) infection, is now recognized as a significant marker in the onset of HPV positive OPSCC, with different epidemiological, clinical, anatomical, radiological, behavioural, biological and prognostic characteristics from HPV negative OPSCC. Aim: The aim of our work was to measure the impact of HPV infection and anti-oncogene p16 on survival and analyze lifestyles in our sample of patients. Material and methods: 61 patients with newly diagnosed oropharyngeal cancer in ENT clinic in Nove Zamky included in our study from March 2011 till February 2014. They were divided into two categories- HPV positive and HPV negative patients (n-39 versus 22). Results: HPV infection was analysed by DNA detection viral DNA with PCR (Cobas 4800 HPV Test) and expression E6/E7 oncogenes by mRNA. In addition, we detected p16 overexpression immunohistochemistry as a surrogate marker for high risk HPV(HR HPV). We analysed clinicopatological characteristic, smoking and alcohol abuse history, sexual behaviours and compared treatment and overall survival between HPV positive and HPV negative patients. The 2- year rates of overall survival were 86% versus 41% in HPV + and HPV – patients and 88% versus 25% in p16+ and p16- tumors, respectively. Conclusion: These observations lead to questions regarding management choices for patients based on tumour HPV and p16status with important consequences on treatment and on the role of targeted therapy and vaccines and over the upcoming years. (author)
Pirog, Edyta C; Lloveras, Belen; Molijn, Anco; Tous, Sara; Guimerà, Núria; Alejo, Maria; Clavero, Omar; Klaustermeier, Joellen; Jenkins, David; Quint, Wim Gv; Xavier Bosch, Francesc; Alemany, Laia; de Sanjosé, Silvia
The goal of our study was to provide comprehensive data on the worldwide human papillomavirus (HPV) genotype distribution in patients with invasive cervical adenocarcinoma in correlation with histologic tumor subtypes, geographical location, patients' age, and duration of sample storage. Paraffin-embedded samples of 760 cervical adenocarcinoma cases were collected worldwide. A three-level pathology review of cases was performed to obtain consensus histologic diagnoses and 682 cases were determined to be eligible for further analysis. HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA(25) system (version 1). Classic cervical adenocarcinoma accounted for 83.1% of cases, while rare histological variants accounted for a few percent of cases individually. HPV positivity varied significantly between the different histologic tumor subtypes. Classic cervical adenocarcinoma showed high HPV positivity (71.8%), while other adenocarcinoma types had significantly lower HPV prevalence (endometrioid 27.3%, serous 25%, clear cell 20%, not otherwise specified 13.9%, and minimal deviation 8.3%). In all, 91.8% of HPV-positive tumors showed the presence of a single viral type and in 7% of cases multiple viral types were detected. Three HPV genotypes, HPV 16, 18, and 45, dominated in all adenocarcinomas and together accounted for 94.1% of HPV-positive tumors. HPV16 was the most common and found in 50.9% of HPV-positive cases, followed by HPV18 (31.6%) and HPV45 (11.6%). HPV prevalence varied depending on geographical region, patient age, and sample storage time. Tumors from older patients and tumor samples with longer storage time showed lower HPV prevalence. Our results indicate that HPV vaccines may prevent up to 82.5% (HPV16/18) and up to 95.3% (9-valent vaccine) of HPV-positive cervical adenocarcinomas, mostly the classic type. HPV testing and vaccination will not provide full coverage for a very small subset of classical adenocarcinomas and most of the rare
Yvonne N Flores
Full Text Available OBJECTIVE: To identify factors that are associated with an increased risk of developing high-grade cervical intraepithelial neoplasia (CIN or cancer among human papillomavirus (HPV-positive women in Mexico. MATERIAL AND METHODS: A case-control study design was used. A total of 94 cases and 501 controls who met the study inclusion criteria were selected from the 7 732 women who participated in the Morelos HPV Study from May 1999 to June 2000. Risk factor information was obtained from interviews and from HPV viral load results. Odds ratios and 95 percent confidence intervals were estimated using unconditional multivariate regression. RESULTS: Increasing age, high viral load, a young age at first sexual intercourse, and a low socio-economic status are associated with an increased risk of disease among HPV-positive women. CONCLUSIONS: These results could have important implications for future screening activities in Mexico and other low resource countries.OBJETIVO: Identificar factores asociados con un mayor riesgo de desarrollar neoplasia intraepitelial cervical (NIC de alto grado o cáncer en mujeres con virus de papiloma humano (VPH, en México. MATERIAL Y MÉTODOS: Se utilizó un diseño de casos y controles. Un total de 94 casos y 501 controles fueron seleccionados de las 7 732 mujeres que participaron en el Estudio de VPH en Morelos, de mayo de 1999 a junio de 2000. La información sobre factores de riesgo se obtuvo de entrevistas y de los resultados de carga virales de VPH. Se estimaron razones de momios e intervalos de confianza de 95% con modelos multivariados de regresión no condicionada. RESULTADOS: El incremento de edad, la carga viral elevada, la edad temprana al inicio de la vida sexual y el nivel socioeconómico bajo se asocian con un mayor riesgo de enfermedad en mujeres VPH positivas. CONCLUSIONES: Estos resultados podrían tener implicaciones importantes a futuro para las actividades de tamizaje en México y en otros países de
Calmon, Marilia Freitas [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil); Sichero, Laura [Molecular Biology Laboratory, Centre for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo (Brazil); Boccardo, Enrique [Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo., São Paulo (Brazil); Villa, Luisa Lina [Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo (Brazil); Rahal, Paula, E-mail: firstname.lastname@example.org [Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil)
Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.
Calmon, Marilia Freitas; Sichero, Laura; Boccardo, Enrique; Villa, Luisa Lina; Rahal, Paula
Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.
Van Wagoner, Nicholas; Elopre, Latesha; Westfall, Andrew O; Mugavero, Michael J; Turan, Janet; Hook, Edward W
The Southeast has high rates of church attendance and HIV infection rates. We evaluated the relationship between church attendance and HIV viremia in a Southeastern US, HIV-infected cohort. Viremia (viral load ≥200 copies/ml) was analyzed 12 months after initiation of care. Univariate and multivariable logistic regression models were fit for variables potentially related to viremia. Of 382 patients, 74 % were virally suppressed at 12 months. Protective variables included church attendance (AOR 0.5; 95 % CI 0.2, 0.9), being on antiretroviral therapy (AOR 0.01; 95 % CI 0.004, 0.04), CD4(+) T lymphocyte count 200-350 cells/mm(3) at care entry (AOR 0.3; 95 % 0.1, 0.9), and education (AOR 0.5; 95 % CI 0.2, 0.9). Variables predicting viremia included black race (AOR 3.2; 95 % CI 1.4, 7.4) and selective disclosure of HIV status (AOR 2.7; 95 % CI 1.2, 5.6). Church attendance may provide needed support for patients entering HIV care for the first time. El Sur Este de los Estados Unidos tiene tasas altas de visitas a iglesias y de infección por VIH. Evaluamos la relación entre visitas a iglesias y viremia por VIH en una cohorte de pacientes infectados con VIH en el Sur Este de los EEUU. La viremia (carga viral ≥ 200 copias/ml) fue analizada a los 12 meses de iniciar el cuidado médico. Los modelos de regresión logística univariado y multivariado fueron ajustados para variables potencialmente relacionadas a viremia. De 382 pacientes, 75 % tuvieron supresión virológica a los 12 meses. Variables que ofrecieron protección fueron visitas a iglesias (AOR 0.5; IC95 % 0.2-0.9), recibir terapia antiretroviral (AOR 0.01; IC95 % 0.004,0.04), recuento de linfocitos T CD4 + 200-350 al iniciar cuidado médico (AOR 0.3; IC95 % 0.1,09), y educación (AOR 0.5; IC95 % 0.2,0.9). Las variables que predijeron viremia incluyeron raza negra (AOR 3.2; IC95 % 1.4,7.4) y la comunicación selectiva del diagnóstico de VIH a otras personas (AOR 2.7; 95 % IC 1
Full Text Available Adolescents who are sexually active have the highest rates of prevalent and incident HPV infection rates with over 50–80% having infections within 2–3 years of initiating intercourse. These high rates reflect sexual behavior and biologic vulnerability. Most infections are transient in nature and cause no cytologic abnormality. However, a small number of adolescents will not clear the infection. Persistence of HPV is strongly linked to the development of high-grade squamous intra-epithelial lesions (HSIL and invasive cancer. The HSIL detected, however, does not appear to progress rapidly to invasive cancer. Understanding the natural history of HPV in adolescents has shed light into optional treatment strategies which include watchful observation of atypical squamous cells of undetermined significance (ASCUS and low grade (LSIL. The association between age of first intercourse and invasive cancer cannot be ignored. Consequently, initiating screening at appropriate times in this vulnerable group is essential. In addition, with the advent of the HPV vaccine, vaccination prior to the onset of sexual activity is critical since most infections occur within a short time frame post initiation.
Dr. Walter Kinney, a gynecologic oncologist with The Permanente Medical Group in Sacramento, California, talks about Pap and human papillomavirus (HPV) cotesting in women aged 30 and over. Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC). Date Released: 6/9/2010.
In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niÃ±os y las niÃ±as de 11 a 12 aÃ±os con la vacuna contra el VPH.)
Assoumou, L; Charpentier, C; Recordon-Pinson, P; Grudé, M; Pallier, C; Morand-Joubert, L; Fafi-Kremer, S; Krivine, A; Montes, B; Ferré, V; Bouvier-Alias, M; Plantier, J-C; Izopet, J; Trabaud, M-A; Yerly, S; Dufayard, J; Alloui, C; Courdavault, L; Le Guillou-Guillemette, H; Maillard, A; Amiel, C; Vabret, A; Roussel, C; Vallet, S; Guinard, J; Mirand, A; Beby-Defaux, A; Barin, F; Allardet-Servent, A; Ait-Namane, R; Wirden, M; Delaugerre, C; Calvez, V; Chaix, M-L; Descamps, D; Reigadas, S
Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: email@example.com.
Pham, Quang Duy; Wilson, David P; Nguyen, Thuong Vu; Do, Nhan Thi; Truong, Lien Xuan; Nguyen, Long Thanh; Zhang, Lei
The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario. Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120-34 600 cases) of TDR and 55 180 cases (95% CI: 40 540-65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%-24%) and ADR of 18% (95% CI: 15%-20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%-31% of TDR (2260-5860 cases), 25%-59% of ADR (9620-22 650 cases), 2%-6% of HIV-related deaths (360-880 cases) and 19 270-51 400 DALYs during 2015-30. The 30% coverage of VL monitoring is estimated to cost US$4848-5154 per DALY averted. The projected additional cost for implementing this strategy is US$105-268 million over 2015-30. Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Martinson, Neil A; Gupte, Nikhil; Msandiwa, Reginah; Moulton, Lawrence H; Barnes, Grace L; Ram, Malathi; Gray, Glenda; Hoffmann, Chris; Chaisson, Richard E
CD4 count is a proxy for the extent of immune deficiency and declines in CD4 count are a measure of disease progression. Decline in CD4 count is an important component: for estimating benefits of ARV treatment; for individual level counselling on the rapidity of untreated disease progression and prognosis; and can be used in planning demand for health services. Our objective is to report CD4 decline and changes in viral load (VL) in a group of HIV-infected adults enrolled in a randomized trial of preventive treatment for TB in South Africa where clade C infection predominates. HIV-infected, tuberculin skin test positive adults who were not eligible for antiretroviral (ARV) treatment were randomized to a trial of preventive treatment from 2003-2005. VL and CD4 count were assessed at enrollment and CD4 counts repeated at least annually. During follow-up, individuals whose CD4 counts decreased to alcohol use had little impact on the estimate of CD4 decline. However, VL at baseline had a major impact on CD4 decline. The percent decline in CD4 count was 13.3% (95% CI 12.0%, 14.7%), 10.6% (95% CI 8.8%, 12.4%), and 13.8% (95% CI 12.1%, 15.5%) per annum for baseline VLs of 100,000 (N = 122) copies/ml. Our data suggests that six and a half years will elapse for an individual's CD4 count to decline from 750 to 350 cells/mm3 in the absence of ART.
Newcomb, Michael E; Mongrella, Melissa C; Weis, Benjamin; McMillen, Samuel J; Mustanski, Brian
Recent advances in biomedical prevention strategies, including pre-exposure prophylaxis (PrEP) and achieving an undetectable viral load (UVL) among HIV-infected persons, show promise in curbing the rising incidence of HIV among men who have sex with men (MSM) in the United States. This mixed-methods study aimed to investigate the frequency with which MSM encounter potential sex partners on geosocial networking apps who disclose biomedical prevention use, and how MSM make decisions about condom use after these disclosures. Participants were recruited through advertisements placed on a large geosocial networking app for MSM. A total of 668 and 727 participants, respectively, responded to questionnaires assessing partner disclosure of PrEP use and UVL. Each questionnaire included an open-ended item assessing reasons for condomless anal sex (CAS) with partners using biomedical prevention. Across both surveys, most respondents encountered potential sex partners who disclosed PrEP use or UVL, and the majority of those who met up with these partners engaged in CAS at least once. Qualitative analyses found that most participants who reported CAS did so after making a calculated risk about HIV transmission. We also describe a novel risk reduction strategy, "biomed-matching," or having CAS only when both individuals use PrEP or have UVL. We report serostatus differences in both quantitative and qualitative findings. Disclosure of PrEP use and UVL is not uncommon among MSM. Many MSM make accurate appraisals of the risks of CAS with biomedical prevention, and mobile apps may aid with disclosing biomedical prevention use.
Belenky, Nadya; Pence, Brian W; Cole, Stephen R; Dusetzina, Stacie B; Edmonds, Andrew; Oberlander, Jonathan; Plankey, Michael W; Adedimeji, Adebola; Wilson, Tracey E; Cohen, Jennifer; Cohen, Mardge H; Milam, Joel E; Golub, Elizabeth T; Adimora, Adaora A
The implementation of Medicare part D on January 1, 2006 required all adults who were dually enrolled in Medicaid and Medicare (dual eligibles) to transition prescription drug coverage from Medicaid to Medicare part D. Changes in payment systems and utilization management along with the loss of Medicaid protections had the potential to disrupt medication access, with uncertain consequences for dual eligibles with human immunodeficiency virus (HIV) who rely on consistent prescription coverage to suppress their HIV viral load (VL). To estimate the effect of Medicare part D on self-reported out-of-pocket prescription drug spending, AIDS Drug Assistance Program (ADAP) use, antiretroviral adherence, and HIV VL suppression among dual eligibles with HIV. Using 2003-2008 data from the Women's Interagency HIV Study, we created a propensity score-matched cohort and used a difference-in-differences approach to compare dual eligibles' outcomes pre-Medicare and post-Medicare part D to those enrolled in Medicaid alone. Transition to Medicare part D was associated with a sharp increase in the proportion of dual eligibles with self-reported out-of-pocket prescription drug costs, followed by an increase in ADAP use. Despite the increase in out-of-pocket costs, both adherence and HIV VL suppression remained stable. Medicare part D was associated with increased out-of-pocket spending, although the increased spending did not seem to compromise antiretroviral therapy adherence or HIV VL suppression. It is possible that increased ADAP use mitigated the increase in out-of-pocket spending, suggesting successful coordination between Medicare part D and ADAP as well as the vital role of ADAP during insurance transitions.
Chantelle J Giesbrecht
Full Text Available Through implementation of combination antiretroviral therapy (cART remarkable gains have been achieved in the management of HIV infection; nonetheless, the neurocognitive consequences of infection remain a pivotal concern in the cART era. Research has often employed norm-referenced neuropsychological scores, derived from healthy populations (excluding many seronegative individuals at high risk for HIV infection, to characterize impairments in predominately male HIV-infected populations.Using matched-group methodology, we assessed 81 HIV-seropositive (HIV+ women with established neuropsychological measures validated for detection of HIV-related impairments, as well as additional detailed tests of executive function and decision-making from the Cambridge Neuropsychological Test Automated Battery (CANTAB.On validated tests, the HIV+ women exhibited impairments that were limited to significantly slower information processing speed when compared with 45 HIV-seronegative (HIV- women with very similar demographic backgrounds and illness comorbidities. Additionally, select executive impairments in shifting attention (i.e., reversal learning and in decision-making quality were revealed in HIV+ participants. Modifiers of neurocognition in HIV-infected women included detectable HIV plasma viral load, active hepatitis C virus co-infection, and self-reported depression symptoms. In contrast, leukocyte telomere length (LTL, a marker of cellular aging, did not significantly differ between HIV+ and HIV- women, nor was LTL associated with overall neurocognition in the HIV+ group.The findings suggest that well-managed HIV infection may entail a more circumscribed neurocognitive deficit pattern than that reported in many norm-referenced studies, and that common comorbidities make a secondary contribution to HIV-related neurocognitive impairments.
Full Text Available Roche modified the COBAS AmpliPrep/COBAS TaqMan human immunodeficiency virus type 1 (HIV-1 test version 1.0 (CAP/CTM v1.0, resulting in the COBAS AmpliPrep/COBAS TaqMan HIV-1 test version 2.0 (CAP/CTM v2.0. The aim of this study was to evaluate the performance of the CAP/CTM v2.0 and to compare this performance with that of the CAP/CTM v1.0. The study was conducted in a small local study group in Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. A total of 86 plasma samples from HIV-1-seropositive patients were tested using the two assays. The correlation and concordance of results between the two assays were calculated. The CAP/CTM v2.0 generated higher values than did the CAP/CTM v1.0, and five samples (5.8% yielded a difference of > 1 log10 copies/mL. In addition, our data show that CAP/CTM v1.0 and CAP/CTM v2.0 yielded relatively consistent values for 23 samples with low viral loads (< 200 copies/mL. Furthermore, when viral loads were in a medium range (2–5 log10 copies/mL, the results of the two assays were more compatible. This study shows a good correlation between CAP/CTM v1.0 and v2.0 in HIV-1 viral load measurement. Further attention must be paid to those cases in which measured viral loads present larger differences between the two assays.
Else, Elizabeth A.; Swoyer, Ryan; Zhang, Yuhua; Taddeo, Frank J.; Bryan, Janine T.; Lawson, John; Van Hyfte, Inez; Roberts, Christine C.
Real-time type-specific multiplex human papillomavirus (HPV) PCR assays were developed to detect HPV DNA in samples collected for the efficacy determination of the quadrivalent HPV (type 6, 11, 16, and 18) L1 virus-like particle (VLP) vaccine (Gardasil). Additional multiplex (L1, E6, and E7 open reading frame [ORF]) or duplex (E6 and E7 ORF) HPV PCR assays were developed to detect high-risk HPV types, including HPV type 31 (HPV31), HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, and H...
Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin
Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.
Zekri, A.; Bahnassy, A.A.
Background and Aim: Human papilloma viruses (HPVs) are small DNA tumor viruses that infect epithelial tissues and cause warts. One of the viral genes responsible for HPV's oncogenic activity is E6 which is known to inactivate the cellular p53 tumor suppressor gene. We aim to detect the presence of HPV infection and its different types in human warts, and to identify the relation between HPV and p53 expression in skin and genital lesions. Patients and Methods: We studied markers of HPV infection in overall of 30 patients (20 with common warts, and 10 with genital warts). Also, 30 normal skin samples were taken from each patient as a normal control. Detection of HPV was done using polymerase chain reaction (PCR), and HPV typing was performed using LiPA (Line immuno Probe Assay). In addition, all skin lesions were examined by immunohistochemistry for p53 expression. Results: In patients with common warts, HPV DNA was found in 4/20 (20%) of cases which was of HPV types 11, 31, 6, 33 (p=0.28). Also, P53 expression was found in 4/20 (20%) of cases (p=0.26). No single patient showed reactivity of both HPV and p53 expression. In patients with genital warts, however, HPV DNA was found in 6/10 (60%) of cases. Of these, 5 cases were positive for HPV type 6 and one case had HPV type 11. Three patients (30%) were positive for p53, and two of them (66%) were positive for both HPV and p53. In the normal skin control, 2/30 (6.6%) were positive for HPV DNA which were of types 5, and 31. Conclusions: We conclude that; (1) Prevalence rate of HPV infection in warts is higher than those of normal control group, and Egyptian patients with genital warts had higher prevalence rate of HPV than those with common warts, (2) In Egypt, HPV types 6, and 11 are the most prevalent genotypes associated with genital warts and HPV types 6, 11, 31, and 33 are associated with common warts, (3) There was no definite relation between p53 expression and HPV detection, (4) Also, there was no association
Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV vaccinated rhesus macaques
Full Text Available Abstract Background An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV vector – simian immunodeficiency virus (SIV envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1. Findings The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals. Conclusions Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.
Di Domenico, Marina; Giovane, Giancarlo; Kouidhi, Soumaya; Iorio, Rosamaria; Romano, Maurizio; De Francesco, Francesco; Feola, Antonia; Siciliano, Camilla; Califano, Luigi; Giordano, Antonio
Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.
Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W
Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.
Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.
Castellsagué, Xavier; Alemany, Laia; Quer, Miquel; Halec, Gordana; Quirós, Beatriz; Tous, Sara; Clavero, Omar; Alòs, Llúcia; Biegner, Thorsten; Szafarowski, Tomasz; Alejo, Maria; Holzinger, Dana; Cadena, Enrique; Claros, Edith; Hall, Gillian; Laco, Jan; Poljak, Mario; Benevolo, Maria; Kasamatsu, Elena; Mehanna, Hisham; Ndiaye, Cathy; Guimerà, Núria; Lloveras, Belen; León, Xavier; Ruiz-Cabezas, Juan C; Alvarado-Cabrero, Isabel; Kang, Chang-Suk; Oh, Jin-Kyoung; Garcia-Rojo, Marcial; Iljazovic, Ermina; Ajayi, Oluseyi F; Duarte, Flora; Nessa, Ashrafun; Tinoco, Leopoldo; Duran-Padilla, Marco A; Pirog, Edyta C; Viarheichyk, Halina; Morales, Hesler; Costes, Valérie; Félix, Ana; Germar, Maria Julieta V; Mena, Marisa; Ruacan, Arzu; Jain, Asha; Mehrotra, Ravi; Goodman, Marc T; Lombardi, Luis Estuardo; Ferrera, Annabelle; Malami, Sani; Albanesi, Estela I; Dabed, Pablo; Molina, Carla; López-Revilla, Rubén; Mandys, Václav; González, Manuel E; Velasco, Julio; Bravo, Ignacio G; Quint, Wim; Pawlita, Michael; Muñoz, Nubia; de Sanjosé, Silvia; Xavier Bosch, F
We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: email@example.com.
Harris, Leanne; McFarlane-Majeed, Laura; Campos-León, Karen; Roberts, Sally; Parish, Joanna L
is a risk factor for cancer development and is partly achieved by the attachment of viral DNA to cellular chromatin during cell division. The HPV E2 protein plays a critical role in this tethering by binding simultaneously to the viral genome and to chromatin during mitosis. We previously showed that the cellular DNA helicase ChlR1 is required for loading of the bovine papillomavirus E2 protein onto chromatin during DNA synthesis. Here we identify a mutation in HPV16 E2 that abrogates interaction with ChlR1, and we show that ChlR1 regulates the chromatin association of HPV16 E2 and that this virus-host interaction is essential for viral episome maintenance. Copyright © 2016 Harris et al.
Allex Jardim Fonseca
Full Text Available Indigenous women from the Amazon regions have some of the highest rates of cervical cancer in the world. This study evaluated cervical cytology and human papillomavirus (HPV in native women that differ by lifestyle and interaction with western society. Yanomami women are isolated deep in the Amazon with a hunter/gatherer lifestyle. Macuxi and Wapishana women live in proximity to western society.To select a representative group of women from each district, random cluster sampling was used, considering each registered village as a cluster. Cervical samples were collected for cytology and HPV detection and typing by PCR amplification and next generation sequencing. The study was approved by the National IRB and by tribal leaders.664 native women were enrolled from 13 indigenous villages (76% participation rate. Yanomami women had higher rates of abnormal cytology (5.1% vs. 1.8%, p = 0.04 and prevalent HR-HPV (34.1% vs. 19.2%, p35 y of age were significantly more likely to have HR-HPV, whereas women ≤ 35 y did not significantly differ between groups. Prevalence of HPV was significantly different amongst geographically clustered Yanomami women (p<0.004. The most prevalent HPV types in the entire group were HPV31 (8.7%, HPV16 (5.9% and HPV18 (4.4%.Isolated endogenous Yanomami women were more likely to be HPV+ and rates increased with age. Study of HPV in isolated hunter-gather peoples suggests that long-term persistence is a characteristic of prehistoric humans and patterns reflecting decreased prevalence with age in western society represents recent change. These studies have implications for cervical cancer prevention and viral-host relationships.
... Transmitted Diseases (STDs) HPV Vaccine Information For Young Women Language: English Español (Spanish) Recommend on Facebook Tweet ... warts at any point in time. Which girls/women should receive HPV vaccination? HPV vaccination is recommended ...
Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.
Kocjan, Boštjan; Poljak, Mario; Oštrbenk, Anja
Introduction: HPV-52 is one of the most frequent human papillomavirus (HPV) genotypes causing significant cervical pathology. The most widely used HPV genotyping assay, the Roche Linear Array HPV Genotyping Test (Linear Array), is unable to identify HPV- 52 status in samples containing HPV-33, HPV-35, and/or HPV-58. Methods: Linear Array HPV-52 analytical specificity was established by testing 100 specimens reactive with the Linear Array HPV- 33/35/52/58 cross-reactive probe, but not with the...
Hu, Zheng; Zhu, Da; Wang, Wei
Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis1. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and ...
Wentzensen, Nicolas; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Sahasrabuddhe, Vikrant V; Chen, Jie; Lorey, Thomas S; Gage, Julia C; Fetterman, Barbara; Boyle, Sean; Sadorra, Mark; Tang, Scott Dahai; Darragh, Teresa M; Castle, Philip E
Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P(trend) < 0.001), HPV18 (P(trend) = 0.07), and other carcinogenic types (P(trend) < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Dorward, Jienchi; Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K
Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shifting to enrolled nurses is non-inferior and cost-effective compared with laboratory-based VL monitoring and standard HIV care. The STREAM (Simplifying HIV TREAtment and Monitoring) study is an open-label, non-inferiority, randomised controlled implementation trial. HIV-positive adults, clinically stable at 6 months after ART initiation, will be recruited in a large urban clinic in South Africa. Approximately 396 participants will be randomised 1:1 to receive POC HIV VL monitoring and potential task shifting to enrolled nurses, versus laboratory VL monitoring and standard South African HIV care. Initial clinic follow-up will be 2-monthly in both arms, with VL testing at enrolment, 6 months and 12 months. At 6 months (1 year after ART initiation), stable participants in both arms will qualify for a differentiated care model involving decentralised ART pickup at community-based pharmacies. The primary outcome is retention in care and virological suppression at 12 months from enrolment. Secondary outcomes include time to appropriate entry into the decentralised ART delivery programme, costs per virologically suppressed patient and cost-effectiveness of the intervention compared with standard care. Findings will inform the scale up of VL testing and differentiated care in HIV-endemic resource-limited settings. Ethical approval has been granted by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC296/16) and University of Washington Institutional Review Board (STUDY
Peter, Trevor; Zeh, Clement; Katz, Zachary; Elbireer, Ali; Alemayehu, Bereket; Vojnov, Lara; Costa, Alex; Doi, Naoko; Jani, Ilesh
The scale-up of effective HIV viral load (VL) testing is an urgent public health priority. Implementation of testing is supported by the availability of accurate, nucleic acid based laboratory and point-of-care (POC) VL technologies and strong WHO guidance recommending routine testing to identify treatment failure. However, test implementation faces challenges related to the developing health systems in many low-resource countries. The purpose of this commentary is to review the challenges and solutions from the large-scale implementation of other diagnostic tests, namely nucleic-acid based early infant HIV diagnosis (EID) and CD4 testing, and identify key lessons to inform the scale-up of VL. Experience with EID and CD4 testing provides many key lessons to inform VL implementation and may enable more effective and rapid scale-up. The primary lessons from earlier implementation efforts are to strengthen linkage to clinical care after testing, and to improve the efficiency of testing. Opportunities to improve linkage include data systems to support the follow-up of patients through the cascade of care and test delivery, rapid sample referral networks, and POC tests. Opportunities to increase testing efficiency include improvements to procurement and supply chain practices, well connected tiered laboratory networks with rational deployment of test capacity across different levels of health services, routine resource mapping and mobilization to ensure adequate resources for testing programs, and improved operational and quality management of testing services. If applied to VL testing programs, these approaches could help improve the impact of VL on ART failure management and patient outcomes, reduce overall costs and help ensure the sustainable access to reduced pricing for test commodities, as well as improve supportive health systems such as efficient, and more rigorous quality assurance. These lessons draw from traditional laboratory practices as well as fields
Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J
HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is
Art F Y Poon
Full Text Available Human immunodeficiency virus type 1 (HIV-1 genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL and CD4+ cell count (CD4 at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184 were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I (-1.7 log₁₀pVL and D67N/G (-2.1[³√CD4] and 0.4 log₁₀pVL were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1
Johan van Griensven
Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained
Ruth S Hermansson
Full Text Available In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above.From September 2013 until June 2015, 1051 women aged 60-89 years (mean 68 years were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC, after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained.The prevalence of HPV was 4.1%, (95%CI 3.0-5.5, n = 43 at the first test, and at the second test 2.6% remained positive (95%CI 1.7-3.8, n = 27. The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27 (4 CIN 2-0.4%, 18 CIN 1-1.7%. HPV-related dysplasia was found in 2.1%, (95%CI 1.3-3.2, n = 22 of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected.A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity.
Full Text Available Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl.Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.
Nicole M. Reusser
Full Text Available Human papillomavirus (HPV infection is the most common sexually transmitted disease worldwide and can result in pre-malignancies or overt malignancies of the skin and mucosal surfaces. HPV-related illnesses are an important personal and public health problem causing physical, mental, sexual and financial detriments. Moreover, this set of malignancies severely affects the immunosuppressed population, particularly HIV-positive patients and organ-transplant recipients. There is growing incidence of HPV-associated anogenital malignancies as well as a decrease in the average age of affected patients, likely related to the rising number of high-risk individuals. Squamous cell carcinoma is the most common type of HPV-related malignancy. Current treatment options for HPV infection and subsequent disease manifestations include imiquimod, retinoids, intralesional bleomycin, and cidofovir; however, primary prevention with HPV vaccination remains the most effective strategy. This review will discuss anogenital lesions in immunocompromised patients, cutaneous warts at nongenital sites, the association of HPV with skin cancer in immunocompromised patients, warts and carcinomas in organ-transplant patients, HIV-positive patients with HPV infections, and the management of cutaneous disease in the immunocompromised patient.
León, David Cantu de; Montiel, Delia Pérez; Nemcova, Jana; Mykyskova, Iva; Turcios, Elmer; Villavicencio, Verónica; Cetina, Lucely; Coronel, Alberto; Hes, Ondraj
Breast cancer is one of the main health problems in developed countries, occupying first place in mortality in women. It is well-known that there are risk factors associated with breast cancer development. Nonetheless, in 50–80% of cases known risk factors have not been identified, this has generated the attempt to identify new factors related with this neoplasia as viral infections. The aim of this work is investigate the prevalence of HPV DNA in patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico. Fifty-one cases of breast cancer were selected from the files of the institute and compared by age and tumor size with 43 cases of non malignant breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor). Paraffin embedded specimens were selected, HPV DNA was analyzed by polymerase chain reaction (PCR) and sequenced for different types of HPV in case of positivity for HPV-DNA. Descriptive analysis of clinical and pathological variables was performed and comparisons between positive and negative cases was done. All patients were mexican, mean age was 53.3, median age of menarche was 13 and median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1 patient (1.9%) of cancer group had HPV and none in the other group, no cases were diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5%) were negative and 15 (29.4%) were positive to HPV-DNA, 10(66.6%) were positive for HPV 16, 3(20%) for HPV 18, two cases (13.4%) were positive for both. In the group of benign conditions all were negative to HPV-DNA. Presence of HPV in breast cancer in our group of cases is high in comparison to other authors; larger numbers of cases need to be analyzed in order to establish the exact role of this virus in the pathogenesis of breast cancer
Full Text Available Abstract Background Breast cancer is one of the main health problems in developed countries, occupying first place in mortality in women. It is well-known that there are risk factors associated with breast cancer development. Nonetheless, in 50–80% of cases known risk factors have not been identified, this has generated the attempt to identify new factors related with this neoplasia as viral infections. The aim of this work is investigate the prevalence of HPV DNA in patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico. Methods Fifty-one cases of breast cancer were selected from the files of the institute and compared by age and tumor size with 43 cases of non malignant breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor. Paraffin embedded specimens were selected, HPV DNA was analyzed by polymerase chain reaction (PCR and sequenced for different types of HPV in case of positivity for HPV-DNA. Descriptive analysis of clinical and pathological variables was performed and comparisons between positive and negative cases was done. Results All patients were mexican, mean age was 53.3, median age of menarche was 13 and median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1 patient (1.9% of cancer group had HPV and none in the other group, no cases were diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5% were negative and 15 (29.4% were positive to HPV-DNA, 10(66.6% were positive for HPV 16, 3(20% for HPV 18, two cases (13.4% were positive for both. In the group of benign conditions all were negative to HPV-DNA. Conclusion Presence of HPV in breast cancer in our group of cases is high in comparison to other authors; larger numbers of cases need to be analyzed in order to establish the exact role of this virus in the pathogenesis of breast cancer.
Sorina Raula Gîrboveanu; Silvia Puiu
With consumers showing increasing resistance to traditional forms of advertising such as TV or newspaper ads, marketers have turned to alternate strategies, including viral marketing. Viral marketing exploits existing social networks by encouraging customers to share product information with their friends.In our study we are able to directly observe the effectiveness of person to person word of mouth advertising for hundreds of thousands of products for the first time
Vasiljevic, Natasa; Hazard, Kristina; Eliasson, Linda
Two novel human papillomaviruses (HPVs), HPV93 and HPV96, with genomes of 7450 and 7438 bp, respectively, are described. The L1 open reading frame of HPV93 showed highest identity to HPV24 (79%) and that of HPV96 had highest identity to HPV92 (71%). Real-time PCR for HPV92, 93 and 96 on stripped ...... per 45 cells to one copy per 10,000 cells. The E7 proteins of HPV92, 93 and 96 were found to bind the retinoblastoma protein (pRb). These results suggest a possible role for these HPV types in skin carcinogenesis that deserves further study....
Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.
In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niÃ±os y las niÃ±as de 11 a 12 aÃ±os con la vacuna contra el VPH.). Created: 1/15/2014 by National Center for Immunizations and Respiratory Diseases (NCIRD). Date Released: 1/15/2014.
K. Theys (Kristof); K. Deforche; J. Vercauteren (Jurgen); P. Libin (Pieter); D.A.M.C. van de Vijver (David); J. Albert (Jan); B. Åsjö (Birgitta); M. Bruckova (Marie); R.J. Camacho (Ricardo Jorge); B. Clotet (Bonaventura); Z. Grossman (Zehava); A. Horban (Andrzej); C. Kücherer (Claudia); D. Paraskevis (Dimitrios); E. Puchhammer-Stöckl (Elisabeth); C. Riva (Chiara); L. Ruiz (Lidia); J.-C. Schmit (Jean-Claude); R. Schuurman (Rob); A. Sonnerborg (Anders); D. Stanekova (Danica); D. Struck (Daniel); K. van Laethem (Kristel); A.M.J. Wensing (Annemarie); E. Puchhammer-Stockl E. (Elisabeth); M. Sarcletti (M.); B. Schmied (B.); M. Geit (M.); G. Balluch (G.); A.M. Vandamme (Anne Mieke); I. Derdelinck (Inge); A. Sasse (A.); M. Bogaert (M.); H. Ceunen (H.); A. de Roo (Annie); M. De Wit (Meike); F. Echahidi (F.); K. Fransen (K.); J.-C. Goffard (J.); P. Goubau (Patrick); E. Goudeseune (E.); J.-C. Yombi (J.); P. Lacor (Patrick); C. Liesnard (C.); M. Moutschen (M.); L.A. Pierard; R. Rens (R.); J. Schrooten; D. Vaira (D.); A. van den Heuvel (A.); B. van der Gucht (B.); M. van Ranst (Marc); E. van Wijngaerden (Eric); T. Vandercam; M. Vekemans (M.); C. Verhofstede; N. Clumeck (N.); K. van Laethem (K.); L.G. Kostrikis (Leondios); I. Demetriades (I.); I. Kousiappa (Ioanna); V.L. Demetriou (Victoria); J. Hezka (Johana); M. Linka (Marek); L. Machala (L.); L.B. Jrgensen (L.); J. Gerstoft (J.); L. Mathiesen (L.); C. Pedersen (Court); C. Nielsen (Claus); A. Laursen (A.); B. Kvinesdal (B.); K. Liitsola (Kirsi); M. Ristola (M.); J. Suni (J.); J. Sutinen (J.); K. Korn (Klaus); C. K̈ucherer (C.); P. Braun (P.); G. Poggensee (G.); M. Däumer (M.); D. Eberle (David); O. Hamouda (Osamah); H. Heiken (H.); R. Kaiser (Rolf); H. Knechten (H.); H. M̈uller (H.); S. Neifer (S.); H. Walter (Hauke); B. Gunsenheimer-Bartmeyer (B.); T. Harrer (T.); A. Hatzakis (Angelos); E. Hatzitheodorou (E.); C. Issaris (C.); C. Haida (C.); A. Zavitsanou (A.); G. Magiorkinis (Gkikas); M. Lazanas (M.); L. Chini; N. Magafas (N.); N. Tsogas (N.); V. Paparizos (V.); S. Kourkounti (S.); A. Antoniadou (A.); A. Papadopoulos (A.); P. Panagopoulos (P.); G. Poulakou (G.); V. Sakka (V.); G. Chryssos (G.); S. Drimis (S.); P. Gargalianos (P.); M. Lelekis (M.); G. Xilomenos (G.); M. Psichogiou (M.); G.L. Daikos (George); G. Panos (G.); G. Haratsis (G.); T. Kordossis (T.); A. Kontos (Angelos); G. Koratzanis (G.); M. Theodoridou (M.); G. Mostrou (G.); V. Spoulou (V.); W. Hall (W.); C. de Gascun (Cillian); C. Byrne (C.); M. Duffy (M.); P. Bergin; D. Reidy (D.); G. Farrell; J. Lambert (Julien); E. O'Connor (E.); A. Rochford (A.); J. Low (J.); P. Coakely (P.); S. Coughlan (Suzie); I. Levi (I.); D. Chemtob (D.); C. Balotta (Claudia); C. Mussini (C.); I. Caramma (I.); A. Capetti (A.); M.C. Colombo (M.); C. Rossi (Cesare); F. Prati (Francesco); F. Tramuto (F.); F. Vitale (F.); M. Ciccozzi (M.); G. Angarano (Guiseppe); G. Rezza (G.); R. Hemmer (R.); V. Arendt (V.); T. Staub (T.); F. Schneider (F.); F. Roman (Francois); C.A.B. Boucher (Charles); P.H.M. van Bentum (P. H M); K. Brinkman (Kees); E.L.M. Op de Coul (Eline); M.E. van der Ende (Marchina); I.M. Hoepelman (Ilja Mohandas); M.E.E. van Kasteren (Marjo); J. Juttmann (Job); M. Kuipers (M.); N. Langebeek (Nienke); C. Richter (C.); R.M.W.J. Santegoets (R. M W J); L. Schrijnders-Gudde (L.); R. Schuurman (Rob); B.J.M. van de Ven (B. J M); B. Asjö (Birgitta); V. Ormaasen (Vidar); P. Aavitsland (P.); J. Stanczak (J.); G.P. Stanczak (G.); E. Firlag-Burkacka (E.); A. Wiercinska-Drapalo (A.); E. Jablonowska (E.); E. Malolepsza (E.); M. Leszczyszyn-Pynka (M.); W. Szata (W.); A. de Palma (Andre); F. Borges (F.); T. Paix̃ao (T.); V. Duque (V.); F. Aráujo (F.); M. Stanojevic (Maja); D.J. Jevtovic (D.); D. Salemovic (D.); M. Habekova (M.); M. Mokras (M.); P. Truska (P.); M. Poljak (Mario); D.Z. Babic (Dunja); J. Tomazic (J.); S. Vidmar (Suzanna); P. Karner (P.); C. Gutíerrez (C.); C. deMendoza (C.); I. Erkicia (I.); P. Domingo (P.); X. Camino (X.); M.A. Galindo (Miguel Angel); J.L. Blanco (J.); M. Leal (M.); A. Masabeu (A.); A. Guelar (A.); J.M. Llibre (Josep M.); N. Margall (N.); C. Iribarren (Carlos); S. Gutierrez (S.); J.F. Baldov́i (J.); C.E. Pedreira (Carlos Eduardo); J.M. Gatell (J.); S. Moreno (S.); C. de Mendoza (Carmen); V. Soriano (Virtudes); A. Blaxhult (A.); A. Heidarian (A.); A. Karlsson (A.); K. Aperia-Peipke (K.); I.-M. Bergbrant (I.); M. Gissĺen (M.); M. Svennerholm (M.); P. Bj̈orkman (P.); G. Bratt (G.); M. Carlsson (M.); H. Ekvall (H.); M. Ericsson (M.); M. Ḧofer (M.); B. Johansson (Bert); N. Kuylenstierna (N.); K. Ljungberg (Karl); S. Mäkitalo (S.); A. Strand; K. Öberg (Kjell); T. Berg (Trine)
textabstractBackground: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory
Lin, Jing; Chen, Lanting; Qiu, Xuemin; Zhang, Na; Guo, Qiting; Wang, Yan; Wang, Mingyan; Gober, Hans-Jürgen; Li, Dajin; Wang, Ling
Human papillomavirus (HPV) infections are common and generally harmless, but persistent infections can bring health problems like cancer and genital warts. For the uninfected group, HPV vaccines provide safe and effective protection, but they're type-restricted and expensive. For those infected, so far there have been a handful of treatments for HPV-associated benign or malignant diseases, traditional Chinese medicine being one of them. This systematic review focuses on the application of traditional Chinese medicine in HPV infection and related diseases on the basis of clinical findings. Moreover it covers compositions and mechanisms based on in vitro laboratory methods and animal models. Traditional Chinese medicine improves clinical index in the treatment of cervical cancer and genital warts; the mechanisms behind the effectiveness might be the regulation of cell apoptosis, viral gene transcription and translation, cell signal transduction pathways, and immune function.
Olivero, Carlotta; Lanfredini, Simone; Borgogna, Cinzia; Gariglio, Marisa; Patel, Girish K
Field cancerisation was originally described as a basis for multiple head and neck squamous cell carcinoma (HNSCC) and is a pre-malignant phenomenon that is frequently attributable to oncogenic human papillomavirus (HPV) infection. Our work on β-HPV-induced cutaneous squamous cell carcinomas identified a novel Lrig1+ hair follicle junctional zone keratinocyte stem cell population as the basis for field cancerisation. Herein, we describe the ability for HPV to infect adult tissue stem cells in order to establish persistent infection and induce their proliferation and displacement resulting in field cancerisation. By review of the HPV literature, we reveal how this mechanism is conserved as the basis of field cancerisation across many tissues. New insights have identified the capacity for HPV early region genes to dysregulate adult tissue stem cell self-renewal pathways ensuring that the expanded population preserve its stem cell characteristics beyond the stem cell niche. HPV-infected cells acquire additional transforming mutations that can give rise to intraepithelial neoplasia (IEN), from environmental factors such as sunlight or tobacco induced mutations in skin and oral cavity, respectively. With establishment of IEN, HPV viral replication is sacrificed with loss of the episome, and the tissue is predisposed to multiple cancer stem cell-driven carcinomas.
Di Pietro, Marisa; Filardo, Simone; Porpora, Maria Grazia; Recine, Nadia; Latino, Maria Agnese; Sessa, Rosa
HPV and Chlamydia trachomatis are the most common causes of sexually transmitted diseases worldwide. Most infections are asymptomatic and left untreated lead to severe reproductive tract sequelae such as cervical cancer and infertility. Interestingly, C. trachomatis may also increase the susceptibility to HPV infection as well as contribute to viral persistence. Recently, a growing body of evidence has suggested that the composition of the cervico-vaginal microbiota plays a key role in the susceptibility and outcome of genital infections caused by several pathogens, including HPV and C. trachomatis. The aim of our study was to undertake a metagenomic analysis of sequenced 16s rRNA gene amplicons to characterize the cervical microbiota from asymptomatic women with HPV/C. trachomatis co-infection. The composition of the cervical microbiota from HPV-positive or C. trachomatis-positive women was also analysed. The main finding of our study showed that the cervical microbiota in HPV/C. trachomatis co-infected women had a higher microbial diversity than the cervical microbiota in healthy controls (pHPV/C. trachomatis co-infected women and the detection of potential microbiological biomarkers of C. trachomatis infection will open the way to innovative approaches that may be helpful to identify women at risk of co-infection.
Full Text Available Background: Low-grade squamous intraepithelial lesions (LSIL are the earliest lesions of the uterine cervix, the persistence and integration of high-risk human papillomavirus (HR-HPV as type 16, which promotes the development of more aggressive lesions. Aim: To select more aggressive lesions with tendency to progress to invasive cervical cancer. Materials and Methods: A total of 75 cytological specimens in liquid base (Liqui-PREP were analyzed: 25 specimens were with no signs of SIL (NSIL and without HPV; 25 NSIL with HPV-16, and 25 with both LSIL and HPV-16. The expression of Ki-67, telomerase, and viral E6 was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR and restriction fragment length polymorphism (RFLPs for genotyping or sequencing of HPV-16. The physical state of HPV-16 was evaluated by in situ hybridization with amplification with tyramide. Results: Of the total group, 58.6% had LSIL associated with persistence and of these 59.3% was associated with integrated state of HPV as intense expression of E6, Ki-67 (P = 0.013, P = 0.055 has except for the expression of telomerase present a non-significant association (P<0.341. Conclusions: Overexpression of E6 and Ki-67 is associated with the integration of HPV-16, favoring viral persistence, and increasing the risk of progression in women with NSIL and LSIL.
Relação entre diagnóstico citopatológico de neoplasia intra-epitelial cervical e índices de células CD4+ e de carga viral em pacientes HIV-soropositivas Association of cervical intraepithelial neoplasia with CD4 T cell counts and viral load in HIV-infected women
Raquel Autran Coelho
-RNA viral load in HIV-positive patients. METHODS: one hundred and fifteen HIV patients were evaluated retrospectively in the present study, during the period from January 2002 to April 2003, at a university hospital. Eighty-three patients presented cervical intraepithelial neoplasia (CIN in Pap smear, in comparison with thirty-two with no lesions. Patients were divided into three groups, according to CD4 counts: CD4 more than 500 cells/mm³, between 200 and 500 cells/mm³, and less than 200 cells/mm³, and other three groups, according to HIV viral load: less than 10,000 HIV-RNA copies/mL, between 10,000 and 100,000 HIV-RNA copies/mL, or more than 100,000 HIV-RNA copies/mL. Correlation was investigated by the Fisher test. RESULTS: of the eighty-three patients with CIN, 73% presented CD4 counts less than 500 cells/mm³. In all CD4 groups, more than 50% of the patients presented CIN. According to the viral load, 71.7% of the patients with less than 10,000 HIV-RNA copies/mL presented CIN I, compared with 11.3% that showed CIN III. In the group with higher viral load (>100.000 HIV-RNA copies/mL, 61.5% showed CIN I and 30.8% presented CIN III. CONCLUSION: association between viral load and CIN was established (p=0.013, which was not observed with CD4 cell counts and CIN. Concomitant cervicovaginal infection was considered a potential confounding factor.
Feb 4, 2009 ... targeting the viral oncoproteins E6 and E7 are markers for HPV-associated ... Luminex XYP plate handler, Luminex SD sheath fluid delivery system, a Pentium 4 .... expression mediated by a potato virus X derived vector of the E7 protein .... inflammation, and antioxidant nutrients – assessing their roles as.
Wilson, Regina; Ryan, Gordon B.; Knight, Gillian L.; Laimins, Laimonis A.; Roberts, Sally
Activation of the productive phase of the human papillomavirus (HPV) life cycle in differentiated keratinocytes is coincident with high-level expression of E1-circumflexE4 protein. To determine the role of E1-circumflexE4 in the HPV replication cycle, we constructed HPV18 mutant genomes in which expression of the full-length E1-circumflexE4 protein was abrogated. Undifferentiated keratinocytes containing mutant genomes showed enhanced proliferation when compared to cells containing wildtype genomes, but there were no differences in maintenance of viral episomes. Following differentiation, cells with mutant genomes exhibited reduced levels of viral DNA amplification and late gene expression, compared to wildtype genome-containing cells. This indicates that HPV18 E1-circumflexE4 plays an important role in regulating HPV late functions, and it may also function in the early phase of the replication cycle. Our finding that full-length HPV18 E1-circumflexE4 protein plays a significant role in promoting viral genome amplification concurs with a similar report with HPV31, but is in contrast to an HPV11 study where viral DNA amplification was not dependent on full-length E1-circumflexE4 expression, and to HPV16 where only C-terminal truncations in E1-circumflexE4 abrogated vegetative genome replication. This suggests that type-specific differences exist between various E1-circumflexE4 proteins
Tesfalul, Martha; Simbiri, Kenneth; Wheat, Chikoti M.; Motsepe, Didintle; Goldbach, Hayley; Armstrong, Kathleen; Hudson, Kathryn; Kayembe, Mukendi K.; Robertson, Erle; Kovarik, Carrie
Objective The primary aim of this study is to describe the prevalence of select oncogenic viruses within vulvar squamous cell carcinoma (VSCC) and their association with Human Immunodeficiency Virus (HIV) status in women in Botswana, where the national HIV prevalence is the third highest in the world. Methods/materials A cross-sectional study of biopsy-confirmed VSCC specimens and corresponding clinical data was conducted in Gaborone, Botswana. Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) viral testing were done for Epstein-Barr Virus (EBV), Human Papilloma Virus (HPV) strains, and Kaposi's Sarcoma Herpesvirus (KSHV), and PCR viral testing alone was done for John Cunningham Virus (JCV). Results HPV prevalence by PCR was 100% (39/39 35/35) among tested samples. HPV16 was the most prevalent HPV strain (82.9% by PCR, 94.7% by either PCR or IHC). KSHV prevalence by PCR had a significant association with HIV status (p = 0.013), but not by IHC (p = 0.650). Conclusions The high burden of HPV, specifically HPV16, in VSCC in Botswana suggests a distinct HPV profile that differs from other studied populations, which provides increased motivation for HPV vaccination efforts. Oncogenic viruses KSHV and EBV were also more prevalent in our study population though their potential role in VSCC pathology is unclear. PMID:24651632
Ma, Barbara; Roden, Richard; Wu, T.C.
Cervical cancer is the second largest cause of cancer deaths in women worldwide, with ~500,000 diagnoses and 274,000 deaths annually. It remains a significant source of morbidity and mortality despite effective screening tools and treatments for its precursor high-grade cervical intraepithelial neoplasia (CIN). Increased understanding of cervical pathogenesis has led to the identification of human papillomavirus (HPV) as the etiological agent for cervical cancer and the development of preventive and therapeutic vaccines targeting HPV antigens for the control of cervical cancer. Herein, we discuss the current status of HPV vaccines. PMID:20677402
Cíntia Tereza Lima Ferraro
Full Text Available Os papilomavírus humanos (HPVs pertencem à família Papillomaviridae e seu ciclo de vida é diretamente ligado à diferenciação das células epiteliais do hospedeiro. Possuem seis genes que se expressam precocemente e dois genes que se expressam tardiamente, sendo denominados respectivamente E (early e L (late. O ácido desoxirribonucleico (DNA viral dentro da célula do hospedeiro pode assumir duas formas: epissomal e integrada. O HPV tem como alvo as células basais de epitélios escamosos, em particular da área genital, onde está associado ao carcinoma da cérvice uterina. Na boca, o HPV está associado a papiloma escamoso oral, condiloma acuminado, verruga vulgar e hiperplasia epitelial focal. Entretanto, seu papel na carcinogênese oral é ainda controverso, sendo também identificado como agente etiológico de alguns carcinomas de células escamosas de cabeça e pescoço. A infecção pelo HPV pode agir sinergicamente com agentes carcinogênicos, como o tabaco e o álcool. Pelo menos 150 subtipos diferentes de HPV já foram identificados, sendo que 25 têm sido detectados em lesões orais. Considerando a relevância do tema para a melhor compreensão da infecção oral pelo HPV, o objetivo desta atualização é rever os aspectos relevantes da biologia do HPV, com ênfase na relação HPV-ceratinócitos, e a importância dos dados clínicos e histopatológicos na definição diagnóstica das lesões orais possivelmente associadas ao HPV.Papillomaviruses belong to the family Papillomaviridae and their life cycle is directly linked to the differentiation of host epithelial cells. They have six genes that are expressed earlier and two genes that are expressed later in their life cycle, named respectively E (early and L (late. Host cell viral DNA can take two forms: episomal and integrated. The human papillomavirus (HPV targets the basal cells of squamous epithelia, particularly from the genital area, which is associated with uterine
de Martel, Catherine; Plummer, Martyn; Vignat, Jerome; Franceschi, Silvia
HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV?attributable cancer burden can boost programs of HPV vaccination and HPV?based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age?standardized incidenc...
H. S. Ibishev
Full Text Available Introduction. Recurrent urinary tract infection is an actual problem of modern urology.Objective. Complex investigation of urinary tract infections including viral etiology for chronic recurrent cystitis in womenMaterials and methods. The study included 31 women with recurrent infection of urinary tract. Inclusion criteria were the presence of lower urinary tract symptoms caused by infection, severe recurrent course, the lack of anatomical and functional disorders of the urinary tract, the absence of bacterial pathogens during the study, taking into account the culture of aerobic and anaerobic culturing techniques.Results. The analysis of the clinical manifestations, the dominant in the study group were pain and urgency to urinate at 100% and 90% of women surveyed, respectively, and less frequent urination were recorded in 16.1% of patients. In general clinical examination of urine in all cases identified leukocyturia and 90% of the hematuria. By using a polymerase chain reaction (PCR in midstream urine of all examined was verified 10 types of human papilloma virus (HPV with the predominance of 16 and 18 types . Considering the presence of recurrent infectious and inflammatory processes of the urinary tract, cystoscopy with bladder biopsy was performed for all patients. When histomorphological biopsies of all patients surveyed noted the presence of the specific characteristics of HPV: papillary hyperplasia with squamous koilocytosis, pale cytoplasm and shrunken kernels. When analyzing the results of PCR biopsy data corresponded with the results of PCR in midstream urine in all biopsies was detected HPV.Conclusions. Human papillomavirus infection may be involved in the development of viral cystitis. In the etiological structure of viral cystitis, both highly oncogenic and low oncogenic HPV types can act.
Chang, J T-C; Kuo, T-F; Chen, Y-J; Chiu, C-C; Lu, Y-C; Li, H-F; Shen, C-R; Cheng, A-J
Infection with high-risk types (type 16 or type 18) of human papillomaviruses (HPVs) increases a patient's risk of cervical cancer. Given the importance of the cervix and the severe side effects resulting from traditional cancer therapies, this study aimed to achieve targeted inhibition of viral oncogenes in tumor cells using small interfering RNAs (siRNA). To accomplish this, we developed nine siRNAs against either the E6 or E7 genes of HPV-16 or HPV-18 in several combinations, yielding siRN...
Rapid detection and quantification of cell free cytomegalovirus by a high-speed centrifugation-based microculture assay: comparison to longitudinally analyzed viral DNA load and pp67 late transcript during lactation.
Hamprecht, Klaus; Witzel, Simone; Maschmann, Jens; Dietz, Klaus; Baumeister, Andrea; Mikeler, Elfriede; Goelz, Rangmar; Speer, Christian P; Jahn, Gerhard
Human cytomegalovirus (HCMV) is reactivated in nearly every seropositive breastfeeding mother during lactation [Lancet 357 (2001) 513]. Conventional tissue culture (TC) and low-speed centrifugation-enhanced microtiter culture methods are not able to detect HCMV from milk during all stages of lactation. Development of a sensitive and quantitative microculture technique to describe the dynamics of HCMV reactivation in different milk compartments during lactation. Milk samples were collected longitudinally from seropositive breastfeeding mothers of preterm infants. Native milk samples were separated into fraction 1 (aqueous extract of milk fat), fraction 2 (cell and fat free milk whey) and fraction 3 (milk cells). Each of these fractions was screened qualitatively (TC, nPCR, pp67 late mRNA) and quantitatively (high-speed centrifugation-based microculture, quantitative PCR). Prior to low-speed centrifugation-enhanced inoculation, virus particles were concentrated by high-speed centrifugation (60 min at 50,000 x g, 4 degrees C). Using fraction 2 we were able to describe the dynamics of viral reactivation during lactation. We present the course of the quantitative virolactia and DNAlactia and qualitative detection of HCMV pp67 late mRNA in milk whey of four mothers (three transmitters and one non-transmitter). In all these cases virolactia described an unimodal and self limited course. Peak levels of virolactia for transmitters (T1: day 44; T2: day 43; T3: day 50) were closely related the onset of viruria of the corresponding preterm infants (U1: day 39; U2a/U2b: day 44/57; U3: day 60). The courses of viral load coincidence with the courses of DNA load. We present a rapid and highly sensitive microculture method for the quantification of cell free HCMV from milk whey and aqueous extracts from milk fat. Viral reactivation during lactation describes an unimodal course. Our findings have strong implications for quality control of any virus inactivation procedure.
Vojtechova, Zuzana; Sabol, Ivan; Salakova, Martina; Smahelova, Jana; Zavadil, Jiri; Turek, Lubomir; Grega, Marek; Klozar, Jan; Prochazka, Bohumir; Tachezy, Ruth
Better insights into the molecular changes involved in virus-associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV-dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology. Fresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection. We defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV-negative keratinocytes. We identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of
Chen, Long; Luan, Shaohong; Xia, Baoguo; Liu, Yansheng; Gao, Yuan; Yu, Hongyan; Mu, Qingling; Zhang, Ping; Zhang, Weina; Zhang, Shengmiao; Wei, Guopeng; Yang, Min; Li, Ke
Human papillomavirus (HPV) infection is the primary cause of cervical cancer. HPV-mediated immune alterations are known to play crucial roles in determining viral persistence and host cell transformation. We sought to thoroughly understand HPV-directed immune alterations in cervical cancer by exploring publically available datasets. 130 HPV positive and 7 HPV negative cervical cancer cases from The Cancer Genome Atlas were compared for differences in gene expression levels and functional enrichment. Analyses for copy number variation (CNV) and genetic mutation were conducted for differentially expressed immune genes. Kaplan-Meier analysis was performed to assess survival and relapse differences across cases with or without alterations of the identified immune signature genes. Genes up-regulated in HPV positive cervical cancer were enriched for various gene ontology terms of immune processes (P=1.05E-14~1.00E-05). Integrated analysis of the differentially expressed immune genes identified 9 genes that displayed either CNV, genetic mutation and/or gene expression changes in at least 10% of the cases of HPV positive cervical cancer. Genomic amplification may cause elevated levels of these genes in some HPV positive cases. Finally, patients with alterations in at least one of the nine signature genes overall had earlier relapse compared to those without any alterations. The altered expression of either TFRC or MMP13 may indicate poor survival for a subset of cervical cancer patients (P=1.07E-07). We identified a novel immune gene signature for HPV positive cervical cancer that is potentially associated with early relapse of cervical cancer. Copyright © 2018. Published by Elsevier Inc.
Akpinar, E.; Berger, Jonah
Given recent interest in social media, many brands now create content that they hope consumers will view and share with peers. While some campaigns indeed go “viral,” their value to the brand is limited if they do not boost brand evaluation or increase purchase. Consequently, a key question is how
Balermpas, Panagiotis; Martin, Daniel; Wieland, Ulrike; Rave-Fränk, Margret; Strebhardt, Klaus; Rödel, Claus; Fokas, Emmanouil; Rödel, Franz
ABSTRACT We examined the prognostic role of immune markers programmed cell death protein-1 (PD-1) and its ligand (PD-L1), CD8+ tumor-infiltrating lymphocytes (TILs), FOXP3+ Tregs and phosphorylated Caspase-8 (T273) in patients with anal squamous cell cancer (ASCC) treated with standard chemoradiotherapy (CRT). The baseline immunohistochemical expression of immune markers was correlated with clinicopathologic characteristics, and cumulative incidence of local failure, disease-free survival (DFS) and overall survival (OS) in 150 patients, also in the context of human papilloma virus 16 (HPV16) DNA load and p16INK4a expression. After a median follow-up of 40 mo (1–205 mo), the 5-y cumulative incidence of local failure and DFS was 19.4% and 67.2%, respectively. Strong immune marker expression was significantly more common in tumors with high HPV16 viral load. In multivariant analysis, high CD8+ and PD-1+ TILs expression predicted for improved local control (p = 0.023 and p = 0.007, respectively) and DFS (p = 0.020 and p = 0.014, respectively). Also, high p16INK4a (p = 0.011) and PD-L1 (p = 0.033) expression predicted for better local control, whereas high FOXP3+ Tregs (p = 0.050) and phosphorylated Caspase-8 (p = 0.031) expression correlated with superior DFS. Female sex and high HPV16 viral load correlated with favorable outcome for all three clinical endpoints. The present data provide, for the first time, robust explanation for the favorable clinical outcome of HPV16-positive ASCC patients harboring strong immune cell infiltration. Our findings are relevant for treatment stratification with immune PD-1/PD-L1 checkpoint inhibitors to complement CRT and should be explored in a clinical trial. PMID:28405521
... What CDC Is Doing Related Links Stay Informed Statistics for Other Kinds of Cancer Breast Cervical Colorectal ( ... Vaginal and Vulvar Cancer Home HPV-Associated Cancer Statistics Language: English (US) Español (Spanish) Recommend on Facebook ...
Lin, Ken; Doolan, Kimberley; Hung, Chien-Fu; Wu, T-C
Cervical cancer is the second most common cause of female cancer death worldwide. Persistent infection with `high risk' HPV genotypes is the major etiological factor in cervical cancer and thus effective vaccination against HPV provides an opportunity to reduce the morbidity and mortality associated with HPV. The FDA has approved two preventive vaccines to limit the spread of HPV. However, these are unlikely to impact upon HPV prevalence and cervical cancer rates for many years. Furthermore, preventive vaccines do not exert therapeutic effects on pre-existing HPV infections and HPV-associated lesions. In order to further impact upon the burden of HPV infections worldwide, therapeutic vaccines are being developed. These vaccines aim to generate a cell-mediated immune response to infected cells. This review discusses current preventive and therapeutic HPV vaccines and their future directions. PMID:20123582
McBride, Kimberly R; Singh, Shipra
High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified sociodemographic characteristics associated with HPV knowledge at the population level. Data from adult men ( n = 1,197) and women ( n = 1,906) who participated in the National Cancer Institute's 2014 Health Information National Trends Survey were analyzed. Multivariable regression was used to identify predictors of four HPV knowledge categories: (1) general knowledge, (2) cervical cancer knowledge, (3) "other" cancer knowledge (i.e., anal, oral, penile), and (4) vaccine knowledge. Significant gender differences in awareness and knowledge of HPV and the HPV vaccine were revealed. Most participants (>70%) knew that HPV could cause cervical cancer, but fewer (14.9% to 31.5%) knew of the association between HPV and "other" cancers. Women were more likely to report that a health care provider recommended vaccination. Significant predictors of general HPV and HPV vaccine knowledge included gender, education, income, race, and other sociodemographic characteristics. Age and income predicted cervical cancer knowledge. Knowledge of "other" HPV-associated cancers was predicted by having a child under 18 years in the household and relationship status. HPV knowledge appears to be socially patterned. Low HPV knowledge among men and some racial minorities suggests a need for further intervention. Health education should emphasize risks of noncervical HPV-associated cancers. Patient-provider communication that includes education, counseling, and clear recommendations favoring vaccination may improve uptake.
Full Text Available Abstract Background Major histocompatibility complex class II deficiency, also referred to as bare lymphocyte syndrome is a rare primary Immunodeficiency disorder characterized by a profondly deficient human leukocyte antigen class II expression and a lack of cellular and humoral immune responses to foreign antigens. Clinical manifestations include extreme susceptibility to viral, bacterial, and fungal infections. The infections begin in the first year of life and involve usually the respiratory system and the gastrointestinal tract. Severe malabsorption with failure to thrive ensues, often leading to death in early childhood. Bone marrow transplantation is the curative treatment. Case reports Here we report two cases with a late outcome MHC class II deficiency. They had a long term history of recurrent bronchopulmonary and gastrointestinal infections. Bone marrow transplantation could not be performed because no compatible donor had been identified. At the age of 12 years, they developed oral papillomatous lesions related to HPV (human papillomavirus. The diagnosis of HPV infection was done by histological examination. HPV typing performed on the tissue obtained at biopsy showed HPV type 6. The lesions were partially removed after two months of laser treatment. Conclusions Viral infections are common in patients with MHC class II and remain the main cause of death. Besides warts caused by HPV infection do not exhibit a propensity for malignant transformation; they can cause great psychosocial morbidity.
Full Text Available Most human papillomavirus (HPV antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies.
Orta Mira, Nieves; Serrano, María del Remedio Guna; Martínez, José-Carlos Latorre; Ovies, María Rosario; Poveda, Marta; de Gopegui, Enrique Ruiz; Cardona, Concepción Gimeno
Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers for the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarized the results obtained in the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads and HCV genotyping. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 3-5 log(10) copies/mL; two of these standards were identical, with the aim of determining repeatability. A significant proportion of the laboratories (22.6% on average) obtained values out of the accepted range (mean ± 0.2 log(10)copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 95% of laboratories reporting results within the limits (Δ<0.5 log(10)copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 86.1% in the case of HCV and 87.1% in HBV, obtained all the results within the accepted range (mean ± 1.96 SD log(10)UI/mL). Post-analytical errors due to mistranscription of the results were detected in these controls. Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to interlaboratory variability, use of the same method and the same laboratory for patient follow-up is advisable. Copyright © 2011 Elsevier España S.L. All rights reserved.
Wells, Susanne I.; Francis, Delicia A.; Karpova, Alla Y.; Dowhanick, Jennifer J.; Benson, John D.; Howley, Peter M.
A hallmark of human papillomavirus (HPV) associated carcinogenesis is the integration of the viral DNA into the cellular genome, usually accompanied by the loss of expression of the viral E2 gene. E2 binds to and represses the viral promoter directing expression of the E6 and E7 oncogenes. The re-introduction and expression of exogenous E2 in HPV-positive cancer cells results in cellular growth arrest, while growth in the context of exogenous E2 can be restored through the expression of exoge...
Full Text Available BACKGROUND: An increasing incidence of anal cancer among men, especially men who have sex with men (MSM suggests a need to better understand anal human papillomavirus (HPV infection among this group. METHODS: A cross-sectional study was conducted among MSM in Shenzhen, China. Blood was collected for HIV serological testing and syphilis serological screening, and anal swabs were collected for HPV genotyping. Difference of HPV prevalence between HIV seropositive and HIV seronegative MSM was assessed by chi-square test. Factors associated with anal canal HPV infection were assessed by univariate and multivariate logistic regression. RESULTS: A total of 408 MSM were recruited. HIV and HPV prevalence were 6.9% and 36.4%, respectively. HPV was detected in the anal canal in 71.4% of the HIV-positive MSM and in 33.8% of the HIV-negative MSM (P<0.001. Oncogenic types were seen more often in anal specimens of HIV-positive MSM than in specimens of HIV-negative MSM (P = 0.001. The HPV genotypes detected most frequently were HPV06 (8.2%, HPV16 (7.2%, HPV11 (6.4%, HPV18 (4.7%, HPV58 (4.7%, and HPV52 (4.2%. CONCLUSIONS: In this study, HIV positive MSM had a higher burden of HPV infection, especially oncogenic HPV infection. HPV types 52 and 58 were as popular as those types designed for the currently available vaccine (HPV6, 11, 16, 18.
Ko, Vincent; Nanji, Shabin; Tambouret, Rosemary H; Wilbur, David C
Inappropriate use of the category of atypical squamous cells of undetermined significance (ASCUS) can result in overtreatment or undertreatment of patients, which may decrease the cost effectiveness of screening. Quality assurance tools, such as the ASCUS to squamous intraepithelial lesion ratio (ASCUS:SIL) and case review, are imperfect. High-risk HPV (hrHPV) testing is an objective test for a known viral carcinogen, and hrHPV may be more useful in monitoring the quality of ASCUS interpretations. hrHPV rates for cytologic diagnoses and patient age groups were calculated for a 2-year period. All hrHPV results for ASCUS and SIL over a 17-month period were analyzed by patient age group, over time, and by individual cytopathologist to compare hrHPV rates with the corresponding ASCUS:SIL. The hrHPV positive rate for SIL was >90%, and it was 32.6% for ASCUS. Stratification by patient age showed that approximately 50% of patients younger than 30 years and older than 70 years of age were hrHPV positive, whereas other patients had a lower rate ranging from 14% to 34%. The overall ASCUS:SIL was 1.42, and the overall hrHPV positive rate was 39.9%. Over time and by individual cytopathologist, the hrHPV rate performed similarly to the ASCUS:SIL. The analysis by patient age showed a high statistical correlation (R(2) = 0.9772) between the 2 methods. Despite differences between these techniques, the hrHPV rate closely recapitulates the ASCUS:SIL. When used together, the 2 methods can complement each other. The desirable hrHPV-positive range appears to be 40% to 50%; however, this may vary based on the patient population. The hrHPV rate is as quick and cost effective as determining the ASCUS:SIL. (c) 2007 American Cancer Society.
Full Text Available High-risk human papillomavirus (HPV infections are the cause of nearly all cases of cervical cancer. Although the detection of HPV DNA has proved useful in cervical diagnosis, it does not necessarily predict disease presence or severity, and cannot conclusively identify the causative type when multiple HPVs are present. Such limitations may be addressed using complementary approaches such as cytology, laser capture microscopy, and/or the use of infection biomarkers. One such infection biomarker is the HPV E4 protein, which is expressed at high level in cells that are supporting (or have supported viral genome amplification. Its distribution in lesions has suggested a role in disease staging. Here we have examined whether type-specific E4 antibodies may also allow the identification and/or confirmation of causal HPV-type. To do this, type-specific polyclonal and monoclonal antibodies against three E4 proteins (HPV-16, -18, and -58 were generated and validated by ELISA and western blotting, and by immunohistochemistry (IHC staining of epithelial rafts containing these individual HPV types. Type-specific detection of HPV and its associated disease was subsequently examined using formalin-fixed paraffin-embedded cervical intra-epithelial neoplasias (CIN, (n = 247 and normal controls (n = 28. All koilocytotic CIN1 lesions showed type-specific E4 expression of their respective HPV types. Differences were noted amongst E4 expression patterns in CIN3. HPV-18 E4 was not detected in any of the 6 HPV-18 DNA-positive CIN3 lesions examined, whereas in HPV-16 and -58 CIN3, 28/37 (76% and 5/9 (55.6% expressed E4 respectively, usually in regions of epithelial differentiation. Our results demonstrate that type-specific E4 antibodies can be used to help establish causality, as may be required when multiple HPV types are detected. The unique characteristics of the E4 biomarker suggest a role in diagnosis and patient management particularly when used in combination.
Lu, Danielle W; Pirog, Edyta C; Zhu, Xiaopei; Wang, Hanlin L; Pinto, Karen R
To determine the prevalence and typing of HPV DNA in pregnant women with a diagnosis of atypical squamous cells (ASC) and to assess whether pregnancy-related changes contribute to the diagnosis of ASC. HPV testing was performed on residual specimens from the ThinPrep Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) in pregnant women diagnosed as ASC (study group, n = 105), low and high grade squamous intraepithelial lesion (LSIL and HSIL) (positive control, n = 33) and negative for epithelial cell abnormality (negative control, n = 20). All cases were reviewed by 2 cytopathologists to obtain consensus diagnoses using the Bethesda System 2001 criteria. The study group cases were further subcategorized into ASC of undetermined significance (ASCUS, n = 99) and ASC cannot exclude HSIL (ASC-H, n = 6). HPV testing was also performed on an ASC control group consisting of 68 consecutive ASC cases in nonpregnant women, matched by age. Mean patient age was 23.7 years for the study group and 25.6 years for the ASC control group. HPV DNA was detected in 88.6% of cases in the study group, including 87.9% of ASC-US and 100% of ASC-H cases. Of the HPV positive cases, 79.6%, 4.3%, 5.4% and 10.8% had high-risk, mixed high- and low-risk, low-risk and unknown HPV types, respectively. The most frequent HPV types detected were: types 52 (31.2%), 16 (15.1%), 39 (11.8%), 53 (10.8%), and 18 and 58 (9.7% each). Multiple viral types were detected in 43.0% of cases. The prevalence of HPV DNA in the positive and negative controls in pregnant women was 100% and 55%, respectively. HPV DNA was detected in 83.8% of the ASC control group. Regardless of pregnancy-related changes, the prevalence of HPV DNA in pregnant women (88.6%) was similar to that found in ASC in nonpregnant women of the same reproductive-age group (83.8%), and the high-risk types accounted for the vast majority of cases (83.9%). These findings demonstrate that pregnancy-related changes do not contribute to the
Skorstengaard, Malene; Thamsborg, Lise Holst; Lynge, Elsebeth
-caused cancers in women and men, and to evaluate the potential of HPV-vaccination in cancer control. Methods: Data were retrieved from the literature on population prevalence of high risk (HR) HPV, on HR HPV-prevalence and genotypes in HPV-related cancers, and on number of cytology samples in cervical screening...... were preventable with HPV vaccination. However, including screening prevented cervical cancers, the burden of cancers caused by HPV-infection would be 1300–2000 in women as compared to 234 in men. Conclusion: Taking screening prevented cervical cancers into account, the cancer control potential of HPV...
Full Text Available ... sq how to do kids infect kids links & resources M.O.V.E. parents for prevention ... go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV We provide ...
Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...
Zeh, Clement; Ndiege, Kenneth; Inzaule, Seth; Achieng, Rebecca; Williamson, John; Chih-Wei Chang, Joy; Ellenberger, Dennis; Nkengasong, John
Routine HIV viral load testing is not widely accessible in most resource-limited settings, including Kenya. To increase access to viral load testing, alternative sample types like dried blood spots (DBS), which overcome the logistic barriers associated with plasma separation and cold chain shipment need to be considered and evaluated. The current study evaluated matched dried blood spots (DBS) and dried plasma spots (DPS) against plasma using the Abbott M 2000 (Abbott) and Roche Cobas Ampliprep/Cobas TaqMan (CAP/CTM) quantitative viral load assays in western Kenya. Matched plasma DBS and DPS were obtained from 200 HIV-1 infected antiretroviral treatment (ART)-experienced patients attending patient support centers in Western Kenya. Standard quantitative assay performance parameters with accompanying 95% confidence intervals (CI) were assessed at the assays lower detection limit (400cps/ml for CAP/CTM and 550cps/ml for Abbott) using SAS version 9.2. Receiver operating curves (ROC) were further used to assess viral-load thresholds with best assay performance (reference assay CAP/CTM plasma). Using the Abbott test, the sensitivity and specificity, respectively, for DPS were (97.3%, [95%CI: 93.2-99.2] and 98.1% [95%CI: 89.7-100]) and those for DBS (93.9% [95%CI: 88.8-97.2] and 88.0% [95%CI: 82.2-92.4]). The correlation and agreement using paired plasma and DPS/DBS were strong, with r2 = 90.5 and rc = 68.1. The Bland-Altman relative percent change was 95.3 for DPS, (95%CI: 90.4-97.7) and 73.6 (95%CI: 51.6-86.5) for DBS. Using the CAP/CTM assay, the sensitivity for DBS was significantly higher compared to DPS (100.0% [95% CI: 97.6-100.0] vs. 94.7% [95%CI: 89.8-97.7]), while the specificity for DBS was lower: 4%, [95% CI: 0.4-13.7] compared to DPS: 94.0%, [95% CI: 83.5-98.7]. When compared under different clinical relevant thresholds, the accuracy for the Abbott assay was 95% at the 1000cps/ml cut-off with a sensitivity and specificity of 96.6% [95% CI 91.8-98.7] and 90
Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C
Infection of high-risk human papillomaviruses (HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that high-risk HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory or signaling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the "cancer hallmarks," and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death, and deregulation of cellular energetics. These information could eventually aid in identifying or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6, and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction
Kuniholm, Mark H; Liang, Hua; Anastos, Kathryn; Gustafson, Deborah; Kassaye, Seble; Nowicki, Marek; Sha, Beverly E; Pawlowski, Emilia J; Gange, Stephen J; Aouizerat, Bradley E; Pushkarsky, Tatiana; Bukrinsky, Michael I; Prasad, Vinayaka R
To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study. We examined 2050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T-cell levels in a multiracial cohort of 1066 antiretroviral therapy-naive women. Six SNPs were associated with both HIV viral load and CD4 T-cell levels at a false discovery rate of 0.01. Bioinformatics tools did not predict functional activity for five SNPs, located in introns of nuclear receptor corepressor 2, retinoid X receptor alpha (RXRA), and tetratricopeptide repeat domain 39B. Rs17111557 located in the 3' untranslated region of proprotein convertase subtilisin/kexin type 9 (PCSK9) putatively affects binding of hsa-miR-548t-5p and hsa-miR-4796-3p, which could regulate PCSK9 expression levels. Interrogation of rs17111557 revealed stronger associations in the subset of women with HIV/hepatitis C virus (HCV) coinfection (n = 408, 38% of women). Rs17111557 was also associated with low-density lipoprotein cholesterol levels in HIV/HCV coinfected (β: -10.4; 95% confidence interval: -17.9, -2.9; P = 0.007), but not in HIV monoinfected (β:1.2; 95% confidence interval: -6.3, 8.6; P = 0.76) women in adjusted analysis. PCSK9 polymorphism may affect HIV pathogenesis, particularly in HIV/HCV coinfected women. A likely mechanism for this effect is PCSK9-mediated regulation of cholesterol metabolism. Replication in independent cohorts is needed to clarify the generalizability of the observed associations.
A European multicientre study on the comparison of HBV viral loads between VERIS HBV assay and Roche COBAS® TAQMAN® HBV test, Abbott RealTime HBV assay, Siemens VERSANT HBV assay, and Qiagen artus HBV RG kit.
Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Izopet, Jacques; Lombardi, Alessandra; Marcos, MaAngeles; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel
Hepatitis B viral load testing is essential to treatment and monitoring decisions in patients with chronic Hepatitis B. Beckman Coulter has developed the VERIS HBV Assay (Veris) for use on the fully automated DxN VERIS Molecular Diagnostics System. 1 OBJECTIVES: To evaluate the clinical performance of the Veris HBV Assay at multiple EU laboratories STUDY DESIGN: Method comparison was performed with a total of 344 plasma specimens from HBV infected patients tested with Veris and COBAS ® TaqMan ® HBV Test (Cobas), 207 specimens tested with Veris and RealTime HBV Assay (RealTime), 86 specimens tested with Veris and VERSANT ® HBV Assay (Versant), and 74 specimens tested with Veris and artus ® HBV RG PCR kit (artus). Bland-Altman analysis showed average bias of -0.46 log 10 IU/mL between Veris and Cobas, -0.46 log 10 IU/mL between Veris and RealTime, -0.36 log 10 IU/mL between Veris and Versant, and -0.12 log 10 IU/mL between Veris and artus. Bias was consistent across the assay range. Patient monitoring results using Veris demonstrated similar viral load trends over time to Cobas, RealTime, and artus. The VERIS HBV Assay demonstrated comparable clinical performance, with varying degrees of negative bias, compared to other currently marketed assays for HBV DNA monitoring. This negative bias should be taken into consideration if switching monitoring methods to Veris. Copyright © 2017 Elsevier B.V. All rights reserved.
Braun, Patrick; Delgado, Rafael; Drago, Monica; Fanti, Diana; Fleury, Hervé; Hofmann, Jörg; Izopet, Jacques; Kühn, Sebastian; Lombardi, Alessandra; Mancon, Alessandro; Marcos, Mª Angeles; Mileto, Davide; Sauné, Karine; O'Shea, Siobhan; Pérez-Rivilla, Alfredo; Ramble, John; Trimoulet, Pascale; Vila, Jordi; Whittaker, Duncan; Artus, Alain; Rhodes, Daniel
Viral load monitoring is essential for patients under treatment for HIV. Beckman Coulter has developed the VERIS HIV-1 Assay for use on the novel, automated DxN VERIS Molecular Diagnostics System. ¥ OBJECTIVES: Evaluation of the clinical performance of the new quantitative VERIS HIV-1 Assay at multiple EU laboratories. Method comparison with the VERIS HIV-1 Assay was performed with 415 specimens at 5 sites tested with COBAS ® AmpliPrep/COBAS ® TaqMan ® HIV-1 Test, v2.0, 169 specimens at 3 sites tested with RealTime HIV-1 Assay, and 202 specimens from 2 sites tested with VERSANT HIV-1 Assay. Patient monitoring sample results from 4 sites were also compared. Bland-Altman analysis showed the average bias between VERIS HIV-1 Assay and COBAS HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay to be 0.28, 0.39, and 0.61 log 10 cp/mL, respectively. Bias at low end levels below 1000cp/mL showed predicted bias to be <0.3 log 10 cp/mL for VERIS HIV-1 Assay versus COBAS HIV-1 Test and RealTime HIV-1 Assay, and <0.5 log 10 cp/mL versus VERSANT HIV-1 Assay. Analysis on 174 specimens tested with the 0.175mL volume VERIS HIV-1 Assay and COBAS HIV-1 Test showed average bias of 0.39 log 10 cp/mL. Patient monitoring results using VERIS HIV-1 Assay demonstrated similar viral load trends over time to all comparators. The VERIS HIV-1 Assay for use on the DxN VERIS System demonstrated comparable clinical performance to COBAS ® HIV-1 Test, RealTime HIV-1 Assay, and VERSANT HIV-1 Assay. Copyright © 2017 Elsevier B.V. All rights reserved.
Testi, D; Nardone, M; Melone, P; Cardelli, P; Ottria, L; Arcuri, C
The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.
A new study from NCI researchers finds that the HPV vaccine protects young women from infection with high-risk HPV types at the three primary anatomic sites where persistent HPV infections can cause cancer. The multi-site protection also was observed at l
McBride, Kimberly R.; Singh, Shipra
High human papillomavirus (HPV) prevalence and low HPV vaccine uptake are significant public health concerns. Disparities in HPV-associated cancers and HPV vaccine uptake rates suggest the need for additional research examining factors associated with vaccine acceptance. This study assessed HPV awareness and knowledge and identified…
Lin, Yi-Hsin; Yang, Ming-Chieh; Tseng, Ssu-Hsueh; Jiang, Rosie; Yang, Andrew; Farmer, Emily; Peng, Shiwen; Henkle, Talia; Chang, Yung-Nien; Hung, Chien-Fu; Wu, T-C
Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16 + buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRas G12V , luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRas G12V , luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV + tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 1-15. ©2018 AACR. ©2018 American Association for Cancer Research.
Sun, Bing; Shen, Feng; McCalla, Stephanie E; Kreutz, Jason E; Karymov, Mikhail A; Ismagilov, Rustem F
Here we used a SlipChip microfluidic device to evaluate the performance of digital reverse transcription-loop-mediated isothermal amplification (dRT-LAMP) for quantification of HIV viral RNA. Tests are needed for monitoring HIV viral load to control the emergence of drug resistance and to diagnose acute HIV infections. In resource-limited settings, in vitro measurement of HIV viral load in a simple format is especially needed, and single-molecule counting using a digital format could provide a potential solution. We showed here that when one-step dRT-LAMP is used for quantification of HIV RNA, the digital count is lower than expected and is limited by the yield of desired cDNA. We were able to overcome the limitations by developing a microfluidic protocol to manipulate many single molecules in parallel through a two-step digital process. In the first step we compartmentalize the individual RNA molecules (based on Poisson statistics) and perform reverse transcription on each RNA molecule independently to produce DNA. In the second step, we perform the LAMP amplification on all individual DNA molecules in parallel. Using this new protocol, we increased the absolute efficiency (the ratio between the concentration calculated from the actual count and the expected concentration) of dRT-LAMP 10-fold, from ∼2% to ∼23%, by (i) using a more efficient reverse transcriptase, (ii) introducing RNase H to break up the DNA:RNA hybrid, and (iii) adding only the BIP primer during the RT step. We also used this two-step method to quantify HIV RNA purified from four patient samples and found that in some cases, the quantification results were highly sensitive to the sequence of the patient's HIV RNA. We learned the following three lessons from this work: (i) digital amplification technologies, including dLAMP and dPCR, may give adequate dilution curves and yet have low efficiency, thereby providing quantification values that underestimate the true concentration. Careful
Full Text Available Antigen presenting cells (APCs in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs.
Xue, Yuezhen; Toh, Shen Yon; He, Pingping; Lim, Thimothy; Lim, Diana; Pang, Chai Ling; Abastado, Jean-Pierre; Thierry, Françoise
Cervical intraepithelial neoplasia (CIN) is caused by human papillomavirus (HPV) infection and is the precursor to cervical carcinoma. The completion of the HPV productive life cycle depends on the expression of viral proteins which further determines the severity of the cervical neoplasia. Initiation of the viral productive replication requires expression of the E2 viral protein that cooperates with the E1 viral DNA helicase. A decrease in the viral DNA replication ability and increase in the severity of cervical neoplasia is accompanied by simultaneous elevated expression of E6 and E7 oncoproteins. Here we reveal a novel and important role for the HPV16-E2 protein in controlling host cell cycle during malignant transformation. We showed that cells expressing HPV16-E2 in vitro are arrested in prophase alongside activation of a sustained DDR signal. We uncovered evidence that HPV16-E2 protein is present in vivo in cells that express both mitotic and DDR signals specifically in CIN3 lesions, immediate precursors of cancer, suggesting that E2 may be one of the drivers of genomic instability and carcinogenesis in vivo.
Alvarez, Ronald D; Huh, Warner K; Bae, Sejong; Lamb, Lawrence S; Conner, Michael G; Boyer, Jean; Wang, Chenguang; Hung, Chien-Fu; Sauter, Elizabeth; Paradis, Mihaela; Adams, Emily A; Hester, Shirley; Jackson, Bradford E; Wu, T C; Trimble, Cornelia L
The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of a plasmid vaccine, pNGVL4a-CRT-E7(detox), administered either intradermally, intramuscularly, or directly into the cervical lesion, in patients with HPV16-associated CIN2/3. Eligible patients with HPV16(+) CIN2/3 were enrolled in treatment cohorts evaluating pNGVL4a-CRT-E7(detox), administered by either particle-mediated epidermal delivery (PMED), intramuscular injection (IM), or cervical intralesional injection, at study weeks 0, 4, and 8. Patients were monitored for local injection site and systemic toxicity. A standard therapeutic resection was performed at week 15. The primary endpoints were safety and tolerability. Secondary endpoints included histologic regression and change in cervical HPV viral load. Exploratory endpoints included immune responses in the blood and in the target tissue. Thirty-two patients with HPV16(+) CIN2/3 were enrolled onto the treatment phase of the study, and were vaccinated. Twenty-two of 32 patients (69%) experienced vaccine-specific related adverse events. The most frequent vaccine-related events were constitutional and local injection site in nature, and were grade 1 or less in severity. Histologic regression to CIN 1 or less occurred in 8 of 27 (30%) patients who received all vaccinations and underwent LEEP. In subject-matched comparisons, intraepithelial CD8+ T cell infiltrates increased after vaccination in subjects in the intralesional administration cohort. pNGVL4a-CRT-E7(detox) was well-tolerated, elicited the most robust immune response when administered intralesionally, and demonstrated preliminary evidence of potential clinical efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.
James Sutherland Lawson
Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of
Acero Fernández, Doroteo; Ferri Iglesias, María José; López Nuñez, Carme; Louvrie Freire, René; Aldeguer Manté, Xavier
For years many clinical laboratories have routinely classified undetectable and unquantifiable levels of hepatitis C virus RNA (HCV-RNA) determined by RT-PCR as below limit of quantification (BLOQ). This practice might result in erroneous clinical decisions. To assess the frequency and clinical relevance of assuming that samples that are BLOQ are negative. We performed a retrospective analysis of RNA determinations performed between 2009 and 2011 (Cobas/Taqman, lower LOQ: 15 IU/ml). We distinguished between samples classified as «undetectable» and those classified as «<1.50E+01IU/mL» (BLOQ). We analyzed 2.432 HCV-RNA measurements in 1.371 patients. RNA was BLOQ in 26 samples (1.07%) from 23 patients (1.68%). BLOQ results were highly prevalent among patients receiving Peg-Riba: 23 of 216 samples (10.6%) from 20 of 88 patients receiving treatment (22.7%). The clinical impact of BLOQ RNA samples was as follows: a) 2 patients initially considered to have negative results subsequently showed quantifiable RNA; b) 8 of 9 patients (88.9%) with BLOQ RNA at week 4 of treatment later showed sustained viral response; c) 3 patients with BLOQ RNA at weeks 12 and 48 of treatment relapsed; d) 4 patients with BLOQ RNA at week 24 and/or later had partial or breakthrough treatment responses, and e) in 5 patients the impact were null or could not be ascertained. This study suggests that BLOQ HCV-RNA indicates viremia and that equating a BLOQ result with a negative result can lead to treatment errors. BLOQ results are highly prevalent in on-treatment patients. The results of HCV-RNA quantification should be classified clearly, distinguishing between undetectable levels and levels that are BLOQ. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.
Hampras, Shalaka S; Giuliano, Anna R; Lin, Hui-Yi; Fisher, Kate J; Abrahamsen, Martha E; McKay-Chopin, Sandrine; Gheit, Tarik; Tommasino, Massimo; Rollison, Dana E
Several new polyomaviruses have been discovered in the last decade, including Merkel cell polyomavirus (MCPyV). Little is known about the natural history of the more recently discovered polyomaviruses. We estimated the incidence, prevalence, and persistence of 9 polyomaviruses (MCPyV, BK polyomavirus, KI polyomavirus, JC polyomavirus, WU polyomavirus, Human polyomavirus 6 [HPyV6], HPyV7, HPyV9, and Trichodysplasia spinulosa-associated polyomavirus) and examined factors associated with MCPyV infection in a prospective cohort of 209 men initially enrolled in the HPV Infection in Men (HIM) study. Participants enrolled at the US site of the HIM study were recruited into a substudy of cutaneous viral infections and followed for a median of 12.6 months. Eyebrow hair and normal skin swab specimens were obtained at each study visit, and the viral DNA load was measured using multiplex polymerase chain reaction. MCPyV infection showed the highest prevalence (65.1% of normal skin swab specimens and 30.6% of eyebrow hair specimens), incidence (81.7 cases per 1000 person-months among normal skin swab specimens, and 24.1 cases per 1000 person-months among eyebrow hair specimens), and persistence (85.8% of normal skin swab specimens and 58.9% of eyebrow hair specimens) among all polyomaviruses examined. Age of >44 years (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.03-4.33) and Hispanic race (OR, 2.64; 95% CI, 1.01-6.88) were associated with an increased prevalence of MCPyV infection in eyebrow hair and normal skin swab specimens, respectively. MCPyV infection is highly prevalent in adults, with age and race being predisposing factors. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Benatti, Paolo; Basile, Valentina; Dolfini, Diletta; Belluti, Silvia; Tomei, Margherita; Imbriano, Carol
The expression of the high risk HPV18 E6 and E7 oncogenic proteins induces the transformation of epithelial cells, through the disruption of p53 and Rb function. The binding of cellular transcription factors to cis-regulatory elements in the viral Upstream Regulatory Region (URR) stimulates E6/E7 transcription. Here, we demonstrate that the CCAAT-transcription factor NF-Y binds to a non-canonical motif within the URR and activates viral gene expression. In addition, NF-Y indirectly up-regulates HPV18 transcription through the transactivation of multiple cellular transcription factors. NF-YA depletion inhibits the expression of E6 and E7 genes and re-establishes functional p53. The activation of p53 target genes in turn leads to apoptotic cell death. Finally, we show that NF-YA loss sensitizes HPV18-positive cells toward the DNA damaging agent Doxorubicin, via p53-mediated transcriptional response.
Zainura, Amrulla; Yalkun, Yasin; Wu, Mei
To investigate the Human papilloma viral types 6 and 11 in a large pediatric population in XinJiang and the different expression in chinese and uyghur pediatric population. Using polymerase chain reaction (PCR), we analyzed paraffin embedded tissue in 42 cases of juvenile Recurrent Respiratory Papillomatosis (JRRP)and determined the HPV types 6 and 11, and to correlate these results with retrospectively analysis about those cases who were consecutively treated in our ENT department, meanwhile we carry out a critical review of the literature of JRRP. A total HPV infection positive rate was 97.61% (41/42), and HPV11 positive rate was 63.41% (41/26), HPV6 positive rate was 36.58% (41/15). In uyghur patient HPV11 positive rate was 65.38% (17/26), HPV6 positive rate was53. 33% (8/15). in Chince patient HPV11 positive rate was 34.61% (9/26), HPV6 positive rate was 46.67% (7/15). Juvenile laryngeal papilloma is associated with HPV11, HPV6 infection and we considered that HPV11 infection may be the important guideline of the evaluation of disease prognosis. but no statistical signtificance was determined in the patients of various ethnic groups in Xin jiang (P > 0.05).
Carpén, Timo; Sjöblom, Anni; Lundberg, Marie; Haglund, Caj; Markkola, Antti; Syrjänen, Stina; Tarkkanen, Jussi; Mäkitie, Antti; Hagström, Jaana; Mattila, Petri
Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody. Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV-/p16- patients but also rather common among HPV+/p16+ patients. This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.
Martínez-Portilla, R J; López-Velázquez, J L; Martínez-Rojas, G C; Aguilar-Villagómez, M I; De la Torre-Rendón, F E; Villafán-Bernal, J R
Is fundamental to determine the prevalence of human papiloma virus (HVP) high-risk serotypes in local and regional population in order for health providers to offer patients, vaccines and treatments against specific population-based serotypes. To determine the prevalence of HPV High risk serotypes detected by PCR in patients with normal cytology from the ISSSTE Adolfo Lopez Mateos Regional Hospital. An observational, descriptive, prospective study was conducted from cervical cytologies and high risk HPV test by PCR in patients from the Regional Hospital Adolfo López Mateos, ISSSTE, during the period January 2013-December 2015. Cases of patients with negative cervical cytology were included. Information about age, the result of cervical cytology and high risk HPV test by PCR was obtained. The overall prevalence of HPV infection and the most prevalent serotypes by age groups were calculated. A total of 3258 cervical smears were performed, of which 2557 were negative (78.4%), from this, the global prevalence of HPV infection was 10.2% (n=262). We found that 1.8% (n = 45) of negative reports had HPV16 infection, 0.5% (n=13) had HPV18 and 8.9% (n = 227) were infected by Viral Pool of other high-risk serotypes. The prevalence of infection by viral pool of high risk serotypes was 11.5% in women <20 years, 12.9% in women between 20-29 years and 22.2% in women between 30-39 years. This prevalence was lower in patients older than 40 years (p<0.05). A higher prevalence of viral pool high risk serotypes was found in patients with normal cytology, than the HPV16 and HPV-8 prevalence, which was significantly higher in women younger than 40 years.
Bidyut Chakrobarty; Jay Gopal Roy; Sumit Majumdar; Divya Uppala
The prevalence of oral squamous cell carcinoma (OSCC) has significantly increased over decades in several countries and human papilloma virus (HPV) has been indicated as one of the underlying causes. This suggests that HPV plays a role in the early stages of carcinogenesis but is not a requisite for the maintenance and progression of malignant state. p53 is a tumor suppressor gene that checks the cell and promotes apoptosis and cell repair that can be deactivated by mutations and a viral inte...
Luisa Del Río-Ospina
Full Text Available This study reports six HR-HPV types' infection prevalence discriminated by species and multiple infection in unvaccinated Colombian female adolescents, as well as some factors modulating the risk of infection. HPV DNA for six high-risk viral types was identified in cervical samples taken from 2,134 12-19 year-old females using conventional generic and type-specific PCR. Binomial logistical regression analysis was used for modelling HR-HPV infection and multiple infection risk. The interaction between variables in a stepwise model was also included in such analysis. Viral DNA was detected in 48.97% of the females; 28.52% of them had multiple infections, HPV-16 being the most frequently occurring type (37.44%. Cytological abnormality prevalence was 15.61%. Being over 16 years-old (1.66: 1.01-2.71 95%CI, white ethnicity (4.40: 1.16-16.73 95%CI, having had 3 or more sexual partners (1.77: 1.11-2.81 95%CI and prior sexually-transmitted infections (STI (1.65: 1.17-2.32 95%CI were associated with a greater risk of HPV infection. Having given birth was related to a higher risk of infection by A7 species and antecedent of abortion to less risk of coinfection. Where the females in this study came from also influenced the risk of infection by A7 species as female adolescents from the Andean region had a lower risk of infection (0.42: 0.18-0.99 95%CI. The presence of factors related to risky sexual behaviour in the study population indicated that public health services should pay special attention to female adolescents to modify the risk of infection by high-risk HPV types and decrease their impact on this age group.
In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niÃ±os y las niÃ±as de 11 a 12 aÃ±os con la vacuna contra el VPH.)
In this 30 second public service announcement, a mother talks about the importance of protecting 11-12 year-old boys and girls with HPV vaccination. (Una madre habla sobre la importancia de proteger a los niÃ±os y las niÃ±as de 11 a 12 aÃ±os con la vacuna contra el VPH.)
Comparison between Roche and Xpert in HIV-1 RNA quantitation: A high concordance between the two techniques except for a CRF02_AG subtype variant with high viral load titters detected by Roche but undetected by Xpert.
Avidor, Boaz; Matus, Natalia; Girshengorn, Shirley; Achsanov, Svetlana; Gielman, Simona; Zeldis, Irene; Schweitzer, Inbal; Adler, Amos; Turner, Dan
HIV-1 viral load (VL) testing is important to predict viral progression and to monitor the response to antiretroviral therapy. New HIV-1 VL tests are continuously introduced to the market. Their performance is usually compared to Abbott and/or Roche HIV-1 VL assays, as reference. The Xpert HIV-1 VL test was recently introduced, but its performance compared to Roche has not been sufficiently studied. To compare the Xpert assay with Roche and to assess its use in the HIV clinical laboratory. A total of 383 plasma samples of HIV-1 infected patients previously tested by Roche, were retrospectively tested by Xpert to determine concordance between the two assays. Samples included a diversity of HIV-1 subtypes and a wide range of VLs. There was a high concordance between the two assays, except for a CRF02_AG subtype variant with high VL titters, that was detected by Roche but undetected by Xpert. The 5' long terminal repeat gene region of this virus, targeted by the Xpert assay, was amplified and sequenced. A 25 nucleotide insert was identified, but was unmatched to any known sequences of HIV-1. This particular insert, however could not explain the false-negativity by the Xpert assay. This study underlines the challenge to routine VL testing due to the high genetic diversity of HIV-1. Clinicians should, therefore be advised that a negative VL in cases where the clinical picture does not match the laboratory report, might in fact be, a false-negative result of the VL assay. Copyright © 2017 Elsevier B.V. All rights reserved.
Persson, Maria; Elfström, K Miriam; Brismar Wendel, Sophia; Weiderpass, Elisabete; Andersson, Sonia
Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology. Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center. Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (cytology were more specific than APTIMA. The results of this population-based study with comprehensive follow-up support the use of APTIMA as a triage test for women with ASCUS. More focused investigation is required for women with LSIL.
Assessing the performance of a Loop Mediated Isothermal Amplification (LAMP) assay for the detection and subtyping of high-risk suptypes of Human Papilloma Virus (HPV) for Oropharyngeal Squamous Cell Carcinoma (OPSCC) without DNA purification.
Rohatensky, Mitchell G; Livingstone, Devon M; Mintchev, Paul; Barnes, Heather K; Nakoneshny, Steven C; Demetrick, Douglas J; Dort, Joseph C; van Marle, Guido
Oropharyngeal Squamous Cell Carcinoma (OPSCC) is increasing in incidence despite a decline in traditional risk factors. Human Papilloma Virus (HPV), specifically subtypes 16, 18, 31 and 35, has been implicated as the high-risk etiologic agent. HPV positive cancers have a significantly better prognosis than HPV negative cancers of comparable stage, and may benefit from different treatment regimens. Currently, HPV related carcinogenesis is established indirectly through Immunohistochemistry (IHC) staining for p16, a tumour suppressor gene, or polymerase chain reaction (PCR) that directly tests for HPV DNA in biopsied tissue. Loop mediated isothermal amplification (LAMP) is more accurate than IHC, more rapid than PCR and is significantly less costly. In previous work we showed that a subtype specific HPV LAMP assay performed similar to PCR on purified DNA. In this study we examined the performance of this LAMP assay without DNA purification. We used LAMP assays using established primers for HPV 16 and 18, and new primers for HPV 31 and 35. LAMP reaction conditions were tested on serial dilutions of plasmid HPV DNA to confirm minimum viral copy number detection thresholds. LAMP was then performed directly on different human cell line samples without DNA purification. Our LAMP assays could detect 10 5 , 10 3 , 10 4 , and 10 5 copies of plasmid DNA for HPV 16, 18, 31, and 35, respectively. All primer sets were subtype specific, with no cross-amplification. Our LAMP assays also reliably amplified subtype specific HPV DNA from samples without requiring DNA isolation and purification. The high risk OPSCC HPV subtype specific LAMP primer sets demonstrated, excellent clinically relevant, minimum copy number detection thresholds with an easy readout system. Amplification directly from samples without purification illustrated the robust nature of the assay, and the primers used. This lends further support HPV type specific LAMP assays, and these specific primer sets and assays
Grigore, Mihaela; Teleman, Sergiu Iuliu; Pristavu, Anda; Matei, Mioara
Cervical cancer is one of the most prevalent gynecological malignancies worldwide. Romania has the highest incidence of this type of cancer in Europe. A successful prevention strategy has to consider the primary prevention measures (including health education on human papilloma virus (HPV) infection but also vaccination). The aim of this study was to assess the knowledge and attitudes of Romanian women about HPV and HPV vaccine. We conducted a cross-sectional study survey of 454 women using an anonymously completed questionnaire covering the awareness and knowledge of HPV infection and attitudes to vaccination. We also analyzed the discussions and conclusion from a focus group of healthcare professionals regarding (1) HPV and HPV awareness and attitude, and (2) suggestions for improving HPV vaccine knowledge and acceptance. 69.2% of women were aware about HPV but their knowledge was minimal and incomplete. While 62.3% had heard about HPV vaccine, only 50.7% had a positive attitude toward it. The main barriers to vaccination were the fear of side effects, the perception that is risky, and the financial concerns. Deficiencies in knowledge were noted for vaccine, genital warts, or risks factors for HPV infection like the early onset of sexual life. The information regarding HPV and vaccine is not always accurate and complete, and only 50.7% of women have a positive attitude toward the vaccine. More educational programs and clearer communication are needed to raise awareness and knowledge regarding HPV and HPV vaccine.
Fonseca, Allex Jardim; Taeko, Daniela; Chaves, Thiciane Araújo; Amorim, Lucia Dayanny da Costa; Murari, Raisa Saron Wanderley; Miranda, Angélica Espinosa; Chen, Zigui; Burk, Robert David; Ferreira, Luiz Carlos Lima
Indigenous women from the Amazon regions have some of the highest rates of cervical cancer in the world. This study evaluated cervical cytology and human papillomavirus (HPV) in native women that differ by lifestyle and interaction with western society. Yanomami women are isolated deep in the Amazon with a hunter/gatherer lifestyle. Macuxi and Wapishana women live in proximity to western society. To select a representative group of women from each district, random cluster sampling was used, considering each registered village as a cluster. Cervical samples were collected for cytology and HPV detection and typing by PCR amplification and next generation sequencing. The study was approved by the National IRB and by tribal leaders. 664 native women were enrolled from 13 indigenous villages (76% participation rate). Yanomami women had higher rates of abnormal cytology (5.1% vs. 1.8%, p = 0.04) and prevalent HR-HPV (34.1% vs. 19.2%, pYanomami women >35 y of age were significantly more likely to have HR-HPV, whereas women ≤ 35 y did not significantly differ between groups. Prevalence of HPV was significantly different amongst geographically clustered Yanomami women (pYanomami women were more likely to be HPV+ and rates increased with age. Study of HPV in isolated hunter-gather peoples suggests that long-term persistence is a characteristic of prehistoric humans and patterns reflecting decreased prevalence with age in western society represents recent change. These studies have implications for cervical cancer prevention and viral-host relationships.
Sabeena, Sasidharanpillai; Bhat, Parvati V; Kamath, Veena; Bhat, Shashikala K; Nair, Sreekumaran; n, Ravishankar; Chandrabharani, Kiran; Arunkumar, Govindakarnavar
Introduction: Cervical cancer probably represents the best-studied human cancer caused by a viral infection and the causal association of this preventable cancer with human papilloma virus (HPV) is well established. Worldwide there is a scarcity of data regarding HPV prevalence with vast differences existing among populations. Objective: The aim of this meta-analysis was to determine the community-based HPV prevalence estimates among asymptomatic women from urban and rural set ups and in participants of cancer screening clinics. Study design: Systematic review and meta-analysis. Methods: PubMed-Medline, CINAHL, Scopus, and Google scholar were systematically searched for studies providing prevalence data for HPV infection among asymptomatic women between 1986 and 2016. Results: The final analysis included 32 studies comprising a population of 224,320 asymptomatic women. The overall pooled HPV prevalence was 11% (95% confidence interval (CI), 9%-12%). The pooled HPV prevalence of 11% (95% CI, 9%-11%) was observed among women attending cervical cancer screening clinics. The pooled HPV prevalences were 10% (95% CI 8%-12%) and 11% (95% CI 4%-18%) from urban and rural areas respectively, indicating higher infection rates among the rural women with the least access to cancer screening and cancer care. Conclusion: The prevalence rates in this systematic quantitative review provide a reliable estimate of the burden of HPV infection among asymptomatic women from developed as well as developing nations. Rural women and women attending cervical cancer screening programmes feature higher genital HPV prevalences compared to their urban counterparts. Creative Commons Attribution License
He, Lin; Yang, Jiezhe; Ma, Qiaoqin; Zhang, Jiafeng; Xu, Yun; Xia, Yan; Chen, Wanjun; Wang, Hui; Zheng, Jinlei; Jiang, Jun; Luo, Yan; Xu, Ke; Zhang, Xingliang; Xia, Shichang; Pan, Xiaohong
Previous studies have shown that the increased coverage of antiretroviral therapy (ART) could reduce the community viral load (CVL) and reduce the occurrence of new HIV infections. However, the impact on the reduction of HIV transmission among men who have sex with men (MSM) is much less certain. The frequency of HIV infections in MSM have been rapidly increasing in recent years in Hangzhou, China. The "Treatment as Prevention" strategy was implemented at a population-level for HIV-infected MSM from January 2014 to June 2016 in Hangzhou; it aimed to increase the ART coverage, reduce the CVL, and reduce HIV transmission. We investigated a subset of MSM diagnosed with HIV pre- and post-implementation of the strategy, using random sampling methods. Viral load (VL) testing was performed for all enrolled individuals; the lower limits of detection were 20 and 50 copies/mL. The data on infections were collected from the national epidemiology database of Hangzhou. Logistic regression analyses were conducted to identify factors associated with the differences in social demographic characteristics and available VL data. The ART coverage increased from 60.7% (839/1383) during the pre-implementation period to 92.3% (2183/2365) during the post-implementation period in Hangzhou. A total of 940 HIV-infected MSM were selected for inclusion in this study: 490 (52.1%) and 450 (47.9%) MSM in the pre- and post-implementation periods, respectively. In total, 89.5% (841/940) of patients had data available on VL rates. The mean CVL was 579 copies/mL pre-implementation and this decreased to 33 copies/mL post-implementation (Kruskal-Wallis implementation of the treatment strategy (P implementation period was 50.0% which increased to 84.7% post-implementation (P implementation (Kruskal-Wallis < 0.05). Our study confirmed a population-level association between increased ART coverage and decreased mean CVL; overall 84.7% of HIV infected MSM had an undetectable VL and were no longer
Schmeink, C.E.; Gosens, K.C.; Melchers, W.J.G.; Massuger, L.F.A.G.; Bekkers, R.L.M.
PURPOSE: To investigate the effect of implementation of the HPV vaccine on HPV knowledge and HPV vaccine acceptance. METHODS: From June until December 2009 in Nijmegen, the Netherlands, 698 male and female students aged 18-25 years were recruited and interviewed about HPV, cervical carcinoma and HPV
Krawczyk, Andrea; Stephenson, Ellen; Perez, Samara; Lau, Elsa; Rosberger, Zeev
Background: The human papillomavirus (HPV) vaccine was recently approved for men. To effectively tailor HPV education efforts toward men, it is important to understand what men know about HPV and how this knowledge relates to their decision to receive the vaccine. This study examines how objective HPV knowledge, objective HPV vaccine knowledge,…
Jiang, Hang; Li, Linhai; Han, Jiang; Sun, Zhiwei; Rong, Yihui; Jin, Yun
Treatment options for chronic hepatitis B (CHB) infection are extremely limited. CXCR5 + CD8 + T cell is a novel cell subtype and could possess strong cytotoxic properties in HIV infection. In this study, we investigated the role of CXCR5 + CD8 + T cells in CHB patients. Compared to healthy individuals, both CHB patients and hepatitis B virus (HBV)-infected hepatocellular carcinoma patients presented significant upregulation of CXCR5 + CD8 + T cells in peripheral blood, in which CXCR5 + CD8 + T cells were negatively correlated with the frequency of CXCR5 + CD4 + T cells in CHB patients. After PMA+ionomycin stimulation, CXCR5 + CD8 + T cells from CHB patients presented significantly higher transcription level of interferon gamma (IFN-γ), interleukin 10 (IL-10), and IL-21, as well as higher IL-10 and IL-21 protein secretion, than CXCR5 - CD8 + T cells. Unlike CXCR5 + CD4 + T cells, when incubated with naive CD19 + CD27 - B cells, CXCR5 + CD8 + T cells alone did not upregulate IgM, IgG, and IgA secretion. However, addition of CXCR5 + CD8 + T cells in B cell-CXCR5 + CD4 + T cell coculture significantly increased the levels of secreted IgG and IgA, demonstrating that CXCR5 + CD8 + T cell could indirectly offer B cell help. Furthermore, high frequencies of CXCR5 + CD8 + T cells tended to associate with low HBV DNA load, and the frequency of CXCR5 + CD8 + T cells was negatively correlated with alanine aminotransferase (ALT) level. Together, these results suggested that CXCR5 + CD8 + T cells were involved in the antiviral immune responses in CHB and could potentially serve as a therapeutic candidate.
Full Text Available Of the ~60 human papillomavirus (HPV genotypes that infect the cervicovaginal epithelium, only 12–13 “high-risk” types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral–host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.
Roč. 52, 1-2 (2006), s. 45-46 ISSN 0015-5500 R&D Projects: GA MZd(CZ) NR7807; GA MZd(CZ) NR8004; GA ČR(CZ) GA301/04/0492; GA AV ČR(CZ) IAA500520605 Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.387, year: 2006
Fernanda Nahoum Carestiato
Full Text Available SUMMARY High-risk human papillomavirus (hr-HPV infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP. HPV frequency was 62.4% (88/141. The most common HPV were HPV16 (37%, HPV18 (16.3% and HPV33/45(15.2%. An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%, low grade lesions (22.9%, high grade (57.1% and carcinoma (93.1% (p < 0.0001. A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001, hr-HPV (p = 0.01, HSIL (p < 0.0007 and malignant lesions (p < 0.0001. Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.
Cohen, Daniel N.; Lawson, Steven K.; Shaver, Aaron C.; Du, Liping; Nguyen, Harrison P.; He, Qin; Johnson, Douglas B.; Lumbang, Wilfred A.; Moody, Brent R.; Prescott, James L.; Chandra, Pranil K.; Boyd, Alan S.; Zwerner, Jeffrey P.; Robbins, Jason B.; Tyring, Stephen K.; Rady, Peter L.; Chappell, James D.; Shyr, Yu; Infante, Jeffrey R.; Sosman, Jeffrey A.
Purpose BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. Ultraviolet (UV) radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC. Experimental Design Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib (Vem) or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. Results Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During Vem therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional-cSCC when controlled for gender and UV-exposure (p-value=0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK and EGFR mutations also detected. Conclusions We examined clinical, histopathologic, viral and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. PMID:25724524
Coşar, E; Gencer, M; Hacivelioğlu, S O; Güngör, A C; Uysal, A
The aim of the study was to explore the knowledge and the awareness of the young Turkish women regarding cervical cancer and human papilloma virus (HPV) vaccines. The authors analyze a probable relationship between the overall knowledge level and a few socio-demographic parameters. The authors interviewed with students from Canakkale 18 March University and young women that did not continue with school in the same city from January to September 2011. All the students answered the questionnaire voluntarily and independently. The participants had low level of knowledge about the risk factors for cervical cancer. Smoking is the major risk factor that was known by the participants (65%). Proportion of the participants that were aware of pap smear test and HPV were 65% and 17% respectively. A small proportion of young women had knowledge regarding protection from HPV. Educational stream, educational level, family income, and family size had significant association knowledge level (p level of knowledge so that general public can easily take preventative measures.
Infection with human papillomavirus (HPV) types targeted by the quadrivalent HPV vaccine has declined by nearly two-thirds among teenage girls since HPV vaccination was recommended in the United States.
... is taken in its entirety from the CDC HPV (Human Papillomavirus) Vaccine Information Statement (VIS): www.cdc.gov/vaccines/hcp/vis/vis-statements/hpv.html . CDC review information for HPV (Human Papillomavirus) ...
Lindel, Katja; Rieken, Stefan; Daffinger, Sigrid; Weber, Klaus J; Villiers, Ethel-Michele de; Debus, Jürgen
Clinical studies have demonstrated that HPV induced tumors constitute a specific subclass of cancer with a better response to radiation treatment. The purpose of this study was to investigate meaning of viral E2-gene for radiosensitivity. W12 cells contain episomal HPV 16 genomes, whereas S12 cells, which derive from the W12 line, contain HPV DNA as integrated copies. Clonogenic survival was analyzed using 96-well in vitro test. Using flow cytometry cell cycle analyses were performed. Expression of pRb and p53 were analyzed using intracellular staining. W12 cells (intact E2 gene) showed a lower survival fraction than S12 cells. W12 cells developed a G2/M block 24 h after irradiation with 2 Gy whereas S12 showed no G2/M bloc. After irradiation S12 cells developed polyploidy and pRb-positive cells decreased. W12 cells showed no change of pRb-positive cells. Depending on E2 gene status differences in cell cycle regulation might cause radioresistance. The E2/E7/pRb pathway seems to influence HPV-induced radiosensitivity. Our experiments demonstrated an effect of HPV on radiosensitivity of cervical keratinocytes via viral transcription regulator E2 pathway
Guichet, Emilande; Aghokeng, Avelin; Eymard-Duvernay, Sabrina; Vidal, Nicole; Ayouba, Ahidjo; Mpoudi Ngole, Eitel; Delaporte, Eric; Ciaffi, Laura; Peeters, Martine
With the increasing demand of HIV viral load (VL) tests in resource-limited countries (RLCs) there is a need for assays at affordable cost and able to quantify all known HIV-1 variants. VLs obtained with a recently developed open and polyvalent universal HIV-1/SIVcpz/SIVgor RT-qPCR were compared to Abbott RealTime HIV-1 assay in Cameroon. On 474 plasma samples, characterized by a wide range of VLs and a broad HIV-1 group M genetic diversity, 97.5% concordance was observed when using the lower detection limit of each assay. When using the threshold of 3.00 log 10 copies/mL, according to WHO guidelines to define virological failure (VF) in RLCs, the concordance was 94.7%, 360/474 versus 339/474 patients were identified with VF with the new assay and Abbott RealTime HIV-1, respectively. Higher VLs were measured with the new assay, +0.47 log 10 copies/mL (95% CI; 0.42-0.52) as shown with Bland-Altman analysis. Eleven samples from patients on VF with drug resistance were not detected by Abbott RealTime HIV-1 versus two only with the new assay. Overall, our study showed that the new assay can be easily implemented in a laboratory in RLCs with VL experience and showed good performance on a wide diversity of HIV-1 group M variants. Copyright © 2016 Elsevier B.V. All rights reserved.
Matlung, Sanne Evelien; van Kempen, Pauline Maria Wilhelmina; Bovenschen, Niels; van Baarle, Debbie; Willems, Stefan Martin
Recent studies have suggested that immune cells as part of tumor's microenvironment could partly explain the better outcome in HPV-associated oropharyngeal carcinoma. We performed a systematic review of the literature focused on differences in immune-infiltrate in HPV+ versus HPV- oropharyngeal
Ferris, Daron G; Waller, Jennifer L; Miller, Jeremiah; Patel, Pratik; Price, George A; Jackson, Lanier; Wilson, Courtesia
To determine correlates of human papillomavirus (HPV) vaccine acceptance for men. A convenience sample of men aged 18 to 45 years read a one-page information sheet about HPV and the HPV vaccine, then completed a 29-item questionnaire. chi(2) tests were used to determine whether differences in demographic, sexual, and vaccine-related variables existed between levels of wanting the HPV vaccine. Positive correlates of HPV vaccine acceptance included higher education (P acceptance of the HPV vaccine by men.
Nogueira, Marcela O.; Hošek, Tomáš; Calçada, Eduardo O.; Castiglia, Francesca [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Massimi, Paola; Banks, Lawrence [International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, Trieste (Italy); Felli, Isabella C., E-mail: email@example.com [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy); Pierattelli, Roberta, E-mail: firstname.lastname@example.org [Magnetic Resonance Center (CERM) and Department of Chemistry “Ugo Schiff”, University of Florence, via Luigi Sacconi 6, Sesto Fiorentino (Italy)
HPV-16 E7 is one of the key proteins that, by interfering with the host metabolism through many protein-protein interactions, hijacks cell regulation and contributes to malignancy. Here we report the high resolution investigation of the CR3 region of HPV-16 E7, both as an isolated domain and in the full-length protein. This opens the way to the atomic level study of the many interactions in which HPV-16 E7 is involved. Along these lines we show here the effect of one of the key post-translational modifications of HPV-16 E7, the phosphorylation by casein kinase II.
Full Text Available The incidence of oropharyngeal cancers has increased in the western world and Human Papilloma Virus (HPV has been recognised as a risk factor in the last decades. During the same period the prevalence of HPV in oropharyngeal tumours has increased and HPV has been suggested responsible for the increase. The HPV-positive tumours are today recognized as a distinct subset of head and neck cancers with its own clinopathological and risk profile and have a significantly improved prognosis regardless of treatment strategy. This review summarizes current knowledge regarding human papillomavirus biology, oncogenic mechanisms, risk factors, and impact of treatment.
Poole, Danielle N.; Tracy, J. Kathleen; Levitz, Lauren; Rochas, Mali; Sangare, Kotou; Yekta, Shahla; Tounkara, Karamoko; Aboubacar, Ben; Koita, Ousmane; Lurie, Mark; De Groot, Anne S.
Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12–17 years and men and women aged ≥18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns. PMID:23431375
Danielle N Poole
Full Text Available Despite a high prevalence of oncogenic human papilloma virus (HPV infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12-17 years and men and women aged ≥ 18 years (N = 51 in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI, 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005, a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns.
Schabath, Matthew B; Villa, Luisa L; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Quiterio, Manuel; Giuliano, Anna R
The influence of smoking on the natural history of HPV infection in men is not well understood. Smoking could influence the incidence and persistence of HPV infections by suppressing local immune function, increased cellular proliferation, upregulated proinflammatory factors, or induced host DNA damage resulting in increased susceptibility to infection. The purpose of this analysis is to assess prevalent HPV infections by smoking status in men, and to determine baseline risk of HPV infection associated with smoking. The HPV in Men (HIM) study is a multinational prospective study of the natural history of HPV infections in men. Samples from the coronal sulcus, glans penis, shaft, and scrotum were combined for HPV DNA testing. Multivariable logistic regression was used to assess the association between smoking and any-, oncogenic-, and nononcogenic HPV infections. Our analyses revealed that current smoking was associated with an increased risk of any HPV infection (OR = 1.19; 95% CI: 1.01-1.41) and oncogenic HPV infection (OR = 1.24; 95% CI: 1.05-1.47). However, the association between smoking and any HPV infection (OR = 1.35; 95% CI: 1.05-1.73) and oncogenic HPV infection (OR = 1.46; 95% CI: 1.11-1.92) was only evident among men reporting fewer lifetime sexual partners. These results suggest that current smokers with the fewest number of sexual partners are associated with an increased risk for oncogenic HPV infection. The relationship between smoking and HPV infection remains understudied in men; these data shed new light on the interplay between smoking, sexual activity, and risk of HPV infection.
Lehr, Elizabeth E.; Qadadri, Brahim; Brown, Calla R.; Brown, Darron R.
Human papillomavirus type 59 (HPV 59) is an oncogenic type related to HPV 18. HPV 59 was recently propagated in the athymic mouse xenograft system. A continuous keratinocyte cell line infected with HPV 59 was created from a foreskin xenograft grown in an athymic mouse. Cells were cultured beyond passage 50. The cells were highly pleomorphic, containing numerous abnormally shaped nuclei and mitotic figures. HPV 59 sequences were detected in the cells by DNA in situ hybridization in a diffuse nuclear distribution. Southern blots were consistent with an episomal state of HPV 59 DNA at approximately 50 copies per cell. Analysis of the cells using a PCR/reverse blot strip assay, which amplifies a portion of the L1 open reading frame, was strongly positive. Differentiation of cells in monolayers was induced by growth in F medium containing 2 mM calcium chloride for 10 days. Cells were harvested as a single tissue-like sheet, and histologic analysis revealed a four-to-six cell-thick layer. Transcripts encoding involucrin, a cornified envelope protein, and the E1-circumflexE4 and E1-circumflexE4-circumflexL1 viral transcripts were detected after several days of growth in F medium containing 2 mM calcium chloride. The E1-circumflexE4 and L1 proteins were detected by immunohistochemical analysis, and virus particles were seen in electron micrographs in a subset of differentiated cells. An extract of differentiated cells was prepared by vigorous sonication and was used to infect foreskin fragments. These fragments were implanted into athymic mice. HPV 59 was detected in the foreskin xenografts removed 4 months later by DNA in situ hybridization and PCR/reverse blot assay. Thus, the complete viral growth cycle, including production on infectious virus, was demonstrated in the HPV 59 immortalized cells grown in a simple culture system
Full Text Available High-risk human papillomavirus (HPV must evade innate immune surveillance to establish persistent infections and to amplify viral genomes upon differentiation. Members of the JAK-STAT family are important regulators of the innate immune response and HPV proteins downregulate expression of STAT-1 to allow for stable maintenance of viral episomes. STAT-5 is another member of this pathway that modulates the inflammatory response and plays an important role in controlling cell cycle progression in response to cytokines and growth factors. Our studies show that HPV E7 activates STAT-5 phosphorylation without altering total protein levels. Inhibition of STAT-5 phosphorylation by the drug pimozide abolishes viral genome amplification and late gene expression in differentiating keratinocytes. In contrast, treatment of undifferentiated cells that stably maintain episomes has no effect on viral replication. Knockdown studies show that the STAT-5β isoform is mainly responsible for this activity and that this is mediated through the ATM DNA damage response. A downstream target of STAT-5, the peroxisome proliferator-activated receptor γ (PPARγ contributes to the effects on members of the ATM pathway. Overall, these findings identify an important new regulatory mechanism by which the innate immune regulator, STAT-5, promotes HPV viral replication through activation of the ATM DNA damage response.
Baron, A V; Osipov, N V; Yashchenko, S V; Kokotukha, Yu A; Baron, I J; Puzyr, A P; Olkhovskiy, I A; Bondar, V S
Adsorption of viral particles from the blood plasma of patients with viral hepatitis B and C on modified nanodiamonds (MNDs) was shown in the in vitro experiments. PCR method showed the treatment of plasma with MNDs leads to a decrease in the viral load by 2-3 orders of magnitude or more in both cases studied. These results make it possible to predict the applicability of MNDs for the development of new technologies of hemodialysis and plasmapheresis for binding and removal of viral particles from the blood of infected patients.
Ferreira, Dennis C; Rôças, Isabela N; Paiva, Simone S M; Carmo, Flávia L; Cavalcante, Fernanda S; Rosado, Alexandre S; Santos, Kátia R N; Siqueira, José F
Viral-bacterial and bacterial synergism have been suggested to contribute to the pathogenesis of several human diseases. This study sought to investigate the possible associations between 9 candidate endodontic bacterial pathogens and 9 human viruses in samples from acute apical abscesses. DNA extracts from purulent exudate aspirates of 33 cases of acute apical abscess were surveyed for the presence of 9 selected bacterial species using a 16S ribosomal RNA gene-based nested polymerase chain reaction (PCR) approach. Single or nested PCR assays were used for detection of the human papillomavirus (HPV) and herpesviruses types 1 to 8. Two-thirds of the abscess samples were positive for at least one of the target viruses. Specifically, the most frequently detected viruses were HHV-8 (54.5%); HPV (9%); and varicella zoster virus (VZV), Epstein-Barr virus (EBV), and HHV-6 (6%). Bacterial DNA was present in all cases and the most prevalent bacterial species were Treponema denticola (70%), Tannerella forsythia (67%), Porphyromonas endodontalis (67%), Dialister invisus (61%), and Dialister pneumosintes (57.5%). HHV-8 was positively associated with 7 of the target bacterial species and HPV with 4, but all these associations were weak. Several bacterial pairs showed a moderate positive association. Viral coinfection was found in 6 abscess cases, but no significant viral association could be determined. Findings demonstrated that bacterial and viral DNA occurred concomitantly in two-thirds of the samples from endodontic abscesses. Although this may suggest a role for viruses in the etiology of apical abscesses, the possibility also exists that the presence of viruses in abscess samples is merely a consequence of the bacterially induced disease process. Further studies are necessary to clarify the role of these viral-bacterial interactions, if any, in the pathogenesis of acute apical abscesses. Copyright © 2011 Mosby, Inc. All rights reserved.
Leeson, Simon C
Current cytology-based screening has a moderate sensitivity to detect cervical intraepithelial neoplasia grade 3 (CIN 3) and cervical cancer even in those states providing rigorous quality control of their cervical screening programs. The impact of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the incorporation of HPV testing on the detection of CIN 3 and cancer is discussed. HPV testing used as a triage for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions, test of cure after treatment, and HPV-based primary screening may improve current cervical screening programs.HPV testing as a triage test for ASCUS seems to offer an improved sensitivity, with a similar specificity as compared to repeat cytology for diagnosing high-grade CIN and has been recommended throughout most EU states. HPV testing as a triage test for low-grade squamous intraepithelial lesions has a low specificity and is not recommended in most member states. HPV test of cure offers an improved sensitivity compared to cytology for women with persistent cervical precancer after treatment. HPV-based cervical cancer screening is more effective than screening with cytology. The effects of HPV-based screening depend on the organization of the program and on adherence to algorithms for screening triage. Otherwise, it is likely that HPV-based screening will increase the referral rate to colposcopy including more women with no detectable cervical lesion. HPV vaccination will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.
Lu, Chun-bin; Luo, Le; Yang, Meng-jie; Nie, Kai; Wang, Miao; Ma, Xue-Jun
A simple, rapid and sensitive colorimetric loop mediated isothermal amplification (LAMP) method was established to detect HPV6 and HPV 16 respectively. The method employed a set of four specially designed primers that recognized six distinct sequences of HPV6-E6 or HPV16-E7 for amplification of nucleic acid under isothermal conditions at 63 degrees C for one hour. The amplification process of LAMP was monitored by the addition of HNB (hydroxy naphthol blue) dye prior to amplification. A positive reaction was indicated by a color change from violet to sky blue and confirmed by real-time turbidimeter and agarose electrophoresis. Thirteen cervical swab samples having single infection with 13 different HPV genotypes were examined to evaluate the specificity. A serial dilution of a cloned plasmid containing HPV-E6 or HPV-E7 gene was examined to evaluate the sensitivity. The results showed that no cross-reaction with other HPV genotypes was observed. The colorimetric LAMP assay could achieve a sensitivity of 1000 copies, 10-20 times lower than that of real-time PCR. The assay was further evaluated with 62 clinical specimens and consistent results were obtained compared with the detection using Kai Pu HPV Genotyping Kit. We concluded that this colorimetric LAMP assay had potential usefulness for the rapid screening of the HPV6 or HPV16 infection in the laboratories and hospitals of provincial and municipal region in China.
Pitisuttithum, Punnee; Velicer, Christine; Luxembourg, Alain
Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.
Cina, Kristin R; Omidpanah, Adam A; Petereit, Daniel G
To evaluate whether or not an educational intervention would lead to a change in knowledge and attitudes about human papillomavirus (HPV), HPV vaccines, and cervical cancer. The HPV status was also investigated for interested participants. We provided HPV and cervical cancer education to urban American Indian (AI) women 18 and older using a pre and post-knowledge exam to assess knowledge and attitudes. Women were also given the option to perform vaginal self-tests for high risk HPV (hrHPV) analysis immediately after the education. Ninety-six women participated in our educational sessions. Improvement in performance on a knowledge exam increased from 61.6 to 84.3 percent. Ninety-three women performed the vaginal self-test with 63.1 percent of women preferring vaginal self-testing over conventional screening methods. Thirty-five out of 91 women (38.5 percent) had hrHPV types with 12 of the 35 harboring multiple hrHPV types (13 percent overall). HPV and cervical cancer education was beneficial for urban AI women with the majority of women preferring vaginal self-testing. HPV self-testing may be a strategy to improve screening rates for cervical cancer. Urban AI women had high rates of hrHPV compared to rural AI populations as reported in previous studies.
Clark, Sarah J; Cowan, Anne E; Filipp, Stephanie L; Fisher, Allison M; Stokley, Shannon
In 2013, approximately one-third of US adolescent males age 13-17 y had received ≥1 doses of HPV vaccines and only 14% had received ≥3 doses. This study used a nationally representative, online survey to explore experiences and attitudes related to HPV vaccination among parents with adolescent sons. Analyses compared the perspective of parents who do not intend to initiate HPV vaccine for ≥1 adolescent son to that of parents who are likely to initiate or continue HPV vaccination. Of 809 parents of sons age 11-17 years, half were classified as Unlikely to Initiate HPV vaccination and 39% as Likely to Vaccinate. A higher proportion of the Likely to Vaccinate group felt their son's doctor was knowledgeable about HPV vaccine, did a good job explaining its purpose, and spent more time discussing HPV vaccine; in contrast, over half of the Unlikely to Initiate group had never discussed HPV vaccine with their child's doctor. The majority of parents in both groups showed favorable attitudes to adolescent vaccination in general, with lower levels of support for HPV vaccine-specific statements. Physician-parent communication around HPV vaccine for adolescent males should build on positive attitude toward vaccines in general, while addressing parents' HPV vaccine-specific concerns.
Fichman, Yoseph; Levi, Assi; Hodak, Emmilia; Halachmi, Shlomit; Mazor, Sigal; Wolf, Dana; Caplan, Orit; Lapidoth, Moshe
Verruca vulgaris (VV) is a prevalent skin condition caused by various subtypes of human papilloma virus (HPV). The most common causes of non-genital lesions are HPV types 2 and 4, and to a lesser extent types 1, 3, 26, 29, and 57. Although numerous therapeutic modalities exist, none is universally effective or without adverse events (AE). Pulsed dye laser (PDL) is a favorable option due to its observed efficacy and relatively low AE rate. However, it is not known which verrucae are most likely to respond to PDL, or whether the causative viral subtype influences this response. The objective of this prospective blinded study was to assess whether the HPV subtype was predictive of response to PDL. For that matter, 26 verrucae from 26 immunocompetent patients were biopsied prior to treatment by PDL. HPV coding sequences were isolated and genotyped using PCR analysis. Patients were treated by PDL (595 nm wavelength, 5 mm spot size, 1.5 ms pulse duration, 12 J/cm 2 fluence) once a month for up to 6 months, and clinical response was assessed. Binary logistic regression analysis and linear logistic regression analysis were used in order to evaluate statistical significance. Different types of HPV were identified in 22 of 26 tissue samples. Response to treatment did not correlate with HPV type, age, or gender. As no association between HPV type and response to PDL therapy could be established, it is therefore equally effective for all HPV types and remains a favorable treatment option for all VV.
Pankey, Tyson; Ramaswamy, Megha
The purpose of this paper is to explore incarcerated women's awareness, beliefs, and experiences with human papillomavirus (HPV) infection and vaccination. Researchers conducted focus groups with 45 incarcerated women in an urban Midwestern US jail to assess how women talked about their Papanicolaou (Pap) test screening and abnormal Pap test follow-up experiences. Some focus group questions specifically assessed individual awareness, beliefs, and experiences with HPV infection and vaccination. Based on these data, the authors described participants' awareness of HPV, as well as used open coding to ultimately extract themes related to beliefs and experiences with HPV infection and vaccine. While all 45 participants reported experiencing an abnormal Pap test event within the last five years, only two-thirds of participants (n=30) reported having heard of the HPV infection. Several themes emerged from the analysis of the data: the women's beliefs about cause and severity of HPV; frustration with age requirements of the vaccine; varied experiences with vaccinations for themselves and their children; the impact of media exposure on knowledge; and desire for more HPV infection and vaccine information. Incarcerated women's awareness and limited experiences with HPV infection and vaccination may be a barrier to adequate screening and cervical cancer prevention. This study has implications for the development of cervical health education for this high-risk group of women, who are four to five times as likely to have cervical cancer as non-incarcerated women.
van Zwol, Ulla Bonde; Joergensen, J. S.; Lamont, R. F.
the subject of HPV vaccine and pregnancy , the databases of PubMed and Embase were searched to find the relevant literature published in English within the last 10 y. Most of the evidence pertaining to fetal adverse events following HPV vaccination relates to spontaneous miscarriage. None of the relevant...
Koneva, Lada A; Zhang, Yanxiao; Virani, Shama; Hall, Pelle B; McHugh, Jonathan B; Chepeha, Douglas B; Wolf, Gregory T; Carey, Thomas E; Rozek, Laura S; Sartor, Maureen A
The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing deescalated treatment approaches for HPV + HNSCC patients. RNA sequencing (RNA-seq) data from HNSCC tumors ( n = 84) were used to identify and characterize expressed integration events, which were overrepresented near known head and neck, lung, and urogenital cancer genes. Five genes were recurrent, including CD274 (PD-L1) A significant number of genes detected to have integration events were found to interact with Tp63, ETS, and/or FOX1A. Patients with no detected integration had better survival than integration-positive and HPV - patients. Furthermore, integration-negative tumors were characterized by strongly heightened signatures for immune cells, including CD4 + , CD3 + , regulatory, CD8 + T cells, NK cells, and B cells, compared with integration-positive tumors. Finally, genes with elevated expression in integration-negative specimens were strongly enriched with immune-related gene ontology terms, while upregulated genes in integration-positive tumors were enriched for keratinization, RNA metabolism, and translation. Implications: These findings demonstrate the clinical relevancy of expressed HPV integration, which is characterized by a change in immune response and/or aberrant expression of the integration-harboring cancer-related genes, and suggest strong natural selection for tumor cells with expressed integration events in key carcinogenic genes. Mol Cancer Res; 16(1); 90-102. ©2017 AACR . ©2017 American Association for Cancer Research.
Nicol, Alcina F; Pirmez, Claude; Pires, Andréa Rodrigues Cordovil; Souza, Simone R de; Nuovo, Gerard J; Grinsztejn, Beatriz; Tristão, Aparecida; Russomano, Fabio B; Velasque, Luciane; Silva, José R Lapa e
The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women. We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection. HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm 2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm 2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls. Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development
Nicol, Alcina F; Pires, Andréa Rodrigues Cordovil; de Souza, Simone R; Nuovo, Gerard J; Grinsztejn, Beatriz; Tristão, Aparecida; Russomano, Fabio B; Velasque, Luciane; Lapa e Silva, José R; Pirmez, Claude
The oncoproteins of human papillomavirus (HPVs) directly effect cell-cycle control. We hypothesize that regulatory and cell cycle protein expression might be additionally modified in the cervix of HIV/HPV co-infected women. We analyzed the expression of Rb, p27, VEGF and Elf-1 transcriptor factor by immunohistochemistry in 163 paraffin-embeded cervical samples using Tissue Micro-Array (TMA) and correlated this to HIV-1 and HPV infection. HIV/HPV co-infection was associated with a significant increase in expression (p < 0.001) of VEGF and p27 in both low and high grade CIN when compared to the cervices of women infected by HPV alone. Decreased Rb expression was evident with increased CIN grade in the cervices of women infected with HPV alone (p = 0.003 average of cells/mm2 in CIN I: 17.9, CIN II/III: 4.8, and tumor 3.9). Rb expression increased 3-fold for both low and high grade CIN with HPV/HIV-1 co-infection compared to HPV infection alone but did not reach statistical significance. There was a significant increase in Elf-1 expression in HPV+/HIV- women with CIN II/III and tumor (average of cells/mm2 in CIN I: 63.8; CIN II/III: 115.7 and tumor: 112.0, p = 0.005), in comparison to controls. Co-infection of HPV and HIV leads to significant increase in the VEGF and p27 expression when compared to HPV+/HIV-negative infection that could facilitate viral persistence and invasive tumor development.
Wang, Chia-ching J.; Sparano, Joseph; Palefsky, Joel M.
SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index. PMID:27889034
Full Text Available BACKGROUND: HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL in treatment-naïve (TN and treatment-experienced (TE individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011. METHODS AND FINDINGS: Resistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%], nucleoside [NRTI (from 78% to 37% and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004. CONCLUSIONS: We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant
Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J
Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.
Economic impact of optimising antiretroviral treatment in human immunodeficiency virus-infected adults with suppressed viral load in Spain, by implementing the grade A-1 evidence recommendations of the 2015 GESIDA/National AIDS Plan.
Ribera, Esteban; Martínez-Sesmero, José Manuel; Sánchez-Rubio, Javier; Rubio, Rafael; Pasquau, Juan; Poveda, José Luis; Pérez-Mitru, Alejandro; Roldán, Celia; Hernández-Novoa, Beatriz
The objective of this study is to estimate the economic impact associated with the optimisation of triple antiretroviral treatment (ART) in patients with undetectable viral load according to the recommendations from the GeSIDA/PNS (2015) Consensus and their applicability in the Spanish clinical practice. A pharmacoeconomic model was developed based on data from a National Hospital Prescription Survey on ART (2014) and the A-I evidence recommendations for the optimisation of ART from the GeSIDA/PNS (2015) consensus. The optimisation model took into account the willingness to optimise a particular regimen and other assumptions, and the results were validated by an expert panel in HIV infection (Infectious Disease Specialists and Hospital Pharmacists). The analysis was conducted from the NHS perspective, considering the annual wholesale price and accounting for deductions stated in the RD-Law 8/2010 and the VAT. The expert panel selected six optimisation strategies, and estimated that 10,863 (13.4%) of the 80,859 patients in Spain currently on triple ART, would be candidates to optimise their ART, leading to savings of €15.9M/year (2.4% of total triple ART drug cost). The most feasible strategies (>40% of patients candidates for optimisation, n=4,556) would be optimisations to ATV/r+3TC therapy. These would produce savings between €653 and €4,797 per patient per year depending on baseline triple ART. Implementation of the main optimisation strategies recommended in the GeSIDA/PNS (2015) Consensus into Spanish clinical practice would lead to considerable savings, especially those based in dual therapy with ATV/r+3TC, thus contributing to the control of pharmaceutical expenditure and NHS sustainability. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar.
Thiha, Nay; Chinnakali, Palanivel; Harries, Anthony D; Shwe, Myint; Balathandan, Thanumalaya Perumal; Thein Than Tun, Sai; Das, Mrinalini; Tin, Htay Htay; Yi, Yi; Babin, François Xavier; Lwin, Thi Thi; Clevenbergh, Philippe Albert
WHO recommends that stavudine is phased out of antiretroviral therapy (ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL) before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment. Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR) to identify associated factors using log binomial regression. Of 4934 patients tested, 4324 (87%) had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8) compared to 25-44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2) compared to the public sector. This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries.
Baloch, Zulqarnain; Yasmeen, Nafeesa; Li, Yuanyue; Zhang, Wenhui; Lu, Hongyu; Wu, Xiaomei; Xia, Xueshan; Yang, Shihua
BACKGROUND It is important to understand the knowledge that various groups of a population have about cervical cancer and human papillomavirus (HPV) and their attitudes toward HPV vaccination, as it will ultimately influence their decision-making for or against the acceptability of vaccines and other preventive methods. This study was designed to determine the level of knowledge and awareness about cervical cancer, HPV, and the HPV vaccine among Chinese women in Yunnan province. MATERIAL AND METHODS A survey was conducted in Yunnan province by the Laboratory of Molecular Virology in collaboration with the Yunnan First People's Hospital in Feb 2015. A total of 388 women were recruited and asked to participate in a questionnaire-based interview that collected information related to their awareness and knowledge about: (1) cervical cancer, (2) HPV and HPV vaccine and willingness to have their children receive vaccination, and (3) demographic characteristics. RESULTS A total of 388 HPV-positive women were included; 300/388 (73.3%) were Han, and 88/388 (22.7%) were other ethnicities. Overall, 204/388 (52.6%) of the women were aware of cervical cancer, with a significant difference between Han women and women of other ethnic groups (168/388, 56.0% and 36/88, 40.9%; P=0.015). Overall, 26.5% of the women were aware of the role of HPV in cervical cancer; 29.0% of the Han women and 18.2% of women of other ethnic groups were aware of this role of HPV (P=0.05). The knowledge that HPV infection leads to cervical cancer was higher among Han women (29.0%) compared to women of other ethnicities (18.2%). Knowledge about the HPV vaccine was very low in all ethnic groups, but the Han women were more willing to allow their children to be vaccinated before they become sexually active. A similar difference has also been found in women from various regions. CONCLUSIONS Although level of awareness and knowledge about cervical cancer was moderate, knowledge and awareness of HPV and the HPV
Allison, Mandy A; Hurley, Laura P; Markowitz, Lauri; Crane, Lori A; Brtnikova, Michaela; Beaty, Brenda L; Snow, Megan; Cory, Janine; Stokley, Shannon; Roark, Jill; Kempe, Allison
Because physicians' practices could be modified to reduce missed opportunities for human papillomavirus (HPV) vaccination, our goal was to: (1) describe self-reported practices regarding recommending the HPV vaccine; (2) estimate the frequency of parental deferral of HPV vaccination; and (3)identify characteristics associated with not discussing it. A national survey among pediatricians and family physicians (FP)