Immune status, and not HIV infection or exposure, drives the development of the oral microbiota.

Even with antiretroviral therapy, children born to HIV-infected (HI) mothers are at a higher risk of early-life infections and morbidities including dental disease. The increased risk of dental caries in HI children suggest immune-mediated changes in oral bacterial communities, however, the impact of perinatal HIV exposure on the oral microbiota remains unclear. We hypothesized that the oral microbiota of HI and perinatally HIV-exposed-but-uninfected (HEU) children will significantly differ from HIV-unexposed-and-uninfected (HUU) children. Saliva samples from 286 child-participants in Nigeria, aged ≤ 6 years, were analyzed using 16S rRNA gene sequencing. Perinatal HIV infection was significantly associated with community composition (HI vs. HUU-p = 0.04; HEU vs. HUU-p = 0.11) however, immune status had stronger impacts on bacterial profiles (p < 0.001). We observed age-stratified associations of perinatal HIV exposure on community composition, with HEU children differing from HUU children in early life but HEU children becoming more similar to HUU children with age. Our findings suggest that, regardless of age, HIV infection or exposure, low CD4 levels persistently alter the oral microbiota during this critical developmental period. Data also indicates that, while HIV infection clearly shapes the developing infant oral microbiome, the effect of perinatal exposure (without infection) appears transient.

Racial disparity in all-cause mortality among hepatitis C virus-infected individuals in a general US population, NHANES III.

There are few long-term nationally representative studies of all-cause mortality among those infected with hepatitis C virus (HCV). When an additional 5 years of data were made publicly available in 2015, the Third National Health and Nutrition Examination Survey Linked Mortality File became the longest nationally representative study in the United States. Our objective was to update the estimated HCV-associated all-cause mortality in the general US population and determine any differences by sex, age and race/ethnicity. HCV status was assessed in 9117 nationally representative adults aged 18-59 years from 1988 to 1994, and mortality follow-up of the same individuals was completed through 2011 and made publicly available in 2015. There were 930 deaths over a median follow-up of 19.8 years. After adjusting for all covariate risk factors, chronic HCV had 2.63 times (95% CI: 1.59-4.37; P=.0002) higher all-cause mortality rate ratio (MRR) compared with being HCV negative. All-cause MRR was stratified by sex, age and race/ethnicity. Only race/ethnicity was a significant effect modifier of MRR (P<.0001) as the highest MRR of chronic HCV compared to HCV negative was 7.48 (95% CI: 2.15-26.10, P=.001) among Mexican Americans, 2.67 (95% CI: 2.67-5.56, P=.009) among non-Hispanic Whites and 2.02 (95% CI: 1.20-3.40, P=.007) among non-Hispanic Blacks. Racial disparity was seen in the all-cause mortality as Mexican Americans with chronic HCV had approximately seven times higher mortality rate than HCV-negative individuals. This suggests that these at-risk individuals should be targeted for HCV screening and treatment, given the availability of new highly effective HCV therapies.

Investigating the informed consent process, therapeutic misconception and motivations of Egyptian research participants: a qualitative pilot study.

Few studies have explored the informed consent process among research participants in developing countries. This study aimed to evaluate the informed consent process, therapeutic misconception and motivation for participation among Egyptians participating in clinical trials. In a cross-sectional qualitative pilot study 103 participants in 10 clinical trials responded to a questionnaire. Over 90% agreed they had time to ask questions and received adequate information about the risks prior to consenting. All participants thought the research and the drug would improve their condition; only 46.1% were aware of receiving a non-approved experimental drug and 21.3% of being randomized. Reasons for participation included: better treatment (100%), to benefit society & advance science (85.4%), to receive free drugs (42.6%) and medical care (43.6%), to get hospitalized (15.8%) and to receive money or gifts (4.9%). Investigators need to emphasize the distinction between research and clinical care to address the high rate of therapeutic misconception.

Investigating the informed consent process, therapeutic misconception and motivations of Egyptian research participants:a qualitative pilot study

لا يوجد إلا القليل من الدراسات التي استكشفت عملية الموافقة المسبقة لدى المشاركين في البحوث في البلدان النامية. وقد هدفت هذه الدراسة إلى تقييم عملية الموافقة المسبقة والمفهوم العلاجي الخاطئ والدافع للمشاركة لدى المصرين المشاركين في تجارب سريرية. ففي دراسة تجريبية كيفية مستعرضة قام 103 مشاركين في 10 تجارب سريرية بالإجابة عى استبيان. فأقر أكثر من 90 % منهم بأنه كان لديهم وقت لطرح الأسئلة وبأنهم تلقوا معلومات كافية عن المخاطر قبل الموافقة. واعتقد جميع المشاركين أن البحث والدواء من شأنه أن يحسن حالتهم، وكان 46.1 % منهم فقط عى علم بأنهم يتلقون دواء تجريبياً غر معتمد، و 21.3 % عى علم بأن اختيارهم تم بصورة عشوائية. وكان من أسباب المشاركة: الحصول عى معالجة أفضل 100%، وإفادة المجتمع والتقدم في العلوم 85.4 %، والحصول عى أدوية مجانية 42.6 % ورعاية طبية مجانية 43.6 %، والحصول عى قبول في المستشفى 15.8 %، وتلقي المال أو الهدايا 4.9 %. يجب عى القائمن بالاستقصاء أن يؤكدوا عى التمييز بن الأبحاث والرعاية السريرية لمواجهة ارتفاع معدل المفهوم العلاجي الخاطئ.

Few studies have explored the informed consent process among research participants in developing countries. This study aimed to evaluate the informed consent process, therapeutic misconception and motivation for participation among Egyptians participating in clinical trials. In a cross-sectional qualitative pilot study 103 participants in 10 clinical trials responded to a questionnaire. Over 90% agreed they had time to ask questions and received adequate information about the risks prior to consenting. All participants thought the research and the drug would improve theircondition; only 46.1% were aware of receiving a non-approved experimental drug and 21.3% of being randomized.Reasons for participation included: better treatment (100%), to benefit society & advance science (85.4%), to receive free drugs (42.6%) and medical care (43.6%), to get hospitalized (15.8%) and to receive money or gifts (4.9%). Investigators needto emphasize the distinction between research and clinical care to address the high rate of therapeutic misconception

Les études ayant examiné le processus du consentement éclairé chez les participants à des études de recherche dans les pays en développement sont peu nombreuses. La présente étude visait à évaluer le processus de consentement éclairé, les idées fausses en matière de traitement et les motivations des Égyptiens pour participer à des essais cliniques. Dans une étude pilote qualitative et transversale, 103 participants dans 10 essais cliniques ont répondu à un questionnaire. Plus de 90 % ont convenu qu’ils avaient eu le temps de poser des questions et qu’ils avaient reçu des informations adéquates sur les risques avant d’accorder leur consentement. Tous les participants pensaient que la recherche et le médicament pourraient améliorer leur état ; seuls 46,1 % savaient qu’ils recevaientun médicament à l’essai n’ayant pas été autorisé et 21,3 % qu’ils étaient randomisés. Parmi les raisons pourparticiper, on peut citer : un meilleur traitement (100 %), qui sera utile pour la société et pour les progrès de lascience (85,4 %), des médicaments gratuits (42,6 %) et des soins médicaux gratuits (43,6 %), une hospitalisation(15,8 %) et des compensations financières ou matérielles (4,9 %). Les chercheurs doivent insister sur la différenceentre recherche et soins cliniques pour s’attaquer au fort pourcentage d’idées fausses en termes de traitement.

Predictors of early treatment discontinuation in a cohort of patients treated with boceprevir-based therapy for hepatitis C infection.

In this real-world cohort, 49% of patients stopped boceprevir-based hepatitis C therapy early, with only 20% stopping due to treatment futility. Having more comorbidities was significantly associated with early discontinuation. Tolerability of boceprevir-based regimens may be substantially worse than reported in clinical trials, particularly for patients with comorbidities.

Hepatitis C virus infection during pregnancy and the newborn period--are they opportunities for treatment?

The worldwide prevalence of hepatitis C virus (HCV) infection in pregnant women is estimated to be between 1 and 8% and in children between 0.05% and 5%. While parenteral transmission is still common in children living in developing countries, perinatal transmission is now the leading cause of HCV transmission in developed countries. The absence of an HCV vaccine or approved therapy during pregnancy means that prevention of vertical transmission is still not possible. However, a low vertical transmission rate of 3-5%, a high rate of spontaneous clearance (25-50%) and delayed morbidity have resulted in HCV being overlooked in pregnant women and their infants. Yet a study of the natural history in mothers and children demonstrates that the prognosis of HCV can vary greatly and should be taken seriously. Factors known to increase the risk of perinatal transmission include HIV coinfection and higher maternal viral loads, while elective C-section and withholding breastfeeding have not been demonstrated to reduce vertical transmission. Current guidelines for the diagnosis of persistent perinatal infection require a positive anti-HCV test in infants born to infected mothers after 12 months or two positive HCV RNA tests at least 6 months apart. Current HCV treatment options using pegylated interferon and ribavirin are both unsuitable for use in pregnancy and infancy. However, new agents currently in preclinical phases of development, along with the recently identified association between single-nucleotide polymorphisms within the IL28 gene and treatment response, may serve to create a therapeutic window for these patients.

Characterization of hepatitis E-specific cell-mediated immune response using IFN-gamma ELISPOT assay.

In developing countries, hepatitis E (HEV) and hepatitis A (HAV) are the major causes of acute viral hepatitis with similar feco-oral modes of transmission. In contrast to the high seroprevalence of hepatitis A infection, a low seroprevalence of HEV among children in endemic areas has been reported. These data suggest the possibility that silent HEV infection is undiagnosed by the current available methods. Many of the serological tests used for HEV diagnosis have poor specificity and are unable to differentiate among different genotypes of HEV. Moreover, the RT-PCR used for HEV isolation is only valid for a brief period during the acute stage of infection. Cell-mediated immune (CMI) responses are highly sensitive, and long lasting after sub-clinical infections as shown in HCV and HIV. Our objective was to develop a quantitative assay for cell-mediated immune (CMI) responses in HEV infection as a surrogate marker for HEV exposure in silent infection. Quantitative assessment of the CMI responses in HEV will also help us to evaluate the role of CMI in HEV morbidity. In this study, an HEV-specific interferon-gamma (IFN-gamma) ELISPOT assay was optimized to analyze HEV-specific CMI responses. We used peripheral blood mononuclear cells (PBMC) and sera from experimentally infected chimpanzees and from seroconverted and control human subjects to validate the assay. The HEV-specific IFN-gamma ELISPOT responses correlated strongly and significantly with anti-HEV ELISA positive/negative results (rho=0.73, p=0.02). Moreover, fine specificities of HEV-specific T cell responses could be identified using overlapping HEV ORF2 peptides.