Immune correlates of CD4 decline in HIV-infected patients experiencing virologic failure before undergoing treatment interruption

<p>Abstract</p> <p>Background</p> <p>The advantage of treatment interruptions (TIs) in salvage therapy remains controversial. Regardless, characterizations of the correlates of CD4 count fall during TI are important to identify since patients with virologic failure commonly stop antiretroviral (ARV) therapy. The objective of this study was to determine the predictive value of pre-TI proliferative capacity and cell surface markers for CD4 count change in HIV-infected patients experiencing virologic failure before undergoing TI.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMCs) from 13 HIV-infected patients experiencing virologic failure at baseline time points before the TI were tested for proliferation using the 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and a Gag p55 peptide pool, staphylococcus enterotoxin B (SEB), cytomegalovirus (CMV) recall antigen, and anti-CD3 antibody as stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells was measured.</p> <p>Results</p> <p>The median changes in the CD4+ T-cell count and viral load from baseline to the TI time point corresponding to the CD4 count nadir were -44 cells/mm³{Interquartile range (IQR) -17, -104} and +85,332 copies/mL (IQR +11,198, +283,327), respectively. CD4+ T-cell proliferation to CMV, pre-TI CD4+ T-cell count, and percent CD4+CD57+ cells correlated negatively with CD4 count change during TI (r = -0.59, p = 0.045, r = -0.61, p = 0.030 and r = -0.69, p = 0.0095, respectively; Spearman correlation). The presence of HIV-specific proliferative responses was not associated with a reduced decline in CD4 count during TI.</p> <p>Conclusion</p> <p>The use of pre-TI immune proliferative responses and cell surface markers may have predictive value for CD4 count decline during TI.</p

Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.</p> <p>Methods</p> <p>Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.</p> <p>Results</p> <p>HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).</p> <p>Conclusions</p> <p>IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.</p

HIV, Gender, Race, Sexual Orientation, and Sex Work: A Qualitative Study of Intersectional Stigma Experienced by HIV-Positive Women in Ontario, Canada

Mona Loutfy and colleagues used focus groups to examine experiences of stigma and coping strategies among HIV-positive women in Ontario, Canada

Knowledge, Perceptions and Information about Hormone Therapy (HT) among Menopausal Women: A Systematic Review and Meta-Synthesis

BACKGROUND: The use of hormone therapy (HT) by menopausal women has declined since the Women's Health Initiative randomized trial (WHI) in 2002 demonstrated important harms associated with long-term use. However, how this information has influenced women's knowledge and attitudes is uncertain. We aimed to evaluate the attitudes and perceptions towards HT use, as well as specific concerns and information sources on HT since the WHI trial. METHOD/RESULTS: We did a systematic review to assess the attitudes and knowledge towards HT in women, and estimate the magnitude of the issue by pooling across the studies. Using meta-synthesis methods, we reviewed qualitative studies and surveys and performed content analysis on the study reports. We pooled quantitative studies using a random-effects meta-analysis. We analyzed 11 qualitative studies (n = 566) and 27 quantitative studies (n = 39251). Positive views on HT included climacteric symptom control, prevention of osteoporosis and a perceived improvement in quality of life. Negative factors reported included concerns about potential harmful effects, particularly cancer risks. Sources of information included health providers, media, and social contact. By applying a meta-synthesis approach we demonstrate that these findings are broadly applicable across large groups of patients. CONCLUSIONS: Although there are clear hazards associated with long-term HT use, many women view HT favorably for climacteric symptom relief. Media, as a source of information, is often valued as equivalent to health providers

Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates

The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and influenza A H5N1, urges the need for deciphering their pathogenesis to develop new intervention strategies. SARS-CoV infection causes acute lung injury (ALI) that may develop into life-threatening acute respiratory distress syndrome (ARDS) with advanced age correlating positively with adverse disease outcome. The molecular pathways, however, that cause virus-induced ALI/ARDS in aged individuals are ill-defined. Here, we show that SARS-CoV-infected aged macaques develop more severe pathology than young adult animals, even though viral replication levels are similar. Comprehensive genomic analyses indicate that aged macaques have a stronger host response to virus infection than young adult macaques, with an increase in differential expression of genes associated with inflammation, with NF-κB as central player, whereas expression of type I interferon (IFN)-β is reduced. Therapeutic treatment of SARS-CoV-infected aged macaques with type I IFN reduces pathology and diminishes pro-inflammatory gene expression, including interleukin-8 (IL-8) levels, without affecting virus replication in the lungs. Thus, ALI in SARS-CoV-infected aged macaques developed as a result of an exacerbated innate host response. The anti-inflammatory action of type I IFN reveals a potential intervention strategy for virus-induced ALI

The Problematization of Sexuality among Women Living with HIV and a New Feminist Approach for Understanding and Enhancing Women’s Sexual Lives

In the context of HIV, women’s sexual rights and sexual autonomy are important but frequently overlooked and violated. Guided by community voices, feminist theories, and qualitative empirical research, we reviewed two decades of global quantitative research on sexuality among women living with HIV. In the 32 studies we found, conducted in 25 countries and composed mostly of cis-gender heterosexual women, sexuality was narrowly constructed as sexual behaviours involving risk (namely, penetration) and physiological dysfunctions relating to HIV illness, with far less attention given to the fullness of sexual lives in context, including more&nbsp;positive and rewarding experiences such as satisfaction and pleasure. Findings suggest that women experience declines in sexual activity, function, satisfaction, and pleasure following HIV diagnosis, at least for some period. The extent of such declines, however, is varied, with numerous contextual forces shaping women’s sexual well-being. Clinical markers of HIV (e.g., viral load, CD4 cell count) poorly predicted sexual outcomes, interrupting widely held assumptions about sexuality for women with HIV. Instead, the effects of HIV-related stigma intersecting with inequities related to trauma, violence, intimate relations, substance use, poverty, aging, and other social and cultural conditions primarily influenced the ways in which women experienced and enacted their sexuality. However, studies framed through a medical lens tended to pathologize outcomes as individual “problems,” whereas others driven by a public health agenda remained primarily preoccupied with protecting the public from HIV. In light of these findings, we present a new feminist approach for research, policy, and practice toward understanding and enhancing women’s sexual lives—one that affirms sexual diversity; engages deeply with society, politics, and history; and is grounded in women’s sexual rights

Molecular mechanisms of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is a new infectious disease caused by a novel coronavirus that leads to deleterious pulmonary pathological features. Due to its high morbidity and mortality and widespread occurrence, SARS has evolved as an important respiratory disease which may be encountered everywhere in the world. The virus was identified as the causative agent of SARS due to the efforts of a WHO-led laboratory network. The potential mutability of the SARS-CoV genome may lead to new SARS outbreaks and several regions of the viral genomes open reading frames have been identified which may contribute to the severe virulence of the virus. With regard to the pathogenesis of SARS, several mechanisms involving both direct effects on target cells and indirect effects via the immune system may exist. Vaccination would offer the most attractive approach to prevent new epidemics of SARS, but the development of vaccines is difficult due to missing data on the role of immune system-virus interactions and the potential mutability of the virus. Even in a situation of no new infections, SARS remains a major health hazard, as new epidemics may arise. Therefore, further experimental and clinical research is required to control the disease