Johanne Samson

Cell cycle effects and cellular pharmacology of 5-AZA-2′-deoxycytidine

SummaryThe cytotoxic action of 5-aza-2′-deoxycytidine (5-AZA-CdR) in synchronized cells and logarithmic- and plateau-phase cultures of EMT6 murine tumor cells was investigated. 5-AZA-CdR produced a greater cell kill of S phase cells than of cells in G1 phase. Cells in the logarithmic phase of growth were more sensitive to the cytotoxic effects of 5-AZA-CdR than cells in the plateau phase of growth. These results indicate that 5-AZA-CdR produces a preferential kill of cells in the S phase of the cell cycle. 5-AZA-CdR did not block the cell cycle progression of cells into S phase. The survival curve of EMT6 cells exposed to 5-AZA-CdR suggests that the cytotoxic action of this analogue is not self-limiting. The mutagenic activity of 5-AZA-CdR was investigated using induction of 6-thioguanine resistance in Chinese hamster ovary cells. 5-AZA-CdR was not a detectable mutagen in this assay system.

Romantic relationships and sexual activities of the first generation of youth living with HIV since birth

Abstract HIV-infected children, now maturing into adolescence and adulthood, must cope not only with adolescent developmental issues, but also with a chronic, socially stigmatised and sexually transmittable illness. Little research on this first generation of survivors has focused on romantic involvement and sexuality. This study, which employs a mixed-method embedded strategy (qualitative supported by quantitative), describes the perspectives of youth living with HIV since birth concerning: (1) romantic involvement and sexuality; and (2) risk management including the risk of HIV transmission and partner serostatus disclosure. Eighteen adolescents aged 13–22 from Montreal, Canada, participated in individual semi-structured interviews and completed self-report questionnaires. Most youths participated in non-penetrative sexual activities. Ten participants reported having had vaginal and three anal intercourses, at an average age of 14 for girls and 15 for boys. All sexually active youth reported having used a condom at least once. Of those who reported that their first sexual relationship was protected, over half had taken risks in subsequent relationships (e.g., unprotected sex, multiple partners, etc.). Interviews conducted with sexually inactive youths illustrate the interrelatedness of romantic involvement, sexual initiation and potential serostatus disclosure. Involvement in a sexual relationship would not be conceivable unless the partner was informed of their serostatus. For sexually active participants, risk management implies HIV transmission and partner disclosure. These youths have emotional issues regarding disclosure in romantic relationships and few risked potential rejection by disclosing. Condom use acts as a reminder of the infection and a barrier to intimacy. The narratives illustrate how risk perception changes and becomes relative with time and experience, especially when the viral load is undetectable and when past experience has convinced the adolescent that his/her partner might not become infected. Findings reinforce the need to prioritise sexual health issues for young people with perinatally acquired HIV.

HIV-1 Genetic Diversity in Antenatal Cohort, Canada

Non-B HIV-1 was consistent with patients’ area of origin.

Transient T Cell Receptor β-Chain Variable Region-Specific Expansions of CD4+ and CD8+ T Cells during the Early Phase of Pediatric Human Immunodeficiency Virus Infection: Characterization of Expanded Cell Populations by T Cell Receptor Phenotyping

T cell receptor (TCR) repertoire perturbations are commonly detected in CD8+ T cells during adult primary human immunodeficiency virus (HIV) infection and have been associated with HIV-specific cytotoxic T cell responses. By use of flow cytometry, transient high-level TCR beta-chain variable region-specific expansions of CD4+ and CD8+ T cells were observed more frequently in HIV-infected children than in children exposed to HIV who remained uninfected. TCR beta-chain diversity analysis and diversity-specific polymerase chain reaction were used to study the clonality of expanded CD4+ and CD8+ subsets. In CD8+ T cells, structural features of the complement-determining regions 3 were altered during the course of the expansion, and persistent TCR clonotypes were observed, consistent with antigen-driven selection. In contrast, TCR beta-chain variable region-specific expansions without clonotypic overrepresentation or persistence were observed in CD4+ T cells, possibly related to HIV-specific helper T cell responses or to the progressive destruction of the CD4+ cell compartment.

Differing Patterns of Liver Disease Progression and Hepatitis C Virus (HCV) Quasispecies Evolution in Children Vertically Coinfected with HCV and Human Immunodeficiency Virus Type 1

ABSTRACT Hepatitis C virus (HCV) quasispeciation was studied in two children vertically coinfected with HCV and human immunodeficiency virus type 1 (HIV-1). HCV quasispecies diversification and liver injury were more significant in patient C1, who was immunocompetent with anti-HIV therapy, than in patient C2, who was immunosuppressed, in consistency with modulation of HCV quasispeciation and liver injury by immunocompetence in coinfected children.

Natural history of Epstein-Barr virus infection in a prospective pediatric cohort born to human immunodeficiency virus-infected mothers.

To determine whether Epstein-Barr virus (EBV) constitutes a contributing factor in AIDS and, conversely, whether the human immunodeficiency virus (HIV) alters the course of primary EBV infection in a pediatric population, 62 children born to HIV-infected mothers and prospectively followed were evaluated. EBV infection was documented by EBV-specific serology and polymerase chain reaction and by clinical history. HIV infection status was determined according to the Centers for Disease Control and Prevention pediatric classification system. Demographics from HIV-infected and HIV-uninfected children were comparable. The data suggest that HIV-infected children may acquire primary EBV infection earlier in life. The incidence of accompanying splenomegaly or hepatomegaly (or both) around the time of EBV seroconversion was higher among HIV-infected children than among HIV-uninfected children. In contrast, HIV disease progression and HIV-1 RNA load did not seem to be influenced by primary EBV infection.

Hepatitis C virus quasispecies evolution during pregnancy and between consecutive pregnancies: influence of maternal immune responses

chronic viral infections transmitted to infants: from mechanisms to prevention and care Meeting

The Importance of Meanings of Antiretroviral Treatment and Care Providers for Adherence and Transitioning to Adult Services Among Youth With Perinatally Acquired HIV Infection

The transition from pediatric to adult services for youth with perinatally acquired HIV (PaHIV) is a critical period. A successful transition is key to ensuring patient treatment adherence as adults. Eighteen youths with PaHIV, aged 13–22, participated in two individual, semistructured interviews conducted 3 years apart. Results indicate that a key factor appearing to help youth in overcoming barriers to adherence and facilitating coping strategies is the way they perceive their medication: youth with positive perceptions are more likely to overcome the barriers than are those with negative perceptions, such as emphasis on the side effects and stigma associated with the medication. Positive relationships with health professionals allowed youth to face transitioning challenges. Interventions targeting PaHIV should focus on these issues.

Barriers to health-care and psychological distress among mothers living with HIV in Quebec (Canada)

Health-care providers play a major role in providing good quality care and in preventing psychological distress among mothers living with HIV (MLHIV). The objectives of this study are to explore the impact of health-care services and satisfaction with care providers on psychological distress in MLHIV. One hundred MLHIV were recruited from community and clinical settings in the province of Quebec (Canada). Prevalence estimation of clinical psychological distress and univariate and multivariable logistic regression models were performed to predict clinical psychological distress. Forty-five percent of the participants reported clinical psychological distress. In the multivariable regression, the following variables were significantly associated with psychological distress while controlling for sociodemographic variables: resilience, quality of communication with the care providers, resources, and HIV disclosure concerns. The multivariate results support the key role of personal, structural, and medical resources in understanding psychological distress among MLHIV. Interventions that can support the psychological health of MLHIV are discussed.

Evolution of HIV-1 envelope sequences and coreceptor tropism during pregnancy

Background HIV-1 Env mediates viral entry into target cells and defines R5 or X4 phenotype. HIV tropism is important in pathogenesis and is associated with mother-to-child transmission. Env is under strong selective pressure within the host. The aim of this study was to determine whether changes in maternal immunity associated with initiation and progression of pregnancy influence Env sequence variation and HIV-1 coreceptor usage.