Stigma Management Trajectories in Youth with Perinatally Acquired HIV and Their Families: A Qualitative Perspective.

This study explores how family, secrecy and silence contribute to the adoption of stigma management strategies among youth with perinatally acquired HIV (PAHIV). A qualitative method was used. Eighteen youths with PAHIV aged 13-22 years old took part in a semi-structured interview. An exploratory content analysis was performed. Analyses of interviews allowed identification of two HIV stigma management trajectories, both sensitive to the family context: [1] a consolidation of family ties, which contributes to solidarity in stigma management; and [2] a weakening or dissolution of family ties, which contributes to solitary stigma management strategy. Family conditions that support the children in their efforts to develop active stigma management strategies are described. Children likely to experience weakening or dissolution family ties must build strong bonds in the clinical environment and maintain these into adulthood so as to afford them the support they need.

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.

Family quality of life in families affected by HIV: the perspective of HIV-positive mothers.

The HIV infection of a family member can impact family quality of life (FQoL). The objectives of this study are to (1) describe patterns of FQoL among mothers living with HIV (MLHIV) and (2) identify key factors associated with FQoL in families affected by HIV. Recruitment took place in HIV-specialized clinics and community organizations. A 100 MLHIV and 67 of their children participated in this study. Mothers were on average 40.8 years old and reported having an average of two dependent children at home (M = 2.1, SD = 1.0). Participating children were 16.2 years old, on average. Half of the children were boys (50.8%). More than half were aware of their mother's positive HIV status (68.2%) and 19.7% were diagnosed with HIV. All HIV-positive children were aware of their status. A latent profile analysis was performed on the five continuous indicators of FQoL, and three main profiles of self-reported FQoL among MLHIV were established: high FQoL (33%), moderate FQoL (58%), and low FQoL (9%). Among the mothers' characteristics, education, physical functioning, social support, and resilience increased FQoL, while anxiety and irritability decreased FQoL. Among the children's characteristics, resilience followed the FQoL profile. A trend was observed toward children's greater awareness of the mother's HIV status in high and low FQoL profiles. Additionally, irritability tended to be higher within the lower FQoL profile. FQoL profiles can be used to identify families needing special care, particularly for family interventions with both parents and children. Other relevant indicators must be studied (e.g., closeness and support between family members, availability and accessibility of care, family structure, father-child relationships, and medical condition of the mother) and longitudinal research conducted to estimate the direction of causality between FQoL profile and individual family member characteristics.

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

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.

Predictive value of interleukin-7 levels for virological response to treatment in HIV-1-infected children.

We recently reported that interleukin-7 (IL-7), a potent stimulator of lymphopoiesis, is an independent predictor of virological response to antiretroviral therapy (ART) in HIV-1 infected adults. To determine if this cytokine also predicts treatment response in HIV-1-infected children, a longitudinal study was performed over 48 weeks in 36 treatment-naïve children vertically infected with HIV-1. Subjects who received treatment (n = 29) were stratified as complete virological responders (n = 12), partial virological responders (n = 11), or non-responders (n = 6), based on decline in viral load from baseline to week 48. Median plasma IL-7 levels at baseline were higher in complete responders (4.85 pg/mL, interquartile range [IQR] = 3.35-6.5) than in untreated controls (2.10 pg/mL, IQR = 1.50-3.50; p = 0.05). Linear regression analysis showed that baseline IL-7 levels were positively correlated with changes in HIV-1 viral load between baseline and week 24 (r = 0.40; p = 0.03) and between baseline and week 48 (r = 0.34; p = 0.07), but not with corresponding changes in CD4+ T-cell percentages and absolute counts. Collectively, these results indicate that IL-7 levels at baseline are predictive of virological but not immunological response to ART in children infected with HIV-1.

[Maternal immunity and mother-to-child transmission of HCV and HIV-1: challenges and recent advances]. / Immunité maternelle et transmission mère-enfant du VIH et du VHC : Progrès récents et nouveaux défis.

Human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are two viral pathogens that establish chronic infections in their hosts and that are at present responsible for serious public health problems on a pandemic scale. HIV-1 and HCV can be transmitted from person to person by contact with bodily fluids. Both can also be transmitted from mother to child during the course of pregnancy and childbirth. There are currently no vaccines available to immunize against HIV-1 and HCV infection or to prevent mother-to-child transmission (MTCT), and accessible treatments have significant yet limited efficacy. However, important progresses have been made since the discovery of HCV and HIV-1 : (a) sensitive screening and detection methods have been perfected ; (b) risk factors for acquisition, replicative cycles, pathogenesis, and mechanisms of transmission have been better characterized ; (c) specific treatments, immunotherapy, and antiretroviral prophylaxis regimen were developed ; (d) immune correlates of protection are better understood ; and (e) vaccine design was undertaken. In addition, co-infection with HCV and HIV-1, which is common among high-risk groups including injection drug users, significantly increases the incidence of MTCT of both viruses. The mechanisms by which this facilitation occurs are still under investigation and may involve direct replicative facilitation, enhancement of placental transfer, and/or interference with host immune responses. Taken together, these developments could lead to the implementation of global scale strategies to prevent MTCT of HCV and HIV-1.

Cost-Consequence Analysis of Nitisinone for Treatment of Tyrosinemia Type I.

BACKGROUND: Tyrosinemia type I is a rare but severe genetic metabolic disorder. Nitisinone combined with a diet low in tyrosine and phenylalanine became first-line therapy in 1994. OBJECTIVES: To estimate the direct medical costs of health care services related to the treatment of tyrosinemia type I, taking into consideration the real-life efficacy of nitisinone. METHODS: A cost-consequence analysis was performed for all children with a confirmed diagnosis of tyrosinemia type I who were treated in Quebec between January 1, 1984, and January 1, 2009. The costs of care were compared for 3 consecutive historical groups: no nitisinone (1984 to 1994), late intervention with nitisinone (first dose received between 1994 and 1997), and early intervention with nitisinone (first dose received between 1997 and 2008). Data were derived from patient charts, hospital databases, and the Régie de l'assurance maladie du Québec and MED-ÉCHO administrative databases. Costs were reported in 2008 Canadian dollars. RESULTS: Nitisinone treatment was associated with significant reductions in the number and duration of hospital admissions, the number of admissions to a pediatric intensive care unit, and the number of liver transplants. The cost of hospitalization per person-year was significantly lower in the 2 groups treated with nitisinone: $673 and $5 590 for the early-intervention and late-intervention groups, respectively, as compared to $12 980 for the no-nitisinone group (p < 0.001). Hospital costs per person-year for liver transplant were $3 198 for the late-intervention group and $5 044 for the no-nitisinone group: there were no transplants in the early-intervention group. The cost of nitisinone per person-year was $51 493 for the early-intervention group and $64 895 for the late-intervention group. CONCLUSIONS: Nitisinone treatment significantly improved the outcomes of patients with tyrosinemia type I, while decreasing utilization of health care resources, liver transplants, and associated costs.

CONTEXTE: La tyrosinémie de type I est un trouble génétique du métabolisme rare, mais grave. La prise de nitisinone en association à un régime pauvre en tyrosine et en phénylalanine est devenue le traitement de première intention en 1994. OBJECTIFS: Offrir une estimation des coûts médicaux directs des services de santé liés au traitement de la tyrosinémie de type I, tout en tenant compte de l'efficacité réelle de la nitisinone. MÉTHODES: Une analyse coûts-conséquences a été réalisée pour chaque enfant ayant reçu un diagnostic de tyrosinémie de type I et ayant été traité au Québec entre le 1er janvier 1984 et le 1er janvier 2009. Les coûts des soins ont été comparés entre trois groupes historiques se suivant dans le temps : sans nitisinone (de 1984 à 1994), traitement tardif à la nitisinone (première dose reçue entre 1994 et 1997) et traitement précoce à la nitisinone (première dose reçue entre 1997 et 2008). Les données ont été obtenues à partir de dossiers médicaux de patients, de bases de données d'hôpitaux, de la base de données administrative de la Régie de l'assurance maladie du Québec et de la banque de données ministérielles MED-ÉCHO. Les coûts sont indiqués en dollars canadiens de 2008. RÉSULTATS: L'on a associé le traitement par nitisinone à d'importantes réductions : du nombre d'hospitalisations et de la durée des séjours à l'hôpital, du nombre d'admissions à l'unité de soins intensifs pédiatrique et du nombre de greffes hépatiques. Les coûts d'hospitalisation (par personne-année) étaient beaucoup plus faibles dans les deux groupes traités par nitisinone : 673 $ et 5 590 $ respectivement pour le groupe de traitement précoce et le groupe de traitement tardif, contre 12 980 $ pour le groupe sans traitement par nitisinone (p < 0,001). Les coûts d'hospitalisation (par personne-année) pour les greffes hépatiques étaient de 3 198 $ pour le groupe de traitement tardif et de 5 044 $ pour le groupe sans traitement par nitisinone; le groupe de traitement précoce n'a fait l'objet d'aucune greffe hépatique. Les coûts du traitement par nitisinone (par personne-année) étaient de 51 493 $ pour le groupe de traitement précoce et de 64 895 $ pour le groupe de traitement tardif. CONCLUSIONS: Le traitement par nitisinone améliore grandement les résultats thérapeutiques des patients souffrant de tyrosinémie de type I et réduit également le recours aux ressources en santé et à la greffe hépatique, diminuant ainsi les coûts associés.

Evolution of HIV-1 coreceptor usage and coreceptor switching during pregnancy.

Coreceptor switch from CCR5 to CXCR4 is associated with HIV disease progression. To document the evolution of coreceptor tropism during pregnancy, a longitudinal study of envelope gene sequences was performed in a group of pregnant women infected with HIV-1 of clade B (n=10) or non-B (n=9). Polymerase chain reaction (PCR) amplification of the V1-V3 region was performed on plasma viral RNA, followed by cloning and sequencing. Using geno2pheno and PSSMX4R5, the presence of X4 variants was predicted in nine of 19 subjects (X4 subjects) independent of HIV-1 clade. Six of nine X4 subjects exhibited CD4(+) T cell counts <200 cells/mm(3), and the presence of X4-capable virus was confirmed using a recombinant phenotypic assay in four of seven cases where testing was successful. In five of nine X4 subjects, a statistically significant decline in the geno2pheno false-positive rate was observed during the course of pregnancy, invariably accompanied by progressive increases in the PSSMX4R5 score, the net charge of V3, and the relative representation of X4 sequences. Evolution toward X4 tropism was also echoed in the primary structure of V2, as an accumulation of substitutions associated with CXCR4 tropism was seen in X4 subjects. Results from these experiments provide the first evidence of the ongoing evolution of coreceptor utilization from CCR5 to CXCR4 during pregnancy in a significant fraction of HIV-infected women. These results inform changes in host-pathogen interactions that lead to a directional shaping of viral populations and viral tropism during pregnancy, and provide insights into the biology of HIV transmission from mother to child.

[Not Available]. / Silence et divulgation dans des familles d'adolescents vivant avec le VIH depuis la naissance : une exploration qualitative.

OBJECTIVE: Studies targeting children born with HIV have principally focused on the period preceding the announcement of the diagnosis to the child. The objective of the present study was to explore intrafamilial communication dynamics following the announcement of the diagnosis. METHODOLOGY: Twenty-nine youths (10 to 18 years of age) living with HIV since birth participated in individual semistructured interviews about the following: 1) serostatus disclosure, 2) family relations and 3) sexual education within the family. The testimonials underwent a content analysis. RESULTS: The youths learned of their HIV-positive diagnosis at the average age of 11 years. The dynamic established after the announcement appears to be regulated by silence: the exchanges that follow mainly involve questions related to medication and prevention of sexual transmission of the virus. This silence preserves the familial equilibrium by performing three functions: protecting the mother from a feeling of guilt regarding transmission, assuring family harmony and feeling normal compared with others. The adolescent's diagnosis is generally not revealed to the extended family, thus preserving their integration within the family by protecting them from rejection, betrayal and judgement. DISCUSSION: The functions of silence and the secret serve as important stabilizers within the family. However, they contribute to the isolation of the adolescents in the form of emotional support that they still need. Suggestions for intervention are presented.

HIV-1 genetic diversity in antenatal cohort, Canada.

We studied HIV genetic diversity in a cohort of 127 pregnant, HIV-infected women who received prenatal care at Sainte-Justine Hospital in Montreal, Canada, between 1999 and 2003. Clade assignments were derived by phylogenetic analysis of amplified pol sequences. Genotyping was successful in 103 of 127 women, 59 (57.3%) of whom were infected with clade B HIV-1, and 44 (42.7%) with nonclade B viruses, including subtypes A, C, D, F, G, and H. Four sequences remained unassigned. Forty-three of 44 women infected with non-clade B viruses were newcomers from sub-Saharan Africa, and subtype identity was consistent with those circulating in their countries of origin. These results highlight the epidemiologic importance of non-B HIV-1 in antenatal populations in a large North American urban center, underscore the influence of population movements on clade intermixing, and identify a group of patients who could be targeted for surveillance and drug therapy followup.

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.

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.