Long-term outcomes of lentiviral gene therapy for the ß-hemoglobinopathies: the HGB-205 trial.

Sickle cell disease (SCD) and transfusion-dependent ß-thalassemia (TDT) are the most prevalent monogenic disorders worldwide. Trial HGB-205 ( NCT02151526 ) aimed at evaluating gene therapy by autologous CD34+ cells transduced ex vivo with lentiviral vector BB305 that encodes the anti-sickling ßA-T87Q-globin expressed in the erythroid lineage. HGB-205 is a phase 1/2, open-label, single-arm, non-randomized interventional study of 2-year duration at a single center, followed by observation in long-term follow-up studies LTF-303 ( NCT02633943 ) and LTF-307 ( NCT04628585 ) for TDT and SCD, respectively. Inclusion and exclusion criteria were similar to those for allogeneic transplantation but restricted to patients lacking geno-identical, histocompatible donors. Four patients with TDT and three patients with SCD, ages 13-21 years, were treated after busulfan myeloablation 4.6-7.9 years ago, with a median follow-up of 4.5 years. Key primary endpoints included mortality, engraftment, replication-competent lentivirus and clonal dominance. No adverse events related to the drug product were observed. Clinical remission and remediation of biological hallmarks of the disease have been sustained in two of the three patients with SCD, and frequency of transfusions was reduced in the third. The patients with TDT are all transfusion free with improvement of dyserythropoiesis and iron overload.

Resilience and Life Expectations of Perinatally HIV-1 Infected Adolescents in France.

BACKGROUND: Resilience of perinatally HIV-infected youth in European countries is poorly studied. Life satisfaction and expectations for adulthood are rarely examined. OBJECTIVE: This cross-sectional, descriptive study of a French cohort of 54 perinatally HIV-infected adolescents raised in France (age 14-20 years) aimed to (1) evaluate their psychosocial adjustment, (2) identify their expectations for adulthood and (3) delineate risk and protective factors associated with mental health, life satisfaction, and HIV-1 viral load level. METHOD: Medical evaluation, psychological semi-structured interview, and self-report questionnaires were used. RESULTS: All the adolescents had been receiving Highly Active Anti-Retroviral Therapy (HAART) for 9 to 11 years and 2/3 were healthy with controlled viral load (<50 copies/mL). The majority had medium to high levels of life satisfaction. They viewed HIV as having only minor impact on their current daily life and had positive expectations for adulthood. However, 46% exhibited psychiatric symptomatology. Multivariable analysis showed that having a deceased parent and current worries about HIV were substantial risk factors for psychiatric symptoms. Having two living parents and being satisfied with life were protective factors for mental health. Good quality of caregiver-adolescent relationships and high life satisfaction were significant protective factors for controlled viral load. CONCLUSION: These data indicate psychosocial resilience among perinatally HIV-1 infected adolescents with 10 years of HAART treatment. These findings demonstrate the influence of life satisfaction, parent's life status and quality of caregiver-adolescent relationships on resilience and health outcomes in these patients. We conclude that healthcare providers should attend to these factors.

Evaluation of a peer support group therapy for HIV-infected adolescents.

OBJECTIVE: To assess the effects of a peer support group therapy on HIV-infected adolescents. DESIGN: A prospective study of a cohort of HIV-infected adolescents participating or not participating in a psychodynamic oriented, emotional support group. METHODS: From a group of 30 perinatally HIV-infected adolescents who attended an outpatient clinic, 10 agreed to participate in the peer support group (group 1), 10 declined (group 2) and 10 others who lived too far from the clinic were not invited to participate (group 3). The three groups were compared at baseline and 2 years later using the outcome measures: perceived illness experience scale, perceived treatment inventory, self-esteem inventory. RESULTS: At baseline, the three groups had similar characteristics overall. The adolescents' self-esteem was in the normal range. After 2 years, worries about illness had decreased in group 1, whereas the scores had increased or remained the same for the other adolescents (P = 0.026). The adolescents in group 1 had less negative perception of treatment at 2 years than those in groups 2 and 3 (P = 0.030). After intervention, the percentage of adolescents with an undetectable viral load had increased in group 1 from 30 to 80% (P = 0.063) but was unchanged in groups 2 and 3. Considering the three groups altogether, the decrease in the viral load correlated with improvement of the perceived treatment inventory (Spearman R = 0.482 P = 0.015). CONCLUSIONS: : This pilot study suggests that a peer support group intervention is associated with an improvement in adolescents' emotional well being, and that this can have a positive influence on medical outcomes.

A novel developmental and immunodeficiency syndrome associated with intrauterine growth retardation and a lack of natural killer cells.

OBJECTIVE: To describe a novel syndrome characterized by severe prenatal and postnatal growth failure, mild skeletal and facial abnormalities, and primary immunodeficiency. DESIGN: The syndrome was observed in 2 sisters. The elder child died of cytomegalovirus infection when she was 18 months old, whereas the younger sister is doing well at 5 years old. We report here clinical, hematologic, and immunologic data for both sisters and compare them with all known inherited disorders with similar clinical or immunologic features. RESULTS: The immune defect consists of a lack of detectable natural killer cells and small numbers of CD8 alphabeta T cells and polymorphonuclear neutrophils. This is the first report of prenatal and postnatal growth failure associated with mild skeletal and facial abnormalities and primary immunodeficiency. CONCLUSION: This novel syndrome probably is caused by an autosomal recessive gene defect impairing both intrauterine growth and natural killer cell development. The identification of other kindreds with this syndrome would facilitate the search for its genetic basis.