Preservation of cytotoxic granule production in response to mycobacterial antigens by T-lymphocytes from vertically HIV-infected Brazilian youth on effective combined antiretroviral therapy

ABSTRACT Background: HIV infection harms adaptive cellular immunity mechanisms. Long-term virological control by combined antiretroviral therapy (cART) reduces the risk of mycobacterial infections. Thus, we aimed to study cellular responses to mycobacterial antigens in 20 HIV-infected adolescents with at least one year of virological control (HIV-RNA <40 copies/mL) and 20 healthy adolescents. Methods: We evaluated CD8 and γδ T-cell degranulation by measurement of CD107a membrane expression after stimulation with lysates from BCG (10 µg/mL) and H37RA Mycobacterium tuberculosis (Mtb, 10 µg/mL). Immune activation and antigen-presenting ability were also assessed by determination of HLA-DR, CD80, and CD86 markers. Results: TCR γδ T-cell CD107a expression was similar between groups in response to mycobacterial antigens, and lower in the HIV-infected group in response to mitogen. Higher baseline HLA-DR expression and lower mycobacterial-stimulated expression was found within the HIV-infected group. Conclusions: Similar degranulation in stimulated CD8+ and TCR γδ T-cells from HIV-infected adolescents, when compared to healthy controls suggests long-term immunological preservation with immune reconstitution under successful cART. However, differences in HLA-DR expression may represent ongoing inflammation and lower specific responses in HIV-infected youth. These features may be relevant in the context of the precocity and severity of vertically acquired HIV infection.

Usefulness of pharmacy dispensing records in the evaluation of adherence to antiretroviral therapy in Brazilian children and adolescents

INTRODUCTION: Adherence, which is crucial to the success of antiretroviral therapy (HAART), is currently a major challenge in the care of children and adolescents living with HIV/AIDS. OBJECTIVE: To evaluate the prevalence of nonadherence to HAART using complementary instruments in a cohort of children and adolescents with HIV/AIDS followed in a reference service in Campinas, Brazil. METHODS: The level of adherence of 108 patients and caregivers was evaluated by an adapted standardized questionnaire and pharmacy dispensing records (PDR). Non-adherence was defined as a drug intake lower than 95% (on 24-hour or seven-day questionnaires), or as an interval of 38 days or more for pharmacy refills. The association between adherence and clinical, immunological, virological, and psychosocial characteristics was assessed by multivariate analysis. RESULTS: Non-adherence prevalence varied from 11.1% (non-adherent in three instruments), 15.8% (24-hour self-report), 27.8% (seven-day self-report), 45.4% (PDR), and 56.3% (at least one of the outcomes). 24-hour and seven-day self-reports, when compared to PDR, showed low sensitivity (29% and 43%, respectively) but high specificity (95% and 85%, respectively). In multivariate analysis, medication intolerance, difficulty of administration by caregiver, HAART intake by the patient, lower socioeconomical class, lack of virological control, missed appointments in the past six months, and lack of religious practice by caregiver were significantly associated with non-adherence. CONCLUSION: A high prevalence of HAART non-adherence was observed in the study population, and PDR was the most sensitive of the tested instruments. The instruments employed were complementary in the identification of non-adherence.