ABSTRACT
Background: Adolescents in Sub-Saharan Africa are disproportionately affected by the HIV epidemic. Comorbid depression is prevalent among adolescents living with HIV (ALWH) and poses numerous challenges to HIV care engagement and retainment. We present a pilot trial designed to investigate feasibility, fidelity, and acceptability of an adapted and an enhanced Friendship Bench intervention (henceforth: AFB and EFB) in reducing depression and improving engagement in HIV care among ALWH in Malawi. Methods: Design:: Participants will be randomized to one of three conditions: the Friendship Bench intervention adapted for ALWH (AFB, n=35), the Friendship Bench intervention enhanced with peer support (EFB, n=35), or standard of care (SOC, n=35). Recruitment is planned for early 2024 in four clinics in Malawi.Participants:: Eligibility criteria (1) aged 13-19; (2) diagnosed with HIV (vertically or horizontally); (3) scored ≥ 13 on the self-reported Beck's Depression Inventory (BDI-II); (4) living in the clinic's catchment area with intention to remain for at least 1 year; and (5) willing to provide informed consent.Interventions:: AFB includes 6 counseling sessions facilitated by young, trained non-professional counselors. EFB consists of AFB plus integration of peer support group sessions to facilitate engagement in HIV care. SOC for mental health in public facilities in Malawi includes options for basic supportive counseling, medication, referral to mental health clinics or psychiatric units at tertiary care hospitals for more severe cases.Outcomes:: The primary outcomes are feasibility, acceptability, and fidelity of the AFB and EFB assessed at 6 months and 12 months and compared across 3 arms. The secondary outcome is to assess preliminary effectiveness of the interventions in reducing depressive symptoms and improving HIV viral suppression at 6 months and 12 months. Discussion: This pilot study will provide insights into youth-friendly adaptations of the Friendship Bench model for ALWH in Malawi and the value of adding group peer support for HIV care engagement. The information gathered in this study will lead to a R01 application to test our adapted intervention in a large-scale cluster randomized controlled trial to improve depression and engagement in HIV care among ALWH.
ABSTRACT
The protein kinase A (PKA) signaling system mediates the effects of numerous hormones, neurotransmitters, and other molecules to regulate metabolism, cardiac function, and more. PKA defects may lead to diverse phenotypes that largely depend on the unique expression profile of the affected subunit. Deletion of the Prkarcb gene, which codes for PKA catalytic subunit ß (Cß), protects against diet-induced obesity (DIO), yet the mechanism for this phenotype remains unclear. We hypothesized that metabolic rate would be increased in Cß knockout (KO) mice, which could explain DIO resistance. Male, but not female, CßKO mice had increased energy expenditure, and female but not male CßKO mice had increased subcutaneous temperature and increased locomotor activity compared with wild-type (WT) littermates. Urinary norepinephrine (NE) and normetanephrine were elevated in female CßKO mice. CßKO mice had increased heart rate (HR); blocking central NE release normalized HR to that of untreated WT mice. Basal and stimulated PKA enzymatic activities were unchanged in adipose tissue and heart and varied in different brain regions, suggesting that Prkacb deletion may mediate signaling changes in specific brain nuclei and may be less important in the peripheral regulation of PKA expression and activity. This is a demonstration of a distinct effect of the PKA Cß catalytic subunit on catecholamines and sympathetic nerve signaling. The data provide an unexpected explanation for the metabolic phenotype of CßKO mice. Finally, the sexual dimorphism is consistent with mouse models of other PKA subunits and adds to the importance of these findings regarding the PKA system in human metabolism.
