E Kinyanda, MRC/UVRI Uganda Research Unit on AIDS - Mental health among HIV infected CHildren and Adolescents in KAmpala, Uganda (CHAKA)

HIV disproportionately affects children and adolescents in sub-Saharan Africa, where 90% of those infected reside. In Uganda, the country with the fifth highest prevalence rate in the region, more than 10% of the 1.2 million people living with HIV are under the age of 15. In addition to its physical impact, HIV infected children and adolescents (CA-HIV) report poor mental wellbeing. Epidemiological research from high-income countries has found high rates of psychiatric disorder (PD; e.g. depression, anxiety and behaviour disorders). Evidence on risk factors for PD in CA-HIV remains inconclusive. However, potential risk factors include: poor maternal health; HIV disease severity; caregiver PD; HIV related neurological/developmental disability; stigma, death in the family and negative environmental factors; pain; and genetic factors. Although sub-Saharan Africa shoulders the greatest burden of youth HIV, little research has been conducted to better understand psychiatric problems among CA-HIV in the region. The aim of this study is to investigate the impact of PD on CA-HIV in Uganda and the implications for service provision.

The objectives of this study are to: (1) determine the prevalence, 12-month incidence and predictors of PD (including neurocognitive impairment) among CA-HIV; (2) investigate the relationship between differences in the serotonin transporter gene and depressive disorder; (3) examine the impact of PD on HIV disease progression; (4) examine the impact of PD on social and academic functioning and risky behaviours (i.e. treatment adherence, alcohol use, sexual behaviour and suicidal behaviour); and (5) investigate help-seeking behaviour and identify service delivery gaps in Ugandan HIV services. These objectives will be met through a cohort study of 1,260 CA-HIV and their caregivers from two paediatric HIV clinics in urban and rural Uganda. Socio-demographic characteristics and psychosocial, clinical, genetic and biological data will be collected by trained psychiatric research nurses and study clinicians at baseline and six and 12 month follow-up.

Nested in the cohort, we will carry out a qualitative sub-study of 48 CA-HIV diagnosed with a psychiatric disorder (PD) and their caregivers to investigate explanatory models of PD help-seeking behaviour, unmet needs of care and expectations from mental health care services. Interviews will be conducted on two occasions, within two months of baseline assessment and at 12 month follow-up.

HIV care services in Uganda are currently in the process of transitioning from a vertical care structure to one fully integrated into the formal health care system which focuses on the needs of people living with HIV/AIDS. The results of this timely study will provide policymakers and service providers with invaluable information to strengthen the provision of appropriate and effective mental health care for this vulnerable group.

Prevalence/incidence of the broad categories of emotional and behavioural disorders, sub-diagnostic categories (including neurocognitive impairment) will be estimated with 95% confidence limits, overall and by site location, age-group and gender. A hierarchical approach will be used to investigate factors associated with PD.

The impact of PD on HIV disease progression on CA-HIV on antiretroviral treatment (ART) will be assessed using a linear mixed model fitted to the longitudinal data consisting of transformed CD4 counts at baseline and six and 12 months, with fixed terms for the presence/absence of PD, gender, age (as a continuous variable) and other prognostic factors, and a random effect for subject. For those not on ART, a binary variable will record whether or not the viral load is greater than 1,000 copies/ml. A similar analysis will then be carried out, except a generalised linear mixed model (GLMM) will be fitted.

The relationship between polymorphisms of the serotonin transporter gene and depressive disorder will be evaluated using mixed-effects logistic regression. We will use a stepwise selection procedure using the Akaike information criteria to select the specific combination of interactions and main effects out of the candidate model containing all individually significant factors.

To assess the impact of PD on social and academic functioning and risky behaviours, these outcome measures will be transformed into binary variables (e.g. the dichotomised "poor academic functioning") and then GLMMs will be fitted to the longitudinal data at each time point (i.e. baseline and six and 12-month follow-up).

Forty-eight CA-HIV diagnosed with a psychiatric disorder (PD) and their caregivers will be asked to participate in the qualitative sub-study. Thematic analysis will be conducted to elicit common experiences that emerged from the participants' narratives. In addition simple frequencies will be tallied for the various symptoms described.

The proposed study will be the largest study addressing mental health of CA-HIV, and the first longitudinal study on their impact, in the sub-Saharan Africa. The impact of this research is anticipated at a number of levels and beneficiaries include service users, caregivers, policymakers, service providers, clinicians, research funders and communities. The primary impact will be a major contribution to knowledge of the burden of psychiatric disorder (PD) and neurocognitive impairment (NI) among children and adolescents living with HIV/AIDS (CA-HIV) in the sub-Saharan African setting of Uganda and the impact of these disorders on HIV disease progression and on risky behaviours. The study will also inform gaps in mental health service provision and lay the foundation for the development of appropriate mental health services, integrated within routine HIV care for CA-HIV. This is especially important in Uganda where HIV services are currently transitioning from a vertical care structure to one fully integrated into the formal health care system and focused on the needs of people living with HIV/AIDS.

The resulting prevalence data and information on the impact of psychiatric disorder (PD) and neurocognitive impairment (NI) might be used by research funders in the short term (3-5 years) to assist in decisions regarding research priorities.

Although the proposed project will largely provide epidemiological data, coupled with the qualitative data extracted from interviews, the results may lead to improvements in service user outcomes in the short and medium term (3-10 years) through improved accessibility and quality of interventions for psychiatric disorders and symptoms. The potential for improving interventions and service provision for CA-HIV with PD or even those displaying only symptoms based on the findings of this research may lead to greatly improved service user and caregiver outcomes (e.g. quality of life and productivity) resulting in economic and social benefit within their communities. The study investigators plan to use the CHAKA study findings to mount an intervention study aimed at addressing mental health problems in CA-HIV and reducing long-term adverse impacts.

The capacity building activities nested have been developed to improve the research and professional skills of members of the research team. Two members of the research team will be selected to undertake a distance learning Master's degree in Epidemiology from the London School of Hygiene and Tropical Medicine. During their course they will also have the opportunity to spend five weeks at the School to take a module, meet other students and receive face-to-face support and supervision from their tutor. In addition they will meet members of the Centre for Global Mental Health. It is anticipated that through this experience, they will begin to form professional relationships and collaborations with UK researchers with similar experiences. The ARL candidate (EK) will complete a six-week UK placement at the Centre for Global Mental Health at LSHTM during the grant. This experience will provide opportunities to present the project to UK researchers and clinicians, receive face-to-face mentoring and assistance with research management and writing up, build upon collaborations within the Centre and learn about mental health research and service provision for CA-HIV at two of the leading paediatric HIV clinics in the UK (Mortimer Market and Great Ormond Street Hospital clinics).