RCT to evaluate an intervention for depressed HIV-positive women in the perinatal period, to enhance child development and reduce maternal depression

The majority of people living with HIV in the world live in sub-Saharan Africa (SSA), with women of child-bearing age carrying the greatest burden. Up to 35% of women attending antenatal clinics in some parts of South Africa are HIV-positive. Many receive their diagnosis during pregnancy when they are screened for HIV. Depression afflicts many HIV-positive women during pregnancy; over 40% score above the threshold for depression on screening questionnaires, and approximately 23% fulfil diagnostic criteria. Depression is associated with reduced adherence to ART, as well as low clinic attendance, suicidal thoughts, and low rates of exclusive breastfeeding. Moreover, perinatal depression has negative effects on parenting and early child development. Children born to depressed mothers are at increased risk of compromised cognitive development, behaviour and growth, especially when faced with socio-economic disadvantage and lack of support. There is also emerging evidence from a separate body of literature that HIV is associated with negative effects on caregiving and children's outcomes (the vast majority of these children are HIV-negative). Improving the wellbeing of mothers and infants requires effective treatment of perinatal depression, ensuring adherence to ART, as well as enhancing key parenting skills. In particular, depressed mothers often need help to sensitively respond to and care for their infants in order to mitigate the negative effects of depression on parenting.
Our aim is to conduct a cluster RCT to test an integrated home-based intervention programme that jointly treats depression and enhances parenting. The intervention, delivered during pregnancy and the postnatal period, comprises a combination of behavioural activation (BA) therapy to treat the symptoms of depression and a parenting programme to improve maternal responsiveness to infants (CCD). BA is a structured therapeutic approach that focuses on increasing behaviours that are rewarding, improving mood and quality of life, and reducing behaviours that maintain or worsen depression such as passivity or avoidance and rumination. It has been shown to be as effective as CBT. This focus on behaviour rather than beliefs makes BA culturally acceptable. Another advantage of BA is that it does not require extensive training for delivery or complex skills from the therapist; thus lay counsellors can deliver this treatment. CCD, developed by WHO/UNICEF, has been shown to improve parenting and promote early child development in LMIC when integrated in existing health services. We have augmented CCD to focus particularly on parenting skills in early infant learning and attention, especially contingent responsiveness and the provision of early stimulation opportunities. The control treatment will be enhanced treatment as usual, comprising standard care with an additional in-person therapy session during pregnancy, two follow-up phone calls, and a parenting booklet in the postnatal period. The RCT will comprise 48 clusters (24 per arm) with 11 mothers (and infants) per cluster. This includes an additional 25% to take account of attrition, for a total of 528 mothers and infants. Women who meet criteria (i.e. have depression during pregnancy and are HIV-positive) will be recruited between 20 and 32 weeks of pregnancy and followed until the child is aged 2 years.
The main aims of the trial are to test whether the intervention:
1. Improves child cognitive development at 2 years of age
2. Reduces maternal depression during pregnancy and the postnatal period
3. Increases maternal adherence to ART
4. Increases rates of exclusive breastfeeding
5. Improves maternal contingent responsiveness to infant cues and quality of cognitive and emotional stimulation
6. Improves child growth, behaviour, and language development, and reduces gastro-intestinal infections

Rates of HIV among pregnant women in parts of South Africa reach 35%. With PMTCT regimes, the vast majority of children are born HIV-negative, but will grow up with at least one HIV-infected parent. Almost a quarter of HIV-positive pregnant women fulfil criteria for a depressive disorder. Perinatal depression is associated with negative effects on children's cognitive development, especially when depression is combined with social adversity (lack of support and socio-economic disadvantage). Depression interferes with parenting, particularly the parent's capacity to support the infant's development of attention and learning. Cognitive development by 2 years of age is a key predictor for school readiness and later life opportunities. We aim to conduct a cluster RCT to test the efficacy of a home-based integrated intervention to treat depression and enhance parenting, delivered during pregnancy and the postnatal period. It comprises BA to treat depression and a parenting programme (CCD) to improve maternal responsiveness. The control arm will be treatment as usual (TAU) with an additional in-person therapy session during pregnancy, two follow-up phone calls, and a parenting booklet. The RCT will comprise 48 clusters (24 per arm) with 11 mothers (and infants) per cluster totalling 528 mothers and infants. This total includes 25% to take account of attrition. Women who meet criteria (have depression during pregnancy and are HIV-positive) will be recruited between 20 and 32 weeks of pregnancy and followed until the child is aged 2 years. The main outcome is child cognitive development at 2 years using the Bayley Scales of Infant and Toddler Development. The secondary outcome is maternal depression. Tertiary outcomes include; maternal adherence to ART; exclusive breastfeeding rates; maternal contingent responsiveness to infant cues; cognitive and emotional stimulation at home; and child growth, language and behaviour problems, and gastro-intestinal infections.

1. The principal beneficiaries will be mothers with HIV and their children. An integrated intervention targeting both depression and early caregiving is likely to have a range of impacts: (a) As depression has a major impact on emotional and social functioning, effective treatment will improve the quality of life for mothers and families. (b) Treating maternal depression is necessary but not sufficient to improve child outcome. Critically, the integrated BA for depression and CCD caregiver intervention should enhance children's development, particularly cognitive functioning. This is vital given that the quality of stimulation and children's cognitive and emotional development in early years of life play a key role in their long-term development, health and human capital. For example, there is evidence from Jamaica that interventions in the first two years of life are associated with benefits in terms of adult educational achievement, psychological function and earning potential. (c) Perinatal depression is associated with poor adherence to ART and low clinic attendance. Enhancing adherence using BA, which treats depression and has been modified to include specific support for adherence, will improve mothers' health. (d) Depression is also associated with low rates of breastfeeding. Breastfeeding, especially exclusive breastfeeding, is associated with benefits for children's health and development, particularly in conditions of socio-economic disadvantage. The CCD includes support for exclusive breastfeeding. Thus our integrated treatment of depression and caregiving has the potential to improve rates of exclusive breastfeeding.
2. This trial has potential to advance our understanding of how disturbed thoughts and attentional processes disrupt parenting and child development, and the mechanisms by which interventions can mitigate these effects. Depression is characterised by repetitive intrusive negative thoughts, which lead to attentional disturbances. These disturbances in turn interfere with critical parenting capacities, especially attention to the infant and contingent responsiveness, which are key to infant cognitive and behavioural development. The trial thus targets core modifiable processes that potentially underlie the intergenerational transmission of cognitive and behavioural disturbances.
3. The study uses BA to treat depression in the context of HIV in a LMIC. BA has been shown to be as effective as CBT, the gold standard psychological treatment of depression. It does not require extensive training or complex skills from therapists, and can be delivered by lay counsellors. Further, BA fits with cultural concepts of depression in southern Africa that place environmental stressors as the cause and targets behavioural changes rather than beliefs and attitudes. It is thus relatively easy to adapt cross-culturally with potential to be widely used to treat depression in LMIC (which has not been done to date) as well as HIC by a range of health care workers.
4. There is strong evidence that perinatal mental illness has long-term economic consequences. The WHO state that depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease. Treating both the mothers' depression and enhancing child development is likely to have positive financial and health benefits, which could translate nationally if this intervention was widely used.
5. Policy makers will be able to use our model linking mental health care provided by lay counsellors with HIV treatment programmes to allow a more comprehensive holistic approach for families with HIV. We have longstanding collaborative relationships with policy makers at all levels; international, national, provincial and local.