Pilot of an Intervention for Malawian Pregnant Women with HIV to Improve Depression, Viral Suppression and Engagement of Partners in HIV Self-Testing

HIV infection remains one of the biggest killers globally. Malawi has a successful programme for prevention of mother to child transmission of HIV based on routine antenatal testing. However, 23% of women attending HIV antenatal care are lost to care at one year. Depression is an important cause of poor adherence to medication for the treatment of HIV and disengagement from HIV care. Depression is two to three times higher in people living with HIV than in the general population, and common in pregnant and post-natal women in Southern Africa. Symptoms of depression such as reduced concentration, memory, problem-solving ability and motivation, adversely affect engagement with health care and adherence to medication.

Malawi's successful programme of antenatal testing presents an opportunity to engage their male partners in HIV testing. Men are less likely than women to test for HIV and know their status. In Malawi over 45% of HIV-positive women in stable relationships have an HIV-negative partner. Without intervention, HIV-negative partners acquire HIV at up to 12% per year. Supporting women to adhere optimally to their HIV medication to ensure their virus is well controlled reduces the risk of transmission to zero. HIV self-testing, whereby an individual collects their own sample, conducts the test and interprets their result increases coverage and frequency of testing. Partner-delivered self-test kits, where woman distribute a test to their male partner, is becoming routine antenatal policy and practice in high HIV prevalence settings including Malawi.

The aim of the proposed research is to finalise and test the feasibility and acceptability of an intervention for pregnant women living with HIV and depression, to reduce depression and optimise engagement in HIV care, and to increase uptake of HIV testing, prevention and care for their male partners. This will be achieved through conducting formative work using qualitative methods to adapt an intervention to treat depression and optimise adherence to HIV medication for the Malawian antenatal context. For the male partners of HIV positive pregnant women, we will develop a mobile phone based SMS platform where the male partner will be able to receive instructions on how to use an HIV self-test kit via SMS. We will develop messages providing key information on living with HIV, or HIV prevention strategies

The study will take place in an antenatal clinic in Blantyre, Malawi. We will recruit 40 HIV positive women in the 2nd trimester of their pregnancy and randomise them to receive the intervention or enhanced usual care. The 'TENDAI Together' intervention will consist of six sessions of therapy for depression and engagement in HIV care delivered by a trained and supervised HIV Diagnostic Assistant, an assessment for an antidepressant. The women recruited to the trial will also be given a self-test kit to distribute to their male partners. Instructions on how to use the self-test kit and key information on living with HIV or with an HIV positive partner to address post-test worries will be sent via SMS.
We will collect assessment measures at baseline and at 6 month follow up. This will include outcomes to determine the feasibility of a larger trial, such as the proportion of eligible participants recruited and then retained in the study. We will assess the acceptability of the intervention by the number of sessions attended and exit interviews with the women who received the intervention. We will also determine feasibility of collecting clinical outcome measures such as HIV and depression outcomes for the women and her male partner, and clinical outcomes for the infant 2 months post-delivery. Locally validated, evidence-based measures will be used for the psychological entry criteria and outcome data.

The aim of the proposed study is to pilot a combination of evidence-based interventions aimed at Malawian pregnant women living with HIV, and their male partners. The long-term goal is to move towards joint management of mental health and strengthening of the HIV care cascade for HIV-positive women. The study will take place in Bangwe antenatal clinic, Blantyre, which registers 145 new ANC patients per week with an HIV prevalence of 15%.

Aim 1: Finalise TENDAI-Together, a task-shifted intervention originally developed and successfully piloted in Zimbabwe, to treat depression and optimise adherence to antiretroviral therapy (ART) for antenatal women living with HIV in Malawi. This will include formative work, comprising focus group discussions and in-depth interviews with 30 key informants. Key aims are to ensure the relevance of the checklist of barriers to ART adherence for the Malawian antenatal context, and to gather views and approaches about involve the woman's partner, or an alternative significant other, in two of the sessions.

Aim 2: Finalise an SMS-based intervention to inform the correct use of HIV self-test kits and provide "U = U" "Undetectable = Untransmittable" HIV education for male partners of antenatal women living with HIV.

Aim 3: Integrate TENDAI-Together with the SMS-based HIV-self testing intervention and carry out a Phase 2 exploratory trial to test feasibility and acceptability of the integrated intervention. We will recruit 40 women in the 2nd trimester and randomise them, with informed consent, 3:1 to the active intervention (n=30) or enhanced usual care (n=10). We will test the feasibility and acceptability of providing the TENDAI Together intervention with the self-testing SMS platform to allow the woman access to simple care for depression, optimise her engagement in HIV care, and engage her partner with HIVST and subsequent HIV care and prevention steps.

The proposed research has the potential to generate impact across six areas.
1. Institutional research capacity: The proposed project will build new, synergistic institutional links between the Centre for Global Mental Health (CGMH) and the Malawi-Liverpool-Wellcome Trust (MLW) Clinical Research Programme. CGMH will learn from MLW expertise on HIV testing, while MLW will benefit from CGMH knowledge of mental health issues in HIV. This innovative, equitable partnership has strong potential for future scale up, drawing other regional institutions into the network.
2. Individual researcher capacity: Two early-career Malawian scientists in the project team will be supported in their career paths towards becoming independent researchers. The proposed project will strengthen their leadership capacity under the wider project team's mentorship. It will contribute to the sustainability of their current research while paving the way for them to become PIs on related future grants.
3. Impact on global mental health agenda for treatment and research: The proposed intervention combines problem-solving therapy for depression with an anti-retroviral therapy (ART) adherence intervention, including joint sessions for couples. If this intervention is shown to be effective, the results could provide compelling evidence to expand the intervention for other low-income countries, as well as indicating further, new areas for research at the intersection of HIV and mental health.
4. Impact on health systems: There is strong potential for impact on policy and health systems capacity within Malawi. At an individual clinic level, staff will be trained in WHO MHGap, increasing and sustaining local capacity to diagnose and treat common mental disorders. One Malawian co-investigator on the proposal also works in a senior clinical services role at the Malawian Ministry of Health, offering a key path to engage government stakeholders and translate research findings into local health system implementation.
5. Impact on antenatal women, their male partners and their new-born infants: The proposed research may benefit HIV-positive pregnant women through treatment of depression and helping them problem-solve barriers to ART adherence, reducing the risk of mother-to-child-transmission. The intervention will also support women to engage their male partners in HIV testing. Men living with HIV may also benefit through increased HIV self-testing, education and linkage to care. These outcomes are vital to prevent the development of Acquired Immunodeficiency Syndrome (AIDS) and improve quality of life. New-born infants may also benefit through the treatment of maternal depression, known to impact infant outcomes.
6. Ensuring recent developments in HIV research are disseminated to communities most in need: The proposed project includes an educational HIV component to disseminate accurate and meaningful information about sexual and reproductive health. This will reduce individuals' shame and fear of HIV transmission to partners by providing evidence-based knowledge, particularly the reassurance that if a person's sexual partner has an undetectable viral load, the seronegative partner will remain uninfected.