Risk factors for genital inflammation among women at high risk of HIV in Uganda: a mixed-method, longitudinal analysis

Globally, HIV/AIDS remains a huge problem, with 37 million people living with HIV/AIDS. Two-thirds of these live in sub-Saharan Africa, where women and girls are more likely to be infected than men and boys. Recent research shows that a woman who has inflammation in her reproductive tract (vagina and cervix) is more likely to acquire HIV infection than a woman without inflammation. However, we do not yet understand the reasons why some women have this inflammation, while others do not. So far, HIV research has focused on reproductive tract physiology and immunology, but recent studies suggest that experiencing violence or heavy alcohol use may increase genital inflammation. This study will bring together these fields of research. It will ask: What are the physical causes of genital inflammation? And which behaviours put us at risk?

To answer these questions, we will conduct a study with Ugandan women at high risk of HIV infection who are already enrolled in a long-term cohort study called The Good Health for Women Project (GHWP). Approximately half of these women will have experienced physical or sexual violence in the previous six months, approximately half are problem drinkers, and approximately 45% are living with HIV. The research project will run for three years. We will enrol the first 750 HIV uninfected women who attend the clinic from October 2018 and who consent to participate in the study. Women will complete a behavioural-biological survey when they enrol in the study (baseline), and again at a follow-up visit, 6-12 months later. We will ask 25 of these women to also participate in two qualitative interviews, conducted close to baseline and 6-12 months later.

The GHWP currently asks women in the cohort to complete a questionnaire each time they visit the clinic, about their age, income, where they live, sexual behaviour, recent alcohol and drug use, and hormonal contraception use. For our study, we will ask additional questions: Have they have ever experienced physical, sexual or emotional violence and who the perpetrator was? Do they have symptoms of a mental health illness (such as depression, anxiety or PTSD)? Are they feeling suicidal? What are their vaginal washing and cleaning practices?

The research team will provide a dedicated counselling service and will offer referrals to the service at each interview. At each clinic visit, we already offer rapid HIV testing and testing for other infections for women who have symptoms. In addition, at the two study visits we will ask women to provide a tube of blood (to test for HSV-2, syphilis, and inflammation in the blood), a urine sample (to test for schistosomiasis infection) and 4 genital swabs (to test for gonorrhoea, chlamydia, trichomonas vaginalis and bacterial vaginalis). We will also ask women to wear a menstrual cup (like a diaphragm) for two minutes to collect genital fluid, which we will use to test for genital inflammation. When we have collected all the data, we will use statistical analyses to answer the following questions:
1. Which behavioural and biological factors cause genital inflammation and how do they cause it?
2. Does genital inflammation remain stable in women or does it change over time?
3. What does the violence landscape look like for women in this population? What kind of violence do they experience, how frequently and who are the perpetrators?
4. How many women have a mental health illness?
5. How many women have genital inflammation?

We will use the findings to design interventions to address women's multiple needs. These might include clinical (e.g. anti-inflammatories), behavioural (e.g. alcohol prevention) and empowerment (e.g. violence prevention) components, to complement existing HIV services.

This project will identify the behavioural and biological risk factors for genital inflammation by conducting a longitudinal, mixed-method study with women at high risk of HIV infection, bringing together the violence/mental health and molecular biology/immunology fields of research. Genital inflammation is causally associated with HIV acquisition but the cause of genital inflammation is often unclear; behavioural risk factors have not been investigated. There are physiological and immunological reasons to suggest that violence experience and heavy alcohol use could increase HIV acquisition risk by increasing genital inflammation, potentially through a mental health pathway, but there have been no epidemiological studies to investigate this. We need to know (i) what the behavioural and biological risk factors for genital inflammation are and the pathways between these risk factors; (ii) if genital inflammation changes over time, according to exposure to and treatment of these risk factors; and (iii) the prevalence, severity and frequency of women's experience of violence, mental health morbidity and genital inflammation. This proposal will bring together different fields of analysis to answer these research questions. The proposed project will conduct a longitudinal, mixed-method study with 750 women at high risk of HIV infection in Kamapala, Uganda and examine all known and potential risk factors for genital inflammation, as well as potential confounders. Longitudinal qualitative research conducted with 25 women at two time-points, will be used to inform the conceptual pathway and the epidemiological analyses. The study findings will be used to design interventions to address women's multiple needs. This may include, for example, targeted clinical (e.g. anti-inflammatories; HIV Pre-exposure Prophylaxis (PreP)), behavioural (e.g. alcohol prevention) and empowerment (e.g. violence prevention) components, to complement existing HIV services.

This project will:
1. identify the behavioural and biological risk factors for genital inflammation among a population at high risk of HIV infection;
2. establish the prevalence, severity and frequency of violence exposure, mental health morbidity and genital inflammation in this cohort;
3. explore women's perceptions and experiences of violence and mental health morbidity and how these inter-relate with alcohol and substance use and sexual risk behaviours;
4. examine the epidemiology of genital inflammation over time.

Women and girls in SSA. The population most likely to benefit from our research are women and girls at high risk of violence and HIV infection in the GHWP cohort and elsewhere in SSA and other LMIC. This will be the first study to have examined violence prevalence, severity and frequency, mental health morbidity and genital inflammation in this cohort. Research which understands the overall violence landscape that women might be encountering and how this relates to mental health and HIV risk can contribute to advocacy and the development of prevention packages and technologies which help protect women from these multiple harms. The study findings will used to inform the design of interventions to address women's multiple needs. This may include, for example, targeted clinical (e.g. anti-inflammatory, PreP), behavioural (e.g. alcohol prevention) and empowerment (e.g. violence prevention) components, to complement existing HIV services. Understanding if behavioural factors (such as violence and alcohol use) increase HIV risk by increasing genital inflammation is important for women and girls at high risk of violence and HIV elsewhere in SSA and other LMIC.

Clinical and programme staff. The findings from this study will also be useful for clinical staff working in violence, mental health and sexual health settings to understand how these factors inter-relate to increase risk of HIV infection. This could help them identify those most in need of violence, alcohol and mental health referral services and HIV prevention technologies such as HIV Pre-Exposure Prophylaxis.

HIV prevention programmers. Understanding the epidemiology of HIV transmission is crucial for designing effective programmes. If women who are at risk of violence or problem drinking are at increased risk of genital inflammation and therefore HIV infection, this research will provide evidence for the importance of addressing violence and alcohol use, and treating mental health morbidity in settings where this is not standard, such as sex worker communities in many LMIC. As HIV prevention technologies become increasingly available in the form of pre- and post-exposure prophylaxis, this research could also help identify women who would especially benefit from these drugs.
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Biotechnologists. Findings from this study will inform researchers from the HIV prevention fields to aid in the development of new technologies to prevent genital inflammation and HIV transmission, suitable for women experiencing ongoing domestic or workplace violence, problem drinking and associated mental health morbidity. This could include for example easily administered, discreet HIV prophylaxis or drugs to reduce genital inflammation.

Policy makers. Understanding the epidemiology of HIV transmission is crucial for designing effective policies. Findings will be of use to policy makers working in the violence prevention, mental health and HIV fields. These fields are often covered under different departments. Understanding how they are inter-related can help policy makers fund prevention programmes, using money from multiple sectors. For example, violence, mental health and HIV span 5 of the 17 sustainable development goals (health, women, inequality, habitation, and institutions).