Pathways to care with HIV-associated cryptococcal meningitis in Botswana and Uganda: Findings from a qualitative methods study.

HIV-associated cryptococcal meningitis remains a key driver of AIDS-related mortality. Mortality is twice as high in those who present later to care and with severe symptoms such as confusion. We embedded a qualitative methods study within a randomised controlled trial in Gaborone, Botswana and Kampala, Uganda with the aim of understanding pathways to care. We conducted in-depth interviews with trial participants and surrogate decision makers and analysed data thematically. Between January 2020 and June 2021 we interviewed 58 individuals. Pathways to care were prolonged because headaches were disregarded by participants and healthcare workers as a common occurrence with a broad differential diagnosis of predominantly benign aetiologies. There was also a lack of awareness of cryptococcal meningitis, and it was often after HIV was diagnosed or disclosed that the pathway accelerated, resulting in hospital admission. We outline key recommendations to reduce mortality and argue for the integration of social and behavioural interventions within differentiated service delivery models for advanced HIV disease.

Contextual, structural, and mental health experiences of children of women engaged in high-risk sexual behaviour in Kampala: a mixed method study.

Children born to women who sell sex for money or commodities may face economic and social insecurity because of their mother's work, particularly in settings where sex work is illegal. From October 2020 to May 2021, we conducted a study with 60 children aged 12-24 years, born to sex workers in Kampala, Uganda. The children took part in 60 semi-structured interviews, 20 life history interviews, and 4 focus group discussions, which were used to explore their social, economic, and mental health experiences and investigate their vulnerabilities and resilience. Quantitative data were collected using REDcap, and descriptive analysis was done using Stata 14. Qualitative data were collected using semi-structured topic guides, and data analysed thematically. We explored findings in relation to a wellbeing framework. The findings showed that children experienced contextual and structural hardships, including incomplete and irregular schooling, a lack of privacy at home, food insecurity, and physical and psychological violence from relatives and sometimes from their mothers. Some children reported mental wellbeing struggles with hopelessness, nervousness, and sadness. Alcohol and drug use were common in most families. Community social network support systems, including neighbours and grandparents, were important; most children had absentee fathers. Some children suspected or knew how their mother earned her income. Resilience for most children was tagged to support from close networks and financial support from the government and civil society. Children of sex workers in Kampala experience structural, contextual, and mental health challenges but have a positive attitude towards the future. It is important to strengthen community support systems for these children and those living in similar circumstances in low- and middle-income countries.

The acceptability of the AMBITION-cm treatment regimen for HIV-associated cryptococcal meningitis: Findings from a qualitative methods study of participants and researchers in Botswana and Uganda.

BACKGROUND: The AMBITION-cm trial for HIV-associated cryptococcal meningitis demonstrated that a single, high-dose of liposomal amphotericin (AmBisome) plus 14-days of oral flucytosine and fluconazole was non-inferior in terms of all-cause mortality to 7-days of amphotericin B deoxycholate and flucytosine followed by 7-days of fluconazole (Control). The AmBisome regimen was associated with fewer adverse events. We explored the acceptability of the AmBisome regimen from the perspective of participants and providers. METHODS: We embedded a qualitative methods study within the AMBITION-cm sites in Botswana and Uganda. We conducted in-depth interviews with trial participants, surrogate decision makers, and researchers and combined these with direct observations. Interviews were transcribed, translated, and analysed thematically. RESULTS: We interviewed 38 trial participants, 20 surrogate decision makers, and 31 researchers. Participant understanding of the trial was limited; however, there was a preference for the AmBisome regimen due to the single intravenous dose and fewer side effects. More time was required to prepare the single AmBisome dose but this was felt to be acceptable given subsequent reductions in workload. The AmBisome regimen was reported to be associated with fewer episodes of rigors and thrombophlebitis and a reduction in the number of intravenous cannulae required. Less intensive monitoring and management was required for participants in the AmBisome arm. CONCLUSIONS: The AmBisome regimen was highly acceptable, being simpler to administer despite the initial time investment required. The regimen was well tolerated and associated with less toxicity and resultant management. Widespread implementation would reduce the clinical workload of healthcare workers caring for patients with HIV-associated cryptococcal meningitis.

Decision making in a clinical trial for a life-threatening illness: Therapeutic expectation, not misconception.

Potential participants for clinical trials which aim to define treatments for life-threatening conditions are often extremely unwell. When exploring why individuals participate in clinical trials one common observation is a misplaced expectation of personal benefit - a therapeutic misconception. The care offered in some clinical trials is of a higher standard than is routinely available and this has led to criticism around the freedom of choice to enrol - structural coercion. We embedded an ethnographic study within a randomised controlled trial for HIV-associated cryptococcal meningitis in Gaborone, Botswana and Kampala, Uganda. We aimed to gain an understanding of decision-making around the trial and how this was impacted by the study design and broader social context. We conducted in-depth interviews with trial participants, surrogate decision makers and researchers, combined these with direct observations and analysed data using thematic analysis. Between January 2020 and June 2021 we interviewed 89 individuals. We found previous exposure to and awareness of clinical research was limited, as was understanding of the trial objectives and design. Through observations and engagement with healthcare facilities decision-makers were able to identify the trial as providing the best possible chance of survival. Hesitation and reluctance were mostly due to fear of lumbar punctures which was sometimes based on rumours but often based on tragic personal experience. Despite fear, and sometimes conviction that they would die, individuals agreed to consent, often against the wishes of family members. Reassurance and confidence came from trust in routine care staff and the research team but also from fellow participants and their surrogates. We argue that participants made informed decisions based on a therapeutic expectation from the trial and that rather than being the result of structural coercion this was an informed and voluntary choice.