Complexity of Adherence Challenges: Understanding Syndemic Factors Affecting HIV Treatment Adherence During Treatment Initiation in Cape Town, South Africa.

People living with HIV and beginning antiretroviral therapy (ART) often struggle with medication adherence and attending appointments due to multi-level challenges such as depression symptoms, substance use, stigma and disclosure, food insecurity, health system challenges, transportation challenges, and gender inequity. The SUSTAIN trial seeks to improve initiation adherence through multiple monitoring and support interventions in three clinics in Mitchells Plain township, Cape Town, South Africa. We qualitatively explored the multi-level challenges impacting adherence at the individual, interpersonal, and structural levels among 60 study participants within the first six months after initiation on ART. The in-depth interview sample was selected purposively based on participant experiences with at least one of these factors reported through a baseline survey, gender, and age. We conducted a content analysis and utilized syndemic theory to understand the synergistic effects of multiple adherence challenges. To manage their HIV diagnosis, participants described positive and negative coping mechanisms, including how substance use affected adherence particularly on big event days (e.g., birthdays, holidays, or funerals). Participants described fears of stigma motivat decisions on disclosure of their HIV status and decreased potential social support, possibly reducing motivation to adhere to ART. Gender inequity reinforced experiences with and perceptions of stigma and disclosure. Participants indicated that food insecurity resulted in feelings of shame when associated with perceived larger appetites due to ART use and with lack of employment. Participants described both positive and negative ways the health system impacted their adherence and retention in care, citing information provided by clinic staff, clinician attitudes, and clinic operations. Misunderstandings regarding the strict timing of ART dose-taking (often from lack of clear information or counselling by clinicians) meant participants often had limited competence to make decisions about their dosing schedule and how to best integrate treatment into their daily lives. Participants described a notable fear of commuting to and from clinics due to dangerous and difficult paths on which muggings occurred frequently; women were at particular risk of violence. Often, participants mentioned multiple factors simultaneously affecting adherence, with additive or synergistic effects. Syndemic factors affecting ART adherence exist across multiple levels. Enhanced adherence counseling, designed as a behavior change intervention, might help PLWH cope with individual adherence barriers and support strategizing about ways to mitigate or overcome structural barriers. Continued efforts by government and implementers to address health system, gender inequity, and security challenges could further support ART adherence.