‘We have goals but [it is difficult]’. Barriers to antiretroviral therapy adherence among women using alcohol and other drugs living with HIV in South Africa

Abstract Background Women living with HIV who misuse alcohol and live in economically disadvantaged settings in South Africa experience a multitude of contextual barriers as they navigate the HIV care continuum. The Women's Health CoOp (WHC), a brief, woman‐focused, behavioural, evidence‐based intervention, has been shown to be effective in reducing heavy drinking and improving HIV‐related outcomes among this key population. However, these women face other broader socioecological barriers to antiretroviral therapy (ART) adherence. Methods The WHC was implemented in a modified, stepped‐wedge implementation science trial in public health clinics and substance use treatment programmes in Cape Town, South Africa. A qualitative substudy was conducted to explore barriers to HIV treatment adherence among women enrolled in this trial. Eight focus group discussions were conducted with 69 participants 6 months after completion of the WHC workshops. Focus groups were audio‐recorded (with consent), transcribed verbatim and analysed using a thematic approach. Results The mean age of the participants was 33 years and the mean self‐reported number of drinks per day was 13. The main contextual factors influencing participants’ ART adherence were intrapersonal‐level factors (substance use, financial constraints, food insecurity; community‐level factors (anticipated and enacted stigma, community violence) and institutional‐level factors (patient–provider relationships, health facility barriers, environmental stigma). Conclusion Comprehensive interventions addressing the contextual barriers and unique challenges faced by women who misuse alcohol in low‐resource settings that intersect with HIV treatment nonadherence should be implemented in tandem with successful biobehavioural HIV interventions for long‐term effectiveness and sustainability. Patient or Public Contribution Our South African community collaborative board has been involved throughout this study; participants and clinic staff voices have been essential in our interpretation of these findings.


| INTRODUCTION
In 2016, South Africa adopted the World Health Organization's Universal Test and Treat policy, making all people living with HIV eligible for antiretroviral therapy (ART) at diagnosis. 1 However, despite successful scaleup of HIV testing and treatment, suboptimal retention in care and poor viral suppression through nonadherence to ART continues to be a major challenge. 1 Women aged 25-49, experience a disproportionate burden of HIV prevalence (33.3%) as compared with men (19.4%); however, only 69%-75% of women on ART are virally suppressed, which is short of the UNAIDS 95-95-95 targets by 2030. 2,3 Various intrapersonal-level factors have been identified to help understand the causes of HIV treatment nonadherence and barriers that women living with HIV face as they try to remain in HIV care. One barrier of concern is substance use, which has been associated with reduced HIV adherence and HIV disease progression. [4][5][6] Estimates suggest that in 2012, approximately 2900 HIV-related deaths and 11,400 years lived with a disability among women living with HIV in South Africa were attributable to substance use and its effect on nonadherence to ART. 7 Other contextual barriers to ART adherence among women living with HIV include gender-based violence and a history of social, legal, and economic disempowerment and gender inequality that impact women's ability to engage in care. [8][9][10][11] Consequently, the intersecting syndemic of HIV, substance use and gender inequality necessitates multifaceted interventions to mitigate the risk of nonadherence and poor health outcomes among women on the individual level. 10,12,13 The Women's Health CoOp (WHC), a brief, woman-focused, behavioural, evidence-based intervention, grounded in empowerment and feminist theory is one such intervention. The WHC uses a skill-building approach to reduce varying risk behaviours, including alcohol and other drug (AOD) use, sexual risk behaviour, gender-based violence and biomedical knowledge of HIV and sexually transmitted infections (STIs).
Based on an intervention developed in the US for African American women who use substances and adapted to various key populations and settings, the WHC has been found to be efficacious in reducing HIV risk for women who use AODs. 9,14,15 In a recent cluster-randomized trial of the WHC with biobehavioural approaches, women in the WHC arm had greater reductions in heavy drinking and other risk-related outcomes, and greater reductions in HIV viral load were observed for a subsample of WHC participants living with HIV. 14 However, addressing the nexus of substance use, gender inequality and HIV is only part of a larger socioecological framework.
Other factors that converge with substance use, such as food insecurity and financial constraints, have been found to be strong predictors of suboptimal HIV treatment outcomes. [16][17][18] Additionally, stigma, access to healthcare and institutional and health-system factors may undermine the sustainability of successful behaviour change evidence-based interventions focused on ART adherence. [19][20][21] The present study explored how multiple factors of the socioecological framework impact HIV treatment and adherence among women living with HIV who use AODs.

| METHODS
This qualitative study was part of a larger implementation science research study to evaluate the effectiveness of the WHC for women living with HIV and who reported AOD use in Cape Town, South Africa. 10,22 The WHC intervention included two interactive group workshops that combined risk-reduction information about AODs, ART initiation, understanding the importance of ART adherence and STIs. Workshops also included material on behavioural skills training, such as practicing male and female condom use, and reducing sexual risk through negotiation and communication skills. The WHC was implemented in four public healthcare clinics with HIV/antenatal clinics and four substance use treatment clinics (hereafter known as Matrix programs), all located in economically underserved communities in Cape Town, from 2015 to 2018 using a modified steppedwedge design of four cycles. 10,22 Each implementation cycle lasted 6 months. Focus group discussions were conducted with study participants approximately 6 months after women had attended the WHC workshops to assess the barriers to ART adherence from a socioecological framework.

| Recruitment and data collection
The 480 women who participated in the WHC implementation science trial met the following eligibility criteria: (1) being between the ages of 18 and 45 years; (2) self-reporting the use of at least one drug, which could include alcohol, at least weekly during the previous 3 months; (3) reporting unprotected sex (sex without a condom) with a male partner in the past 6 months; (4) having a positive verifiable HIV test result; (5) reporting the intention to remain in the study area for at least the next 6 months; (6) providing contact information and (7) being willing to participate in AOD use screening. 10 An additional NDIRANGU ET AL. | 755 criterion for participation in the focus group discussions was the completion of both WHC intervention workshops, which 84% of trial participants met. Eligible participants from each of the eight study clinics in which they were enrolled were randomly within each cycle selected and contacted for the follow-up focus group discussions. A total of 110 women were contacted from across the cycles, with 69 attending the focus group discussion. We conducted eight focus group discussions-one focus group discussion from each of the eight clinics consisting of between 5 and 11 participants in each group (median = 9). Each focus group lasted approximately 1 hour.
All focus group discussions were conducted in a private room at the research study site. Participants provided written and signed informed consent before each focus group. Focus group discussions were primarily

| Analysis
All focus group discussions were audio-recorded (with consent) and transcribed by trained research staff. A second staff transcriber reviewed recordings and transcripts to ensure completeness. We used an applied thematic analysis approach to guide analysis, 23 we began by conducting a deep reading of the transcripts to familiarize ourselves with the data and wrote memos to identify recurring concepts. We developed an initial codebook using a priori codes based on the Focus Group Discussion guide and common concepts observed during transcript review. Interrater reliability was assessed using Cohen's kappa (κ). 24 One analyst applied codes to the transcripts and the other analyst coded the same transcript blinded to the first analyst's codes. Analysts then met several times to compare coding, refine code definitions and resolve disagreements. On reaching a high agreement (κ = 0.81), the remaining transcripts were double coded by the two analysts. Coded data were summarized in visual matrices to identify themes within and across focus group discussions.
Dedoose software (v.8.0.42) was used for the management, coding and analysis of the data.

| Ethics
This study protocol was approved by the South African Medical Association Research Ethics Committee (SAMAREC); City of Cape Town: City Health Research Committee, and the RTI International Committee for the Protection of Human Subjects.

| RESULTS
The mean age of the participants in this substudy was 33 years (see Table 1). A majority of the women were Black African (94%) and 84% reported having a male partner and an average of two children. Although over two-thirds of the participants had completed Grade 9 and above, only 5% had completed high school (Grade 12). Approximately 45% of the participants did not have running water in their homes. The mean self-reported number of drinks per day was 13. The main contextual factors influencing participants' ART suboptimal adherence found in the analysis are presented under three components of the socioecological framework: intrapersonal level, community level and institutional level ( Figure 1).

Living condition
No running water inside the house 45% House whose walls is made of metallic sheet 45% Gone to bed hungry at least once in the past year 34%

Substance use
Mean drinks per day in the last 30 days 13 (SD = 7.0) that because both ART and alcohol are drugs, mixing them would lead to adverse health outcomes. Toxicity beliefs often stemmed from clinic staff who emphasized alcohol abstinence but concurrently provided conflicting messages on the safety of taking ART while using AODs.
They are confusing us at the clinic because some are saying we must not take our medication if we will be drinking alcohol on that day, then some will say take them before drinking alcohol and wait at least 4 to 5 hours before you start drinking. (HIV/antenatal clinic) These conflicting messages resulted in women not taking their ART over the weekends when their drinking levels were higher.

| Financial constraints
Unemployment and lack of income were reported as a significant challenge to ART adherence. Some participants felt they were not financially stable enough to responsibly commit to taking daily medication and were dependant on their male partners or family for assistance. For some participants who qualified for government financial assistance programmes through disability grants-a lifeline for ART patients that enables them to meet healthcare-related costs, including transportation, food and treatment access-this assistance was short-lived as they would lose their grant once their health had rebounded.
And the treatment that we take makes us very hungry and we cannot take treatment on an empty stomach.
They refuses to register us for the grants, they will just look at us and assume that we OK or doing good, and we struggling not working. For some participants, this clinic environment led them to seek care in clinics that were outside of their communities.

| DISCUSSION
The overarching goal of the evidence-based WHC is to empower women to take better care of their health by reducing alcohol use and adhering to ART. However, although the WHC has been shown to be effective, 22 there were, in a broader context, barriers to ART adherence and retention in care among women who had completed this intervention. Emerging themes of this substudy revealed these interwoven socioecological factors.
We found that at the individual level, AOD use was the most salient reason for ART interruption. Previous studies have found that individuals who used AODs were more likely to have low adherence 6 months following ART initiation 25 where the comorbidity of substance use disorders reduces self-efficacy and self-care, leading people living with HIV to disengage in healthcare. 26 Additionally, interactive toxicity concerns between substance use and ART medication have been shown to adversely impact ART adherence. 27,28 These toxicity concerns often lead to intentional nonadherence or treatment interruptions where people living with HIV stop taking their ART during certain periods when they are using AODs, compromising optimal ART adherence and increasing the likelihood of NDIRANGU ET AL.
| 759 medication drug resistance. Healthcare providers often discourage substance use while on ART, stressing that substance use undermines the effect of ART. 29 However, research suggests that the pharmacological effectiveness of ART is not diminished by substance use. 30 Consequently, educating providers on the minimal impact of substance use on ART efficacy may decrease ART toxicity beliefs and increase ART adherence among those who use substances. Providing further resources for substance use counselling and treatment also may be more effective in increasing ART adherence than exclusively focusing on abstinence. 22,31,32 It also is well documented that the HIV disease burden among those of lower socioeconomic status is disproportionally high. 33,34 These findings indicate that lack of financial resources caused by