Stakeholder efforts to mitigate antiretroviral therapy interruption among people living with HIV during the COVID‐19 pandemic in China: a qualitative study

Abstract Introduction The COVID‐19 pandemic has affected antiretroviral therapy (ART) continuity among people living with HIV (PLHIV) worldwide. We conducted a qualitative study to explore barriers to ART maintenance and solutions to ART interruption when stringent COVID‐19 control measures were implemented in China, from the perspective of PLHIV and relevant key stakeholders. Methods Between 11 February and 15 February 2020, we interviewed PLHIV, community‐based organization (CBO) workers, staff from centres for disease control and prevention (CDC) at various levels whose work is relevant to HIV care (CDC staff), HIV doctors and nurses and drug vendors from various regions in China. Semi‐structured interviews were conducted using a messaging and social media app. Challenges and responses relevant to ART continuity during the COVID‐19 pandemic were discussed. Themes were identified by transcript coding and mindmaps. Results Sixty‐four stakeholders were recruited, including 16 PLHIV, 17 CBO workers, 15 CDC staff, 14 HIV doctors and nurses and two drug vendors. Many CDC staff, HIV doctors and nurses responsible for ART delivery and HIV care were shifted to COVID‐19 response efforts. Barriers to ART maintenance were (a) travel restrictions, (b) inadequate communication and bureaucratic obstacles, (c) shortage in personnel, (d) privacy concerns, and (e) insufficient ART reserve. CBO helped PLHIV maintain access to ART through five solutions identified from thematic analysis: (a) coordination to refill ART from local CDC clinics or hospitals, (b) delivery of ART by mail, (c) privacy protection measures, (d) mental health counselling, and (e) providing connections to alternative sources of ART. Drug vendors contributed to ART maintenance by selling out‐of‐pocket ART. Conclusions Social and institutional disruption from COVID‐19 contributed to increased risk of ART interruption among PLHIV in China. Collaboration among key stakeholders was needed to maintain access to ART, with CBO playing an important role. Other countries facing ART interruption during current or future public health emergencies may learn from the solutions employed in China.


I N T R O D U C T I O N
Access and adherence to antiretroviral therapy (ART) is needed for people living with HIV (PLHIV) to achieve viral suppression, reduce HIV-associated morbidity and mortality, and prevent HIV transmission [1,2]. Over the last two decades, China has made large strides in expanding access to ART. In 2003 China adopted the 'Four-Free One-Care' policy, under which all PLHIV in the country are able to access free ART from designated healthcare facilities, including hospitals specialized in infectious diseases and clinics affiliated to centres for disease control and prevention (CDC) at various levels [3]. Thanks to this policy, the coverage of free ART among diagnosed PLHIV in China increased from 64.2% in 2006 to 86.6% in 2019 [4]. PLHIV who do not receive government-subsidized ART often purchase medications out-of-pocket at pharmacies or from drug vendors via the internet [5].
HIV-themed community-based organizations (CBO) in China provide health education, counselling, advocacy and treatment monitoring services for PLHIV and people at risk of HIV infection, including men who have sex with men (MSM), sex workers, and people who inject drugs. From 1988 to 2009, the number of CBO working in the field of HIV prevention and care in China increased from zero to over 400, with one-third and one-fourth of these organizations focusing on the needs of MSM and PLHIV, respectively [6]. The number of CBO dedicated to HIV prevention and care in China exceeded 700 in 2019 [7]. CBO play an important role in promoting and connecting PLHIV and at-risk groups to free health services, including HIV testing and ART [8].
To control the spread of COVID-19, China introduced a series of public health responses. On 23 January 2020, a citywide lockdown was imposed in Wuhan. On 26 January 2020, COVID-19 control measures were imposed nationwide [9]. Travel restrictions and suspension of postal services were implemented across all 31 provinces and administrative regions in mainland China. Citywide lockdowns and enforced home quarantine were implemented in areas with confirmed COVID-19 cases. While China achieved significant success in containing COVID-19, these measures also impeded the HIV care services. To maintain access to ART, the National Center for AIDS/STD Control and Prevention (NCAIDS) published updated policy guidelines on 26 January 2020, which allowed PLHIV to refill one-month of ART from any designated hospital or clinic [10]. Despite these efforts, more than one-third of PLHIV in China reported risk of ART interruption at the early stage of the COVID-19 outbreak [11]. PLHIV residing in areas that implemented citywide lockdowns and travel restrictions were at higher risk of ART interruption. Themes and theory generated in qualitative study can explain and predict various outcomes within diverse contexts of the healthcare system [12,13]. However, to date, there is still a lack of qualitative information on ART maintenance in the context of COVID-19. To better characterize barriers to ART maintenance and solutions to ART interruption in China during the implementation of stringent COVID-19 control measures, we conducted a qualitative study among PLHIV and relevant key stakeholders.

Data collection
Each interview was conducted online via WeChat, a multipurpose messaging and social media application (Tencent, Shenzhen  Figure S1-S5 in Additional file 1 (Supporting Materials). Data collection was stopped after thematic saturation was reached (i.e., when new data produced little or no new information to address the study question).

Data analysis
Voice calls were audio recorded, transcribed in Mandarin and then encoded using NVivo 11.0 (QSR International, Melbourne, Australia). Thematic analysis was used to analyse and explore potential themes. We followed an analytical process recommended by previous studies [14][15][16]: (a) familiarizing yourself with your data, (b) generating initial codes, (c) searching for themes, (d) reviewing themes, (e) defining and naming themes, and (f) producing the report. We formed detailed codebooks for each of the five stakeholder groups. An inductive approach was used to develop datadriven themes. We applied two prespecified themes: (a) barriers to ART maintenance, and (b) solutions to ART interruption. We used a mindmap (see Figure S1 in Additional file 2) [17] to summarize our prespecified themes before beginning thematic analysis. After discussion, we found CBO participated in all identified aspects of barriers to ART maintenance and solutions to ART interruption. Consequently, we refined and renamed themes from the perspective of CBO. Consensus on identified themes was reached after discussion. Descriptive statistics were used to summarize demographic characteristics. Informative quotations from participants were translated to English and checked for accuracy. A relationship framework among different stakeholders was generated to visually summarize our results ( Figure 1) [15]. After conducting inductive analysis in a data-driven way, we performed higher order analysis based on the findings, aiming to raise the generated themes to a conceptually theoretical level. We applied the theoretical framework based on the Andersen's Behavioral Model of Health Service Use (ABM) [18], which is available to understand how patient and environmental factors impact health behaviours and outcomes, and has been applied in other qualitative studies about barriers and facilitators of health programmes [19]. We combined our results presented in Figure 1 with the ABM, to further explore how patients and environmental factors affect ART maintenance.

Ethical statement
This study was approved by the Sun Yat-sen University Ethics Committee (SYSU-SPH2020008). Informed consent was obtained from each participant prior to interview. Median age of PLHIV was 29 years (interquartile range (IQR): 24 to 37 years) and median duration since ART initiation was 2.5 years (IQR: 0.5 to 3.5 years). All CBO workers were men, more than 50% of whom had worked in HIV care services for over 10 years (IQR: six to twelve years) ( Table 1). Among the 17 CBO workers we interviewed, 11 CBO provided services to PLHIV exclusively and six provided services to both PLHIV and MSM.

Barriers to ART maintenance
Despite NCAIDS policy guidelines designed to facilitate ART maintenance during the COVID-19 pandemic, travel restrictions continued to have an impact on obtaining ART. Refilling ART prescriptions was also impeded by inadequate communication between PLHIV and HIV care facilities as well as cumbersome bureaucratic processes. CDC staff, HIV doctors and nurses struggled to balance their time between ART delivery and COVID-19 response efforts. Some HIV doctors and nurses were redeployed to respond to COVID-19 fulltime, leaving no time for ART delivery. For PLHIV, privacy and unwanted disclosure of HIV status was a salient concern when obtaining ART, particularly among those who were unexpectedly forced to home quarantine with family members. Insufficient ART reserve in CDC clinics and hospitals, and among drug vendors, was a barrier to ART maintenance. Detailed quotations are shown in Table 2.

CBO solutions to ART interruption
CBO played an important role in ART maintenance during the COVID-19 pandemic. Specifically, CBO provided PLHIV with guidance and coordination to refill ART, mail and home Abbreviations: ART, antiretroviral therapy; CBO, community-based organization; CDC, centres for disease control and prevention; IQR, interquartile range; PLHIV, people living with HIV. a One missing b One missing.
delivery services, assistance in privacy protection, mental health counselling and connections to alternative sources of ART. Furthermore, CBO assisted CDC clinics and hospitals by coordinating ART delivery to PLHIV.

Coordination to refill ART from local CDC clinics or hospitals
While the NCAIDS directive allowed PLHIV to refill ART from any HIV care facility in China, the specific process was initially unclear to both PLHIV and healthcare providers. CBO played an intermediary role by guiding PLHIV in their attempts to refill ART. For PLHIV who did not know how to contact CDC clinics or hospitals, CBO contributed by finding and providing contact information.
[PLHIV] needed their designated hospital to provide a work letter, but many PLHIV do not know the phone number of their designated hospital. I found the number for them, then they could contact their designated hospitals, and a nurse would provide them with the needed documentation. (CBO, No. 13, 56-year-old man, Tianjin)

Delivery of ART by mail
In-person ART collection was limited by travel restrictions during the COVID-19 pandemic, so mail delivery became a major source for ART refills for PLHIV in China. Because CDC staff, HIV doctors and nurses were overwhelmed by COVID-19 work, CBO workers became responsible for obtaining ART and mailing it to PLHIV. Some hospitals did not offer ART delivery through mail. When PLHIV provided their information, we could go to the hospital to collect their ART, and then assisted the hospital in mailing ART to them. (CBO, No. 7, 38-yearold man, Nanning) Although public transportation was closed or suspended in many locations, hospitals still tried to deliver ART to PLHIV with the help of CBO.
[We] tried our best to send [ART] to PLHIV through CBO. For example, if ground mail wasn't possible, we'd

Privacy protection measures
Privacy was a major concern surrounding ART delivery. PLHIV in China often do not disclose their HIV status to family members. Due to home quarantine, many PLHIV were confined at home with family members who did not know their HIV status. Stakeholders, including CBO workers, tried to protect the privacy of PLHIV by removing labelling from ART, mailing medications anonymously and mailing from home rather than workplace addresses. Most [PLHIV] asked us to remove all packaging from the [ART], including labels. We are quite experienced at this since clients have often asked us to help remove medication labelling in the past. In this way even if family members find a bottle of medication, there is nothing for them to read. Some asked us to write a nickname rather than their real name on the delivery packaging because they were very worried that a neighbour might see their name and say something to their family members. Others asked us to specify on the delivery packaging that the included item was a 'daily necessity' rather than medication. (CBO, No. 15, 38-year-old man, Qingdao) Mailing ART from a worker's home address rather than the CBO's workplace address helped PLHIV protect their HIV status from unwanted disclosure.
We did not mail ART from our workplace, because it is inappropriate to write the name of our organization on the delivery packaging. Instead, we mailed it from our home address. (CBO, No. 1, 31-year-old man, Shenzhen)

Mental health counselling
At the time interviews were conducted, PLHIV had been quarantined at home for more than half a month. In addition to fears about ART interruption, many also worried their HIV status may place them at higher risk of critical illness from COVID-19. PLHIV frequently mentioned secretly taking ART at home and fears of inadvertently revealing their HIV status to family members were sources of mental stress. To respond to increasing rates of anxiety, depression and insomnia among PLHIV, CBO provided mental health counselling to PLHIV through smartphone-based instant messaging applications. Some (PLHIV) were anxious and irritable. We would use periods of free time, like after 8 PM or 9 PM, to chat with them via WeChat or QQ, and in the process provide some mental health counselling. (CBO, No. 12, 54year-old man, Cangzhou) Some PLHIV did not seek mental health counselling even if they had underlying mental illness. CBO took the initiative to support this vulnerable group.
Of course, we would also actively find PLHIV who were prone to depression. I would ask how they were doing at home and give them some recommendations, such as reading, listening to music and exercise, and through these activities relieve the mental pressure of home quarantine. (

Providing connections to alternative sources of ART
While CBO are typically not responsible for ART delivery in China, some do have small reserves of ART. During the COVID-19 pandemic, these ART reserves were used to address ART interruption. ART reserves were typically collected through donations from PLHIV or larger CBO.
ART reserves at CBO had been collected in normal times. For instance, when patients changed their ART prescription, they may have a half bottle of ART left, which would be donated for others to use in an emergency. CBO gradually accumulated ART over time, which were all free medications. Other CBO might also have extra ART that they could donate to us. (CBO, No. 12, 54-year-old man, Cangzhou) As the pandemic continued, CBO ran out of free ART to distribute. Buying ART out-of-pocket became an option for some PLHIV to avoid ART interruption.
We also suggested some PLHIV purchase ART out-ofpocket for a short period if they could not get free ART. We would help them pick up ART after purchasing it and mail it to them. But in the end this solution was only appropriate for a small number of people because most still need free medication. (CBO, No. 2, 35-yearold man, Hefei)

Other solutions
Drug vendors also mitigated the risk of ART interruption by selling ART to PLHIV who could afford out-of-pocket ART. ART like Kocitaf (combination of dolutegravir, emtricitabine and tenofovir) have few side effects and are well tolerated, so it is relatively safe to replace [free ART] temporarily. (drug vendor, No. 2, man, Beijing) Overall, stakeholders made significant contributions to efforts to avoid interruption in ART during the COVID-19 pandemic. CBO acted as a bridge between PLHIV, CDC clinics and hospitals. Figure 1 depicts the relationship among stakeholders. Factors of patient and environment, both contributed to barriers to ART maintenance and solutions to ART interruption. And detailed analysis and description grouped by ABM domains are given in Table 3.

D I S C U S S I O N
This is one of the first qualitative studies of multiple stakeholders to describe barriers to ART maintenance and solutions to ART interruption during the COVID-19 pandemic in China. Travel restrictions, inadequate communication and bureaucratic obstacles between stakeholders, shortage in personnel, privacy concerns and insufficient ART reserve were barriers to ART maintenance. CBO took on an important role in responding to these barriers, acting as a bridge between PLHIV and ART providers. CBO workers helped PLHIV navigate bureaucratic requirements to refill ART from local CDC clinics and hospitals. They also took on new responsibilities during the COVID-19 pandemic, delivering ART to PLHIV through the mail or in person, helping PLHIV protect their HIV status from unwanted disclosure and providing mental health counselling through social media applications. We found that travel restrictions and home quarantine measures made it difficult for some PLHIV in China to refill ART from the designated CDC clinics or hospitals where they typically receive HIV care. This finding is consistent with large-scale nationwide surveys of PLHIV in China where risk of ART interruption was correlated with travel away from home and living in areas that implemented citywide lockdowns during the COVID-19 pandemic [11]. Despite nationwide policy reform efforts by the Chinese central government, PLHIV found local CDC clinics and hospitals to be slow and inconsistent in operationalizing policies designed to minimize the impact of COVID-19 control measures on HIV care. CBO adopted new roles and novel measures to address these barriers. CBO workers learned how to refill ART through any local CDC clinic or hospital and then guided PLHIV through bureaucratic obstacles. Peer navigation has been identified as an important tool to optimize the HIV care continuum [20] and became particularly important during the COVID-19 pandemic. CBO coordination of ART mail and home delivery services also helped PLHIV in China avoid ART interruption when faced with restrictions on mobility. Similar strategies have been employed in other low-and middleincome countries (LMICs) responding to disruptions in HIV care from COVID-19, including the Philippines and Pakistan [21][22][23]. Prior to the COVID-19 pandemic, home delivery of ART by CBO was shown to improve early ART adherence and outcomes [24], and during the COVID-19 pandemic this strategy has been identified as key to maintaining ART access in remote rural locations without reliable access to postal services [23,25,26]. Many regions including America, Europe, Asia and Africa benefited from CBO contributions to ART delivery during the COVID-19 pandemic [25, [27][28][29][30]. The role of CBO in ART provision could be similarly expanded in other low-and middle-income countries to optimize ART maintenance. Efforts to maintain ART should take into consideration variation and complexity among different settings and apply suitable solutions in the country.
HIV-related stigma and fear of disclosure of HIV status were common themes identified in our interviews of PLHIV in China. Stigma has been identified as a significant barrier to ART adherence in multiple contexts, and recent research has shown home quarantine during the COVID-19 pandemic can exacerbate its influence [1,31]. Many PLHIV in this study were reluctant to take ART while quarantined at home or apply for legal authorization to leave home to refill ART for fear that family members, partners, friends or neighbours would discover their HIV status. Delivery of ART by mail was preferred by some PLHIV because it allowed for refills to be obtained discretely. However, unwanted disclosure of HIV status to household members through labelling on packaging remained a concern identified in our interviews and in previous research of PLHIV in China [31]. CBO workers addressed this concern by removing identifying labels from both packaging and medication bottles before delivering ART to PLHIV in the mail or in person. CBO also provided a platform for PLHIV in China to voice their anxiety about privacy during home quarantine and solicit support from peers. Previous studies in other settings have highlighted the importance of addressing stigma among PLHIV through listening, counselling and communication when providing HIV care and ART [1,32,33]. Our findings also reflect challenges of stigma in maintaining ART and underscore the importance of sustained efforts to destigmatize HIV status and address PLHIV marginalization worldwide, both during and after the COVID-19 pandemic. Additionally, expediencies such as removing ART label, anonymous mailing could help in privacy protection in constrained settings of social inclusiveness, and increase the ART adherence.
PLHIV in China reported increased anxiety, depression and insomnia during the COVID-19 pandemic. Concerns regarding increased risk of critical illness from COVID-19 infection and difficulty in obtaining ART were commonly reported sources of emotional stress in our interviews. Previous research found disruption caused by COVID-19 has disproportionately affected the mental health of PLHIV in China as well as internationally [30,31,34]. CBO have historically provided mental health support to PLHIV in China, and these efforts were strengthened during the COVID-19 pandemic. CBO workers provided counselling services outside of normal business hours, contacting clients at times when they could maintain privacy despite being quarantined at home with fam-ily members. Social media platforms and mobile apps were used to deliver counselling services to overcome barriers imposed by travel restrictions and citywide lockdowns. Studies in some high-income countries and LMICs have found emotional support from CBO workers can help develop positive attitudes and beliefs among PLHIV, contributing to improved ART adherence [29,[35][36][37][38]. Our results highlight that mental health counselling could be one effective option to mitigate mental stress and increase confidence to treatment among vulnerable groups like PLHIV in countries with strict travel restrictions.
Our study has several limitations. First, participants were recruited through purposive sampling. China is a large country of 1.5 billion people with significant regional diversity in terms of socio-economic conditions and HIV care services. Consequently, our interviews may not represent the experiences of PLHIV or stakeholders in the whole country. To maximize the representativeness of our sample, we recruited participants from seven distinct geographical regions in China as well as from urban and rural settings. Second, we focused on the views of multiple stakeholders, while the actual feelings from PLHIV may be more practicable. Third, the flexibility inherent in our inductive approach to generating themes may lead to inconsistency and lack of coherence in identifying themes [14]. We closely followed a six-step procedure in our thematic analysis to maximize consistency and reproducibility in our results [39]. Fourth, interviews were conducted during the early phase of the COVID-19 outbreak in February 2020. Barriers to ART adherence and stakeholder responses may have changed as the pandemic continued to evolve, and these changes would not have been captured in this study. Finally, significant differences exist between PLHIV and delivery of HIV care across countries and regions. The barriers and solutions identified through our interviews may not be relevant or applicable to other contexts.

C O N C L U S I O N S
We found CBO played an important role in ART maintenance during the COVID-19 pandemic in China. Innovative solutions implemented by Chinese CBO, including peer navigation to refill ART and CBO-coordinated provision of ART through mail or home delivery services, could be useful in other regions of China as well as internationally. Expansion of CBO services faces deep structural limitations in China, which has prevented nongovernmental organizations in China from taking on a larger role in providing HIV care [40]. Healthcare policymakers should recognize the important role CBO have played in ensuring access to ART, particularly during the COVID-19 pandemic, and further incorporate CBO into the existing ART delivery mechanism. Further research is needed to evaluate the long-term cost-effectiveness and feasibility of continuing CBO solutions to ART interruption after the COVID-19 pandemic has ended. Efforts to maintain ART access during future public health emergencies should leverage collaborations between stakeholders, with CBO playing a crucial bridging role between government agencies and PLHIV.

S U P P O R T I N G I N F O R M AT I O N
Additional information may be found under the Supporting Information tab for this article: Additional file 2 Figure S1. Prespecified themes of barriers to ART maintenance and solutions to ART interruption. ART, antiretroviral therapy; CBO, community-based organizations; CDC, centres for disease control and prevention; PLHIV, people living with HIV. Supporting Materials