key: cord-1014493-37m3qkji authors: Sun, Yinghui; Li, Hui; Luo, Ganfeng; Meng, Xiaojun; Guo, Wei; Fitzpatrick, Thomas; Ao, Yunlong; Feng, Anping; Liang, Bowen; Zhan, Yuewei; Sande, Amakobe; Xie, Feng; Wang, Ying; Qian, Han‐Zhu; Cai, Yong; Zou, Huachun title: Antiretroviral treatment interruption among people living with HIV during COVID‐19 outbreak in China: a nationwide cross‐sectional study date: 2020-10-28 journal: J Int AIDS Soc DOI: 10.1002/jia2.25637 sha: 256b035ab8f63d29ca5d5ce0b9a2f7c9dc915fd4 doc_id: 1014493 cord_uid: 37m3qkji INTRODUCTION: Social disruption associated with coronavirus disease 2019 (COVID‐19) threatens to impede access to regular healthcare, including for people living with HIV (PLHIV), potentially resulting in antiretroviral therapy (ART) interruption (ATI). We aimed to explore the characteristics and factors associated with ATI during the COVID‐19 outbreak in China. METHODS: We conducted an online survey among PLHIV by convenience sampling through social media between 5‐17 February 2020. Respondents were asked to report whether they were at risk of ATI (i.e., experienced ATI, risk of imminent ATI, threatened but resolved risk of ATI [obtaining ART prior to interruption]) or were not at risk of ATI associated with the COVID‐19 outbreak. PLHIV were also asked to report perceived risk factors for ATI and sources of additional ART. Factors associated with risk of ATI were assessed using logistic regression. We also evaluated factors associated with experienced ATI. RESULTS: A total of 5084 PLHIV from 31 provinces, autonomous regions and municipalities in mainland China completed the survey, with a response rate of 99.4%. Median age was 31 years (IQR 27‐37), 96.5% of participants were men, and 71.3% were men who had sex with men. Over one‐third (35.1%, 1782/5084) reported any risk of ATI during the COVID‐19 outbreak, including 2.7% (135/5084) who experienced ATI, 18.0% (917/5084) at risk of imminent ATI, and 14.4% (730/5084) at threatened but resolved risk. PLHIV with ATI were more likely to have previous interruptions in ART (aOR 8.3, 95% CI 5.6‐12.3), traveled away from where they typically receive HIV care (aOR 3.0, 95% CI 2.1‐4.5), stayed in an area that implemented citywide lockdowns or travel restrictions to control COVID‐19 (aOR 2.5, 95% CI 1.4‐4.6), and be in permanent residence in a rural area (aOR 3.7, 95% CI 2.3‐5.8). CONCLUSIONS: A significant proportion of PLHIV in China are at risk of ATI during the COVID‐19 outbreak and some have already experienced ATI. Correlates of ATI and self‐reported barriers to ART suggest that social disruptions from COVID‐19 have contributed to ATI. Our findings demonstrate an urgent need for policies and interventions to maintain access to HIV care during public health emergencies. ). Recognizing that access to ART may be hampered, especially for those quarantined away from 54 home, the Chinese Center for AIDS/STD Control and Prevention issued a nationwide directive on 26 55 January 2020 to relax restrictions on where PLHIV could obtain ART(10) . Under this directive, 56 PLHIV could obtain one month of ART from any local HIV care clinic or hospital. This article is protected by copyright. All rights reserved Despite efforts by government agencies and professional societies to mitigate the impact of COVID-59 19, many PLHIV have likely experienced some disruption in primary HIV care, including ART 60 interruption (ATI). These disruptions may negatively impact the health of PLHIV as ATI is associated 61 with both increased likelihood of opportunistic infections, more severe illnesses, HIV-associated 62 mortality, and HIV transmission (11) (12) (13) (14) . Initial reports suggest as many as one-third of PLHIV in 63 China may be at risk of experiencing ATI during the outbreak(15), however there are few available 64 data describing which PLHIV are most at risk and which adaptive strategies have been used to avoid 65 ATI. This study aims to better characterize the extent of and important correlates with ATI in China 66 during the COVID-19 outbreak. Kong, an account with over 76,000 PLHIV subscribers. As such up to 100,000 PLHIV would have 79 noticed our recruitment information. All participants read a consent form and selected 'agree' before beginning the survey hosted on the 82 online questionnaire platform Wenjuanxing (www.wjx.com). The survey first screened for eligibility. Eligible participants were at least 18-years-old, had a known diagnosis of HIV, and were currently on 84 ART. We excluded those who did not provide informed consent. A preliminary survey of 15 PLHIV This article is protected by copyright. All rights reserved 85 was conducted to modify questionnaire content before formal recruitment. Recruitment was stopped 86 the day when the total number of participants exceeded 5000. The primary outcome of interest was ATI during the COVID-19 outbreak. We defined ATI as missing 90 one or more days of ART. Participants were asked to self-report whether they had experienced ATI of 91 any duration after 10 January 2020 as well as whether they continued to be off ART at the time of 92 survey completion. Participants were also asked to report their self-assessed risk of ATI, which 93 included (1) having experienced ATI, (2) nearly experiencing ATI but obtaining ART prior to 94 interruption (i.e. threatened but resolved risk of ATI), (3) having fewer than 10 days of antiretroviral 95 (ARV) drugs on hand without a clear way to obtain or refill antiretroviral medications (i.e. risk of 96 imminent ATI), and (4) no risk of ATI. The survey instrument also asked about potential correlates of ATI. We collected sociodemographic 99 information (sex, age, highest level of education, occupation, income, permanent residence) and HIV 100 treatment history (route of HIV acquisition, age at HIV diagnosis, age at ART initiation, prior ATI, 101 date of most recent CD4 cell count and HIV viral load, site of primary HIV care, and source of ART 102 prior to the COVID-19 outbreak). The survey also asked where participants lived and travelled during 103 the COVID-19 outbreak and whether they had been impacted by certain COVID-19 prevention and 104 control measures, including citywide lockdowns and travel restrictions. Participants were asked to 105 report strategies they employed to address threatened or experienced ATI, sources from which they 106 attempted to obtain additional ART, and knowledge of government policies regarding ART access 107 during the COVID-19 outbreak. For this study time period of the COVID-19 outbreak was defined as This article is protected by copyright. All rights reserved 114 Descriptive statistical analysis was applied to summarize experiences with ATI as well as 115 sociodemographic information and potential correlates of ATI. Differences between PLHIV at risk of 116 ATI (either experienced, risk of imminent, or threatened but resolved ATI) and PLHIV without risk of 117 ATI were compared using Pearson's Chi squared test. Associations between risk of ATI and 118 correlates were analyzed using multivariate logistic regression that adjusted for potential confounders 119 selected a priori as well as significant correlates of risk of ATI. Similarly, associations between 120 PLHIV who did and did not experience ATI were analyzed using multivariate logistic regression. Results were reported as adjusted ORs (aOR) with corresponding 95% confidence intervals (95% CI). Chordal graphs were generated to present movement of PLHIV between provinces in the leadup to 128 the COVID-19 outbreak, using R software 3.6.0 (R Core Team, Vienna, Austria Geographic distribution of risk of ATI by province is presented in Table 2 . Highest rate of 155 experienced, threatened, or imminent ATI, as a single endpoint, was found in Hubei (58.7%), 156 followed by Xinjiang (51.8%) and Zhejiang (51.5%) Provinces, while highest rate of experienced ATI 157 occurred in Xinjiang (7.9%), followed by Gansu (5.9%) and Henan (5.0%) Provinces. (Table 3) . Among the 1782 participants who reported experiencing or being at risk 163 of ATI, the most common self-reported barrier to obtaining ART was fear of disclosing HIV status to 164 others by seeking refills of ARV drugs during the COVID-19 outbreak (77.3%). Other frequently 165 reported barriers included inability to travel to obtain ARV drugs because of lockdown and traffic 166 restrictions (65.8%), and cumbersome administrative procedures to obtain ARV drugs from clinics or 167 hospitals other than one's site of primary HIV care (51.1%). The frequency of self-reported barriers to 168 obtaining ARV drugs was similar between participants who experienced ATI, were at risk of 169 imminent ATI, and had threatened but resolved risk of ATI (Table 4) . This article is protected by copyright. All rights reserved 171 The most common strategies used to address experienced, threatened, or imminent ATI included 172 asking one's primary HIV clinic to post additional ART (47.4%), attempting to borrow ART from 173 other PLHIV (30.9%), and attempting to borrow ART from community-based organizations (CBOs) 174 serving PLHIV (21.3%). The success rate of obtaining additional ART through these routes was 175 35.9%, 38.6%, and 30.3%, respectively ( Figure 1 and Supplementary Table S1 ). When faced with 176 imminent ATI, nearly half of participants (48.4%) obtained urgent healthcare evaluation by 177 pretending to have a disease other than HIV. Few participants disclosed their HIV status and applied 178 for permission to travel to their site of primary HIV care (4.9%) ( Table 4) . intolerable ART side effects (16.2%) ( Table 3) . ARV drugs to last more than one month, and 28.6% reported being stranded in a location away from 194 their primary residence longer than anticipated because of lockdown measures or travel restrictions. Only 1.9% did not carry enough pills for the number of days they originally planned to travel. In multivariate regression analysis, PLHIV who experienced ATI during the COVID-19 outbreak 199 were more likely to have previous interruptions in ART (aOR 8.3, 95% CI 5.6-12.3), traveled away This article is protected by copyright. All rights reserved 200 from where they typically receive HIV care (aOR 3.0, 2.1-4.5), stayed in an area that implemented 201 citywide lockdown and travel restrictions (aOR 2.5, 1.4-4.6), and permanent residence in a rural area 202 (aOR 3.7, 2.3-5.8). Self-reported risk of ATI was associated with similar correlates, including 203 previous interruptions in ART (aOR 1.6, 1.3-1.8), travel away from where one typically receives HIV 204 care (aOR 3.3, 2.9-3.8), rural residence (aOR 2.3, 2.0-2.7), and living in an area that implemented 205 citywide lockdown and travel restriction (aOR 2.4, 2.0-2.8). Risk of ATI was also positively 206 correlated with relying on ART to be delivered by post (aOR 1.4, 1.2-1.6) and negatively associated 207 with buying ART out of pocket (aOR 0.7, 0.5-0.9) ( This article is protected by copyright. All rights reserved 227 investigated the impact of COVID-19 on HIV care, and our findings suggest an urgent need for 228 interventions to maintain access to ART during public health emergencies. Among the 5084 PLHIV who responded to our online survey, more than one third were at risk of 231 ATI, including 2.7% who had experienced ART and 18.0% who had fewer than 10 days of ART on 232 hand without an avenue to obtain additional medication, the continuing traffic control might This article is protected by copyright. All rights reserved 284 We identified several correlates of ATI that suggest certain subpopulations of PLHIV may be at 285 higher risk of interruption in ART during COVID-19. PLHIV who had experienced ATI prior to the 286 COVID-19 outbreak were 8 times more likely to experience ATI during the COVID-19 outbreak 287 compared to PLHIV without history of ATI. PLHIV who have difficulty adhering to ART are a 288 vulnerable group requiring special care and support, particularly because they are at higher risk of 289 HIV-associated mortality and contributing to HIV transmission(25). ATI was also more common There are several limitations to our study. First, the cross-sectional design of our study prevents us 312 from making firm conclusions about causes of ATI, and we can only report associations between ATI This article is protected by copyright. All rights reserved 313 and a narrow set of self-reported variables. Second, we defined ATI as not taking ART for one day or 314 more. The definition was relatively loose compared to other studies which defined ATI as not taking 315 ART for at least two days(27), and might limit the generalizability of the conclusion. However, our 316 survey was conducted in the midst of strict traffic control for COVID-19, PLHIV who did not take 317 ARV for one day during this period were very likely to experience continued ATI. Third, we used 318 convenience sampling, and consequently those who participated in our study may not be 319 representative of PLHIV in China overall. Participants in our study were mostly younger males. In days on the Internet and we did not recruit people who injected drugs during that short time. Contacting PLHIV who use drugs may require the help of local methadone clinics or related 330 organizations, however, inconveniences caused by COVID-19 increased the difficulty of such efforts. PLHIV willing to complete our online survey may systematically differ from those unwilling or 332 unable to participate in online research. Fourth, all information in this study was self-reported, and is 333 thus subject to significant risk of bias. Fifth, PLHIV who acknowledged previous ATI maybe more 334 likely to report ATI or risk of ATI during COVID-19. This article is protected by copyright. All rights reserved 342 access to ART during public health emergencies. As COVID-19 spreads internationally and has 343 developed into a global pandemic, other countries may be able to learn from the Chinese experience 344 to better protect the health of PLHIV. Collaborations between CBOs and public health authorities to 345 expand access to home deliveries of ART may be particularly helpful in preventing ATI in the face of 346 citywide lockdowns, travel restrictions, and social disruption from COVID-19. Countries and regions 347 that are still challenged by the COVID-19 outbreak are suggested to draw experiences from strategies 348 adopted by both the PLHIV community, community-based organizations and health authorities to 349 mitigate the impact of ATI in China and implement contextualized strategies in their own settings. This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved HIV transmission, reclassified for multiple choices of "Your route of HIV transmission", HIV transmission of "intravenous drug use", "Former commercial blood donors", "Mother-to-child", "Other", "Not sure" classified as "Other or not sure". Notes: Provinces which had less than 30 participants were not included in this analysis, including Tibet (3), Qinghai (9), and Ningxia (21). Participants resided in foreign area (49) were not shown. PLHIV, people living with HIV; ATI, antiretroviral therapy interruption. This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved This article is protected by copyright. All rights reserved The observations of "No. days of pills prepared before travel" were 1964, far less than total sample (5077, missing 7, less than 0.1%), so this was not included in the multivariable logistic regression analysis. Update on COVID-19 outbreak as of 384 24:00 on 29 February Beijing: National Health Commission of the People's Republic of China 2. National Health Commission of the People's Republic of China Beijing: National Health Commission of the People's Republic of China Early containment strategies and core 392 measures for prevention and control of novel coronavirus pneumonia in China Expert recommendations for 395 management and treatment of cardiovascular diseases under the epidemic situation of novel coronavirus 396 pneumonia in Hubei province COVID-19-We urgently need to 398 start developing an exit strategy. 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The lancet HIV This article is protected by copyright. All This article is protected by copyright. All rights reservedNo. days of planned travel a <0.001 This article is protected by copyright. All rights reserved