key: cord-0934423-g1m17vjd
authors: Lesko, Catherine R.; Keruly, Jeanne C.; Moore, Richard D.; Shen, Nicola M.; Pytell, Jarratt D.; Lau, Bryan; Fojo, Anthony T.; Mehta, Shruti H.; Kipke, Michele; Baum, Marianna K.; Shoptaw, Steven; Gorbach, Pamina M.; Mustanski, Brian; Javanbakht, Marjan; Siminski, Suzanne; Chander, Geetanjali
title: COVID-19 and the HIV continuum in people living with HIV enrolled in Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) cohorts
date: 2022-02-12
journal: Drug Alcohol Depend
DOI: 10.1016/j.drugalcdep.2022.109355
sha: ba5ee80b45614d6c83abc11400985ab1e05aad98
doc_id: 934423
cord_uid: g1m17vjd

BACKGROUND: The COVID-19 pandemic disrupted the normal delivery of HIV care, altered social support networks, and caused economic insecurity. People with HIV (PWH) are vulnerable to such disruptions, particularly if they have a history of substance use. We describe engagement in care and adherence to antiretroviral therapy (ART) for PWH during the pandemic. METHODS: From May 2020 to February 2021, 773 PWH enrolled in 6 existing cohorts completed 1495 surveys about substance use and engagement in HIV care during the COVID-19 pandemic. We described the prevalence and correlates of having missed a visit with an HIV provider in the past month and having missed a dose of ART in the past week. RESULTS: Thirteen percent of people missed an HIV visit in the past month. Missing a visit was associated with unstable housing, food insecurity, anxiety, low resiliency, disruptions to mental health care, and substance use including cigarette smoking, hazardous alcohol use, cocaine, and cannabis use. Nineteen percent of people reported missing at least one dose of ART in the week prior to their survey. Missing a dose of ART was associated with being a man, low resiliency, disruptions to mental health care, cigarette smoking, hazardous alcohol use, cocaine, and cannabis use, and experiencing disruptions to substance use treatment. CONCLUSIONS: Social determinants of health, substance use, and disruptions to mental health and substance use treatment were associated with poorer engagement in HIV care. Close attention to continuity of care during times of social disruption is especially critical for PWH.

The coronavirus disease 2019 (COVID-19) pandemic disrupted the normal delivery of medical care, altered social support networks, and caused economic insecurity. People with HIV, in particular those whose social determinants of health and mental health symptoms place them at high risk for poor health outcomes, may have been especially impacted by disruptions to care. Documenting patterns of engagement in HIV care, adherence to antiretroviral therapy (ART), and viral suppression, is important for understanding the potential long-term, collateral impact of the COVID-19 pandemic. When people with HIV maintain viral suppression they have better health outcomes and their infection is untransmissible to others (Cohen et al., 2011; Fauci et al., 2019; Insight Start Study Group et al., 2015) .

Retention in care and adherence to antiretroviral therapy are key upstream indicators of successful viral suppression (Gardner et al., 2011; Greenberg et al., 2009) .

The goal of this study was to describe engagement in care and adherence to ART for people with HIV living in North America (the United States and Canada) during the COVID-19 pandemic, and risk J o u r n a l P r e -p r o o f 4 factors for poor care continuum outcomes during the pandemic. We focused our investigation on demographics (based on well-documented racial and ethnic disparities in HIV care outcomes), social determinants of health, substance use, mental health symptoms and treatment, and the impact of the COVID-19 pandemic. Many HIV clinics adapted care models quickly to allow patients to engage in care without requiring in-person visits (e.g., offering telehealth and telephone visits) (Brody et al., 2021; Yelverton et al., 2021) . Prior research has suggested that visit completion during the pandemic was similar or better than during the pre-pandemic period (El-Nahal et al., 2021) . We hypothesized that accomodations to encourage visit completion might reduce barriers to visit completion (Auchus et al., 2021; Spinelli et al., 2020) , and result in relatively few disparities in retention in care. Although prior research has reported the prevalence of viral suppression in the pandemic is similar to pre-pandemic (El Moussaoui et al., 2021; Giacomelli et al., 2021; Izzo et al., 2021) , these studies restricted their analysis too patients who had a measured viral load. We did not measure viral load (which would have required an in-person study visit and presented unnecessary risk to participants) and instead focus on ART adherence. We hypothesized that ART adherence would be inversely associated with substance use, mental health symptoms, and other measures of social vulnerability. ART, and receipt of laboratory monitoring of viral load. To measure retention, we used metrics of both kept visits and missed visits (Mugavero et al., 2012) . As an indicator of being retained according to kept visits, we report the proportion of participants who had a visit with a doctor, nurse, or other medical provider in the last 6 months. As an indicator of being unretained according to missed visits (Mugavero et al., 2009a; Mugavero et al., 2009b) , we looked at participants who reported missing a visit with their HIV care provider in the last month (among those with a visit scheduled in the last month). We report, for completeness, a description of the reasons respondents gave for missing appointments with their HIV care provider.

We also report the proportion of respondents on ART, adherent to ART, and whose viral load was recently measured. Because respondents were not seen in person, viral load values were not available and we could not measure viral suppression. ART use was defined as reporting being on any daily medications for HIV. Non-adherence to ART was defined as reporting missing any HIV medications in the past 7 days; this would include periods in which people missed all HIV medications in the past 7 days. To contextualize these results, we report the reasons respondents gave for missing ART doses.

Recent viral load monitoring was defined as reporting having a viral load measurement ≤6 months before their survey.

We considered demographic, social, mental health, and substance use factors and the impacts of the COVID-19 pandemic as correlates of engagement in HIV care. Demographics included age, sex at birth (male sex at birth is inclusive of any transgender women included in the sample; gender was not ascertained on the survey), and race/ethnicity. Social determinants of health J o u r n a l P r e -p r o o f 7 that were measured included self-reported housing stability, employment status, and food security.

Housing was defined as unstable if respondents reported usually sleeping somewhere other than a house, apartment, dorm, home health facility, or rehabilitation facility. This included things like sleeping at someone else's house, in a car, on the street, or in a shelter. Employment status was classified as employed if respondents endorsed the statement "I am employed," unstable employment if respondents indicated having faced a reduction in work hours or furlough or not having formal employment, and unemployed if respondents said they were not working. Food insecurity was defined as reporting not having enough money for food or rationing food. Mental health variables included the GAD-7 as a measure of anxiety, with responses classified according to standard cutoffs as minimal, mild, moderate, or severe anxiety, and the Brief Resiliency Scale with responses classified as low, normal, or high resiliency. Substance use was ascertained for the month prior to the survey and participants reported on presence or absence of tobacco, cocaine, opioids, and cannabis use. We measured hazardous alcohol consumption with a modified USAUDIT-C (Higgins-Biddle and Babor, 2018) that only asked about past month rather than past year alcohol use, and classified use as "hazardous" using standard sex-specific cut-offs,. Participants reported whether or not they had engaged in any substance use treatment including alcohol, 12-step programs, and opioid substitution therapy. We also asked whether people in substance use treatment experienced disruptions in their treatment. Finally, we considered the degree of disruptions to day-to-day life due to the COVID-19 pandemic (reporting the pandemic impacted day-to-day life "much", "very much", or "extremely") and the degree to which the COVID-19 pandemic was impacting respondents mental health. Respondents who reported their level of worry about the pandemic was ≥5 on a scale of 1-10 were classified as having a substantial amount of worry.

We described the prevalence of care continuum outcomes using simple proportions. We described univariable and multivariable associations between each of the covariates J o u r n a l P r e -p r o o f 8 listed above and 1) having missed a visit with an HIV provider in the past month and 2) having missed a dose of ART in the past week. We estimated crude (adjusted only for cohort) and fully adjusted prevalence ratios using Poisson models with robust variance estimators (an approximation to a logbinomial model when the log-binomial model fails to converge). The robust variance estimator also accounted for possibly correlated outcomes arising from multiple measurements within the same individual.

There were 1495 surveys completed among HIV-positive respondents. We excluded 209 surveys (14% of all surveys) that were missing information on covariates (10 surveys were missing information on housing, employment=6, food insecurity=18, resiliency=1, mental health treatment=4, smoking=2, alcohol=2, cocaine=3, opioids=3, cannabis=10, substance use treatment=12, COVID-19 disruptions=6) or outcomes (most recent kept visit=21, missed HIV care visit=14, missed ART=139, most recent viral load=21). This analysis included 1286 surveys contributed by 773 unique respondents, 66% of whom contributed 2 surveys.

The study sample was mostly male (75%), older (median age was 50), and self-identified as Black, non-Hispanic race/ethnicity (69%). Study participants were socially vulnerable and had a high prevalence of substance use. One in five respondents (21%) reported they were in substance use treatment, but of those in treatment, disruptions were common (73%). One in eleven respondents (9%)

were receiving opioid agonist therapy and 26% of those reported a disruption in their treatment. Finally, the COVID-19 pandemic caused "much" to "extreme" disruption to 67% of respondents' lives and caused substantial worry for 77% of them (Table 1) .

J o u r n a l P r e -p r o o f 9

The study sample reported a high engagement in medical care: 93% had had a medical visit in the past month (including telehealth visits) and 90% had had a viral load measurement in the past 6 months. Despite the intensity of care, the prevalence of missed HIV visits in the past month was 13%.

Across cohorts, prevalence of missed HIV visits ranged from 8% to 26%. Nearly all people in the study sample were on ART (98%). However, 19% of the sample reported missing at least one dose of ART in the week prior to their survey. Across cohorts, prevalence of suboptimal ART adherence ranged from 9% to 37%. Excluding May 2020, the probability of missing a scheduled HIV visit in the past month increased very slightly (0.8% per month, p=0.08) each calendar month, and the probability of missing a dose of ART in the past week was relatively stable (0.1% increase per month, p=0.81) (Figure 1 ). forgot. A substantial proportion of respondents (15%) reported they missed taking ART because they could not get a refill of their medications or because they were concerned about going to the pharmacy because of the COVID-19 pandemic (7%).

In this sample of people with HIV during the COVID-19 pandemic, the majority of whom had a if we assume that the COVID-19 pandemic did not increase the probability of missing a visit, missed visits are associated with subsequent loss of viral suppression, mortality, and racial/ethnic disparities in HIV outcome and 13% probability of a missed visit in the past month is cause for concern and a possible point of intervention (Batey et al., 2020; Mugavero et al., 2014; Zinski et al., 2015) .

Retention in and engagement in care during the COVID-19 pandemic looked very different from pre-pandemic. In response to the need for increased social distancing, HIV clinics implemented telehealth options for visit completion or postponed visits (Budak et al., 2021; Ridgway et al., 2020) .

While traditionally, "telehealth" has implied video visits accessed over the internet, and therefore has required access to smartphones or computers and the internet, during the pandemic, many HIV clinics offered telephone-only telehealth visits, or made other accomodations, such as providing patients with J o u r n a l P r e -p r o o f 12 smartphones, in order to reduce the impact of these barriers (Auchus et al., 2021; Brody et al., 2021; Budak et al., 2021; Dandachi et al., 2020; Yelverton et al., 2021 Hopkins HIV Clinic (some patients of which contributed to this analysis), during the first 6.5 months of the pandemic, 70% of "telehealth" visits were conducted over the telephone only (El-Nahal et al., 2021) .

The impact of telehealth on long-term outcomes such as viral suppression and non-AIDS-related comorbidities (e.g., substance abuse treatment, cancer screening, and chronic non-infectious diseases) has yet to be seen.

In unadjusted analyses, we found that missing an HIV visit was associated with social determinants of health, mental health symptoms, and substance use. In prior studies, social determinants of health (Aidala et al., 2007; Aidala et al., 2016; Terzian et al., 2015; Yehia et al., 2015) , mental health symptoms (Yehia et al., 2015) , and substance use (Hartzler et al., 2018) Other researchers have reported the prevalence of viral suppression during the pandemic is similar to pre-pandemic (El Moussaoui et al., 2021; Giacomelli et al., 2021; Izzo et al., 2021) . However, these reports should be interpreted cautiously as they have been restricted to people who had a viral load measured in each period, and the frequency of viral load testing appears to have gone down during the pandemic (El Moussaoui et al., 2021) . Despite the implementation of mail delivery of prescriptions during the pandemic, intended to reduce barriers to ART adherence (Budak et al., 2021) , ART adherence in our sample remained below the 90% goal for viral suppression set in the End the HIV Epidemic plan (Fauci et al., 2019) . As with the retention outcome, we were unable to measure changes in ART adherence from pre-pandemic levels, however, and therefore cannot attribute this to the COVID pandemic. A previous analysis in this cohort that included a different subset of patients than we included here, reported 33% of patients had missed at least one dose of ART in the past 7 days prepandemic (Gorbach et al., 2020). Therefore, although the level of ART adherence during the pandemic was still too low, it may actually be better than pre-pandemic. One small study of people with HIV in Atlanta actually reported increased ART adherence during, versus in the month before, the COVID-19

pandemic (Kalichman et al., 2020) . In line with our findings, a cross-sectional survey of MSM in 20 countries from April to May 2020 found that 18% of respondents were unable to or had difficulty refilling their ART prescriptions (Rao et al., 2021) . In Haiti, there was an abrupt 18% decline in the proportion of ART refills that were dispensed on time corresponding to the start of the pandemic (Celestin et al., 2021) . The proportion of patients who don't refill prescriptions on time represent perhaps a lower bound on the proportion of patients who have problems with adherence to ART (since these numbers exclude persons who have sufficient ART in their possession but forget to take doses as prescribed).

Missed ART was associated with mental health symptoms and substance use. Additionally, we found missing ART doses were associated with being a man and with experiencing disruptions to J o u r n a l P r e -p r o o f 14 substance use treatment. While some studies have reported similar findings (e.g. no association between housing stability and ART adherence) (Terzian et al., 2015) our findings stand in contrast to most pre-pandemic studies that found housing insecurity (Aidala et al., 2016; Harris et al., 2017; Leaver et al., 2007; Mugavero et al., 2012; Palepu et al., 2011) and female sex (Arnsten et al., 2002; Berg et al., 2004) to be associated with poor ART adherence. It may be that traditional risk factors are operating differently during the pandemic, or that in our sample of people with a high prevalence of substance use, substance use is superseding other risk factors in determining ART adherence. Finding substance use associated with ART non-adherence was consistent with prior studies, in particular the finding that the strongest association was with cocaine use (Arnsten et al., 2002) .

Our finding that disruptions to mental health care and substance use treatment were associated with ART non-adherence is consistent with prior studies that have found mental health and substance use treatment, in general, improves ART adherence (Berg et al., 2004) . We caution against making a causal claim about the impact of treatment disruptions, however, because experiencing disruptions may be a marker of social vulnerability, internet literacy, or socioeconomic status. However, mental health care and substance use treatment are valuable independent of any potential link with ART adherence.

The challenge is determining how to continue to provide mental health care and substance use treatment while maintaining social distancing. We don't have information on what disruptions people experienced. It may have been that mental health and substance use treatment were stopped completely, or that therapy sessions were switched to telemedicine and patients were unable to access them, or that patients accessed telemedicine therapy sessions but found them less engaging than inperson sessions. Encouragingly, disruptions to opioid treatment programs do not have the same strong relationship with ART adherence. It may be that 'disruptions' to services provided at opioid treatment programs was mitigated by the relaxing of federal regulations that allowed for increased take-home methadone doses and reduced barriers to continued opioid agonist therapy (Peavy et al., 2020) .

J o u r n a l P r e -p r o o f 15 Finally, . as with self-reported measures, patients may have over-reported attendance at HIV care visits and ART adherence. Additionally, we do not have a comprehensive list of all patients who were eligible for this survey but who chose not to participate; it may be that individuals who participated in this study were the least vulnerable to/least impacted by the pandemic and we have overestimated the prevalence of retention and adherence in these cohorts.

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Role of Funding Source: The funding source had no role in the design and conduct of the study, the analysis and interpretation of data, or in the preparation, review, or approval of the manuscript. Contributors: Dr. Lesko designed the study, analyzed the data, and drafted the manuscript under the mentorship of Drs