HIV outcomes during the COVID‐19 pandemic in people of Black ethnicities living with HIV in England

To describe HIV care outcomes in people of Black ethnicities living in England during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2; coronavirus disease 2019 [COVID‐19]) pandemic.


INTRODUCTION
The World Health Organization declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 ) a pandemic on 11 March 2020, resulting in the introduction of substantial public health prevention measures.In the UK, by late March 2020, the Government had introduced legally enforced 'stay-at-home' orders and 'shielding' for those deemed extremely clinically vulnerable, which initially included people with HIV [1].The pandemic caused widespread disruption to healthcare services because of COVID-related hospitalizations and interruption of delivery of non-emergency services, including HIV care and in-person provision of antiretroviral therapy (ART) [2].Data on the impact of the COVID-19 pandemic on HIV care outcomes are mixed.Some studies suggest that the pandemic increased rates of HIV viraemia while receiving ART, morbidity, and mortality [3][4][5]; others have shown no substantial impact on virological control [6].However, little is known about the impact of the COVID-19 pandemic on HIV care outcomes in people of Black ethnicities in England, communities that experience multiple and intersecting disadvantages and poorer health outcomes [7][8][9].
The COVID-AFRICA study explored how these communities were affected by the COVID-19 pandemic.Here, we report HIV care outcomes during the COVID-19 pandemic.

Study population
Data were obtained from the GEN-AFRICA (Genetic Determinants of Kidney Disease in People of African Ancestry with HIV; NCT05685810) cohort, which was established between May 2018 and January 2020; participation in GEN-AFRICA was open to all adults of selfreported Black ethnicities receiving HIV care in England who were able and willing to provide informed consent, demographic and clinical data, and a blood and urine sample for research.GEN-AFRICA participants who remained in HIV care on 1 January 2020 were eligible for inclusion in the COVID-AFRICA study.Between June 2021 and November 2022, individuals attending HIV clinics who provided written informed consent were asked to complete questionnaires on HIV care, COVID-19 illnesses, and SARS-CoV-2 vaccination.For those not enrolled during HIV care visits, we obtained peak HIV RNA, COVID-19 infection status, SARS-CoV-2 vaccination, and vital status from medical records between July and November 2022.The study was approved by a national health service research ethics committee (21/ES/0047) and the Health Research Authority (IRAS 294887).

Exposure variables
The following data were obtained from the GEN-AFRICA study visit (median date of enrolment March 2019): region of ancestry, year of HIV diagnosis, prior AIDS diagnoses, nadir CD4 cell count, and most recent (pre-pandemic) CD4 cell count, HIV RNA, and comorbid conditions [10].COVID-19 disease (illnesses consistent with COVID-19 after 1 January 2020, irrespective of diagnostic test result) and SARS-CoV-2 vaccination status (one or more dose) were ascertained through questionnaires and review of medical records.

Outcomes
Our composite outcome comprised any ART interruption and/or HIV RNA ≥200 copies/mL between January 2020 and November 2022.Questionnaires were used to ascertain whether participants had run out of or stopped their ART and whether their viral load had remained undetectable or become detectable at any stage during the pandemic, with the option to provide reasons if it had.Sites were asked to report any known ART interruptions, the highest viral load measurement after 1 January 2020, andfor those with the composite outcomethe most recent viral load.

Statistical analyses
Statistical analyses were restricted to the nine clinics that provided HIV outcomes for at least 80% of GEN-AFRICA participants.Baseline (pre-pandemic) characteristics of the study population, and their COVID-19 disease and SARS-CoV-2 vaccination status, were evaluated in those who experienced an ART interruption/HIV viraemia compared with those whose HIV remained supressed (HIV RNA <200 copies/mL) throughout, using Pearson's χ 2 test for categorical variables and two-sample Wilcoxon rank-sum (Mann-Whitney) test for comparing the median values of continuous variables.Multivariable logistic regression was used to investigate associations between baseline characteristics and pandemic ART interruption/ HIV viraemia.Factors associated (p < 0.1) in univariable analysis were included in the multivariable models.All analyses were performed using STATA v17 (StataCorp, College Station, TX, USA).

RESULTS
Of the 2397 GEN-AFRICA participants considered for participation in COVID-AFRICA, 2312 (97%) were included, of whom 801 provided questionnaire data.The current analyses were restricted to the 2290 (99%) individuals for whom ART interruption/HIV viraemia could be evaluated (Figure S1).At the start of the pandemic, the median age of participants was 49.3 (interquartile range [IQR] 42.7-55.7)years; 56% were female, and most were of sub-Saharan African ancestry, had long-standing (median 14 years) and well-controlled HIV (median CD4 cell count 555 cells/mm 3 , 92% HIV RNA <200 copies/ mL) (Table 1).Between January 2020 and November 2022, 518 (30%) participants had experienced one or more episode of COVID-19, of which 314 (61%) were confirmed by diagnostic tests, and 1763 (87%) had received one or more dose of SARS-CoV-2 vaccine.
Participants who experienced ART interruption/HIV viraemia were younger, less likely to be of East African ancestry, and more recently diagnosed with HIV and had lower pre-pandemic CD4 cell counts and rates of HIV suppression (Table 1).They were also less likely to have received SARS-CoV-2 vaccination.In univariable analysis, being older, being of East African ancestry, having been diagnosed with HIV for longer, having a higher recent CD4 cell count, having pre-pandemic HIV RNA <200 copies/mL, and having received one or more dose of SARS-CoV-2 vaccine were all associated with reduced odds of ART interruption/HIV viraemia during the COVID-19 pandemic.In the adjusted analysis, a prepandemic HIV RNA <200 copies/mL and having received one or more dose of SARS-CoV-2 vaccine remained strongly associated with ART interruption/HIV viraemia; however, age and recent CD4 cell count >350 cells/mm 3 were no longer statistically significant (Table 2).
In total, 52 participants who reported ART interruption/HIV viraemia provided reasons for this (Figure S2): 20 (39%) cited logistical barriers such as changes to clinic appointments, pharmacy and home delivery service disruptions, or pandemic restrictions on leaving the house, and 14 (27%) had travelled abroad, where they had run out of ART.Other reasons included low mood, changes to daily routine brought about by the governmentimposed pandemic restrictions, and personal choice.
Post-pandemic vital status/viral load data were available for 392 (98%) of the 401 participants who experienced ART interruption/HIV viraemia: 288 (74%) had HIV RNA <200 copies/mL at their most recent clinic visit, whereas 43 (11%) were not in care and eight (2%) had died.

DISCUSSION
One in six people of Black ethnicities living with HIV in this cohort experienced ART interruption/HIV viraemia between January 2020 and November 2022.Nonsuppression of HIV RNA before the pandemic and not having received SARS-CoV-2 vaccination were the factors most strongly associated with ART interruption/HIV viraemia; participants additionally cited COVID-19-related disruptions to HIV care and more widely in their daily lives as important factors.
Most studies have reported little impact of the COVID-19 pandemic on HIV care outcomes.A systematic review found that, although few studies reported on viral suppression during the pandemic, most reported no significant differences before and during the pandemic [6,[11][12][13][14], apart from a study from San Francisco, which reported 31% increased odds of viral non-suppression in April 2020 compared with December 2019-February 2020; participants of Black ethnicity were disproportionally affected (adjusted OR 1.60; 95% confidence interval 1.33-1.91)[4].A Spanish study reported a 37% increase in loss-to-follow-up during 2020 compared with 2006-2019 [15].
Our data suggest that HIV clinics were unable to fully mitigate the impact of pandemic disruptions on HIV care outcomes among people of Black ethnicities in England.Limited digital health literacy and competing health needs may have worsened existing health inequities in these populations [4,5,16].Reassuringly, most (74%) of those who experienced viral non-suppression during the pandemic subsequently re-suppressed on ART.However, this highlights the importance of understanding the reasons for continued viral non-suppression in those whose HIV viral loads remained detectable following return to more regular models of HIV service delivery, and for providing tailored support.
We found an association between ART interruption/ HIV viraemia and not having received SARS-CoV-2 vaccination.Uptake of and adherence to ART is influenced by T A B L E 1 Baseline and pandemic characteristics of study participants stratified by the outcome of interruption of antiretroviral therapy and/or HIV viraemia during the study period.

Participant characteristics
Total   HIV viraemia refers to a documented HIV RNA >200 copies/mL during the pandemic (January 2020-November 2022).implicit judgements of personal need for the treatment (necessity beliefs) and concerns about the potential adverse consequences of taking it [17].For some of our participants, ART interruptions may have been intentional.Previously reported perceptual barriers to taking ART among people of Black ethnicities in the UK include doubts about the necessity of ART, stemming from feeling well, a belief that treatment is futile because it does not cure HIV, and religious beliefs.Concerns about ART include fears about side effects, accidental disclosure of HIV status, and stigma associated with attending HIV services [18].The Necessity-Concerns Framework similarly applies to SARS-CoV-2 vaccines: COVID-AFRICA participants who remained unvaccinated had lower vaccination-necessity and higher vaccination-concerns scores [19].The relationship between ART interruptions, non-uptake of SARS-CoV-2 vaccines, wider health beliefs, and pandemic lived experiences among these communities deserves further study.However, it is important to also acknowledge that not receiving SARS-CoV-2 vaccination may result from broader barriers to healthcare access (e.g., competing priorities, hard-to-access services, and experiences of racism and discrimination within healthcare systems), which could also affect access to ART.
The strengths of our study include the availability of an established, well-characterized cohort, use of both self-reported ART interruptions and clinic virological measurements to define our composite outcome, and near complete data on HIV viral load before the pandemic andfor those with ART interruption/HIV viraemiaat their most recent clinic visit in 2023.Selection bias was mitigated by including participants through active enrolment as well as review of medical records of those who were unable to provide informed consent.However, self-reported ART interruptions and the reasons for these were not available for all participants and may have been under-reported or subject to recall bias.The duration of ART interruption was not captured, and not all ART interruptions were accompanied by measurements of HIV RNA.Furthermore, previous participation in the GEN-AFRICA study may reflect more stable engagement in HIV care; rates of ART interruption/HIV viraemia may have been higher in other people of Black ethnicities with HIV.
In summary, we identified that both pre-pandemic uptake and adherence to ART and having received SARS-CoV-2 vaccines were associated with ART interruption/HIV viraemia in people of Black ethnicities in England.The COVID-19 pandemic and subsequent public health prevention measures are likely to have amplified existing health inequalities and posed additional challenges in achieving and sustaining HIV viral suppression in these populations.This may have not only potentially affected individual morbidity and mortality risk but also increased the risk of sexual transmission of HIV.Our forthcoming qualitative analyses will allow us to better understand the reasons underlying ART interruption and adherence challenges during the pandemic.Ultimately, identifying and supporting those most at risk of disengaging from HIV care is of high public health importance and a key component of pandemic preparedness and resilience within HIV clinical care.

eCOVID- 19 =
illnesses consistent with COVID-19 after 1 January 2020, irrespective of pathological confirmation.f SARS-CoV-2 vaccination = having received one or more doses of any SARS-CoV-2 vaccine. g based on country of birth of both parents; regions of sub-Saharan African ancestry (East, Southern, Central and West Africa) as defined by the African Union.Participants whose parents' country of birth was unknown, of different African regions, or outside sub-Saharan Africa or the Caribbean, and those of mixed African/Caribbean ancestry were grouped together as 'Other'.
Note: Age and time since HIV diagnosis are calculated to reflect status on 1 January 2020; other components of HIV and comorbid status reflect pre-pandemic status.Data are presented as N (%) or median (interquartile range) unless otherwise indicated.Abbreviation: ART, antiretroviral therapy.a Region of ancestry = b Obesity = body mass index ≥30 kg/m 2 .c Kidney disease = estimated glomerular filtration rate <60 mL/min/1.73m 2 .d Cardiovascular disease = myocardial infarction, coronary artery disease, peripheral vascular disease, stroke, heart failure, and/or cardiomyopathy.
T A B L E 2 Associations between demographic, clinical, immunovirological parameters and antiretroviral therapy interruption/HIV viraemia.COVID-19 vaccination = having received one or more SARS-CoV-2 vaccination.
Note: HIV viraemia defined as HIV RNA >200 copies/mL during the pandemic (January 2020-November 2022).Abbreviations: CI, confidence interval; OR, odds ratio.a Region of ancestry = Based on country of birth of both parents; regions of sub-Saharan African ancestry (East, Southern, Central and West Africa) as defined by the African Union.Participants whose parents' country of birth was unknown, of different African regions or outside sub-Saharan Africa or the Caribbean, and those of mixed African/Caribbean ancestry were grouped together as 'Other'.b Obesity = body mass index ≥30 kg/m 2 .c Kidney disease = estimated glomerular filtration rate <60 mL/min/1.73m 2 .d Cardiovascular disease = myocardial infarction, coronary artery disease, peripheral vascular disease, stroke, heart failure, and/or cardiomyopathy.e COVID-19 = illnesses consistent with COVID-19 after 1 January 2020, irrespective of pathological confirmation.f