Syndemic effect of COVID-19 outbreak on HIV care delivery around the globe: A systematic review using narrative synthesis

Background: The burden of the COVID-19 pandemic on healthcare systems worldwide has been compromising the progress made in the fight against HIV. This paper aims to determine how the COVID-19 pandemic has impacted HIV comprehensive care service delivery globally as well as to consolidate the evidence and recommendations that may be useful in averting future crisis. Methods: This review adheres to PRISMA guidelines. PubMed, DOAJ, Science Direct and other sources like Google Scholar and citations from included studies were searched methodically to locate studies evaluating the effects of COVID on services for HIV care. The NIH and JBI quality assessment tools were used for the quality assessment of individual studies. Results: In the present review 31 eligible studies were included and the impact on HIV care cascade were summarised under six themes: Lab services, Treatment and allied services, Counselling services, Outreach services, Psycho-social impact and Implementation of sustainable strategies. The studies also presented many innovative alternatives which were lucidly highlighted in the present article. Conclusion: Current evidence depicts multiple factors are responsible for the interruption of HIV care service delivery during the pandemic, especially in low resources settings. The prospective, alternative solutions that have been used to circumvent the threat have also been addressed in this review, in addition to the negative aspects that have been observed. Transition with new innovative, sustainable care paradigms may prove to be the building blocks in removing HIV-AIDS as a public health threat. Registration: Open Science Framework (DOI: 10.17605/OSF.IO/74GHM).


Introduction
The first documented case of COVID-19 infection was detected in China's Wuhan province on December 2019, and it was proclaimed a worldwide pandemic by the World Health Organization (WHO) on March of 2020. 1 With the rapid spread across the globe, the successive waves of the pandemic have reversed the progress of various healthcare programs leaving serious short as well as long-term impacts on essential healthcare services.Many essential healthcare activities were paused temporarily and healthcare workers from different streams were diverted to COVID-19 care resulting in disruption of the services.HIV comprehensive care services being one of them were no exception.Like the general population, people living with HIV (PLHIV) were also forced to stay indoors with limited access to health facilities, loss to follow-up, and discontinuation of antiretroviral therapy. 2 According to the UNAIDS Global AIDS Update 2022, in 2021 HIV-AIDS took a life each minute, leading to 650 000 AIDS-related deaths worldwide.In 2021, a new case of HIV infection occurred among adolescent girls or young women every two minutes.In the given situation, COVID-19 pandemic jeopardized the treatment and prevention services for HIV infection. 3According to WHO, 73 countries reported antiretroviral therapy (ART) disruptions during the pandemic in varying degrees. 4lthough the lockdown was the need of the hour to break the transmission chain, it limited public mobility and access to various healthcare services.This study intends to address the evidenced threats faced by HIV care services during the pandemic; so that it helps in further research to combat such disruptions in care delivery during any public-health crisis.
Evidence before this study A substantial number of primary studies have been conducted representing different low and middle-income countries to understand the pandemic's effect on HIV care services at the regional level.These studies proved that COVID-19 has impacted all aspects of the HIV healthcare system specifically treatment and testing services.To the best of our knowledge, studies that are objectively similar to our latest review curating shreds of evidence from March 2020 could be found.However, majority of the studies have focussed only on the adverse effects of the pandemic on HIV care delivery services, none has reported a robust framework for recommendations.

Added value of this study
Despite of irreversible damage faced in the progress made in the fight against HIV; alternative, resilient approaches were adopted worldwide to combat the loss.In this review alongside assessing the aftermath of the pandemic on HIV care delivery services, we attempted to summarise what was successful in sustaining the services, innovative approaches that have evolved, and suggestions to accelerate the recovery.
Therefore, this systematic review has been planned with a novel approach to achieve a deeper insight into addressing the compensatory measures which were adopted as temporary alternatives to alleviate the burden of interruptions alongside the negative outcomes of the pandemic on HIV care services along with reasonable recommendations for the healthcare advocates to envisage at the policy level.

Implications of all available evidence
The available evidence will help in planning and in the implementation of the novel strategies which came up during the pandemic not only in HIV care delivery but also in routine healthcare programmes wherever applicable.
This review attempted to address the reverberations of the coronavirus pandemic on HIV care service delivery in a multi-dimensional, holistic approach.It will guide to win over the losses as well as to protect the HIV care delivery services in any future public health crisis.

Protocol and registration
A detailed plan for this systematic review was registered with the Open Science Framework (DOI: 10.17605/ OSF.IO/74GHM).The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for systematically reviewing the available evidences.Any deviation from the protocol has been described accordingly.

Strategy for searching
Search strategies were developed in collaboration with the research team.Databases namely PubMed, DOAJ, Science Direct were searched methodically to retrieve the eligible studies.The keywords "COVID-19", "pandemic", "HIV", "HIV care continuum", "impact", "systematic review" were identified and then the key terms were customised to form the possible combination of search strings seeking to capture the most appropriate studies (Supplementary file 1) respectively for each database.The search strategy was restricted to papers in English language between December, 2019 to December,2022.Additionally, for other sources studies were searched in Google Scholar and using citation analysis of included studies from the three databases.NIH quality assessment tool and JBI Critical Appraisal Checklist (for qualitative studies) was used for assessing the quality of individual studies.

Inclusion and exclusion criteria
The inclusion and exclusion criteria were set based on PICOT (Population, Intervention, Comparison, Outcome and Time) criteria. 5We included original research, short communications, report and viewpoint articles in English language, relevant to the repercussions of COVID-19 pandemic on services for HIV care.Studies without an available free full text, published in languages other than English, irrelevant to the scope of our study objective were excluded.Review articles, case studies, programme reports, policy documents, commentary and scientific letters were excluded.

Study selection
Out of the 1556 records identified from the three electronic databases searching, 129 studies were found to be duplicate records.After removing the duplicate records, 1427 studies were title screened, out of which 292 were sought for retrieval.From here, 142 studies had to be excluded after abstract screening.After eligibility assessment, finally 25 studies met the methodological criteria and were found to be appropriate for the final inclusion in this review.Parallelly with regard to other sources, studies were retrieved from Google Scholar using customized search strings and some more studies were fetched using forward and backward citation analysis of the already selected studies (Figure 1).Finally, 31 studies were retained to be included in this review.
The screening procedures were carried out independently by three authors (RC, DA and RT).Any disagreements among the authors were settled through discussion to reach a consensus, if needed.In scenarios where agreement could not be reached, disagreements were resolved by a senior author (MB).

Data collection Data extraction and analysis
Three authors (RC, DA, RT) independently extracted data from the included studies and any disagreement was resolved after discussing with a senior author (MB).We extracted data on study location, design, objective, target population, interventions or newer strategies adopted (if any) during pandemic period, primary and secondary outcomes using Microsoft Excel spreadsheet.

Quality assessment
The quality of included studies were assessed using NIH quality assessment tools and JBI Critical Appraisal Checklist (for qualitative studies). 6Detailed coverage of the quality evaluation has been provided in Figures 2, 3 and 4. Three authors (RC, DA and RT) performed a collaborative quality assessment, and any differences were addressed by involving a senior author (MB).All 31 studies have been considered in this review.However, studies with fewer items checked in the quality assessment checklist (Supplementary file 1) received limited attention.The summary score of each study was calculated and expressed as percentage for both NIH and JBI quality assessment tools.The studies were categorized into four categories: poor (0-25%), fair (25-50%), good (50-75%) or excellent (75-100%). 7

Characteristics of included studies
The 31 included studies across the globe consists of high, low and middle-income countries namely USA, India, Kenya, Ethiopia, Italy, China, Haiti, South Africa, Netherlands, Vietnam, Guatemala, Belgium, Indonesia, Zimbabwe, Malawi and Uganda etc.

Findings
We found, 39% of the included studies (12/31 studies) collected data from online repositories such as electronic  health records of the healthcare facilities, available program data and 48% (15/31) studies used traditional offline mode of data collection from hospital settings and telephonic surveys.Qualitative research included (n = 6) in this review, primarily utilized methods such as in-depth interviews and focus-group discussion for gathering data.
Based on the key highlights (Table 1), we have condensed the consequences of the pandemic on the HIV comprehensive care services under six major themes namely: (1) Lab services (2) Treatment and allied services, (3) Counselling services, (4) Outreach services, (5) Psycho-social impact, (6) Implementation of sustainable strategies.

Lab services
One of the most studied topic among the literatures included in this review is the access to the laboratory services under the HIV comprehensive care services during the pandemic.Despite of considerable heterogeneity of settings and services, 14 out of the 31 included studies (45%) reported decreased testing or reduced lab monitoring during the COVID-19 pandemic resulting in delay in diagnosis. 15,22,25,26,28,29,33,35

Treatment and allied services
The pandemic has significantly impacted the provision of HIV-related treatment and related services.This study has arrived to a pooled opinions on the consequences of the coronavirus pandemic on the HIV-related treatment and other allied services.The most common observation was regarding anti-retroviral therapy.Shortage of medicines, 24 delay in ART initiation, 11,33 delay in receiving medications or ART refills, 9,18,29,31 resulting in suboptimal or decreased ART adherence 1,36 were reported.Other focal points derived were decreased screening of opportunistic infections, 1,9,36 disruption in follow up services, 1,31 decreased allied services like Voluntary Male Medical Circumcision 34 and preventive services. 25

Counselling services
In most of the countries HIV care comes in a comprehensive package.Along with treatment and reduction of viral load, screening of opportunistic infections, laboratory services, it is also equally dependent on the counselling services for risk reduction, safe practices, ensuring patients' adherence to the care process in an integrated manner.Among the 31 included studies, only 2 studies covered the aspect of counselling services for HIV care.Both the studies reported that counselling services were ensured for the high-risk group amid the worldwide lockdown caused by the pandemic. 18,28

Outreach activities
The principal purpose of outreach activities in HIV comprehensive care services is case finding so that they become aware of their sero-status, and may get enrolled in care and treatment services. 38The provision of outreach services was negatively impacted by the diversion and strikes of health care personnel, 11,20,22 cuts in funding for HIV care services, 13 and decreased access to HIV care resources. 10Home delivery of ART medications and nutritional supplements was one of the strategies used to enhance outreach efforts. 29

Psycho-social impact
Social stigma and discrimination are known to be already prevalent among the high-risk groups for contracting HIV.The COVID-19 added to it and made it worse.12 out of the included 31 studies has highlighted the various psycho-social factors faced by the high-risk groups during the COVID-19 pandemic worldwide.Financial burden 10,12,19,21,30 and fear of COVID-19 12,18,19,24 has been the most common psycho-social impact in our findings, followed by increased stigma, 12,30,31 mental distress or psychological stress, 17,21,28 barriers due to lockdown like food insecurity 19,36 and transport disruption 10,30 leading to missed ART appointment.

Implementation of sustainable strategies
During the COVID-19 pandemic, though the global scenario was depicting interruptions in accessibility of HIV facility based-care, but it has also accelerated the growth of alternative options with increased flexibility.The decrease in traditional facility-based clinic  To assess the effects of the lockdown on crucial aspects of HIV care specifically, HIV testing, the initiation of ART, and the continuation of care for HIV patients measured through ART collection visits and instances of absenteeism.
• HIV services were generally maintained among people already receiving ART This study aimed to understand the impact of restrictions due to the pandemic on the first pillars of the HIV care continuum in clinical settings.
is study investigated the importance of ensuring continuity of care for maintaining the momentum in achieving the 90-90-90 goals and also considered PLHIV as a high priority group for any kind of intervention.This research investigated the impact of the consecutive waves of the COVID-19 pandemic in 2020, along with the resultant lockdown measures, on the HIV care process.Furthermore, it aimed to put forth potential strategies for sustaining efficient HIV prevention and care practices.
• Telehealth alternatives were created to guarantee medical care through virtual and remote means • Automatized follow-up for co-morbidities and co-infection screening.This study identified the difficulties in HIV services that were linked to patient care results amid the COVID-19 pandemic.

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Strengthen the ability of HIV-related institutions to withstand challenges by consistently assessing and improving their organizational resilience.
• Disruption in follow-up service • Delay in ART refills • Increase in opportunistic infections appointments were compensated by virtual telemedicine platforms. 9,12,15,18,22,23,25,26,28,37Sustainable strategies like home delivery of ART medications, 15,30 multi-month dispensing of ART for stable PLHIVs, 13,22 provision of HIV self-testing to know one's sero-status 14,20,33 has been reported.A study conducted by Parikh et al in Indian setting, reported nutritional supplementation and doorto-door ration delivery along with ART. 29

Discussion
Multiple waves of COVID-19 outbreak prompted a huge public health response on a global scale, making it an unparalleled public health emergency.The pandemic forced HIV clinics to alter their approach from efforts to link and keep patients in care reducing in-person clinical appointments for PLHIVs, which severely weakened the HIV healthcare delivery system. 39This review has tried to examine the pandemic's effect on the various facets of HIV care and listed suitable recommendations (Table 2) that were adopted to alleviate the burden of interruptions caused by the novel coronavirus pandemic.
To examine the noteworthy influence of the COVID-19 pandemic on HIV care services, this analysis of 31 studies from various nations discovered consistent proof of substantial declines in the usage of comprehensive HIV care services during the subsequent pandemic waves.
Although a meta-analysis was not possible due to a lack of quantitative summary from the available literature, this review has tried to summarize the repercussions of the coronavirus pandemic on HIV comprehensive care services under six major themes and has been discussed using a framework (Figure 5).Results revealed that the majority of the studies reported decreased testing or reduced lab monitoring, 15,22,25,26,28,29,33,35 ultimately leading to a delay in diagnosis and hence interrupting the treatment cascade. 9,11,18,29,31,33t has been found that few countries have adopted multi-month dispensing of drugs 8,13,22,32 while most of the countries could not, due to a shortage of drugs.Such a buffer to health systems against external shocks is advisable.An interrupted supply of drugs under any unforeseen situations will hinder the progress of removing HIV/AIDS as a public health threat by 2030.Moving forward, countries should maintain a steady supply of ART drugs, especially keeping in mind of such public health crisis.
HIV comprehensive care components are highly interdependent.One such component is the counselling services.From the findings, it can be inferred that ensuring the counselling service was compromised during the COVID-19 pandemic.This review has not only highlighted the detrimental points that the world has seen regarding HIV care services during the pandemic but also highlighted the potential alternatives or compensatory measures that have been adopted to bypass the threat.Despite the diversion and strikes of health care personnel, 11,20,22 cuts in funding for HIV care services 13 and decreased access to care resources, 10 our findings revealed some best possible alternatives like door-to-door distribution of ART medications and nutritional supplements that were adopted to combat the issue. 29This research assessed how the COVID-19 pandemic affected the detection, diagnosis, and treatment outcomes of TB cases, as well as HIV ART, using enhanced real-time surveillance.
• Human resource support was provided to support and sustain ART service and HIV testing.
• Voluntary male medical circumcision services (VMMC) were stopped • Stock outs of HIV test kits.
Thekkur et al, 2021 35 To compare pre-COVID service delivery (HIV & TB) as compared to the COVID period.
• ART referral was maintained during pandemic • Reduction in HIV testing in the initial stage of the pandemic.
Wagner et al, 2021 36 Examined the impact of the pandemic on HIV care in Uganda by analysing electronic health records from the country's major HIV care providers, both pre and post lockdown.Comprehending the utilization of telehealth for HIV care, encompassing both medical and non-medical services and additionally, seeking to pinpoint obstacles to delivering remote services and devising strategies to enhance HIV care via telehealth during the pandemic.
• Education and training sessions were conducted to enable telehealth.

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Wi-Fi enabled smartphones were handed over to the clients for their ease in contacting the healthcare provider.As HIV mostly deals with a marginalized section, there is already a stigma and discrimination prevalent amongst the population.COVID-19 being another infectious infection, added fear, 12,18,19,24 psychological stress, 17,21,28 barriers due to lockdown like transport disruption, 10,30 food, 19,36 and financial insecurity 10,19,21,30 to it and magnified the condition.
In high-resource settings, interruptions in the accessibility of HIV comprehensive care services were compensated by the accelerated provision of alternative options with increased flexibility.For example, teleconsultation or virtual platforms, 9,12,18,22,23,25,26,28,37 was adopted for the smooth functioning of routine HIV care services.In some countries, home delivery 30 of ART medications, multi-month dispensing of ART, 6,8,13,32 provision of self-testing 14,20,33 and nutritional support 29 were adopted.
For improving service provision "Differentiated service delivery" (DSD) model, a people-centric approach to HIV service delivery have been successfully implemented in countries like Malawi, South Africa, and Zambia. 42his kind of model can change the "when, where, who, and what" of HIV service delivery to a diverse group of PLHIVs while maintaining the principles of public health approach.

Implementation of sustainable strategies
• Integration of services to reduce missed opportunities or drop-outs and to enhance ART adherence support, for example appointment reminders, incentives to attend post ART initiation visits etc.

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Extra clinic hours on evenings and weekends, family models (WHO recommended) can be adopted.

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People-centred care and specific models for nonstable patients.
• Integration of HIV care with other routine health services to generate evidence on out-of-pocket health expenditure, effect of incentive on adherence etc.

Strengths & Limitations
This study has incorporated the most recent data from primary studies since the inception of the COVID-19 pandemic till December 2022, which covers the peak of the pandemic in most countries.Secondly, it has consolidated the consequences of the pandemic and related changes on the utilization of HIV care services.Thirdly, the risk of bias in the selection of studies has been minimized using standard quality assessment tools.Citations from retrieved publications were checked and necessary studies have been included.A clear explanation of the PRISMA flow diagram, formulation of search strategy, data curation, and analysis methods to eliminate any potential confusion has been provided.The results have been interpreted with a special focus on the pandemic scenario, hence broad generalization of inference may be restricted to situations related to any public health crisis only.Also, some potential primary studies with significant results might have been missed out due to limited access to multiple databases.Excluding literature in non-English language is a limitation of this study.Meta-analysis could not be done due to the lack of a quantitative summary of available literature.The effectiveness of all the compensatory measures that has been addressed from various literatures may not be uniform and has the potential to vary across different settings, here leaves scope for future research.

Recommendations
Same-day start of ART or rapid ART initiation, provision of ART initiation outside-the-clinic, reducing the frequency of clinical visits for stable patients via virtual platforms, and provision for ART refills from external pick-up points or community drug distribution points 40 will help in fast-tracking HIV care services.This study recommends measuring adherence using novel strategies like 'pill count' 40 ; tracing and re-engagement of drop-out cases in care; psychosocial support for people living with HIV; task sharing for diagnostic services and integration of HIV service deliveries.These recommendations may help the programme managers and policy-makers in developing countries to design models and strategies that will help in the smooth functioning of the HIV care continuum and the standard of care for PLHIVs to mitigate any further public health crisis.

Conclusion
This study has tried to consolidate the evidence available from a global perspective.Though the COVID-19 containment measures like quarantine and lockdown measures have put the HIV care continuum in many parts of the world into a challenging situation, the transition with new innovative, sustainable care paradigms, and resilient interventions calibrated to combat such vulnerabilities are vital to ensure continuity of care and may prove to be the building blocks in removing HIV-AIDS as a public health threat.Strong organizational preparedness, inter-sectoral coordination, enhanced and improved service delivery techniques, need based timely and effective support to the community are required to combat this public health crisis.

Figure 1 .
Figure 1.Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for selection of studies.

Figure 3 .Figure 4 .
Figure 3. NIH Quality Assessment tool for Pre-Post studies without Control Group

Figure 5 .
Figure 5. Framework showing impact of COVID-19 on the HIV Care cascade

Table 1 .
Summary of included studies

Table 2 .
Recommendations and scope of future research 40 Peer-driven and family-based intervention to promote mental health and prevent negative behaviour.For example, youth models like teen clubs in Malawi and Scholar model in Zambia. 41

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Specifically designed interventions for PLHIVs (adolescents and young adults) with disabilities, mental health conditions, acquired HIV perinatally and those with extreme poverty.