Adapting HIV services for pregnant and breastfeeding women, infants, children, adolescents and families in resource‐constrained settings during the COVID‐19 pandemic

Abstract Introduction The COVID‐19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID‐19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource‐constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole‐family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services. Discussion Essential HIV case‐finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self‐testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID‐19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community‐based ART initiation and multi‐month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services. Conclusions Protecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS‐CoV‐2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case‐finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS‐CoV‐2 transmission while ensuring the continuity of life‐saving HIV case identification and treatment efforts.


| INTRODUCTION
As the impact of the COVID-19 pandemic unfolds, the high person-to-person, nosocomial and community transmission rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]including from asymptomatic carriersare placing an immense burden on healthcare systems and vulnerable populations who may be increasingly deterred from accessing care [2]. In resource-constrained settings with HIV disease burden, ensuring continuity of safe case identification and life-saving, life-long antiretroviral therapy (ART) remains a global health priority [3]. Little data are available on the impact of the COVID-19 epidemic on established healthcare systems designed to respond to the HIV epidemic; therefore, global health partners and Ministries of Health are working to develop and adapt guidance for healthcare systems, including supply chain, healthcare workforces and communities to reduce risk of exposure to COVID-19 while avoiding interruptions to essential HIV services [4][5][6].
Data are currently limited on whether people living with HIV (PLHIV) are more likely to acquire SARS-CoV-2, or if COVID-19 disease progression is different among PLHIV [7,8]. A recent analysis from South Africa reveals that PLHIV, especially those with comorbidities, have elevated risk of poor COVID-19 outcomes, irrespective of viral suppression [9]. However, information is scarce on the potential impact of HIV/SARS-CoV-2 co-infection on vulnerable populations including pregnant and breastfeeding women (PBFW), HIVexposed infants (HEI), children/adolescents living with HIV (C/ALHIV) and orphans and vulnerable children (OVC).
Although some COVID-19 health service adaptations address the needs of PBFW, HEI, C/ALHIV and OVC, many do not. Aligning with updated PEPFAR guidance, we propose programme adaptations along the clinical continuum to protect the gains made in combating the global HIV epidemic among these high-risk populations during the COVID-19 response (Table 1). These adaptations should be supported by tailored community messaging to reassure clients who may otherwise be fearful of COVID-19 infection risk and may not access routine services. Programme adaptations can also be utilized during times of high community transmission of COVID-19, especially when mitigation measures and travel restrictions are in place, and access to health facilities is reduced.

PBFW with HIV and their infants
Given the high rates of maternal and infant mortality in resource-constrained settings with high HIV prevalence, HIV testing in antenatal and maternal child health services for PBFW and their infants should continue during COVID-19. The adaptation for these HIV services, including maternal testing, retesting, linkage to HIV prevention (e.g. pre-exposure prophylaxis) [10] for HIV-negative at risk women [11], and early infant diagnostic testing and prophylaxis, can be provided in a one-stop-shop model during routine prenatal, postnatal and child wellness visits. For facility-based HIV testing in the context of maternal/child health, the adaptation of moving services external to the facility (e.g. wellness tents) may benefit PBFW and their infants while maintaining privacy and confidentiality.
An additional adaptation to maximize access to testing for PBFW is HIV self-testing kit distribution in the community, provided alignment with national guidelines, the risk screen is negative for intimate partner violence, and the supply chain is intact [12]. If virtual follow-up is unsuccessful following distribution of HIV self-tests to PBFW, facility or home-based visits may be required, and all COVID-19 precautions should be followed [6]. For clients with initial reactive tests, prioritization should be given to completing the diagnostic algorithm and same-day linkage to ART. Confirmation of reactive test results and active linkages will be challenging given restrictions on inperson interactions, thus additional resources will be needed to expand virtual, telephonic, SMS or online follow-up [6]. Importantly, virtual follow-up approaches will only be successful if updated and accurate patient contact information is available; this information as well as alternative means of contact should be collected and confirmed during clinical, homebased or virtual encounters.
For infant testing, as a result of precautions taken during COVID-19, mentor mothers and facility-based providers may need to closely support postpartum mothers after birth via SMS and phone consults to instruct on dosages, appointment scheduling and location for sample collection for early infant diagnosis (EID). In Zimbabwe, birth testing for HEI is now being offered at sites with point-of-care testing, since mothers and infants may not be able to return for the six-week EID test given the reduced mobility due to COVID-19 (CDC Zimbabwe, internal communication). Other countries utilize community-based EID sample collection and co-delivery of EID and routine immunization through facility and communitybased platforms; these interventions reduce over-crowding in health facilities and exposure to COVID-19 (CDC Tanzania and CDC Zimbabwe, internal communications).

| Adaptations for case-finding for undiagnosed C/ALHIV
During the COVID-19 pandemic, facility-based HIV testing services (HTS) remain an important priority, especially for children and adolescents, including those presenting or admitted to health facilities with comorbidities (e.g. tuberculosis, malnutrition, sexually transmitted infections) or other risk factors for HIV. While active case-finding may temporarily need to be decelerated to ensure the safety and security of providing services during COVID-19, passive index testing for sexual partners, spouses and biological children of PLHIV newly diagnosed or currently on ART (and child and adolescent siblings of C/ALHIV) who present to the health facility should continue, with immediate linkage to ART for newly identified C/ALHIV [6].
The World Health Organization recently approved healthcare worker-assisted HIV self-testing for children two to eleven years of age, which can be employed as an adaptive, decentralized measure if supported by country guidelines [13]. Programmes may also consider, as a temporary adaptation during COVID-19, dispensing oral-fluid HIV-screening kits in the community to parents living with HIV (index clients) to screen biological children for HIV at home, provided that criteria are met (detailed for PBFW above). In Kenya, HIVselftest kits are being distributed to adolescent girls and young women through community health workers; they are then accompanied for confirmatory diagnosis and linkage to ART if needed (PATH: Afya Ziwani, Kenya, presentation at USAID's Partner Operational Solutions in Response to COVID-19 Meeting, April 28, 2020). A written standard operating procedure for home testing, training for healthcare providers, intact supply chain plan, community or facility-based linkage to treatment and caregiver education to mitigate potential inadvertent social harm should be in place to support this approach [12,14].
Case identification during COVID-19 should incorporate virtual approaches within existing OVC and other community case management platforms to allow for continuity of cost-effective case-finding while further strengthening collaboration between community and clinical platforms. Risk screening for children and adolescents for HIV, abuse, harm and violence should continue by phone using established risk-assessment tools, with strong bi-directional linkage to peer and group support and HIV testing and treatment services if needed [15].

| Differentiated service delivery adaptations for PBFW, infants and C/ALHIV
Differentiated service delivery models, including family based multi-month dispensing (MMD) of ART and community-based ART services, are potentially impactful programme adaptations for individuals initiating or continuing ART while adhering to national guidelines for COVID-19. These approaches address the frequency with which clients visit the health facility, and the need for triage, clinic flow and infection control measures [16].
Community-based ART approaches have demonstrated high retention rates among paediatric and adult clients and are supported for children, adolescents and PBFW [17][18][19][20][21]. These approaches leverage either the public or private sector for decentralized ART distribution and include fixed community distribution points, mobile outreach ART delivery, home delivery from pharmacies or via mail and adherence clubs [22]. In addition, same-day ART initiation in the community for PBFW, infants and C/ALHIV is a reasonable alternative to facilitybased initiation coupled with virtual adherence follow-up [23][24][25]. During COVID-19, community-based ART services can provide cost savings for clients and facilities by leveraging the health workforce (community health workers, support group members and lay cadres) to provide COVID-19 prevention education to clients [26], provided that such support does not place health workers at increased risk of COVID-19 infection and personal protective equipment is available if needed. Where feasible, facility-based staff can be reallocated to support community-based ART distribution and other essential activities [6].
Being able to access timely ART refills during the COVID-19 pandemic is a reported concern among PLHIV and rapid scaleup of MMD is one strategy to address these concerns [2,27]. With MMD, families can access longer ART refills from health facilities or through community-based distribution approaches. Implementation of family-based MMD within the context of COVID-19 warrants proactive flexibility with optimized ARV formulations and treatment regimens, as well as bundling with other prescriptions for tuberculosis preventive therapy and cotrimoxazole. If in accordance with national guidelines, providers should ensure that all eligible family members have at least a three-month supply of ART and when feasible, a six-month supply [4,6]. Transition of adolescents and PBFW to tenofovir/lamivudine/dolutegravir should be accelerated with uninterrupted continuation of MMD (if they were already receiving MMD) and virtual follow-up to assess for side effects and tolerability. For those who miss ART refills, continuing retention support should be adapted through virtual approaches, with homebased visits only when necessary [6].
Even prior to COVID-19, family-based MMD has been recommended for PBFW, yet implementation has been limited [17,25,28]. As part of the early response to COVID-19, Malawi, Ethiopia and Mozambique increased flexibility for MMD among PBFW using several strategies, including initiating all pregnant women on a three-month supply of ART (3MMD) at the first ANC visit and initiating breastfeeding women on 3MMD between three and six months after delivery (P. Preko, CQUIN, ICAP and A. Wate, USAID/Mozambique personal communications). For pregnant women living with HIV who will not be able to return to the facility for delivery, providers should consider "mother-baby packs" containing multi-month ART for mothers, infant prophylaxis and cotrimoxazole with dosing instructions and a clear reminder of when and where EID testing can be completed. In some countries, HEI are now eligible for 3MMD with cotrimoxazole preventive therapy. Clinic staff and community cadres, especially OVC case workers, can provide instructions on these bundled services and offer virtual adherence follow-up at intervals recommended in national guidelines [6].
For C/ALHIV, healthcare providers should maximize use of 3MMD for CLHIV two to five years of age, and six-month dispensing (6MMD) of ART for C/ALHIV ≥ 5 years of age [28]. Given current manufacturing constraints of pediatric lopinavir/ ritonavir solid formulations [29], this may result in providing 3MMD to all CLHIV ≥ 2 years of age and who weigh <20 kg, while providing 6MMD for C/ALHIV ≥ 20 kg. While some national guidelines may recommend that C/ALHIV, especially those initiating ART, return to the health facility sooner, it is unlikely that an interval dose change will be required during this time [17]. Virtual adherence and retention follow-up for C/ALHIV and their caregivers that aligns with national guidelines appointment intervals will also reduce exposure risk and facility burden.
Special considerations should be given when including certain C/ALHIV in MMD. Caregivers of infants living with HIV should receive enough ART to last until the infant's next routine immunization appointment. C/ALHIV who are doing well on second-or third-line ART should receive at least 3MMD, even if such children do not qualify for MMD under normal circumstances [6]. C/ALHIV who are virologically unsuppressed should receive at least three months of their current regimen while working on adherence through monthly virtual assessment with facility, community and OVC staff.
Due to disruptions in global and national supply chains related to COVID-19, countries should immediately implement inclusive MMD and promptly order ART regimens needed through the end of 2021, combined with supply chain modifications including reducing buffer stock and pushing ARVs out of central stores and into health districts, sites and patients' hands [5,6,30].

| Adaptations for C/ALHIV unstable on ART,
including advanced disease, treatment failure and second-/third-line ART C/ALHIV unstable on ART suffer from increased all-cause morbidity and mortality [31]. For these C/ALHIV, it is important to quickly address failing ART regimens while prioritizing clinical support and virtual case management (including OVC services) when resources and staffing are limited. All children ≥20kg should be switched to a regimen with dolutegravir 50mg, and those failing non-nucleoside reverse transcriptase inhibitorbased therapy should be transitioned to a protease inhibitorbased (if < 20kg) or dolutegravir-based (if ≥ 20kg) regimen [32]. C/ALHIV who change regimens should receive at least 3MMD and should have virtual assessments at two weeks and then as needed if doing well. Moreover, viral load (VL) monitoring should not be a prerequisite to ART transitions.
C/ALHIV unstable on ART are a particularly vulnerable group that should be prioritized for clinical support and virtual case management when resources and staffing are limited. Every effort should be made to ensure families with unstable

| CONCLUSIONS
It is an immense global health challenge to protect families from acquiring SARS-CoV-2 while sustaining essential HIV services in the context of the COVID-19 pandemic. Countries must take decisive action with enabling policies to ensure that targeted, family-friendly programme adaptations are implemented for PBFW, infants, and C/ALHIV to limit SARS-CoV-2 transmission, while ensuring the continuation of high-quality, life-saving HIV services. It will be crucial for programmes to support programme adaptations using positive messaging to instil confidence in clients who may otherwise be fearful of accessing routine services due to COVID-19 infection risk. The efficiencies and cost savings gained through these adaptations have the potential topreserve investments made in controlling the HIV epidemic and to protect clients and healthcare workers from COVID-19, while also driving innovations that could result in more efficient and effective HIV programmes for years to come.