Outcomes of community-based differentiated models of multi-month dispensing of antiretroviral medication among stable HIV-infected patients in Lesotho: a cluster randomised non-inferiority trial protocol

Lesotho is undergoing a significant health transition characterised by high burden of infectious diseases such as HIV/AIDS, tuberculosis and an emergence of non-communicable diseases [1]. Among adults, HIV prevalence in Lesotho is reported to be 25% and 53% of adults are receiving antiretroviral treatment (ART) [2]. An estimated 310,000 people were living with HIV and 18,000 died from AIDS related issues in 2015 [3]. PEPFAR adopted the UNAIDS 90–90-90 targets and the new WHO guidelines on when to initiate ART [4]. The WHO guidelines recommend ART initiation immediately after testing positive, regardless of CD4 count, with lifelong continuation to warrant and improve individual ‘s health and reduce HIV transmission [5]. To realize the full benefits of this approach, high levels of adherence and retention are needed. In low to middle income countries (LMICs) including Lesotho, long waiting times in ART clinics, cost of travel to clinics and other life commitments are known to disrupt and reduce the adherence and retention levels. A need for monthly dispensing and/or systems that require multiple separate visits for refills and clinical evaluations can raise significant challenges for people living with HIV (PLHIV) and result in treatment interruptions or complete disengagement from care [6]. Hence, extending of interval ART refills may improve outcomes, if supply can be guaranteed for up to six months for stable patients in low resourced settings.

Currently, many LMICs including Lesotho dispense ART monthly which places demands on the health system and can lead to suboptimal adherence and disengagement in care due to the time and cost of frequent visits to clinic. There is need to implement novel strategies for ART dispensing to enable health systems cope with the ever-increasing number of HIV patients needing care and treatment. A gap exists in allowing stable patients to have an adequate and longer-term supply of ART especially if this does not compromise outcomes of interest including retention and viral load (VL) suppression.

Community based models of care i.e. CAGs are postulated to further strengthen adherence, retention and viral suppression. These models give peer support among patients. CAGs have been successfully implemented in Lesotho and introducing MMD into them can have the same intended outcomes as facility-based interventions, whilst additionally decongesting and decentralising facilities.

Potential benefits for this approach includes (i) higher adherence to ART and retention in care, (ii) reduced per-patient cost of providing ART, by reducing the number of clinic visits required, (iii) decongestion of clinics to allow for increased capacity to manage patients newly diagnosed with HIV, those with infectious complications, treatment failure, and other co-morbidities and (iv) decreased waiting time and improved efficiency at clinics allowing for improved quality of care and patient satisfaction [7, 8].

Limited data are available from LMICs on multi-month scripting and dispensing and on studies using community-based models of care. A review of the literature reveals a lack of randomized studies of different ART dispensing intervals. An abstract presented at the Conference on Retroviruses and Opportunistic Infections, 2016 using Zambian data, suggested that requirements for monthly dispensing and/or systems that require multiple separate visits for refills and clinician evaluation can raise significant challenges for people living with HIV and result in treatment interruptions or complete disengagement from care [6].

This study’s primary objectives are (i) to determine if stable patients receiving 3 monthly dispensing of ART within CAGs have non-inferior retention in care and viral load suppression than stable ART patients receiving 3 monthly dispensing at health facilities after 12 and 24 months, (ii) 6 monthly dispensing of ART within the community from a health care worker have non-inferior retention in care than stable ART patients receiving 3 monthly dispensing at health facilities after 12 and 24 months and (iii) 6 monthly dispensing of ART within the community from a healthcare worker have non-inferior retention in care than stable ART patients receiving 3 monthly dispensing within CAGs after 12 and 24 months. The secondary objectives are to compare cost outcomes (cost per patient retained and cost per patient retained with viral suppression) between the three models, investigate the acceptability of 3 and 6 monthly community-based ART distribution among patients and service providers and to assess if there are measurable gains in clinic productivity realized following the introduction of community based MMD of ART.

In this paper, we present and describe a demonstration study protocol that will evaluate retention in care, virologic suppression, feasibility and cost effectiveness of community based differentiated models of MMD approaches of ART among stable HIV patients in Lesotho. Community based models for delivering ART have potential of being an integral part of strengthening the HIV treatment cascade. To meet the UNAIDS targets to end the AIDS epidemic by 2030, a need exists in diversifying ART delivery in ways that are acceptable to communities and maintaining good outcomes including retention and viral suppression [4, 10]. However, community systems must be adequately resourced, including infrastructure that allows for linking and integration with health facilities, allowing for better sustainability and scaling -up.

The WHO has recommended provision of ART through community models, only if operating guidance and monitoring are provided [5]. These strategies are to ultimately significantly reduce the burden experienced by patients and health care providers. Though all models, are to include stable patients, in this context virologically suppressed, and those who are able to adhere to ART [11], the community multi month dispensing approaches including both CAGs and community ART distribution points have been shown and postulated to provide gains for patients by (i) reducing time and transport costs (WHO, 2016), (ii) increasing peer support for adherence (through clubs and CAGs) [11, 12] (iii) reduced defaulting and enhancing community participation [5]. Whereas, for health providers it (i) reduces workload (ii) and maintains and improves health outcomes and improves self-management of patients. Additionally, these approaches, could be extended to key populations including migrants in Sub Saharan Africa, where patients move away from their homes for work and other economic reasons [13]. A study among migrants, assessing healthcare needs, preferences and accessibility barriers of HIV-positive migrant patient populations in high disease burden, borderland districts of Lesotho showed that less than 7% opted for a 1–2 month ARVs refills [14]. Whereas 30.2%and 63% indicated a preference for 3–4 month and 5–6 month refills respectively. More than 65% encountered barriers to receiving their ARVs and about 25% defaulted while abroad [14].

Previous lessons have been learnt to allow for improved management of risk when implementation multi month dispensing ART projects. We anticipate this will include a need for reliable supply of medication [15], access to quality clinical data and linkages, including VLs results, frameworks to support lay worker’s cadre [16, 17], involvement of community stakeholders, and reliable data systems and records of key indicators. The design to be used namely a pragmatic, parallel, cluster-randomized non-inferiority design has the following advantages that add rigor to findings [18]. Additionally, the non-inferiority design aims to determine whether a new approach is not worse than a standard approach by more than a preset margin [19].

In Lesotho, viral load monitoring is performed annually for stable adult’s patients on ART. We anticipate missing viral results. Viral load suppression is thus a secondary outcome. Our findings will be interpreted with care when generalizing to other settings, as there are varying definitions of the term stable patients [20], which is an inclusion criterion in the current study. Additionally, we will not ascertain outcomes of unstable ART patients that will be screened out who may have potentially benefited from the interventions. Large quantities of drugs will be supplied to those that will enroll in the 3 and 6-month arms (including ART, CPT and IPT). This will be challenging for patients who have not disclosed their HIV status to family members leading to erroneous disclosure of HIV status. There is risk for patients to share medication with peers. Both participants and providers will not be blinded, and this might lead to participants wanting to transfer to another arm. Regardless of arm, participants are more likely to be retained if they are aware they are part of a study.

Despite these limitations, this study has a robust design, it is will be the first randomized study to explore the outcomes of retention, virologic suppression and cost effectiveness through differentiated community ART distribution approaches in Lesotho. The study will provide important data regarding the effectiveness of community models for ART distribution and is anticipated to inform policy regarding best practice among HIV-positive patients receiving ART and what is needed to strengthen health systems for rapid scaling up of ART in a contextualized, sustainable and cost-effective manner.