Evidence for reducing the frequency of clinical visits and extending the duration of antiretroviral therapy (ART) refills for clients who are stable on ART is increasing. The World Health Organization (WHO) recommends both clinical visits and ART refills to be delivered every 3-6 months and is currently reviewing this guidance .
A recent systematic review to assess the impact of reduced frequency of clinic visits and drug dispensing on client outcomes reported that less frequent clinic visits led to high rates of being retained in care (odds ratio, OR: 1.90; 95% confidence interval, CI: 1.21-2.99). Although no differences were found in virological failure, morbidity or mortality, most estimates favoured reduced clinical visits. Reduced frequency of antiretroviral (ARV) pickups also supported improved retention (OR 1.93; 95% CI: 0.62-6.04) . The principle of differentiating between the need for a clinical visit versus an ART refill visit, combined with extended ART refills, has been used in a number of facility-based individual models of ART delivery. These models go beyond only extending ART refills to reducing time spent at the facility setting up fast track or quick pick-up service organisation.
Evidence of the effectiveness of facility-based individual models has been reported from three studies in Uganda [3,4,5]. The first was a cost-effectiveness study conducted after implementing a pharmacy-only refill programme (PRP) (six-monthly clinical reviews and two-monthly ART refills from the pharmacy). The PRP was less costly (US$520/year versus $655/year) and more cost effective than the standard of care . The second study assessed clinic efficiencies after implementation of a fast-track system (six-monthly clinical visits with two-monthly ART refills after seeing a triage nurse). Median waiting time was reduced from 102 to 20 minutes, with increased client and provider satisfaction in the intervention group compared with the standard of care . The third was a descriptive study after implementation of a refill pick-up system (six-monthly clinical review and ART refill of 30-90 days at clinician discretion). There were significant reductions in missed appointments from 24.4% to 20.3% (adjusted odds ratio, AOR: 0.67; CI: 0.59-0.77) and medication gaps of three days or more from 20.2% to 18.4% (AOR: 0.69; CI: 0.60-0.79) in the intervention group compared with the standard of care .
Data reported from Malawi describes a growing cohort of clinically stable clients receiving multi-month ART refills or enrolled in a fast-track clinic system (six-monthly clinical review and three-monthly ART refills from lay healthcare workers) known as the six-monthly appointment (SMA) strategy. In a mixed-methods process evaluation, 69% of clients at 730 Malawian ART sites were accessing multi-month ART refills .
In a study reporting initial 12-month outcomes, of the 5,800 clients in the SMA model, 97% (95% CI: 96-97%) were retained [7, 8]. A 2016 retrospective study that assessed all clinically stable clients eligible for the SMA model between 2008 and 2015 (n=18,957) found that 80.8% enrolled with median time from eligibility to enrolment of six months (interquartile range: 0-17 months). Cumulative probability of death or loss to follow up (LTFU) five years after first SMA eligibility was 56.3% (95% CI: 52.4-60.2%) among those never enrolled for SMA, 13.9% (95% CI: 12.5-15.6%) among early SMA enrolees (within six months of eligibility) and 8.1% (95% CI: 7.2-9.0%) among late SMA enrolees (more than six months after eligibility). In addition, a significantly higher rate of attrition (death or LTFU) was observed among clients during non-SMA periods compared with those during SMA periods (adjusted rate ratio: 1.87; 95% CI: 1.68-2.08, p<0.001) .
A 2019 study reported long-term retention outcomes of SMA enrolees. The cumulative probability of retention in care one year after first SMA eligibility was 86.8% (CI: 85.6-87.8%) among those who never enrolled, 97.3% (CI: 96.8-97.6%) among early SMA enrolees and 99.8% (CI: 99.7-99.9%) among late SMA enrolees. The corresponding figures at five years were 47.4% (CI: 45.0-49.7%), 85.5% (CI: 84.0-86.9%) and 93.4% (CI: 92.8-94.0%). Among eligible clients enrolling for SMA, the adjusted hazard of attrition was 2.4 (95% CI: 2.0-2.8) times higher during periods of SMA discontinuation than during periods on SMA. Male gender, younger age, more recent SMA eligibility and WHO Stage 3/4 conditions in the past year were also independently associated with attrition from SMA. Approximately 26,000 consultations were “saved” during 2014 alone .
The Sustainable East Africa Research in Community Health (SEARCH) study, a test-and-treat trial in Uganda and Kenya, streamlined HIV care for adults (≥15 years; CD4 ≥350 cells/μl), including nurse-driven triage and referral for visits with physician for complex cases; three-month combined clinical and ART refill visits for stable clients; consolidation of multiple chronic disease services at encounter; client appointment flexibility; and missed appointment tracing and children (2-14 years; CD4 ≥500 cells/μl) from ART start at first visit. This resulted in 48-week retention and viral suppression among adults of 92% (897/972) and 93% (778/838) and retention and viral suppression among children of 89% (74/83) and 92% (65/71)  in Uganda and Kenya, respectively. There were also significant reductions in time spent at the health facility and away from work or other usual activities. Out-of-pocket expenses for clients from baseline to one year later were reduced in Uganda, but not in Kenya . Costing of streamlined HIV care was similar or lower to standard of care cost estimates after accounting for viral load (VL) testing and VL result counselling session costs . In the Western Cape, South Africa, a “quick pick-up” model for clinically stable clients documented that 12 months after joining the model, 96% of clients were still in care, with 85% of them remaining in the model .
In Zambia, an analysis of 62,084 clinically stable clients (on treatment for >6 months with CD4 >200 cells/μl and not on TB treatment or unwell) showed that the longer the appointment interval and ART refill (up to six months), the less likely the client was to have missed appointments, have a gap in medication or become lost to follow up . Qualitative work to explore healthcare workers and client experiences of a fast-track model demonstrated that healthcare workers and clients viewed the model as being able to decongest the clinic and reduce waiting times. Overall, the model was highly applicable and acceptable. There were requests to carry out additional activities, such as taking weight and blood pressure that were continued, in the dedicated fast-track service room . The need for additional screening activities during ART refill visits should be further explored.
The majority of differentiated ART delivery models have been demonstrated using two- to three-monthly ART refills. In Ethiopia, six-monthly refills were introduced with biannual clinical visits. In total, 51% of clients were assessed to be eligible for this model, of whom 49% enrolled . Of the 51% who declined enrolment, the most commonly cited fear was disclosure due to the large volume of medication; there were also concerns regarding safety of storage. Data on retention is not yet available.
Appointment spacing has also been shown to have benefits in low-prevalence settings. In Guinea in West Africa, the SMA model was piloted in 2013 and expanded in 2014 followed the outbreak of the Ebola virus disease . The six-monthly spacing approach, Rendez-vous de Six Mois (R6M), was scaled up to 60% of the cohort (n=1,166). Clients outside of the capital city of Conakry received six-monthly clinical visits and ART refills, and those in Conakry received three-monthly ART refills and six-monthly appointments. The R6M group had a 60% reduction in the risk of attrition compared with the standard of care after adjusting for duration on ART and TB co-infection.
Outside of sub-Saharan Africa, a facility-based individual differentiated ART delivery model implemented in Yangon, Myanmar, has reported good early outcomes. Clients were differentiated between unstable, short-term stable (29.2% of cohort) and long-term stable (51.2% of cohort). Short-term stable clients received three-monthly combined clinical review and ART refills visits alternating between a physician and nurse. Long-term stable clients received six-monthly clinical reviews from a nurse and three-monthly fast-tracked ART refills from a pharmacist or dispenser. The number of clients that a team made up of a physician, nurse and counsellor could manage increased from 745 in 2011 to 1,627 in 2014, averting 41,116 physician visits. Aggregated 12-month retention for both clinically stable groups was 98.7%, with clinical treatment failure of 0.8% and immunological treatment failure of 5.8% .
In politically unstable settings, such as the Central African Republic, South Sudan and the Democratic Republic of the Congo, the ability to provide extended refills of three to six months has also enabled continuity of ART delivery during periods of acute conflict .
Extended ART refills and fast-track service delivery models have also shown benefits for children. In a study assessing the implementation of multi-month prescriptions (MMPs) for children across six sub-Saharan African countries, clients aged 0-19 years were transitioned to MMPs when they were defined as clinically stable. The study analysed outcomes from more than 22,000 children, 66% of whom were transitioned to MMPs. Of those transitioned, 2.6% were lost to follow up and 2% died. Virological suppression remained high over the first five years in MMPs, ranging by year from 79% to 85%. These results provide reassuring evidence that children and adolescents who are clinically stable can have good outcomes with reduced visit frequencies and extended ART refills .
A second model implemented in Tanzania utilized multi-month prescriptions, but also introduced a fast-track component where children could go directly to the pharmacy to collect their ART refills after an initial triage. Clients in this model received ART refills every two months and had a clinical visit every four months. A total of 51.3% of the paediatric, adolescent and young adult ART clients were able to be enrolled in this model, with 98.8% remaining in care . Reduced clinical visits and extended ART refills for clinically stable adults, children and adolescents should be a priority model of differentiated service delivery that can yield benefits in both high- and low-prevalence settings.