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 patient 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) pick-ups 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.
Evidence of the effectiveness of facility-based individual models has been reported from three studies in Uganda. The first was a cost-effectiveness study conducted after implementing a pharmacy-only refill programme (PRP) (6-monthly clinical reviews and 2-monthly ART refills from the pharmacy). The PRP was less costly (US$520 versus $655 annually) and more cost effective compared with the standard of care . The second study assessed clinic efficiencies after implementation of a fast-track system (6-monthly clinical visits with 2-monthly ART refills after seeing a triage nurse). Median waiting time was reduced from 102 to 20 minutes with increased patient 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 (6-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 stable clients receiving multi-month ART refills or enrolled in a fast-track clinic system (6-monthly clinical review and 3-monthly ART refills from lay health care 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 more recent retrospective study that assessed all 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 SMA enrolled, 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 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) .
The SEARCH test and treat trial undertaken in Uganda and Kenya streamlined HIV care (nurse-driven triage and visits with physician referral for complex cases; 3-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) for adults (≥15 years; CD4 ≥350) and children (2-14 years; CD4 ≥500) 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 stable clients documented that at twelve months, 96% of clients who entered the model were still in care, with 85% of them remaining in the model .
In Zambia, an analysis of 62,084 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 patient was to be have missed appointments, have a gap in medication or become lost to follow up . Qualitative work to explore healthcare workers and patient 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, 6-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 and 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 6-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 6-monthly clinical visits and ART refills and those in Conakry received 3-monthly ART refills and 6-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 (29.15% of cohort) and long-term stable (51.19% of cohort). Short-term stable clients received 3-monthly combined clinical review and ART refills visits alternating between a physician and nurse. Long-term stable clients received 6-monthly clinical reviews from a nurse and 3-monthly fast-tracked ART refills from a pharmacist or dispenser. The number of clients that a team 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 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 youth across six African countries, clients aged 0-19 years were transitioned to MMPs when 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 differentiated model received ART refills every two months and had a clinical visit every four months. A total of 51.3% of the 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 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.