Antiretroviral therapy dispensing for patients who are clinically stable
Authors: Euphemia Sibanda, Miriam Taegtmeyer
Journal: The Lancet Global Health (2021)

Achieving HIV treatment targets, such as the 95-95-95 target,1UNAIDS90-90-90: an ambitious treatment target to help end the AIDS epidemic. UNAIDS, Geneva2014Google Scholar will help to control the HIV epidemic. Implementing efficient models for optimising patient engagement is key to accomplishing these targets. WHO recommend multimonth dispensing of antiretroviral therapy (ART) for intervals of up to 6 months in patients who are clinically stable, because of the positive effects of reducing the burden on health systems, as well as saving time and opportunity costs for patients.2WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendation for a public health approach. World Health Organization, Geneva2016Google Scholar In previous studies, 6-monthly ART dispensing intervals delivered in the community were non-inferior to 3-month dispensing when delivered through facility-collection models (eg, at HIV clinics).3Tukei BB Fatti G Tiam A et al.Twelve-month outcomes of community-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho: a cluster-randomized noninferiority trial.J Acquir Immune Defic Syndr. 2020; 85: 280-291Crossref PubMed Scopus (6) Google Scholar, 4Fatti G Ngorima-Mabhena N Mothibi E et al.Outcomes of three- versus six-monthly dispensing of antiretroviral treatment (ART) for stable HIV patients in community ART refill groups: a cluster-randomized trial in Zimbabwe.J Acquir Immune Defic Syndr. 2020; 84: 162-172Crossref PubMed Scopus (12) Google Scholar In this issue of The Lancet Global Health, Risa M Hoffman and colleagues5Hoffman RM Moyo C Balakasi KT et al.Multimonth dispensing of up to 6 months of antiretroviral therapy in Malawi and Zambia (INTERVAL): a cluster-randomised, non-blinded, non-inferiority trial.Lancet Glob Health. 2021; 9: e628-e638Summary Full Text Full Text PDF Scopus (2) Google Scholar add to this evidence by reporting on a pragmatic, non-inferiority, cluster-randomised trial of facility-based multimonth dispensing in Malawi and Zambia (the Varying Intervals of Antiretroviral Medication Dispensing to Improve Outcomes for HIV [INTERVAL] trial). The authors randomly assigned 30 health facilities providing outpatient ART care (clusters) to dispense ART refills to patients who were clinically stable in three dispensing interval durations. These three groups were: (1) standard of care, guidelines of which specified facility ART refills at 3-month intervals, but was variably implemented at baseline; (2) facility-based 3-monthly (ie, 90-day) ART dispensing; and (3) facility-based 6-monthly (ie, 180-day) ART dispensing. Questionnaires completed at enrolment included sociodemographic information and visit costs. Follow-up regarding missed refill visits was done by health facilities according to standard of care, with research teams providing support for implementation fidelity but having no further interaction with the participants. After 14 months, study staff abstracted ART refill data from health facility records. Costs of providing ART services were collected from representative sites and national sources. The primary outcome of retention in care at 12 months was defined as the proportion of patients who had less than 60 consecutive days without ART during study follow-up. Secondary outcomes included costs of service provision, viral suppression (defined as <1000 copies/mL in Malawi and <20 copies/mL in Zambia), and feasibility and acceptability of dispensing intervals to participants and providers. 6-monthly ART dispensing was non-inferior to standard of care and to 3-monthly ART dispensing, showing a percentage point increase in retention of 9·1% (95% CI 0·9–17·2) versus standard of care and of 5·0% (1·0–9·1) versus 3-monthly dispensing. Patients in the 6-monthly ART dispensing group spent an average of 17·6 days (16·1–19·2) without ART versus 30·6 (28·5–32·7) days for 3-monthly ART dispensing and 36·1 (33·8–38·4) days for standard of care. Viral load data were not available, and they would be key to investigate given the lower suppression levels in another multimonth ART dispensing study.4Fatti G Ngorima-Mabhena N Mothibi E et al.Outcomes of three- versus six-monthly dispensing of antiretroviral treatment (ART) for stable HIV patients in community ART refill groups: a cluster-randomized trial in Zimbabwe.J Acquir Immune Defic Syndr. 2020; 84: 162-172Crossref PubMed Scopus (12) Google Scholar Although the non-inferiority margin was achieved in Malawi, the overall increase in retention was mainly driven by a large increase in retention in Zambia, where the percentage point increase in retention was 15·5% (0·4–29·8) for 6-monthly ART dispensing compared with standard of care and 7·4% (1·7–13·1) compared with 3-monthly ART dispensing. One reason for improved retention might be the observed reduction in out-of-pocket costs to patients. Costs to patients were lowest in the 6-monthly ART dispensing group, with 45% reductions in annual costs for time losses in Malawi and 33% reductions in annual costs for time losses in Zambia. Lost potential income was reduced by 25% in Malawi and 33% for Zambia, and transport costs were lowest in the 6-monthly dispensing group by at least 25% in both countries relative to the costs in the standard of care group. The trial also showed slight reductions in ART programme costs; the average cost per patient retained was $89 for standard of care, $88 for 3-monthly ART dispensing, and $86 for 6-monthly ART dispensing in Malawi. The corresponding costs in Zambia were $144 for standard of care, $142 for 3-monthly ART dispensing, and $132 for 6-monthly ART dispensing. The slight reductions in cost could translate to large savings if implemented at scale. It should, however, be noted that programme costs were possibly underestimated by non-inclusion of costs for support offered by the study staff. Countries need to be supported to ensure successful implementation of HIV programmes. In the INTERVAL standard of care group, for whom no support was given, the 3-month dispensing interval was only used 59% of the time. Robust supply chain systems are key to successful implementation of multimonth dispensing, particularly in low-income and middle-income countries where complex global supply chains and shortage of trained logistics staff are associated with antiretroviral drug stockouts and shortages.6Minior T Douglas M Edgil D et al.The critical role of supply chains in preventing human immunodeficiency virus drug resistance in low- and middle-income settings.J Infect Dis. 2017; 216: S812-S815Crossref PubMed Scopus (6) Google Scholar It will be important for programmes implementing multimonth dispensing intervals to share lessons learned so that barriers can be addressed. Optimisation of dispensing programmes also requires investigation to ensure practices that uphold the positive effects of the intervention for patients are adopted. Although qualitative studies in patients show the strong acceptability of 6-monthly ART dispensing,7Hubbard J Phiri K Moucheraud C et al.A qualitative assessment of provider and client experiences with 3- and 6-month dispensing intervals of antiretroviral therapy in Malawi.Glob Health Sci Pract. 2020; 8: 18-27Crossref PubMed Scopus (9) Google Scholar concerns raised by health workers about poor storage of long-term drug supplies and sharing of medicines need to be investigated and addressed. Given the difference between Malawi and Zambia in the primary outcome, it would be important to do additional research to determine what components of programmes and contexts led to increased retention in patients. In summary, the INTERVAL trial adds timely evidence on multimonth dispensing of ART in the midst of the COVID-19 pandemic when programmes are looking to develop person-centred approaches for limiting exposure of people living with HIV to health facilities.8Traub AM Ifafore-Calfee T Phelps BR Multimonth dispensing of antiretroviral therapy protects the most vulnerable from 2 pandemics at once.Glob Health Sci Pract. 2020; 8: 176-177Crossref PubMed Scopus (2) Google Scholar Implementation is presently suboptimal—only 21 of 32 countries supported by the US President's Emergency Plan for AIDS Relief have 6-month dispensing policies,9Traub AM Ifafore-Calfee T Frymus D Phelps BR Multimonth dispensing of antiretroviral therapy for HIV.Lancet HIV. 2020; 7: e457-e458Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar although interest in 6-monthly ART dispensing is accelerating. As ART programmes worldwide shift patients who are clinically stable to receive multimonth dispensing, additional data for health outcomes, operational challenges, and barriers to implementation will help refine and optimise service delivery models to the needs of individuals and their contexts. We declare no competing interests. Multimonth dispensing of up to 6 months of antiretroviral therapy in Malawi and Zambia (INTERVAL): a cluster-randomised, non-blinded, non-inferiority trialClinical visits with ART dispensing every 6 months was non-inferior to standard of care and 3-monthly ART dispensing. 6-monthly ART dispensing is a promising strategy for the expansion of ART provision and achievement of HIV treatment targets in resource-constrained settings. Full-Text PDF Open Access