Integrating GRADE-ADOLOPMENT into the essential medicine review process for dapivirine vaginal ring for the South African primary care setting

Oral
2024 Prague [Global Evidence Summit]
Cohen K1, Dawood H2, Jamieson L3, Johnson L4, Leong T5, McCaul M6, Nel J7, Osih R8, Subedar H9
1South African Primary Healthcare and Adult Hospital Level Expert Review Committee, , Pretoria, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa, Cape Town, South Africa
2Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, South Africa ,, KwaZulu-Natal, South Africa; Department of Internal Medicine, Grey’s Hospital, Pietermaritzburg, South Africa
3Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, South Africa, Johannesburg, South Africa; The South African Department of Science and Innovation/National Research Foundation Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, South Africa, Stellenbosch, South Africa
4Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa, Cape Town, South Africa
5Health Systems Research Unit, South African Medical Research Council (SAMRC), Cape Town, South Africa
6South African Primary Healthcare and Adult Hospital Level Expert Review Committee, , Pretoria, South Africa; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa, Stellenbosch, South Africa
7Infectious Diseases Division, Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; South African Primary Healthcare and Adult Hospital Level Expert Review Committee, , Pretoria, South Africa
8South African Primary Healthcare and Adult Hospital Level Expert Review Committee, , Pretoria, South Africa; Boston Consulting Group, Johannesburg, South Africa
9Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, South Africa, Johannesburg, South Africa; HIV Directorate, South African National Department of Health, Pretoria, South Africa

Background:

South Africa’s Primary Healthcare (PHC) Essential Medicine List (EML) and Standard Treatment Guidelines recommend oral pre-exposure prophylaxis (PrEP) to prevent HIV acquisition in high-risk individuals. Given the country’s high incidence of HIV amongst women aged 15 to 49 years, there was a need for a rapid review of dapivirine vaginal ring as an alternative option. This informed the ministerially appointed National Essential Medicines List Committee’s (NEMLC) decision to include dapivirine in the national EML.

Method:

NEMLC’s PHC technical subcommittee developed clear question and eligibility criteria for the rapid review during the initial topic prioritization phase. This scoping exercise identified 1 guideline and no randomized controlled trials (RCTs) comparing dapivirine ring to oral PrEP. A multidisciplinary team of experts was established to implement the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT process to avoid duplication and improve efficiency. We reviewed and appraised up-to-date matched guidelines with supporting systematic review evidence and used the GRADE Evidence-to-Decision framework. We also conducted a cost-effectiveness analysis, from the “payer’s” perspective, and contextual concerns.

Results:

We rapidly adapted 2021 World Health Organization (WHO) PrEP guidelines for South Africa in 3 months using the GRADE-ADOLOPMENT approach. We identified a systematic review of 2 placebo-controlled RCTs of dapivirine, which informed the 2021 WHO PrEP Guidelines. The dapivirine ring resulted in 23 fewer HIV acquisitions per 1000 users compared with placebo, with no increase in adverse events (moderate certainty evidence). There were no trials in adolescent/pregnant/breastfeeding clients. The review also identified a paucity of local research characterizing social harms or quantifying and comparing dapivirine adherence with other PrEP options. Dapivirine was found to be less cost-effective than oral PrEP, currently priced at $14.59/ring.

Conclusion:

The GRADE-ADOLOPMENT approach integrated into NEMLC’s decision-making process was found to be reproducible, credible, and transparent. It balanced efficiency with methodological rigor, essentially staying true to the evidence while considering contextual needs. Based on the rapid review, NEMLC suggested not including dapivirine ring as an additional PrEP option for women. This recommendation may be revisited if the price is reduced; there are evidence in pregnancy/breastfeeding/adolescents and local data on adherence and associated social harms.