- Keywords > active pharmacovigilance surveillance
- Keywords > active surveillance system - antiretroviral program
- Keywords > antiretroviral medicines
- Keywords > HIV/AIDS, malaria and TB
- Keywords > national reporting systems - adverse reactions to medicines
- Keywords > neglected tropical diseases (NTD)
- Keywords > quality assurance of antiretrovirals
- Keywords > signals - (Drug safety/Clinical trials)
- Keywords > toxicity of new ARV medicines
- Keywords > WHO pharmacovigilance indicators
(2018; 56 pages) [French]
The 2016 WHO consolidated guidelines on the use of antiretroviral (ARV) drugs recommended initiating ART earlier and new first-line alternative treatment options such as dolutegravir (DTG) and efavirenz at the lower dose of 400 mg (EFV 400). The guidelines also recommend darunavir/ ritonavir (DRV/r) and raltegravir (RAL) as alternative ARV drugs for second-line treatment. To date, more than 50 low- and middle‑income countries have included or plan to include dolutegravir (DTG) as first-line treatment in their national guidelines. Moreover, such countries such as Cambodia, China, the United Republic of Tanzania and Zimbabwe have or are considering introducing EFV 400 for use in first-line ART.
With the availability of a generic fixed-dose combination of dolutegravir with tenofovir and lamivudine (TLD) and recent pricing agreements that have significantly reduced its cost, more countries are considering transitioning to using DTG for preferred first-line ART. To date, however, data on the safety of DTG and other new ARV drugs are limited in important subpopulations, including young children, pregnant women, people with HIV and TB coinfection and individuals with advanced disease. Among the general population, there are currently limited data from real-world settings on the safety of new ARV drugs, including DTG, within large-scale national treatment programmes. Moreover, central nervous system adverse drug reactions, especially insomnia, have been reported in observational cohorts among individuals receiving DTG. Reports from cohort studies of a higher risk of immune reconstitution inflammatory syndrome among people receiving integrase inhibitors have also raised concerns about safety. As a result, early-adopter countries are implementing approaches for monitoring toxicity with the support of partners that are described in later sections of this tool.
In the current context of treatment being rapidly scaled up, prolonged exposure to ARV drugs and transition to new ARV drugs, ARV toxicity clearly needs to be monitored to better understand the risks of ARV drugs under the conditions of actual use. Systematically collecting information about medicines used in a defined population helps to ensure that medicines have an acceptable safety profile and are used appropriately. To address these gaps in safety data, WHO recommended enhanced monitoring and surveillance of toxicity in a recent technical update on transition to new ARV drugs in HIV programmes: clinical and programmatic considerations.
This implementation tool builds on the above guidance as well as the WHO 2015 consolidated strategic information guidelines for HIV in the health sector, the 2016 consolidated guidelines on the use of ARV drugs for treating and preventing infection and the 2017 consolidated guidelines on person-centred HIV patient monitoring and case surveillance. It describes in more detail the recommended approaches for routine monitoring of toxicity integrated with the national monitoring and evaluation system and targeted approaches to monitoring toxicity to enable enhanced monitoring and reporting of treatment-limiting toxicity to support country implementation and generation of local data. In addition to recognizing the linkages, coinfected populations and commonalities across TB, hepatitis B and C and with the aim of encouraging integration, this tool also highlights the recommended toxicity monitoring approaches and existing tools across these disease areas. The approaches presented in this tool describe the methods and tools that can be used for monitoring treatment-limiting toxicity associated with new ARV drugs. In this version, the reporting tools provided in the annexes relate to monitoring the toxicity of DTG as a priority since many countries are moving towards adopting it in first‑line regimens. Going forward, additional annexes and tools will be developed as countries approve and/or adopt new ARV drugs, and WHO will publish these online.