Since the approval of zidovudine monotherapy for treatment of AIDS in 1987, remarkable progress has been made in developing ARV drugs that are more effective against HIV infection. In recent decades, the standard of care has evolved from less potent and more toxic mono and dual therapies, which were used in the early 1990s, to highly active and better-tolerated combined drug regimens, including the adoption of fixed-dose combinations and harmonization of treatment regimens among different populations. This improved therapeutic and safety profile supports the current policy to treat all individuals with HIV as soon as diagnosis is confirmed. This has been shown to reduce mortality and improve life expectancy and quality of care for patients with HIV on antiretroviral therapy, even in low-income settings.

The expansion of therapeutic options and new drug formulations for adults living with HIV has been facilitated by a joint collaborative effort between international organizations, academic institutions, drug manufacturers and other stakeholders. This collective work has resulted in a number of initiatives to support ARV drug optimization. This includes at least 3 major international Conferences on Antiretroviral Drug Optimization (CADO), as well as several think tank meetings and technical working group activities aimed at proactively shaping the global research and policy agenda.

Despite significant progress in scaling up HIV services for children living with HIV, the treatment gap persists, with children continuing to present lower rates of viral suppression than adults. In the past 10 years, global stakeholders have come together to enable more focused and coordinated action to make age-appropriate optimal formulations more rapidly available for infants, children and adolescents living with HIV. These include the WHO-led Paediatric Antiretroviral Drug Optimization (PADO) group, which has established medium- and long-term priorities for drug development to accelerate access to optimal formulations, in the context of fragmented markets for ARV drugs in children. First released in 2013, the PADO list provides an evidence-based priority list and a clear, consistent message to guide industry and interested stakeholders on the most needed ARV formulations for children to be investigated and developed. This list has reduced the number of unnecessary formulations, and become a critical tool to focus research and development efforts and resources.

There are also significant gaps in the pharmacokinetics, safety and use of existing and novel ARV drugs to treat pregnant and lactating women living with HIV, while preventing the perinatal transmission of HIV. The PADO and CADO groups closely interact and collaborate with various stakeholders to identify key principles to guide focused, accelerated generation of critical data, in order to increase access to safer, more potent and better-tolerated ARV drugs for pregnant and lactating women. This aligns with the agenda to optimize research on antiretroviral therapy that has been established for adults.

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