POA

The challenge

Antiretroviral treatments have revolutionised HIV care. However, they are not a cure, and people living with HIV must continue to take a daily cocktail of drugs to control their infections. Over time, this daily pill-taking can become difficult to maintain and creates a risk of stigmatisation.

Long-acting injectable treatments overcome the need for daily pill-taking but have drawbacks. They require cold chain infrastructure, must be administered by trained health workers, and disrupt the regular contacts with HIV services that are now integral to HIV care.

A possible alternative approach is offered by a new oral drug combination, lenacapavir plus islatravir, which needs to be taken just once a week. In addition, the components of this combination may have fewer side effects than current standard treatments. Although a phase II trial of lenacapavir plus islatravir has been carried out in the USA, there are no data on its use in sub-Saharan Africa, even though the region accounts for 75% of people living with HIV.

The project

The POA project is conducting the first trial of lenacapavir plus islatravir in sub-Saharan Africa to generate critical data to support its introduction in the region.

A phase III trial is being carried out, involving more than 500 people living with HIV in Côte d’Ivoire, Kenya, Uganda and Zimbabwe. It will compare how well viral replication is controlled by standard antiretroviral drug treatments and by the weekly use of lenacapavir plus islatravir. The study will also examine patients’ preferences and the impact on daily life, as a weekly treatment option could substantially improve quality of life.

Other key aspects of the project include: 

• Pharmacokinetic studies to check circulating drug levels, as the drugs may be metabolised differently in African populations.
• Implementation science studies to identify facilitators and barriers that could influence the speed of introduction into routine care.
• Development and evaluation of a new assay to measure drug metabolite levels in urine samples, which could provide a simple-to-use tool for monitoring patients’ adherence to treatment. 

In addition, although pregnant women will not be recruited into the trial, the study will carefully monitor women who become pregnant during the trial and carry out pharmacokinetic modelling to assess the suitability of the new treatment for this group. Such work would provide a foundation for studies of lenacapavir plus islatravir in pregnant women, potentially accelerating their access to this new treatment. 

Impact

Weekly lenacapavir plus islatravir treatment could have a profound positive impact on HIV treatment in sub-Saharan Africa. The project will:

• Generate the first data on weekly oral lenacapavir plus islatravir treatment in sub-Saharan African people living with HIV.
• Provide sufficient data to support licensing approvals of the new combination.
• Provide policymakers with key evidence on cost-effectiveness and potential barriers to implementation.
• Potentially shorten the pathway to approval of lenacapavir plus islatravir for use in pregnant women.

Introduction of weekly oral lenacapavir plus islatravir treatment could have a potentially transformative impact on HIV care in sub-Saharan Africa. By making adherence easier, it would deliver health benefits, reduce demands on health services, and improve the quality of life of people who currently face a demanding schedule of daily drug-taking.