As HIV has transitioned from an acute to a chronic, managed condition, the quality of life and life expectancy of people living with HIV have both improved significantly. The new health challenges for people living and ageing with HIV are the prevention and treatment of non-HIV conditions. But what information do we have about how treatments for non-HIV conditions may impact on a person living with HIV and their antiretroviral (ARV) medication?
Data gaps in pharmacological data are not unusual. The need for clinical trials to gather ‘clean’ data and guarantee commercial gain often leads to the exclusion of ‘complicating factors’, such as participants with pre-existing conditions or other groups such as women of child-bearing age or those perceived as ‘hard to reach’. The result is that medication-related data is skewed, for example, towards mainly white cisgender males (Criado Perez, 2019).
The lack of Black and ethnic minority groups included in clinical trials has been highlighted in cancer care (Iyizoba-Ebozue et al, 2022) and cardiology (Clark et al, 2019). Recently, there have been attempts to include more diversity in clinical trials. The UK's Health Research Authority (2024) has been working in collaboration with the Medicines and Health products Regulatory Agency to produce guidelines that ensure research includes people who could be impacted by the findings.
The HIV context
The importance of relevant data is crucial to reduce bias, maximise health equity and address unmet needs. HIV becoming a chronic and manageable condition has required a shift in priorities towards the management of comorbidities such as heart disease, cancer and conditions associated with ageing. Several studies, including that by Morales et al (2022), confirm that, because the life expectancy of people living with HIV is now significantly increased, it is vital to ensure there is effective management of conditions that may arise.
Data gaps due to the exclusion of people living with HIV from clinical research trials means little is known about how drugs commonly used in other conditions interact with ARVs and on the physiology of people living with HIV. Safety and efficacy data on the treatment of non-HIV-related health conditions affecting people living with HIV are significantly lacking due to a historical and systematic exclusion from clinical research (European AIDS Treatment Group (EATG), 2022). This is despite other studies confirming the benefits of their inclusion, for example, in cancer research (Reuss et al, 2020).
Physiological differences between genders or people of different ages, and the wide variety of HIV subtypes, mean that research that is not suitably diverse leads to unrepresentative results. For example, in HIV cure research, women, girls, trans people and people over 50 years of age are ‘grossly underrepresented’ (Cairns, 2024). Also, in ARV drug research, because pregnant women (or those who conceive during a trial) are excluded or leave the trial, there is limited data about the safety and efficacy of ARV treatments in this context (Fairlie et al, 2019). Women have historically been under-represented in clinical trials relating to HIV research (Johnston et al, 2023), and to use the justification that women are ‘difficult to reach’ is stigmatising and inaccurate (American Public Health Association, 2022). In 2021, the World Health Organization (WHO) published recommendations on how to address this challenge (WHO, 2021).
How can communities of people living with HIV and practitioners advocate for more diversity in clinical trials, especially inclusion in non-HIV trials to ensure data are available for all pathologies? A lesson can be taken from an initiative led by EATG, begun in 2007 (EATG, 2024). The following is extracted from a case study developed for EATG (2023a) and presented in part at the HIV Glasgow 2024 conference.
The Belong project and lessons from the Sitges case study
EATG is currently involved in the Belong project, advocating for the inclusion of people living with HIV in non-HIV clinical trials (EATG, 2023b). As part of this project, a case study was developed from a series of meetings held between 2007 and 2017 in Sitges, Spain. The meetings had two clear aims: ensuring the inclusion of people living with HIV and co-infected with hepatitis C virus (HCV) in clinical trials for emerging treatments for HCV; and promoting rapid access to new and effective treatments.
In the 2000s, treatment for HCV was highly effective, and HCV was for the first time curable. However, for people co-infected with HIV and HCV, HCV treatment was not established as safe, with several adverse side-effects. Co-infected people were also less likely to respond to treatment, making HCV-associated end-stage liver disease a leading cause of death for people living with HIV in Europe. Despite these critical factors, HIV/HCV co-infected people were routinely excluded from participating in clinical trials.
The meetings in Sitges were innovative, with strong community leadership and involving multiple stakeholders. They were organised and led by community activists, HIV and hepatitis organisations, and people living with HCV and HIV. Other key stakeholders attending the meetings included medicines regulators, physicians, academics and researchers, public health agencies, and industry representatives. Attendees were from Europe and the USA.
The meetings used a collaborative approach to find solutions based on the contribution of all stakeholders. The discussions were enriched by personal narratives of lived experience shared by people affected by HIV and HCV.
The Sitges meetings had several important outcomes. First, they increased awareness of HIV/HCV comorbidity and co-infection through a powerful synergy between human experience and robust advocacy in the context of medical research and medication development. Second, following the early meetings, exclusion criteria were amended to include co-infected people in clinical trials, and European Medicines Agency guidelines were reworked to reflect this. Another outcome was the meaningful bridge building between stakeholders, especially the HIV and hepatitis communities, and between the community, pharma and physicians.
Application to other diseases
The Sitges meetings demonstrated that it is important to bring together organisations that represent all the diverse populations, and to create networks ready to promote an inclusive approach to clinical trial development and gather the maximum amount of data. This includes in the field of ageing with HIV, where increasing risk of cardiovascular disease requires a much broader data set on the impact of different medicines on HIV-affected people. There are also limited data relating to people living with HIV and fatty liver disease. Specifically, for practitioners and communities advocating for better clinical trial representation, advocacy can be strengthened in the following four ways:
- Getting the right people in the room: there should be a broad base of participants bringing their knowledge, experience, and influence around trial designs, drug development, and people's lived experience, working together to seek solutions
- Having the right information: current information about pathology, epidemiology, and standards of care is vital. This helps to make an informed selection of which trials and which drugs to focus on. Scientific savvy coupled with moral urgency increases the impact of advocacy initiatives. Affected people can share their personal insights
- Getting the right people to lead: community leadership with focused demands can be extremely effective. It is vital that affected people, patient groups, and patient-focused organisations are central in the planning, facilitation, and reporting of events. People who are co-infected and/or who have comorbidities will benefit most from effective treatment
- Using an appropriate format in planning and facilitation: meetings required significant commitment and co-ordination. There were clear agendas showing expectations, goals, actions and the next steps.
The importance of inclusion
Data generated from clinical research must be representative, diverse and equitable. Everyone should have the confidence that treatments provided for them are based on a strong and inclusive evidence base. For people living with HIV it is important that, for the non-HIV conditions and diseases they may face, there is clinical data that also includes their cohort.
Advocacy for the inclusion of people living with HIV in non-clinical trials must be continued. Moral outrage and ethical concerns drove discussions in 2007 about access to effective and evidence-based HCV treatments for people living with HIV, and there should be no less outrage and concerns today in the context of other conditions.