People living with HIV must be included in clinical trials for new tuberculosis vaccine candidates currently in the development pipeline, say experts on an international panel convened last year to address gaps in the current TB vaccine landscape.
Their recommendations, which appear in a new paper published Oct. 11, 2022, in The Lancet HIV, are designed to shape the future of TB vaccine development and help ensure people living with HIV have access to safe and effective TB vaccines like those for the general population.
The panel was convened by the DAIDS Cross-Network TB Vaccine Working Group comprised of the HIV Vaccine Trials Network (HVTN), the AIDS Clinical Trials Group (ACTG) and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT). The three networks worked collaboratively with the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) and its Division of AIDS.
Meeting at a series of symposia in January and February 2021, panel members developed consensus statements that serve as strategic recommendations designed to address current TB vaccine gaps and prioritize clinical trials for people with HIV.
"People living with HIV are at high risk for tuberculosis infection and subsequent disease and tend to develop less robust vaccine-induced immune responses," said James G. Kublin, MD, executive director of HVTN, which is based at Fred Hutchinson Cancer Center, and co-senior author of the paper. "Yet, many questions remain unanswered about developing an effective TB vaccine for this group."
Background
Tuberculosis was responsible for 1.5 million deaths in 2020 and continues to pose a threat to global health, particularly for those living in nations with high TB incidence. The World Health Organization estimated that almost 10 million people developed the disease in 2020, 8% of whom were coinfected with HIV. That translated to almost 800,000 diagnosed cases that caused some 214,000 deaths among people living with HIV.
The paper notes that people living with HIV have a 15- to 21-fold greater likelihood of developing TB disease and dying from it compared with those not living with HIV. That's likely due to HIV-associated immunosuppression that results in a weaker immune response and lower vaccine efficacy for people living with HIV.
"TB remains the leading cause of morbidity and mortality in people with HIV, and those with advanced HIV disease have the highest risk for TB disease," said Gavin Churchyard, MBBCH, FCP (SA), FRCP (Edin), MMED, PhD, founder and CEO of The Aurum Institute NPC, a member of HVTN and ACTG, and co-senior author on the article. "Even with antiretroviral therapy (ART) lowering viral loads to undetectable levels, people living with HIV remain at significantly greater risk for TB and worse outcomes than the general population."
Moreover, people living with HIV historically have been excluded from TB vaccine trials so developers could maximize the ability to demonstrate strong immunity and effectiveness with their vaccine candidates, Kublin explained. There also have been concerns about using live-attenuated vaccines, such as Bacillus Calmette-Guérin (BCG), in people living with HIV who are not on ART, for fear of spreading live bacteria.
It is important to note that even among persons living with HIV, some communities are often excluded from TB vaccine trials – children, adolescents and pregnant women.
"It is critical that persons living with HIV across the lifespan be included in TB vaccine trials," said Amita Gupta, MD, MHS, FIDSA, director of the Division of Infectious Diseases at Johns Hopkins School of Medicine, vice-chair of the IMPAACT TB Scientific Committee and a study co-author. "Data for children, adolescents and pregnant women are much-needed but are often slow to be generated. The goals of TB elimination require novel TB vaccines, and we must focus on these populations who are at especially high risk for TB disease after exposure," Gupta added.
Gap in New Road Map
Recently, the Amsterdam Institute for Global Health & Development, in cooperation with the European & Developing Countries Clinical Trials Partnership, produced a comprehensive road map with short- and long-term goals for TB vaccine research and development.
But the road map had a glaring omission: It failed to specifically address TB vaccines in people living with HIV.
"That oversight served as the impetus for gathering the expert panel tasked with making strategic recommendations to address these gaps for people living with HIV and establish priorities for future TB vaccines," said Kublin.
"Our paper with the panel's recommendations makes a strong case for including people living with HIV in clinical development of TB vaccines as early as possible," Churchyard concluded. "Doing so will help maximize the safety and effectiveness of TB vaccines for this at-risk group while benefiting the population at large."
