New research from the Boston Medical Center found that people living with HIV who had pulmonary tuberculosis had more extensive and potent HIV antibody responses and differences in HIV sequences that were predicted to be resistant to antibodies in compared to those without suspected or documented tuberculosis. Published in science, the study suggests that concomitant tuberculosis disease has a significant impact on immune responses to HIV and circulating viruses in people living with HIV.
Tuberculosis infects more than 2 billion people worldwide, and although tuberculosis is the most common coinfection in people living with HIV, previous studies have not examined how tuberculosis affects HIV immune responses and virus characteristics.
This study suggests that tuberculosis may affect the efficacy of antibody-based prevention and therapeutic strategies. Vaccines to elicit antibodies and antibodies are also being investigated as a means to treat and cure HIV. A higher prevalence of antibody-resistant strains in conjunction with tuberculosis disease implies that these antibody-based interventions are more likely to fail in these individuals.
“Tuberculosis is extremely common, especially in regions of the world with high levels of ongoing HIV transmission, and it affects both immune responses and characteristics of the circulating virus in people living with HIV, so it is imperative that we understand the relationship between the two,” said Manish Sagar, MD, an internist at Boston Medical Center and professor of medicine at Boston University Chobanian & Avedisian School of Medicine. “These studies have implications for HIV vaccines and antibody-based HIV therapies.”
The researchers worked closely with investigators in Uganda and at the AIDS Clinical Trial Group (ACTG) to collect samples from people newly diagnosed with HIV who did or did not have tuberculosis. From these individuals, they examined samples collected before and approximately 6 months after the start of HIV medications. The investigators compared antibodies, plasma inflammatory markers, and HIV sequences in the control and treatment samples.
Tuberculosis disease is associated with a higher prevalence of some resistant HIV antibodies. The ongoing high transmission of HIV in areas of the world with frequent TB disease suggests that a potential vaccine that elicits broad and potent antibodies may not work because these geographic regions are more likely to have antibody-resistant strains.
The researchers note that this study has implications for HIV vaccine strategies, as they aim to generate antibodies that can block the virus after exposure. The generation of broad and potent antibodies to HIV has not been achieved and remains a monumental challenge. But TB disease generates broadly potent antibody responses, and dissecting biological pathways that provide insights into how TB enhances antibody responses to HIV could be harnessed to develop novel strategies to elicit broadly potent HIV antibodies.
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