Tuberculosis Disease Improves Antibody Response in Patients Coinfected With HIV

Patients with HIV who have also had pulmonary tuberculosis (TB) showed broader and more potent HIV antibody responses and differences in HIV sequences that are predicted to be antibody-resistant compared with individuals without suspected or documented TB, according to a study by researchers at Boston Medical Center published in iScience.

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"[TB] is extremely common, especially in regions of the world with high levels of ongoing HIV transmission, and impacts both the immune responses and the characteristics of the circulating virus in people living with HIV so it is imperative we understand the relationship between the two," Manish Sagar, MD, internist at Boston Medical Center and professor of Medicine at Boston University Chobanian and Avedisian School of Medicine, said in a press release. "These studies have implications for HIV vaccines and antibody-based HIV therapeutics."

The findings of the study indicate that concomitant TB produces a significant impact on HIV immune responses in patients with both diseases, according to the study authors. They added that more than 2 billion people worldwide have been infected with TB, which has become the most common coinfection in patients with HIV. However, prior research efforts have not analyzed how TB impacts the immune response and virus characteristics of HIV.

Findings from the current study indicate that TB may affect the efficacy of antibody-based prevention and therapeutic strategies, according to the investigators. Vaccines that produce antibodies are also being evaluated as a treatment and potential cure for HIV. The investigators noted that a greater prevalence of antibody-resistant strains, in addition to TB infection, suggests a higher likelihood of failure for antibody-based interventions among these patients.

The authors of the current study collaborated with researchers from Uganda and at the AIDS Clinical Trial Group to gather samples from newly diagnosed patients with HIV who either did or did not also have TB. Investigators analyzed samples that were gathered prior to and approximately 6 months following the initiation of HIV medication therapy. The research team then compared antibodies, plasma inflammatory markers, and baseline HIV sequences and treatment samples.

The results showed that TB was associated with a greater prevalence of antibody-resistant HIV. Additionally, ongoing elevated transmission of HIV in regions with frequent TB incidence suggests that a potential vaccine eliciting broad and potent antibodies may not work because these geographic regions are more likely to have antibody-resistant strains.

Researchers noted that their findings carry implications for HIV vaccine strategies that seek to produce antibodies that can block HIV post exposure. However, doing so has yet to be accomplished and producing broad and potent HIV antibodies remains a significant hurdle.

The investigators added that TB produces broadly potent antibody responses. Therefore, dissecting the biological pathways that shed light into how TB enhances the antibody response against HIV may lead to the development of novel strategies for eliciting broad and potent HIV antibodies, according to the study.

“Extrapolation of our observations would suggest that individuals with suppressed virus levels who undergo an active immunization intervention that mimics aspects of [mycobacterium tuberculosis] disease may develop a broad and potent HIV-1 nAb and ADCC response,” the study authors wrote. “If the augmented [neutralizing antibodies] and [antibody-dependent cellular cytotoxicity] are effective against the autologous strains, it could change the size and nature of the residual HIV-1 latent reservoir as long as virus suppression prevents the emergence of escape variants.”

Reference

Bukola Adeoye, Lydia Nakiyingi, Yvetane Moreau, Ethel Nankya, Alex J. Olson, Mo Zhang, Karen R. Jacobson, Amita Gupta, Yukari C. Manabe, Mina C. Hosseinipour, Johnstone Kumwenda, Manish Sagar. Mycobacterium tuberculosis disease associates with higher HIV-1-specific antibody responses. iScience, 2023; 26 (5): 106631 DOI: 10.1016/j.isci.2023.106631.