Active infection with Mycobacterium tuberculosis (TB) enhances anti-HIV-1 antibody response, which may then lead to the emergence of broadly neutralizing antibodies (bnAbs) that target conserved envelope domains. These results were presented at the virtual Conference on Retroviruses and Opportunistic Infections held from March 8 to 11, 2020.
The anti-HIV-1 antibody responses among in plasma samples from 15 patients with HIV-1 who had never received treatment and who also had with active pulmonary TB were compared with the responses in samples from 16 patients with HIV-1 only. The ability to inhibit 12 different tier 1 and 2 HIV-1 variants of diverse subtypes in the TZM-bl neutralization assay was used to estimate a neutralization breadth and potency score.
Both groups had a similar baseline plasma virus levels (P = .33) and CD4 counts (P = .40). Patients coinfected with HIV-1 and TB had a significantly higher neutralization breadth and potency score of 0.59±0.05 (range, 0.34-0.98) than patients with HIV-1 only, who demonstrated a score 0.43±0.02 (range, 0.25-0.59, P =.006). In the coinfection group, 4 individuals had a similar or higher neutralization breadth and potency score as that observed in the second generation bnAbs (score range, 0.71-0.98; P =.04); there were none in the HIV-1 only group.
The neutralizing breadth and potency score correlated with total plasma immunoglobulin G (r=0.51; P =.003), but not with baseline viral load, absolute CD4 count, interlukin-6, soluble CD163 or MCP-1 concentrations. While not statistically significant (P = .56), patients with coinfection continued to show higher neutralizing capacity after completing TB treatment and starting HIV-1 therapy (score, 0.68±0.07; n= 6; range, 0.28-0.88) compared with patients in the HIV-1 only group (score, 0.57±0.07; n= 8; range 0.34-0.82). Results also showed that plasma activity of 4 patients with HIV-1 and TB who showed a high baseline neutralizing breadth and potency score clustered with CD4 binding site and membrane-proximal external region targeting bnAbs.
The investigators highlighted that dissecting the mechanisms that account for enhanced HIV-1 neutralization in patients with TB and HIV-1 may be leveraged in the generation of a more effective humoral response in HIV-1 vaccination and treatment.
Adeoye B, Olson AJ, Nakiyingi L, et al. Pulmonary tuberculosis disease enhances HIV-1 antibody responses. Poster presented at: CROI 2020; March 8-11, 2020; http://www.croiconference.org/sites/default/files/uploads/croi2020-boston-abstract-ebook.pdf. Accessed March 18, 2020.