Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir
Department of Pediatrics; Program in Molecular Medicine
AIDS Vaccines; CD4-Positive T-Lymphocytes; HIV Infections; Humans; Treatment Outcome; Vaccination; Vaccines, Synthetic; Young Adult
Immunology and Infectious Disease | Pediatrics
OBJECTIVES: Therapeutic HIV vaccinations may alter the size of the resting memory CD4 T-cell latent HIV reservoir as HIV establishes latency when memory responses are formed, including those toward HIV. Alternatively, latently infected CD4 T cells maybe killed, while exiting the reservoir upon activation.
METHODS: The effect of therapeutic immunization with modified vaccinia Ankara and Fowlpox-based HIV vaccines on the latent reservoir was examined in 19 young adults who were receiving effective antiretroviral therapy. Correlations between size of the reservoir [measured in infectious units per million (IUPM)] resting CD4 T cells and HIV-specific immune responses, including immune activation were examined. Decay of the reservoir was assessed using random-effects model.
RESULTS: A modest transient decrease in the size of the reservoir was observed at week 40 [mean -0.31 log(10) IUPM (95% confidence interval: -0.60 to -0.03; P = 0.03] following HIV vaccinations. The estimated half-life (T1/2) of the reservoir during the 40 weeks following vaccination was 9.8 months and statistically different from zero (P = 0.02), but 35.3 months and not different from zero (P = 0.21) over 72 weeks of study. Latent reservoir size at baseline was not correlated with HIV-specific CD4, CD8 responses or immune activation, but became correlated with CD4 IFNγ (r = 0.54, P = 0.02) and IL-2 responses at 6 weeks after immunization (r = 0.48, P = 0.04).
CONCLUSION: Therapeutic HIV vaccinations led to a transient increase in decay of latently infected CD4 T cells. Further studies of therapeutic HIV vaccines may provide important insights into facilitating decay of the latent reservoir.
DOI of Published Version
AIDS. 2011 Nov 28;25(18):2227-34. doi:10.1097/QAD.0b013e32834cdaba
AIDS (London, England)
Persaud D, Luzuriaga K, Ziemniak C, Muresan P, Greenough T, Fenton T, Blackford A, Ferguson K, Neu N, Cunningham CK. (2011). Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir. Immunology/Infectious Disease. https://doi.org/10.1097/QAD.0b013e32834cdaba. Retrieved from https://escholarship.umassmed.edu/peds_immunology/71