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, Deborah; Luzuriaga, Katherine; Ziemniak, Carrie; Muresan, Petronella; Greenough, Thomas; Fenton, Terry; Blackford, Amanda; Ferguson, Kimberly; Neu, Natalie; and Cunningham, Coleen K., "Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir" (2011). Immunology/Infectious Disease. 71.