Effect of therapeutic HIV recombinant poxvirus vaccines on the size of the resting CD4+ T-cell latent HIV reservoir.

Abstract

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.

• Authors: Deborah Persaud, Katherine Luzuriaga, Carrie Ziemniak, Petronella Muresan, Thomas Greenough, Terry Fenton, Amanda Blackford, Kimberly Ferguson, Natalie Neu, Coleen K Cunningham
• Journal: AIDS (London, England) (AIDS) Vol. 25 Issue 18 Pg. 2227-34 (Nov 28 2011) ISSN: 1473-5571 [Electronic] England
• PMID: 21918423 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Chemical References

• AIDS Vaccines
• Vaccines, Synthetic

Topics

• AIDS Vaccines (immunology, therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• HIV Infections (drug therapy, virology)
• Humans
• Treatment Outcome
• Vaccination
• Vaccines, Synthetic (immunology, therapeutic use)
• Young Adult