Journal
AIDS
Volume 25, Issue 18, Pages 2227-2234Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e32834cdaba
Keywords
resting memory CD4(+) T-cell latent reservoir; therapeutic HIV vaccines
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Funding
- Children's Hospital Los Angeles Clinical Translational Science Institute [1UL1RR031986]
- National Center for Research Resources (NCRR), NIH
- International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network of the National Institute of Allergy and Infectious Diseases (NIAID) [NCT00107549]
- National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632, RO1 32391]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-DK-9-001/HHSN267200800001C]
- National Institute of Mental Health (NIMH) [AI068632]
- Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5U01 AI41110]
- Pediatric AIDS Clinical Trials Group (PACTG) [1 U01 AI068616]
- IMPAACT Group
- NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network
- IMPAACT Immunology Laboratory
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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 (T(1/2)) 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(+) IFN gamma (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. (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
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