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.

Conflict of interest statement

There are no conflicts of interest.

Conflict of interest

Grant support: This clinical trial (ClinicalTrials.gov identifier NCT00107549) was supported by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network of the National Institute of Allergy and Infectious Diseases (NIAID). Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) [AI068632]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). Immunology studies were supported byan IMPAACT Immunology Laboratory grant and NIAID grant RO1 32391 to K. Luzuriaga.

2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Figures

Fig. 1. Change in frequencies of resting CD4+ T cells containing replication-competent HIV in log 10 infectious units per million relative to baseline

The bold line represents the mean change in log10 infectious units per million (IUPM) per time point analyzed. The 95% confidence interval for each time point analyzed is included. The P value for the change relative to baseline at the week 40 visit is denoted.