Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce the Size of HIV-1 Reservoirs?

Yonas Bekele,Maurizio Zazzi,Sandra Soeria-Atmadja,Anna Nilsson,Lars Naver,Rebecka Lantto Graham,Francesca Chiodi,Aikaterini Nasi,Ilaria Vicenti

doi:10.3389/fimmu.2017.01966

Yonas Bekele, Maurizio Zazzi + Show 7 more

Open Access

https://doi.org/10.3389/fimmu.2017.01966

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Abstract

During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs, mostly represented by CD4+ memory T cells. Several approaches are currently being undertaken to develop a cure for HIV-1 infection through elimination (or reduction) of these reservoirs. Few studies have so far been conducted to assess the possibility of reducing the size of HIV-1 reservoirs through vaccination in virologically controlled HIV-1-infected children. We recently conducted a vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and postvaccination. In addition, we investigated by immunostaining whether the frequencies of CD4+ and CD8+ T cells and parameters of immune activation and proliferation on these cells were modulated by vaccination. At 1 month from the last vaccination dose, we found that 20 out of 22 children mounted a serological response to HBV; a majority of children had antibodies against HAV at baseline. The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in comparison to baseline although this reduction was not statistically significant. A significant reduction of HIV-1 DNA copies in blood following vaccination was found in 12 children. The frequencies of CD4+ (naïve, effector memory) and CD8+ (central memory) T-cell subpopulations changed following vaccinations and a reduction in the activation and proliferation pattern of these cells was also noticed. Multivariate linear regression analysis revealed that the frequency of CD8+ effector memory T cells prior to vaccination was strongly predictive of the reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1-infected children. The results of this study suggest a beneficial effect of vaccination to reduce the size of virus reservoir in HIV-1-infected children receiving ART. A reduced frequency of activated CD4+ cells and an increase in central memory CD8+ T cells were associated with this finding. Further studies should assess whether vaccination is a possible tool to reduce HIV-1 reservoirs.

Highlights

Anti-retroviral therapy (ART) provided to HIV-1-infected patients infected with human immunodeficiency virus type 1 (HIV-1) does not lead to virus eradication as HIV-1 persists in memory CD4+ T cells which represent a stable and long-lived reservoir for this infection [1, 2]
None of the 22 HIV-1-infected children included in the study displayed measurable levels of antibody to HBsAg (Figure 1A) and all samples scored below the cutoff value of 1 log IU/L
The decline of HIV-1 DNA copies was detected in children presenting with a reduced frequency of proliferating CM CD4+ T cells and an increased frequency of CM CD8+ T cells following vaccination; this result may suggest that the declined levels of HIV-1 DNA copies in blood of HIV-1-infected children vaccinated with hepatitis A virus (HAV) and hepatitis B virus (HBV) may be due to a reduction of HIV-1 target cells in the presence of a larger number of CD8+ T cells flushing HIV-1-infected cells

Summary

Introduction

Anti-retroviral therapy (ART) provided to HIV-1-infected patients infected with human immunodeficiency virus type 1 (HIV-1) does not lead to virus eradication as HIV-1 persists in memory CD4+ T cells which represent a stable and long-lived reservoir for this infection [1, 2]. Approximately 40 million people live with HIV-1 infection and this number will increase as a result of new infections and ART scale-up limiting mortality. Until new medicines will be available for curing HIV-1 infection it is important to provide ART to HIV-1-infected patients as early as possible, ideally already at the phase of primary HIV-1 infection, as early ART administration reduces inflammation linked to HIV-1 pathogenesis and confines the size of HIV-1 reservoirs [10]

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