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J Virus Erad. 2016;2:43-48.

Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection.

Author information

1
SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
2
SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
3
Department of Microbiology, Infectiology, and Immunology, Université de Montréal, Faculty of Medicine, and Centre de Recherche du CHUM, Montreal, Quebec, Canada.
4
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA; Armed Forces Research Institute of Medical Sciences, US Component, Bangkok, Thailand.
5
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
6
Leidos Biomedical Research Inc, Virus Isolation and Serology Laboratory, Frederick, MD, USA.
7
HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
8
Armed Forces Research Institute of Medical Sciences, US Component, Bangkok, Thailand.
9
Department of Neurology, Yale University, New Haven, CT, USA.
10
Department of Neurology, University of California, San Francisco, CA, USA.
11
National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
12
United States Military HIV Research Program; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
13
SEARCH, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Abstract

BACKGROUND:

The challenges of identifying acute HIV infection (AHI) have resulted in a lack of critical information on early AHI that constrains the development of therapeutics that are designed to eradicate HIV from the infected host.

METHODS:

AHI participants were recruited from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand into the RV254/SEARCH010 protocol and categorised according to Fiebig stages as follows: Fiebig I (HIV-RNA+, p24 Ag-, HIV IgM-) and Fiebig II-IV (HIV-RNA+, p24 Ag + or -, HIV IgM- or +, Western blot- or indeterminate). Proviral and viral burden and immune activation levels were compared between Fiebig stage groups at the time of AHI. CD4 and CD4/CD8 ratio were also compared between groups before and up to 96 weeks of ART.

RESULTS:

Median age was 27 years and 96% were male. Fiebig I individuals had lower median HIV-DNA in mononuclear cells from blood (3 vs. 190 copies/106 cells) and gut (0 vs. 898 copies/106 cells), and lower HIV-RNA in blood (4.2 vs. 6.2 log10 copies/mL), gut (1.7 vs. 3.1 log10 copies/mg) and cerebrospinal fluid (2.0 vs. 3.8 log10 copies/mL), when compared to Fiebig II-IV individuals (all P<0.01). Median plasma sCD14 level was lower (1.1 vs. 1.6 μg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6 vs. 14.9%, both P<0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig I vs. 0.5 pg/mL in Fiebig II-IV, P>0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1 vs. 2.6%, P>0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508 vs. 340 cells/mm3 and 1.1 vs. 0.7, respectively (both P<0.001). After ART, CD4 cell count normalised by week 24 in Fiebig I and week 48 in Fiebig II-IV. However, CD4/CD8 ratio was lower in both groups after 96 weeks of ART compared to healthy Thais (P=0.02).

CONCLUSIONS:

Compared to later AHI stages, Fiebig I was associated with lower HIV burden in blood and tissue compartments, lower immune activation and higher CD4 and CD4/CD8 ratio. ART in Fiebig I-IV resulted in normalisation of CD4 cell count within the first year, supporting the benefit of early ART. However, the CD4/CD8 ratio was not normalised after 2 years of ART in all AHI stages, suggesting some degree of persistent immunological dysfunction even when ART was instituted as early as Fiebig I.

KEYWORDS:

CD4; CD4/CD8 ratio; Fiebig I; acute HIV infection; immune activation; reservoir

PMID:
26889497
PMCID:
PMC4754199

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