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

Jintanat Ananworanich; Carlo P Sacdalan; Suteeraporn Pinyakorn; Nicolas Chomont; Mark de Souza; Tassanee Luekasemsuk; Alexandra Schuetz; Shelly J Krebs; Robin Dewar; Linda Jagodzinski; Sasiwimol Ubolyam; Rapee Trichavaroj; Sodsai Tovanabutra; Serena Spudich; Victor Valcour; Irini Sereti; Nelson Michael; Merlin Robb; Praphan Phanuphak; Jerome H Kim; Nittaya Phanuphak

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

J Virus Erad. 2016;2(1):43-48.

Authors

Jintanat Ananworanich¹, Carlo P Sacdalan², Suteeraporn Pinyakorn¹, Nicolas Chomont³, Mark de Souza², Tassanee Luekasemsuk², Alexandra Schuetz⁴, Shelly J Krebs⁵, Robin Dewar⁶, Linda Jagodzinski⁵, Sasiwimol Ubolyam⁷, Rapee Trichavaroj⁸, Sodsai Tovanabutra⁵, Serena Spudich⁹, Victor Valcour¹⁰, Irini Sereti¹¹, Nelson Michael¹², Merlin Robb⁵, Praphan Phanuphak¹³, Jerome H Kim¹², Nittaya Phanuphak²

Affiliations

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.

PMID: 26889497
PMCID: PMC4754199

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.

Abstract

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