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

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 . 190 copies/10 cells) and gut (0 . 898 copies/10 cells), and lower HIV-RNA in blood (4.2 . 6.2 log copies/mL), gut (1.7 . 3.1 log copies/mg) and cerebrospinal fluid (2.0 . 3.8 log copies/mL), when compared to Fiebig II-IV individuals (all <0.01). Median plasma sCD14 level was lower (1.1 . 1.6 μg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6 . 14.9%, both <0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig I . 0.5 pg/mL in Fiebig II-IV, >0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1 . 2.6%, >0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508 . 340 cells/mm and 1.1 . 0.7, respectively (both <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 (=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.