Characteristics of suboptimal immune response after initiating antiretroviral therapy among people living with HIV with a pre-treatment CD4 T cell count <200 ​cells/mm3 in Thailand

Abstract

Background: Complete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais.

Methods: Treatment-naïve participants (n ​= ​375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level ​< ​400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4⁺ T cell count <200 ​cells/mm³ for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n ​= ​17) and non-SIR (n ​= ​24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated.

Results: Among 375 participants with pre-ART CD4 T cell counts < 200 ​cells/mm³, the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count ≤100 ​cells/mm³ (adjusted odds ratio [aOR] 9.45, 95% CI 2.92-30.61, p ​< ​0.001), older age (aOR 1.07, 95% CI 1.01-1.13, p ​= ​0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21-0.59, p ​< ​0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases ​= ​17, controls ​= ​24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p ​= ​0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log₁₀ ​pg/mL, p ​= ​0.04), lower CD8 T cell counts (mean, 514 vs. 876, p ​= ​0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p ​= ​0.01) and higher expression of PD1 on CD8⁺ T cells (74.2% vs. 65.1%, p ​= ​0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation.

Conclusions: Nearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm³ after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.

Keywords: Antiretroviral treatment; Asian; Immune characteristics; Suboptimal immune recovery.

Fig. 1

The graphs show CD4 (1 A), CD8 (1 ​B) T cell counts and CD4/CD8 (1 ​C) recovery among participants with suboptimal immune response (SIR) and non-SIR group.

Fig. 2

Scattered plot shows the immunological characteristics of the matched case-control (case ​= ​SIR, control ​= ​non-SIR) sub-study at year 3 after initiating ART. Abbreviations: SIR, suboptimal immune recovery; ART, antiretroviral therapy. The bars in the scattered plots represent the mean values.