Background
Negative HIV serology in children treated early is thought to result from low exposure of the immune system to antigenic stimulation provided by HIV replication. This serological profile might be used to identify pediatric patients eligible for HIV cure strategies. We, thus, aimed to characterize parameters associated with negative HIV serology in children who initiated ART early.
Methods
The present analysis included children (aged 5-12 years) from the French ANRS-EP59-CLEAC study who initiated combined antiretroviral therapy (cART) before six months of age, reached virological success (HIV-RNA < 400 copies/mL in the 24 months after cART initiation), did not subsequently experience viral rebound > 400 copies/mL, and had HIV RNA < 50 copies/mL at the time of the study. The presence of HIV-1 antibodies was determined using the EIA VIDAS HIV DUO ULTRA test (Biomérieux). Blood lymphocytes were quantified by flow cytometry. PBMCs were stimulated by a TLR7/8 agonist and IL-2 to assess the expansion of B lymphocytes producing HIV-specific antibodies. Fisher and Mann-Whitney tests were used to analyze variables associated with negative HIV serology.
Results
Seventeen children met the selection criteria: four males, median age 9 [Interquartile range: 5.5; 11] years, and CD4 T-cell count 1090 [735; 1388] cells/µl. Seven participants had negative HIV serology (seronegative, SN, 41%) and 10 had positive HIV serology (seropositive, SP, 59%). SN children tended to be younger at cART initiation than SP children (14 vs 97 days, P = 0.06). At the time of the study, surrogate markers of past HIV exposure did not distinguish SN from SP children (total HIV DNA, 1.9 [1.4; 2.2] vs. 2.2 [1.2; 2.5], log10 copies/106 PBMCs, P = 0.64, plasma HIV-1 p24 detection: 25% vs 38%, P = 0.67).
SN children had a higher percentage of circulating follicular CXCR5+CCR4– CD8 TEM lymphocytes than SP children (3.1% [2.0; 3.2] vs 1.3% [0.7; 2.0], P = 0.01). Although rarely detected, HIV-specific B cells were present in both SN and SP children.
Conclusions
Among children over the age of five years with limited exposure to HIV replication, negative HIV serology could not be attributed to B lymphocyte defects. Rather, it was associated with expanded circulating follicular CD8 T lymphocytes, previously reported to have high antiviral activity. Thus, negative HIV serology may be a biomarker of a good potential for HIV immune control in the context of future HIV cure strategies.