Influence of early combine antiretroviral therapy on maintenance of long term serological and cellular immune response to varicella vaccination in perinatally HIV infected children and adolescents

Background: It is not clear if cART started prior to the initiation of the standard American Academy of Pediatrics recommended vaccinations results in improved levels of immunity among perinatally HIV infected individuals. In this study, we seek to gain insight on the timing of cART initiation with respect to vaccination on the capacity of the B cells from perinatal HIV infected children and adolescents to maintain humoral and cellular immunity to varicella (VAR).

Methods: Antibody titers (Abs) and memory antibody secreting cells (mASC) to VAR are measured by ELISA or ELISPOT. We compare a HIV+ population with an adult HIV- population as a rigorous test of persistence of memory. HIV+ are parsed into 4 groups based on the time of cART initiation (before or after immunization) and plasma HIV RNA viral load (VL) level (< 50 or ≥ 50 copies/ml ). Group 1: before, VL < 50; group 2: before, VL ≥ 50; group 3: after, VL <50 and group 4: after, VL ≥ 50. We used Wilcoxon rank-sum to compare groups and linear regression to determine predictors of immune response.

Results: 24 HIV+ individuals are included; 16 (66.7%) started cART before initiation of VAR immunization. Of the 16, 9 (56.2%) have a VL < 50. Eight (33.3%) started cART after VAR immunization and two (25%) have plasma HIV RNA < 50.

Median age at study is 11.5 years (IQR 9.8-15.7) with a CD4% of 32.4 (24.9-42.5) and a plasma HIV RNA of 1.9 log₁₀ copies/ml (1.7-3.8). The median cumulative years of HIV RNA suppression (VL<50) is 2.7 (1.4-6.3). Individuals who started cART before immunization and maintained VL < 50 have significantly higher levels of VAR Abs and specific VAR mASC compared with the other 3 HIV+ groups (Figure). In addition, VAR Abs and specific VAR mASC for this group are similar to the adult HIV- population (Figure). There are no other significant differences between the other HIV+ groups. Linear regression analysis shows that for each year on continuous HIV RNA suppression there is a significant increase in VAR Ab titters (β=0.074; 95% CI= 0.004;0.14: p= 0.039)  and VZV mASC (β=0.177; 95% CI= 0.03;0.32: p= 0.02).

Conclusion: Our data show that maintenance of VAR plasma antibodies and VZV cellular memory following VZV vaccination in perinatally HIV infected individuals is significantly improved if cART is started before immunization and viral suppression is sustained.