Background: Immune responses to childhood vaccines are often impaired by HIV infection. PACTG 727 examined tetanus specific immune reconstitution in HIV infected children who had lost their tetanus immunity.

Methods: Participants were selected from 192 children with stable HIV infection who initiated a HAART regimen that included both PI and NNRTI under protocol PACTG 377. We re-immunized with DTaP 37 children, 2 to 9 years old with negative baseline tetanus antibody titers (TT) (<1:243 in a standard hemagglutination assay), either 16 or 36 weeks after starting the assigned drug regimen. Wilcoxon rank-sum test was used to compare non-normally distributed parameters. Lymphoproliferative response  (LPR) data was log transformed.

Results: No significant differences in any of the immunologic or demographic parameters studied were seen between the 16- and 36-week vaccinees. Subjects had median baseline values as follows:  CD4% = 34, CD4 number = 976, age = 6.1 years, (log₁₀), viral load = 2.41, TT=1:27, and tetanus stimulation index = 1.58. There was a 27-fold rise in median TT over the baseline values at 4 and 8 weeks post immunization (IMZ). TT decreased to 9- and 3-fold over baseline at 18 and 32 weeks post IMZ, respectively. Median TT just prior to IMZ was 1:27 and at 4, 8, 18 and 32 weeks post IMZ had risen to 1:2187, 1:729, 1:421, and 1:107, respectively (p <0.0001 for weeks 4, 8, and 18 and p = 0.015 for week 32). HAART alone resulted in 8% of subjects increasing TT to >1:243 by IMZ week 0. At IMZ weeks 4, 8, 18, and 32, TT were >1:243 in 74%, 67%, 53%, and 38% of subjects representing > 4-fold TT rise in 82%, 94%, 56%, and 46% respectively. Subjects with higher (>68%) naïve CD4⁺45RA+62L+ T-cells at baseline had slightly greater rises in TT at 18 and 32 weeks post IMZ (p = 0.04 and 0.03, respectively). LPR to tetanus antigen peaked 8 weeks post IMZ at stimulation index = 15.1 (p = 0.061) and fell to 3.3 (p = 0.26) by 32 weeks. A matched pairs analysis of immunized and unimmunized subjects confirmed higher TT in immunized subjects 48 weeks after enrollment in PACTG 377 (p <0.001 signed rank test) and no increases in toxicity, viral load or CD4 subset changes associated with DTaP vaccination.

Conclusions: Although children with stable HIV infection on effective HAART can mount specific responses to tetanus immunization, the durability of these responses may be limited. Long-term monitoring of specific immune function in such children is indicated.

Keywords: tetanus immunity; children; HIV