Background
Therapeutic HIV-1 vaccines may enable ART-free remission in perinatal HIV-1. We report the virologic effects of HIVIS DNA/MVA-CDMR vaccinations with and without a TLR4 agonist administered as Cervarix in youths with perinatal HIV-1 in the HVRRICANE Trial.
Methods
25 South African youths were randomized into one of 3 arms: Arm 1: HIVIS DNA/MVA-CDMR, n = 10; Arm 2: HIVIS DNA/MVA-CDMR + Cervarix, n = 10; and Arm 3: Cervarix only, n = 5. HIVIS DNA was given at 0 and 4 Wks and MVA-CDMR at 24 and 36 Wks. Cervarix was given at 0, 4 and 24 Wks. HIV-1 DNA concentrations were determined in PBMCs at Wks 0, 24, 48, 60 & 72 with an LTRGAG singleplex droplet digital PCR assay. Intact and defective proviruses were quantified with a subtype C-specific, triplex (gag, pol and env) Intact Proviral DNA Assay at Wks 0 and 72. Low-level viremia (LLV) was determined at all time-points (single copy HIV-1 RNA assay, HMMC-gag). Differences in total, intact and defective proviruses, across and within study arms, were analyzed using Kruskal-Wallis, Mann-Whitney, Friedman’s and Wilcoxon signed rank tests.
Results
Table 1 summarizes the age and sex at study entry by study arm and HIV-1 DNA loads. Total HIV-1 DNA and intact proviral loads were not different across study arms at Wk 0. Within Arms 1 and 3, total HIV-1 DNA significantly increased across the 5 study visits (p=0.011 and 0.030). Significant differences in the change of total HIV-1 DNA by the triplex assay from weeks 0 to 72 were found between Arms 1, 2 and 3 (p = 0.043), and between Arms 2 and 3 (p = 0.009). The median intact load decreased in Arm 2 (HIV vaccine and Cervarix), compared to increases in Arm 1 (p=0.076) and Arm 3 (p=0.098) (Table 1). At Wk 0 and across all study arms, LLV by SCA was present in 52% of youths and was correlated with total HIV-1 DNA (r=0.46, p=0.037). At Week 72, LLV was correlated with intact HIV-1 DNA (r=0.47, p=0.034).
Conclusions
In youths with perinatal HIV-1, the combination of HIV vaccine and Cervarix led to the largest decrease in intact HIV-1 DNA compared to the other arms. Significant increases in HIV DNA with HIV vaccine or Cervarix only may reflect expansion of clones reacting to vaccines. These findings highlight the utility of incorporating TLR-agonists in HIV-1 vaccine strategies.
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