Pegylated (peg) IFNα monotherapy after ART interruption results in increased HIV control in association with NK cell activation. The relationship between inducible or other HIV proviral reservoir measurements with subsequent time to rebound during ART interruption and Peg IFN-α monotherapy are unknown.
13 individuals randomized to arm 1 of the BEAT-HIV study (NCT02227277: HIV VL < 50 copies/ml on ART, CD4 count > 450/μl) receiving 1 μg/kg of peg-IFNα-2b (Pegintron, Merck) for 20 weeks, interrupting ART at week 4 and resuming it upon viremia (VL > 50 copies/μl, bi-weekly evaluations) or at week 20.
P24 SIMOA (iP24) was measured in CD4+ T cells cultured for 16-hour with medium or PMA/Ionomycin using single molecule array (SIMOA). Intact, 5’ defective, 3’ defective and total proviral DNA were measured by Accelevir, Inc. on CD4+ T cells; Integrated HIV proviral DNA was assessed using Alu-gag RT-PCR on CD4+ T cells. Time to viremia was first VL > 50 copies/ml after stopping ART.
HIV-specific responses in PBMC: a) T cell – 6-hour cultures of PBMC with of 15-mer gag peptides. B) NK ADCC: 4-hour co-cultures with anti-HIV sera with gp120-coated CEM NKres targets. Multicolor flow cytometry was used to assess HIV-specific degranulation and cytokine production.
Associations were tested with Pearson or Spearman tests, and linear regression models.
12 of 13 participants became viremic during ART interruption, one remained suppressed and was imputed to week 20. ip24 was positively associated (p<0.05) with time to viremia (effect estimate 0.362; p= 0.029; Adj R2 = 0.305), first detected VL (Fig 1), and Fc receptor-dependent expression of intracellular MIP1β in CD56dim/CD57neg NK cells, but not with T-cell responses to Gag peptides. Proviral measures were correlated to each other, as expected, but not with time to viremia or level of first VL measured.
In vitro-inducible HIV proteins (i.e.: p24 SIMOA), but not total proviral HIV DNA measures, are associated with level of first viral load and time to viremia during peg-IFNα-2b mono therapy. In contrast to expectation that higher latent reservoirs would lead to shorter time to viremia, the immune correlates measured are consistent with NK ADCC response and chemokine responses contributing to viral control off ART