PKC agonists and compounds releasing active P-TEFb induce HIV-1 recovery in CD8⁺-depleted PBMCs and in resting CD4⁺ T cells from cART-treated HIV⁺ aviremic patients.

<p>Panel <b>A.</b><i>Ex vivo</i> cultures of CD8⁺-depleted PBMCs purified from blood of 24 patients were mock-treated, treated with anti-CD3+anti-CD28 antibodies (C+), prostratin (0.5μM), bryostatin-1 (5nM), JQ1 (0.25μM), I-BET (0.25μM), I-BET151 (0.25μM) or HMBA (5mM) alone or in combination as indicated. Six days post-treatment, concentrations of genomic viral RNA were measured in culture supernatants. Statistical comparisons to positive control are indicated if p<0.05 (superiority to positive control). Panel <b>B.</b><i>Ex vivo</i> cultures of resting CD4⁺ T cells purified from blood of 15 patients were mock-treated, treated with anti-CD3+anti-CD28 antibodies (C+), prostratin (0.5μM), bryostatin-1 (5nM), ing-B (10nM), JQ1 (0.25μM), alone or in combination as indicated. Six days post-treatment, concentrations of genomic viral RNA in culture supernatants were determined. Statistical comparisons to positive control are indicated if p>0.05 (non-inferiority). Panels <b>A</b> and <b>B</b>. Dashed line indicates the 150 HIV-1 RNA copies/ml limit of detection. Panel <b>C</b>. <i>Ex vivo</i> cultures of CD8⁺-depleted PBMCs purified from blood of 7 HIV⁺ patients were mock-treated, treated with anti-CD3+anti-CD28 antibodies (C+), bryostatin-1 (5nM), JQ1 (0.25μM) or ing-B (10nM) alone or in combination in the presence of cART. One day post-treatment, concentrations of genomic viral RNA in culture supernatants were determined. Statistical comparisons to positive control are indicated if p<0.05 (superiority to positive control). Panel <b>D.</b><i>Ex vivo</i> cultures of CD8⁺-depleted PBMCs purified from blood of 11 HIV⁺ patients were mock-treated, treated with anti-CD3+anti-CD28 antibodies (C+), bryostatin-1 (5nM), JQ1 (0.25μM) or ing-B (10nM) alone or in combination in the presence of cART. Three days post-treatment, concentrations of genomic viral RNA in culture supernatants were determined. Statistical comparisons to positive control are indicated if p>0.05 (non-inferiority to positive control). Panel <b>E.</b><i>Ex vivo</i> cultures of CD8⁺-depleted PBMCs purified from blood of 11 HIV⁺ patients were mock-treated, treated with anti-CD3+anti-CD28 antibodies (C+), bryostatin-1 (5nM), ing-B (10nM) or JQ1 (0.25μM) alone or in combination in the presence of cART. Six days post-treatment, concentrations of genomic viral RNA in culture supernatants were determined. Statistical comparisons to positive control are not indicated because p<0.05 for all the conditions (superiority of the positive control). Panels <b>C-E.</b> Dashed line indicates the 15 HIV-1 RNA copies/ml limit of detection. Panels <b>A-E.</b> Each symbol represents one cART-treated HIV⁺ patient. The means are represented.