2015 was treated with lobectomy and adjuvant chemotherapy (cisplatin and pemetrexed). Relapse occurred <6 months after the end of chemotherapy and nivolumab was introduced as a second line in December 2016, upon the CANCERVIH working group recommandations. CANCERVIH is a national French multidisciplinary network dedicated to HIVinfected patients with cancer. Pre-treatment plasma HIV load was undetectable (<20 copies/ml) under emtricitabin, tenofovir and dolutegravir started in August 2016. Fifteen injections were administered every 14 days until July 2017, with a stable disease, and a good tolerance with stable CD4 and CD8 counts despite a slight CD4 drop at D30 (Figure 1A). The plasma HIV load progressively and modestly increased up to 101 copies/ml at D45, decreasing afterwards to 31 copies/ml at D120. In parallel, T-cell activation slightly increased between D14 and D45 while PD-1þ CD4 and CD8 T cells declined at D30 (Figure 1B and C). Then frequencies of HIV RT-and Nef-specific CD8 T cells markedly increased from D30 to D120 (Figure 1D). Finally, the cellassociated HIV-DNA showed a drastic and persistent decrease from 369 at D0 to 30 copies/10 6 cells at D120 (Figure 1A).Taken together, those results suggest that nivolumab in this patient had induced synergistic 'shock and kill' mechanisms: (i) a transient reactivation of HIV replication within infected CD4 T cells together with a T-cell activation and (ii) a decrease in exhausted CD4 and CD8 T cells followed by a durable and major restoration of HIV-specific CD8 T cells function that might have killed the HIV-producing cells, altogether resulting in a drastic and durable diminution of the reservoir.This first report of a successful depletion of the HIV reservoirs opens new therapeutic perspectives towards an HIV cure. Whether this encouraging result is reproducible is also currently being analyzed in the French cohort of HIV-infected people treated with ICPIs (ANRS-CO24, OncoVIHAC cohort).
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