NSCLC Nivolumab Case Study Reports HIV Reservoir Depletion

HIV reservoir depletion reported after immune checkpoint inhibitor therapy in an HIV-positive patient with non-small-cell lung cancer

medwireNews: A case study suggests that treatment with the PD-1 inhibitor nivolumab might have led to HIV reservoir depletion in an HIV-positive patient with non-small-cell lung cancer (NSCLC).

However, lead investigator Jean-Philipe Spano, from Sorbonne Universités in Paris, France, cautioned in a press release that the report, published in the Annals of Oncology, is the “first case of such a drastic decrease of the HIV reservoir” and notes that there was no such effect in an earlier case study.

The 51-year-old man with stage IIIa NSCLC – negative for mutations in EGFR, BRAF and KRAS, and for PD-L1 expression – had undergone lobectomy but relapsed 6 months after completing adjuvant cisplatin plus pemetrexed chemotherapy. Second-line nivolumab was initiated at 2-week intervals for 8 months, during which time his disease was stable. Further nivolumab therapy is planned.

Before nivolumab initiation, the patient had achieved an undetectable (<20 copies/mL) HIV load using emtricitabin, tenofovir and dolutegravir, but his plasma load “progressively and modestly” increased up to 101 copies/mL on day 45 of treatment, reducing to 31 copies/mL by day 120.

Meanwhile, the patient's T-cell activation increased between day 14 and 45 of treatment, while his PD-1-positive CD4 and CD8 cells reduced at day 30. But between days 30 and 120, his HIV RT- and Nef-specific CD8 T cell count "markedly increased" and his cell-associated HIV DNA showed a "drastic and persistent decrease" from 369 copies/106 cells on day 0 to 30 copies/106 cells on day 120.<\p>

“Taken together, those results suggest that nivolumab in this patient had induced synergistic ‘shock and kill’ mechanisms”, suggest Jean-Philippe Spano and co-authors.

These appeared to be a “transient reactivation of HIV replication within infected CD4 T cells together with a T-cell activation and […] 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”, they postulate.

As well as assessing the reproducibility of this finding and the safety of immune checkpoint inhibitor therapy in a group of patients with HIV infection, Jean-Philippe Spano highlighted the need to “identify markers that can predict HIV response to the anti-PD-1 therapy so that treatment can be personalised, especially as we observed one responder and one non-responder.”

Reference

Guihot A, Marcelin A-G, Massiani M-A, et al. Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer. Ann Oncol; Advance online publication 1 December 2017. https://doi.org/10.1093/annonc/mdx696

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