Nivolumab shrinks HIV reservoir for French patient with lung cancer

Nivolumab appeared to drastically reduce HIV reservoirs for a patient with HIV and lung cancer, according to a letter to the editor published in Annals of Oncology.

“Increasingly, researchers have been looking into the use of certain drugs that appear to re-activate the latent HIV-infected cells,” Jean-Philippe Spano, MD, PhD, head of the medical oncology department at Pitie-Salpetriere Hospital AP-HP in Paris, said in a press release. “This could have the effect of making them visible to the immune system, which could then attack them. … It was thought, but until now not demonstrated, that inhibitors of immune checkpoints could, in a similar way, wake up dormant HIV-infected cells and, also, the immune defenses against the virus.”

Spano and colleagues used nivolumab to treat a 51-year-old man with relapsed stage IIIa epidermal growth factor receptor BRAF/KRAS PD-L1 non-small cell lung cancer. The patient — a smoker who had been diagnosed with HIV in 1995 — received initial treatment with lobectomy in May 2015, as well as adjuvant chemotherapy with cisplatin and pemetrexed. He relapsed less than 6 months following therapy. Spano and colleagues administered second-line nivolumab in December 2016.

The patient had an undetectable plasma HIV load under antiretroviral treatment before receiving cancer treatment. His viral load increased to 101 copies/mL at 45 days on nivolumab and T-cell activation increased slightly. During this period, PD-1+ CD4 and CD8 T-cells declined at 30 days. From days 30 to 120, HIV RT- and Nef-specific CD8 T-cells increased.

The patient’s cell-associated HIV DNA demonstrated what researchers described as “a drastic and persistent decrease,” falling from 369 copies/10⁶ cells at baseline to 30 copies/10⁶ cells at 120 days.

“This is the first demonstration of this mechanism working in humans,” Spano said in the press release. “It could have implications for HIV patients, both with and without cancer, as it can work on HIV reservoirs and tumor cells independently. The absence of side effects in this patient is also good news, and suggests this could be an optimum treatment for HIV-infected patients with cancer.”

Spano added, however, that this was only one case, and that the researchers had previously published an account of another patient who saw no decrease in HIV reservoir.

“We have to evaluate — in clinical trials and in a group of 50 French patients we are treating currently — the potential toxicities of these drugs in HIV-infected people,” Spano said. “And finally, we have to identify markers that can predict HIV response to the anti-PD-1 therapy so that treatment can be personalized, especially as we observed one responder and one nonresponder.” – by Andy Polhamus

Disclosures: Spano reports consulting or advisory roles, or meeting invitations, from BMS, Gilead, Janssen-Cilag, MSD, Novartis, Pfizer, PFO and Roche.