Safety and virologic impact of haploidentical NK cells plus IL-2 or N-803 in HIV infection.

BACKGROUND:NK cells are dysfunctional in chronic HIV infection as they are not able to clear virus. We hypothesized that an infusion of NK cells, supported by IL-2 or IL-15, could decrease virus-producing cells in the lymphatic tissues. METHODS:We conducted a phase 1 pilot study in 6 persons living with HIV (PLHIV), where a single infusion of haploidentical related donor NK cells was given plus either IL-2 or N-803 (an IL-15 superagonist). RESULTS:The approach was well tolerated with no unexpected adverse events. We did not pre-treat recipients with cyclophosphamide or fludarabine to "make immunologic space", reasoning that PLHIV on stable antiretroviral treatment remain T-cell depleted in lymphatic tissues. We found donor cells remained detectable in blood for up to 8 days (like what is seen in cancer pretreatment with lymphodepleting chemotherapy) and in the lymph nodes and rectum up to 28 days. There was a moderate decrease in the frequency of viral RNA+ cells in lymph nodes. CONCLUSION:There was a moderate decrease in HIV-producing cells in lymph nodes. Further studies are warranted to determine the impact of healthy NK cells on HIV reservoirs and if restoring NK-cell function could be part of an HIV cure strategy.