Background:
We evaluated if PWH with chronic myeloid leukemia (CML) on antiretrovirals (ART) and tyrosine kinase inhibitors (TKI) had cell populations with high antiviral capacity that may explain the reduced reservoir size observed in these individuals.
Methods:
Blood samples were obtained from 6 PWH with CML on ART and TKI (n=3 imatinib; n=3 dasatinib) and 18 PWH on ART recruited as controls. Cell immunophenotyping was performed by flow cytometry. Cytotoxic activity was determined using NK-specific target cells K562 and HIV-1-infected TZM-bl. Cytokine release was measured after stimulation with HIV-1 peptide pool. Statistical analysis was performed with Mann-Whitney or unpaired t-test.
Results:
1)Most participants were male (100% PWH on ART+TKI and 73% of controls). Median age was 53 (IQR 42-51) and 54 years-old (IQR 47-62), respectively. Age at HIV+ diagnosis was 39 (IQR 32-45) and 31 years-old (IQR 25-36); age at CML diagnosis was 47 years-old (42-63). Time with HIV-1 infection was 22 (IQR 15-30) and 23 years (15-30). Nadir CD4 and CD4 count was 97 (IQR 63-382) and 370 cells/μl (186-843) in PWH on ART+TKI and 292 (IQR 176-385) and 983 cells/μl (IQR 798-1174) in controls. CD4/CD8 was 0.6 (IQR 0.3-1.5) and 1.0 (IQR 0.7-1.5), respectively. PWH on ART+TKI showed CML molecular response of 5.0 log (IQR 4.1-5.1) and they were on imatinib or dasatinib for median 3.3 years (IQR 1.7-9.6). All participants were on standard ART. 2)PBMCs from PWH on ART+TKI showed higher cytotoxicity against NK-specific (p=0.0050) and HIV-1-infected target cells (p=0.0205) than controls. 3)PWH on ART+TKI had higher levels of NK cells (p=0.0179) with higher expression of maturation/memory marker CD57. 4)PWH on ART+TKI showed increased levels of CD8 (p=0.0325) with higher degranulation capacity (CD107a+; p=0.0084) and increased release of GZB (p=0.0002). No changes were observed in the release of IFNγ. 5)CD8 from PWH on ART+TKI released lower levels of TNFα (p=0.0469), which is essential in HIV-1-associated chronic inflammation. 6)No differences were found in the expression of immunosenescence/exhaustion markers in CD4 and CD8 except for KLRG1 that was increased in PWH on ART+TKI (p=0.0176 and p<0.0001, respectively).
Conclusions:
PWH on ART+TKI show low HIV-1 reservoir size, which may be partly related to higher levels of cytotoxic cells with antiviral activity. These cell populations may have been stimulated by the presence of cancerous cells, so these results have to be confirmed in clinical trials with PWH without CML.