Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and test persistently negative in tests of immune sensitization tuberculin skin test (TST) and interferon gamma release assays (IGRA) for Mycobacterium tuberculosis (Mtb). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophil Mtb infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMN_HITTIN) and 11 HIT (PMN_HIT) were isolated and infected with Mtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. At 1h of Mtb infection, PMN_HITTIN displayed 151 significantly upregulated and 40 significantly downregulated differentially expressed genes (DEGs) and PMN_HIT 98 significantly upregulated and 11 significantly downregulated DEGs. At the 6h timepoint, PMN_HITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated DEGs while PMN_HIT had 3816 significantly up- and 3794 significantly downregulated DEGs. There was no significant differential transcriptional response at 1h between infected PMN_HITTIN and PMN_HIT. However, when contrasting the log2FC 6h infection response to Mtb from PMN_HITTIN against PMN_HIT, 2285 genes showed significant differential response between the two groups. Apoptosis and NETosis were key pathways linked to the enrichment of genes in PMN_HITTIN when contrasted to PMN_HIT after 6h infection with Mtb. Fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMN_HITTIN compared to PMN_HIT, showing that PMN_HITTIN have a distinct response to Mtb.