HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4 + and CD8 + T cell activation, lower CD4 + T cell exhaustion, and more robust Gag-specific CD4 + T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4 + T cell% and CD4 + /CD8 + ratio, more functional NK cells, and a lower CD4 + T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.
Background: This study aimed to (1) describe long-term patient-reported outcomes of surgically treated symptomatic radial sensory nerve neuromas on function, pain interference, pain intensity, and satisfaction; (2) assess which factors were associated with worse function, higher pain intensity, and more pain interference; and (3) describe the secondary surgery rate and factors associated with secondary surgery. Methods: The authors conducted a retrospective review of patients surgically treated for radial sensory nerve neuroma from 2002 to 2016 (n = 54). Twenty-five of these 54 patients completed a follow-up survey including the Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity, pain interference, and depression scales; numerical rating scale pain and satisfaction instruments; and the global rating scale of change, at a mean period of 10.7 ± 4.3 years after neuroma surgery. Results: The mean PROMIS scores were 45.0 ± 12.1 for upper extremity, 55.5 ± 10.3 for pain interference, and 49.9 ± 10.2 for depression, and were within 1 SD of the general population. Eight patients (32 percent) reported symptoms as unchanged or worse following neuroma surgery. The median numerical rating scale pain was 3 (interquartile range, 1 to 6) and the global rating scale of change satisfaction was 10 (interquartile range, 7 to 10). Older patients (p = 0.002) and patients with higher PROMIS pain interference (p < 0.001), higher numerical rating scale for pain (p = 0.012), and lower global rating scale of change scores (p = 0.01) had worse PROMIS upper extremity scores. The secondary surgery rate was 20 percent and was associated with the presence of multiple neuromas (p = 0.001). Conclusions: Radial sensory nerve neuromas remain difficult to treat. They have a high secondary surgery rate (20 percent), with only 68 percent of patients reporting improvement after surgical intervention. Patient-reported outcomes after surgery are similar to conditions of the general population; however, the range of outcomes is wide.
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