- Hatano, Hiroyu;
- Jain, Vivek;
- Hunt, Peter W;
- Lee, Tzong-Hae;
- Sinclair, Elizabeth;
- D., Tri;
- Hoh, Rebecca;
- Martin, Jeffrey N;
- McCune, Joseph M;
- Hecht, Frederick;
- Busch, Michael P;
- Deeks, Steven G
Background
Studies aimed at defining the association between host immune responses and human immunodeficiency virus (HIV) persistence during therapy are necessary to develop new strategies for cure.Methods
We performed a comprehensive assessment of ultrasensitive plasma HIV RNA levels, cell-associated HIV RNA levels, proviral HIV DNA levels, and T cell immunophenotyping in a cohort of 190 subjects in whom HIV levels were suppressed by highly active antiretroviral therapy.Results
The median CD4(+) T cell count was 523 cells/mm(3), and the median duration of viral suppression was 31 months. Cell-associated RNA and proviral DNA levels (but not ultrasensitive plasma HIV RNA levels) were positively correlated with frequencies of CD4(+) and CD8(+) T cells expressing markers of T-cell activation/dysfunction (CD38, HLA-DR, CCR5, and/or programmed cell death protein 1 [PD-1]) (P < .05). Having a low CD4(+) T-cell count despite receipt of virologically suppressive therapy was associated with high cell-associated RNA and proviral DNA levels (P < .01) and higher frequencies of CD4(+) T cells expressing CD38, HLA-DR, CCR5, and/or PD-1 (P < .0001).Conclusions
Cell-based measurements of viral persistence were consistently associated with markers of immune activation and the frequency of PD-1-expressing CD4(+) T cells. Treated patients with a low CD4(+) T-cell count had higher frequencies of PD-1-expressing CD4(+) T cells and cell-based measures of viral persistence, suggesting that HIV infection in these individuals may be more difficult to cure and may require unique interventions.