Size of HIV Reservoir
In a study published in the Journal of Infectious Diseases, Tae-Wook Chun et al. have analyzed the correlations between the size of HIV proviral DNA reservoirs, residual plasma viremia and immune activation in 127 individuals on effective ART.
This study (1) included 127 individuals who had received ART (various regimens) for a median of 6.5 years (range, 1.3–15.8 years) and who had achieved suppression of plasma viremia. The median CD4+ and CD8+ T-cell were 580 cells/mm3 of blood and 760 cells/mm3, respectively. All participants included in this study maintained undetectable levels of plasma viremia (<50 copies/mL) and had fewer than 3 viral ‘‘blips’’ (defined as <100 HIV RNA copies/mL) after initiation of ART, as determined by frequent blood sampling (at least 3 times per year).
The plasma from the majority of the study participants (63.0%) contained detectable plasma viremia, whereas there was no measurable HIV RNA in the plasma of 37.0% (median HIV RNA level: 2.6 copies/ml). The median copy number of HIV proviral DNA for all study participants examined was 775.1 copies (range, <2.6–6890.6 copies) per 106 CD4+ T cells.
The frequency of CD4+ T cells carrying HIV proviral DNA in infected individuals with undetectable plasma viremia (median, 448.5 copies per 106 CD4+ T cells) as a group was lower than that of individuals with detectable plasma viremia (median, 1027.2 copies per 106 CD4+ T cells).
However, 38% of the study participants with undetectable plasma viremia carried >775 copies per 106 CD4+ T cells (median), suggesting that, at least in some individuals, the size of the HIV reservoir in the CD4+ T-cell compartment in the peripheral blood may not necessarily equate to the level of residual plasma HIV.
No correlation was found between markers of immune activation (C-reactive protein, D-dimer, IL-6, soluble TNF receptor I, CD4+ CD38+, and CD8+ CD38+) and residual plasma viremia.
This study suggests that reactivation of the latent viral reservoir may not be the sole source of residual plasma viremia. Considering the relatively high frequency of HIV infection in the CD4+ T-cell compartment of nearly 40% of the study participants exhibiting undetectable plasma viremia (0 copy) and the lack of any correlation between residual plasma viremia and various markers of immune activation in blood, there is a possibility that residual viral replication, with or without the detection of plasma viremia, may also originate from productively infected CD4+ T cells in various lymphoid tissues.
Chun TW, Murray D, Justement JS, Hallahan CW, Moir S, Kovacs C, Fauci AS. Relationship Between Residual Plasma Viremia and the Size of HIV Proviral DNA Reservoirs in Infected Individuals Receiving Effective Antiretroviral Therapy. J Infect Dis. 2011; 204(1):135-8.
Key words: HIV proviral DNA, hiv residual viremia, immune activation