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  15th CROI
Conference on Retroviruses and Opportunistic Infections Boston, MA
Feb 3-6, 2008
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"Elite Controller" Study Suggests No "Harmless" Level of HIV, Lose CD4s Faster
  15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Mark Mascolini
"Elite controllers" whose viral load stays undetectable without antiretroviral therapy still lose CD4 cells at a steady pace, according to results of a small case-control study [1]. At the end of observation CD4 counts in some elite controllers had drifted below the normal range for their age, while counts in a control group of antiretroviral-treated people rose into the normal range with continuing therapy.
Hans-Jurgen Stellbrink (IPM Study Center, Hamburg) and clinical colleagues in Munich compared CD4 trends in three small groups:
· Eight elite controllers whose viral load remained below 50 copies without treatment. Elite controllers could have isolated viral blips to a maximum of 200 copies.
· Thirteen intermediate controllers whose viral load stayed between 50 and 5000 copies with no antiretroviral therapy.
· Twenty antiretroviral-treated controls who maintained a sub-50-copy load during therapy but could have blips no higher than 200 copies.
All study participants had at least 1 year of follow-up and at least three CD4 and viral load measures during follow-up. The analysis included no CD4 or viral load measures during treatment with anti-HCV drugs, cytotoxic agents, or interleukin-2. For people taking antiretrovirals, Stellbrink calculated CD4 changes only from 3 years after the start of therapy to eliminate the initial CD4 jump seen when treatment begins.
Elite controllers had a lower median age (25.5 years, range 19 to 49) than intermediate controllers (41 years, range 19 to 73) or antiretroviral-treated controls (45 years, range 35 to 68) (P = 0.0033). People taking antiretrovirals had more CD4 measures (median 13) than intermediate controllers (9) or elite controllers (8) (P = 0.06). The groups did not differ significantly in initial median CD4 count (742 for elites, 512 for intermediates, and 567 for antiretroviral takers) or length of follow-up (5.2 years for elites, 3.0 years for intermediates, and 13 years for the antiretroviral group).
Over a median of 5.2 years, 7 of 8 elite controllers lost CD4 cells, as did 9 of 13 intermediate controllers over a median of 3.0 years. Elites lost a median of 42 cells yearly, compared with 15 cells yearly among intermediate controllers. Through a median 4.0 years of follow-up, antiretroviral-treated people gained a median of 30 cells yearly (P = 0.0012 versus intermediate controllers and P = 0.00045 versus elite controllers). CD4 trend differences between elite and intermediate controllers did not differ significantly.
Using age- and gender-adjusted CD4 counts from healthy blood donors to figure normal CD4 tallies, Stellbrink determined that 7 of 8 elite controllers had normal counts at the start of follow-up, but only 4 of 8 did at the end. Nine of 20 antiretroviral-treated people had normal CD4s when follow-up began, compared with 15 of 20 when follow-up ended. Despite CD4 declines among elite and intermediate controllers, none had signs of clinical progression. CD8-cell changes did not differ between the three study groups.
Stellbrink and coworkers propose that stable or rising CD4 counts in people taking effective antiretroviral regimens suggest that the CD4 declines in untreated controllers are "directly or indirectly related to HIV replication, possibly due to local destruction of lymphoid tissue."
They concluded that "there could indeed be no 'harmless' level of HIV replication with respect to CD4 loss."
1. Stellbrink HJ, Schewe K, Hoffmann C, Wolf E. Is there a harmless level of plasma viremia in untreated HIV infection? CD4+ T cells in the long-term follow-up of elite controllers and controls. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 351.