Impact on the immune system of undetectable plasma HIV-1 RNA for more than 2 years.
OBJECTIVE
To investigate the impact of prolonged HIV suppression on the immune system by analysing the expression of several lymphocyte surface markers in a group of HIV-1-infected patients who maintained undetectable HIV-1 RNA levels for more than 24 months.


METHODS
The study included a highly selected group of nine HIV-1-infected asymptomatic subjects and seven HIV-1-seronegative controls. The inclusion criteria of HIV-1-infected patients was to have plasma HIV-1 RNA levels below 20 (1.3 log10) copies/ml for at least 24 months while under antiretroviral treatment with nucleoside analogues. The patient population was retrospectively taken from a cohort of 1418 treated subjects. Mean initial absolute CD4+ T-cell count and percentage were 468+/-234 x 10(6)/l (range, 202-935 x 10(6)/l) and 25+/-6% (range, 16-33%), respectively. Plasma HIV-1 RNA quantification was determined using a standard and ultrasensitive reverse transcriptase polymerase chain reaction assay. Median HIV-1 RNA plasma level before antiretroviral treatment was 3.14 log10 copies/ml (range, 1.74-3.73 log10 copies/ml). Two or three-colour immunophenotyping was performed on whole blood and frozen peripheral blood mononuclear cells by flow cytometry.


RESULTS
A significant increase was noted in CD4+ lymphocyte counts at the end of the study in HIV-1-positive patients. In addition, the CD4: CD8 ratio rose significantly with respect to baseline, although it remained lower than in the controls. CD45RA+ and CD45RO+ population percentages did not differ between groups. A significant rise in CD45RA+ T cells was observed. Analysis of T-cell activation measuring the expression of human leukocyte antigen-DR and CD25 did not differ between groups. The proportion of CD8+ lymphocytes that were CD28+ was similar in both groups at the end of the follow-up. T-cell receptor Vbeta subfamily analysis showed that an expansion of the T-cell receptor repertoire might occur in these patients.


CONCLUSIONS
Patients who maintain undetectable viral load for prolonged periods of time with antiretroviral therapy may achieve a partial immune restoration of the immune system. Our results suggest that treatment of patients at early stages of HIV infection is warranted.
Arnó
A
A
Retrovirology Laboratory, IrsiCaixa Foundation, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain.
Ruiz
L
L
Juan
M
M
Zayat
M K
MK
Puig
T
T
Balagué
M
M
Romeu
J
J
Pujol
R
R
O'Brien
W A
WA
Clotet
B
B
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D012367:RNA, Viral / Q000097:blood*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
D012367:RNA, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta