Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy.
BACKGROUND
Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined.


METHODS
For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels </=200 copies/mL were followed prospectively: HIV RNA level and CD4 and CD8 cell counts were investigated every 3 months, and proviral DNA and T cell subsets were investigated every 6 months.


RESULTS
During follow-up, 33 patients had HIV RNA levels </=20 copies/mL at all visits (uVL patients), whereas 68 patients had HIV RNA levels >20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05).


CONCLUSIONS
These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.
Ostrowski
Sisse R
SR
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. sro@dadlnet.dk
Katzenstein
Terese L
TL
Thim
Per T
PT
Pedersen
Bente K
BK
Gerstoft
Jan
J
Ullum
Henrik
H
D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets; D014766:Viremia / Q000188:drug therapy / Q000276:immunology* / Q000821:virology
D004279:DNA, Viral; D012367:RNA, Viral