Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection.
BACKGROUND
During the acute phase of HIV infection, large CD4+ T-cell depletion occurs in the gastrointestinal tract. The kinetics of CD4+ T-cell decrease and highly active antiretroviral therapy (HAART)-mediated immune reconstitution were evaluated.


METHODS
Rectosigmoid colonic (RSC) biopsies and blood samples of nine patients with acute HIV infection were collected. CD4+ T-cell count, HIV RNA, intracellular HIV DNA and messenger RNA cytokine expression were evaluated before and after 6 months of HAART.


RESULTS
All nine patients presented symptomatic retroviral infection. Early HAART was associated with a sustained and comparable reduction of HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs) and RSC biopsies. HIV DNA decreased in PBMCs, but was only marginally reduced in RSC biopsies. Comparisons between reduction rates of HIV DNA in these two compartments confirmed that HIV DNA clearance was less efficient in RSC biopsies compared with PBMCs. Assessment of immunological profiles in PBMCs and RSC biopsies showed that the T-helper (Th)1-like/Th2-like ratio was sharply decreased in RSC biopsies and increased in PBMCs throughout the study period. A persistent Th2-like profile was detected in RSC biopsies. Efficient clearing of HIV DNA observed in PBMCs correlated with the establishment of a more favourable Th1-like profile.


CONCLUSIONS
A less efficient clearance of intracellular HIV DNA following early introduction of HAART is associated with persistent immunological impairment in gut-associated lymphoid tissue (GALT), which is reflected by the skewed expression of cytokines in this reservoir. The present study shows that early initiation of HAART, in the short-term, is not effective in containing the establishment of HIV infection and in reversing associated immunological GALT abnormalities.
Tincati
Camilla
C
Department of Internal Medicine, Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, University of Milan, Milan, Italy.
Biasin
Mara
M
Bandera
Alessandra
A
Violin
Michela
M
Marchetti
Giulia
G
Piacentini
Luca
L
Vago
Gian Luca
GL
Balotta
Claudia
C
Moroni
Mauro
M
Franzetti
Fabio
F
Clerici
Mario
M
Gori
Andrea
A
D000208:Acute Disease; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D012809:Colon, Sigmoid / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000097:blood; D012007:Rectum / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D017211:Treatment Failure; D055815:Young Adult
D016207:Cytokines; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral