CD4 T cell recovery is slower in patients experiencing viral load rebounds during HAART

Abstract

SUMMARYTo determine whether viral load rebounds during HAART impact on CD4 1 T cell recovery and immune reconstitution, we studied a prospective cohort of 355 antiretroviral naive patients enrolled to be randomized in a trial of three strategies of induction/maintenance HAART. The extent of immune reconstitution in blood through 72 weeks of antiretroviral treatment was evaluated. Lymphocyte subset markers (CD4, CD8, CD45RA, CD62L, CD16, CD19), activation markers (HLA-DR, CD38, CD25) were performed by cytometry analysis. Our results showed that plasma HIV-1 RNA was suppressed to below 500 copies per ml through week 72 in 240 patients (group 1) while the remaining 115 patients experienced at least one viral rebound (group 2). At baseline, CD4 cell count was higher and HIV-1 RNA was lower in group 1 than in group 2. Over 72 weeks, mean increase in CD4 1 T cell count was 0´32 cell/mm 3 /day in group 1 and only 0´14 cell/mm 3 /day in group 2 (P , 0´0001). However, the patterns of changes in CD4 1 and CD8 1 T cell subsets during therapy were very similar across the two groups with only subtle and very limited differences. We conclude that permanent control of HIV replication could be necessary for faster immune reconstitution.

Limited long‐term naive CD4+ T cell reconstitution in patients experiencing viral load rebounds during HAART

“…However, this does not concur with other reports [Lu and Andrieu, 2000;Baldanti et al, 2001;Scott-Algara et al, 2001], that documented similar results in the two groups. This could be due to a different definition of partial responders and/or …”

“…þ T cell count long-term response is related to the degree and durability of viral load suppression, as other researchers have also reported in a 2-year followup studies [Deeks et al, 1999[Deeks et al, , 2000Mezzaroma et al, 1999;Notermans et al, 1999;Renaud et al, 1999;Connick et al, 2000;Kaufmann et al, 2000;Wood et al, 2000;Scott-Algara et al, 2001] and in up to 32 months follow-up [Teixeira et al, 2001]; however other researchers have found a similar increase in the two groups [Lu and Andrieu, 2000;Baldanti et al, 2001].…”

“…In addition to the quantitative increase of CD4 þ T lymphocytes and the expression of the costimulatory molecule CD28, the CD38 activation antigen appears to decrease during HAART Carcelain et al, 2001]. In short-term studies with a follow-up of 6 months to 2 years, the immune system did not recover to a level comparable with that of HIV-1 uninfected controls [Autran et al, 1997;Connors et al, 1997;Angel et al, 1998;Gea-Benacloche and Clifford Lane, 1999;Mezzaroma et al, 1999;Pontesilli et al, 1999;Søndergaard et al, 1999;Scott-Algara et al, 2001]. In addition, this recovery could be influenced by the level of viral suppression achieved; furthermore, several studies suggest that low-level viral replication may still be present despite such suppression of HIV-1 replication in the plasma [Zaunders et al, 1999].…”

Loss of memory B cells impairs maintenance of long-term serologic memory during HIV-1 infection

“…Although the occurrence of measles reinfection has not been reported in HIV-1-infected adults, an increased rate of measles infections and deaths occur in infants born to HIV-1-infected mothers living in geographic areas with poor access to measles vaccination. 16,17,19,23 Moreover, although not exhaustively addressed here, it is conceivable that memory B cells specific to other relevant antigens are reduced in HIV-1 infection. This would, for instance, include pathogens such as S pneumoniae, which has a well-characterized clinical relevance for HIV-1 patients.…”

“…Previous studies have suggested that a compromised memory B-cell response and/or low specific antibody titers may increase the risk of infections for the HIV-1 carrier 10,[13][14][15] and for children born to HIV-1-infected mothers. [16][17][18][19] To further dissect the relationship between loss of memory B cells, reduction of specific antibody levels, and disease progression, we studied subjects at different stage of disease (ie, PHI, CHI, and long-term nonprogressor [LTNP]) and also evaluated the effects of ART. In order to cover the spectrum of currently held views on maintenance of B-cell memory, we measured Ab titers against a T-cell-dependent antigen (measles) and a T-cell-independent antigen (pneumococcal polysaccharide capsule antigen [PPS]).…”