Anti-human immunodeficiency virus type 1 humoral immune response and highly active antiretroviral treatment

Abstract

Highly active antiretroviral treatment (HAART) of human immunodeficiency type 1 (HIV-1) infection is very effective in controlling infection, but elimination of viral infection has not been achieved as yet, and upon treatment interruption an immediate rebound of viremia is observed. A combination of HAART with an immune stimulation might allow treatment interruption without this rebounding viremia, as the very low viremias observed with successful HAART may be insufficient to permit maintenance of a specific anti-HIV-1 immune response. The objective of this study was to compare the humoral immune response of individuals undergoing successful HAART (NF=no failure) with that of individuals with evidence of failure of therapy (FT) and to verify if the viremia peaks observed in individuals with therapy failure would act as a specific stimulus for the humoral anti-HIV-1 immune response. Antibodies binding to gp120 V3 genotype consensus peptides were more frequently observed for FT, mainly against peptides corresponding to sequences of genotypes prevalent in the Rio de Janeiro city area, B and F. HIV-1 neutralization of HIV-1 IIIB and of four primary isolates from Rio de Janeiro was less frequently observed for plasma from the NF than the FT group, but this difference was more expressive when plasma from individuals with detectable viremia were compared to that of individuals with undetectable viral loads in the year before sample collection. Although statistically significant differences were observed only in some specific comparisons, the study indicates that presence of detectable viremia may contribute to the maintenance of a specific anti-HIV-1 humoral immune response.Key words: antibodies -seroreactivity -neutralization -antiretroviral treatment -treatment failure Anti-HIV highly active antiretroviral treatment (HAART) reduces HIV in peripheral blood and reverts the characteristic immunodeficiency, and has benefited patients increasing individual survival at least 13-14 years (Vermund et al. 2006). However, no elimination of viral infection has been achieved, and the antiretroviral drugs will probably have to be taken throughout the life of the patient. Attempts to stimulate a potent specific anti-HIV-1 immune response to permit control of viral replication. After HAART has reduced viremia to undetectable levels, have so far been less than successful. During successful HAART, a decline in antibody response is generally observed (Fournier et al. 2002, Devito et al. 2006, with cases of seroreversion being described (Amor et al. 2006) and the extent of immune reconstitution in HAART treated individuals is controversial, apparently depending on the immune status of the individuals at the start of therapy (Cheonis et al. 2005). However, the benefits of HAART are evident even when treatment apparently fails, leading neither to a complete control of viremia nor to a complete reconstitution in CD4 T lymphocytes (Brígido et al. 2004, Kovacs et al. 2005).During successful anti-HIV therapy, a reduction in virus specific ce...

Prevalence of antiretroviral drug resistance among treatment-naive and treated HIV-infected patients in Venezuela

“…The prevalence of mutations conferring resistance to ARV drugs found in treated patients was similar to those described recently in Chile for PIs and NRTIs (46% and 61%, respectively) and similar to the prevalence reported in Rio de Janeiro, Brazil (70% to NRTIs, 55% to NNRTIs and 45% to PIs) (Bongertz et al 2007, Rios et al 2007). This prevalence was also higher than that reported for Venezuela earlier this decade by Delgado et al (2001).…”

Immune activation and antibody responses in non‐progressing elite controller individuals infected with HIV‐1

“…The overall low levels of general and specific immune activation seen in the non-progressing elite controllers may reflect the extremely low levels of HIV-1 antigenic stimulation due to the suppression of viral replication, supporting the hypothesis that an antigenic threshold must be reached to sustain high-level chronic immune activation and HIV-1-specific immune responses [Ferbas et al, 1995;Hogervorst et al, 1995;Jin et al, 2000;Bailey et al, 2006;Verity et al, 2007]. Consistent with this model, reduction of viral replication to undetectable levels in patients under HAART also coincides with a decline of general immune activation markers [Autran et al, 1997;Bisset et al, 1998;Bouscarat et al, 1998;Giorgi et al, 1998], and the titers of HIV-1-specific binding and neutralizing antibodies [Morris et al, 1998;Markowitz et al, 1999;Binley et al, 2000;Killian et al, 2006;Bongertz et al, 2007;Hayashida et al, 2008]. At the same time, however, abnormally high CD8 þ T-cell activation levels [Greenough et al, 1999;Wang et al, 2002;Hunt et al, 2008] and strong HIV-1-specific humoral responses [Wang et al, 2002;Kloosterboer et al, 2005;Pereyra et al, 2008] have been described in some elite controller and non-progressing elite controller subjects.…”

“…Neutralizing antibodies. Heat inactivated plasma samples from the different individuals were tested for their capacity to neutralize the reference X4 HIV-1 III B and SF162 strains expanded in the PBMCs, as previously described [Bongertz et al, 2007]. Briefly, neutralization was tested using pre-activated normal human PBMCs (10 5 cells/well), and a multiplicity of infection (MOI) of 0.001-0.005 (10-50 infective units per well).…”

Efficient Neutralization of Primary Isolates by the Plasma from HIV-1 Infected Indian Children

“…Kim et al (2001) found that neutralization of primary isolates was higher in ART-treated individuals with prolonged suppressed viremia (12). Other studies have found that the neutralization titers were decreased in ART-treated individuals with suppressed viremia (3,17). The variation in the results observed could be due to the difference in the primary isolates tested in these studies.…”