Primary Isolate Neutralization by HIV Type 1-Infected Patient Sera in the Era of Highly Active Antiretroviral Therapy

Dreyer, Kimberly; Kallas, Esper G.; Planelles, Vicente; Montefiori, David C.; McDermott, Michael P.; Hasan, Muhammad; Evans, Thomas G.

doi:10.1089/088922299309856

Cited by 34 publications

(26 citation statements)

References 33 publications

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“…Each virus-serum sample combination was analyzed in triplicate at two dilutions (1/200 and 1/2,000). These dilutions were selected in order to minimize the inhibitory effect of the antiretroviral present in sera (10,26). Table 3 summarizes the neutralization results for the 508 serum samples.…”

Section: Resultsmentioning

confidence: 99%

Broadly Cross-Neutralizing Antibodies in HIV-1 Patients with Undetectable Viremia

Medina-Ramírez

Sánchez-Merino

Sánchez-Palomino

et al. 2011

J Virol

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Several recent studies have identified HIV-infected patients able to produce a broad neutralizing response, and the detailed analyses of their sera have provided valuable information to improve future vaccine design. All these studies have excluded patients on antiretroviral treatment and with undetectable viral loads, who have an improved B cell profile compared to untreated patients. To better understand the induction of neutralizing antibodies in patients on antiretroviral treatment with undetectable viremia, we have screened 508 serum samples from 364 patients (173 treated and 191 untreated) for a broadly neutralizing antibody (bNAb) response using a new strategy based on the use of recombinant viruses. Sera able to neutralize a minipanel of 6 recombinant viruses, including envelopes from 5 different subtypes, were found in both groups. After IgG purification, we were able to confirm the presence of IgG-associated broadly neutralizing activity in 3.7% (7 of 191) of untreated patients with detectable viremia and 1.7% (3 of 174) of aviremic patients receiving antiretroviral treatment. We thus confirm the possibility of induction of a broad IgG-associated neutralizing response in patients on antiretroviral treatment, despite having undetectable viremia. This observation is in stark contrast to the data obtained from long-term nonprogressors, whose little neutralizing activity has been attributed to the low levels of viral replication.

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Section: Resultsmentioning

confidence: 99%

Broadly Cross-Neutralizing Antibodies in HIV-1 Patients with Undetectable Viremia

Medina-Ramírez

Sánchez-Merino

Sánchez-Palomino

et al. 2011

J Virol

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“…It is also thought that the low level of HIV replication during successful HAART may prevent induction of a high titer antibody response (Popovic et al 2005, Bailey et al 2006, and, although sporadic cases of a high autologous neutralizing antibody (NAb) have been reported, the NAb response during HAART is poorly understood , Dreyer et al 1999. Titers of "binding antibodies" (bAb = antibodies detectable through their in vitro binding to synthetic proteins or peptides) have been shown to decrease during successful HAART (Morris et al 2001, Bailey et al 2006.…”

Section: Highly Active Antiretroviral Treatment (Haart) Of Human Immumentioning

confidence: 99%

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

Bongertz

Ouverney

Fernandez

et al. 2007

Mem. Inst. Oswaldo Cruz

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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...

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“…Contrary to this notion, however, current evidence suggests that the B-cell response wanes when HAART is initiated during chronic infection and fails to mature when HAART is begun early in infection (17,20,22,28). In the few cases where neutralizing antibodies were examined, widely disparate effects of HAART have been observed (6,13,19,29). Interestingly, anecdotal cases of an improved neutralizing-antibody response in a small number of HIV-1-infected individuals who were intermittently nonadherent to HAART have been reported (6,29).…”

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confidence: 99%

Neutralizing Antibodies Associated with Viremia Control in a Subset of Individuals after Treatment of Acute Human Immunodeficiency Virus Type 1 Infection

Montefiori

Hill

et al. 2001

J Virol

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Immediate treatment of acute human immunodeficiency virus type 1 (HIV-1) infection has been associated with subsequent control of viremia in a subset of patients after therapy cessation, but the immune responses contributing to control have not been fully defined. Here we examined neutralizing antibodies as a correlate of viremia control following treatment interruption in HIV-1-infected individuals in whom highly active antiretriviral therapy (HAART) was initiated during early seroconversion and who remained on therapy for 1 to 3 years. Immediately following treatment interruption, neutralizing antibodies were undetectable with T-cell-line adapted strains and the autologous primary HIV-1 isolate in seven of nine subjects. Env-and Gag-specific antibodies as measured by enzyme-linked immunosorbent assay were also low or undetectable at this time. Despite this apparent poor maturation of the virus-specific B-cell response during HAART, autologous neutralizing antibodies emerged rapidly and correlated with a spontaneous downregulation in rebound viremia following treatment interruption in three subjects. Control of rebound viremia was seen in other subjects in the absence of detectable neutralizing antibodies. The results indicate that virus-specific B-cell priming occurs despite the early institution of HAART, allowing rapid secondary neutralizing-antibody production following treatment interruption in a subset of individuals. Since early HAART limits viral diversification, we hypothesize that potent neutralizing-antibody responses to autologous virus are able to mature and that in some persons these responses contribute to the control of plasma viremia after treatment cessation.

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Primary Isolate Neutralization by HIV Type 1-Infected Patient Sera in the Era of Highly Active Antiretroviral Therapy

Cited by 34 publications

References 33 publications

Broadly Cross-Neutralizing Antibodies in HIV-1 Patients with Undetectable Viremia

Broadly Cross-Neutralizing Antibodies in HIV-1 Patients with Undetectable Viremia

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

Neutralizing Antibodies Associated with Viremia Control in a Subset of Individuals after Treatment of Acute Human Immunodeficiency Virus Type 1 Infection

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