Initiation of Antiretroviral Therapy During Acute HIV-1 Infection Leads to a High Rate of Nonreactive HIV Serology

Souza, Mark S. de; Pinyakorn, Suteeraporn; Akapirat, Siriwat; Pattanachaiwit, Supanit; Fletcher, James; Chomchey, Nitiya; Kroon, Eugène; Ubolyam, Sasiwimol; Michael, Nelson L.; Robb, Merlin L.; Phanuphak, Praphan; Kim, Jerome H.; Phanuphak, Nittaya; Ananworanich, Jintanat

doi:10.1093/cid/ciw365

Cited by 105 publications

(104 citation statements)

References 37 publications

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“…Currently ongoing post-treatment control cohort studies focus on patients that start treatment very early after infection. Recent studies showed that the antibody response in patients that start in the earliest phase of acute infection in some cases not even develops [54]. Together with our data this study indicates that at least a certain extent of viral exposure is required for the selection of memory B cells that would give rise to a neutralizing antibody response.…”

Section: Discussionsupporting

confidence: 79%

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

Bree¹,

Wheatley²,

Lynch³

et al. 2017

PLoS ONE

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BackgroundNeutralizing antibodies develop in natural HIV-1 infection. Their development often takes several years and may rely on chronic virus exposure. At the same time recent studies show that treatment early in infection may provide opportunities for immune preservation. However, it is unknown how intermittent treatment in early infection affects development of the humoral immune response over time. We investigate the effect of cART in early HIV infection on the properties of the memory B cell compartment following 6 months of cART or in the absence of treatment. The patients included participated in the Primo-SHM trial where patients with an early HIV-1 infection were randomized to no treatment or treatment for 24 or 60 weeks.MethodsPrimo-SHM trial patients selected for the present study were untreated (n = 23) or treated for 24 weeks (n = 24). Here we investigate memory B cell properties at viral set-point and at a late time point (respectively median 54 and 73 weeks) before (re)-initiation of treatment.ResultsAt viral set-point, the memory B cell compartment in treated patients demonstrated significantly lower fractions of antigen-primed, activated, memory B cells (p = 0.006). In contrast to untreated patients, in treated patients the humoral HIV-specific response reached a set point over time. At a transcriptional level, sets of genes that showed enhanced expression in memory B cells at viral setpoint in untreated patients, conversely showed rapid increase of expression of the same genes in treated patients at the late time point.ConclusionThese data suggest that, although the memory B cell compartment is phenotypically preserved until viral setpoint after treatment interruption, the development of the HIV-specific antibody response may benefit from exposure to HIV. The effect of viral exposure on B cell properties is also reflected by longitudinal changes in transcriptional profile in memory B cells over time in early treated patients.

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Section: Discussionsupporting

confidence: 79%

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

Bree¹,

Wheatley²,

Lynch³

et al. 2017

PLoS ONE

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“…Anti-HIV antibody levels decline when a patient is treated during primary HIV infection (PHI) and may not even develop to fulfill the criteria for HIV infection by standard confirmatory assays 1 . Recently, quantitative humoral profiling of the presumably “cured” Berlin patient revealed no antibodies to several HIV-1 antigens except reverse transcriptase (RT), Tat and gp41 2 .…”

Section: Introductionmentioning

confidence: 99%

Quantitative humoral profiling of the HIV-1 proteome in elite controllers and patients with very long-term efficient antiretroviral therapy

Zhang

Morshed

Noyan

et al. 2017

Sci Rep

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A major challenge in evaluating the success of HIV eradication approaches is the need for accurate measurement of persistent HIV during effective antiretroviral therapy (ART). Previous studies have reported that the anti-HIV antibody assay “luciferase immuno-precipitation systems (LIPS)” can distinguish HIV-infected individuals harboring different sizes of the viral reservoirs. We performed antibody profiling of HIV-1 proteomes using LIPS in viremic progressors (n = 38), elite controllers (ECs; n = 19) and patients with fully suppressive long-term antiretroviral therapy (ART) (n = 19) (mean 17 years). IgG was quantified against six HIV-1 fusion proteins: p24, gp41, RT, Tat, integrase and protease. Lower antibody levels to all six-fusion proteins were observed in long-term ART patients compared to viremics (p < 0.05). In contrast ECs had lower antibody levels only against Tat and Integrase (p < 0.05). Principal component analysis and cluster-network analysis identified that 68% (13/19) of the long-term ART patients clustered together with 26% (5/19) ECs. The remaining ECs clustered together with the viremics indicating non-homogeneity among the ECs. The low anti-HIV levels in the long-term treated patients may indicate a restricted remaining viral replication. In contrast, the higher levels in ECs suggest a continuous viral expression with a limited concomitant release of extracellular virus.

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“…As HIV RNA levels were either barely or non-detectable, the presence of antibodies to HIV-1 was suggested, although the confirmatory immunoassay (Multispot HIV 1/2) remained repeatedly non-reactive over 5 weeks. Delayed seroconversion may be observed in those administered cART during acute infection 18 and in one other case report of an individual becoming HIV-infected during repeated courses of post-exposure prophylaxis with TDF/FTC 19 . Essential to this case is that the combination of the reactive 4 th generation combination Ag/Ab test and the qualitative NAAT test established the diagnosis of HIV infection.…”

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confidence: 89%

Newly Acquired Infection With Multidrug-Resistant HIV-1 in a Patient Adherent to Preexposure Prophylaxis

Markowitz

Grossman

Anderson

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Initiation of Antiretroviral Therapy During Acute HIV-1 Infection Leads to a High Rate of Nonreactive HIV Serology

Abstract: NCT00796146 and NCT00796263.

Cited by 105 publications

References 37 publications

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

Longitudinal dynamics of the HIV-specific B cell response during intermittent treatment of primary HIV infection

Quantitative humoral profiling of the HIV-1 proteome in elite controllers and patients with very long-term efficient antiretroviral therapy

Newly Acquired Infection With Multidrug-Resistant HIV-1 in a Patient Adherent to Preexposure Prophylaxis

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