A Multicenter Observational Study of the Potential Benefits of Initiating Combination Antiretroviral Therapy during Acute HIV Infection

Hecht, Frederick; Wang, Lei; Collier, Ann C.; Little, Susan J.; Markowitz, Martin; Margolick, Joseph B.; Kilby, J Michael; Daar, Eric S.; Conway, Brian; Holte, Sarah

doi:10.1086/506616

Cited by 156 publications

(135 citation statements)

References 24 publications

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Section: Lymphocyte Counts Before and After Artsupporting

confidence: 91%

“…Thus, in contrast to previous findings showing a slow normalization of CD8 ϩ T cells after ART in chronically HIV-infected individuals, 25 the findings here and elsewhere show a more rapid normalization of CD8 ϩ T cells in early-treated individuals. 32,33 These data also confirm the observation made in our previous study, namely that , and CD8 ϩ (C) T cells in the peripheral blood were measured over time after initiation of ART at day 0. Each line represents the trajectory for 1 individual and was generated using regression from a minimum of 3 time points after initiation of ART.…”

Section: Lymphocyte Counts Before and After Artsupporting

confidence: 90%

“…Furthermore, we provide evidence that early initiation of ART is associated with a better recovery of B-cell function against non-HIV and certain HIV antigens compared with the initiation of ART during the chronic stage of HIV infection, adding a compelling argument to other indications that early initiation of ART is beneficial to preserving immune function in HIV-infected individuals. 32,33 In a previous study, we reported that the number of total B cells in the peripheral blood of chronically HIV-infected individuals increased significantly after initiation of ART, similar to the increases in CD4 ϩ but not CD8 ϩ T cells after initiation of ART. 25 In the present study, we extended these findings by demonstrating that the early phase of HIV infection was distinct from the chronic stage, both in terms of immunologic parameters before the initiation of ART and the dynamics of response after initiation of ART.…”

Section: Discussionsupporting

confidence: 55%

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B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy

Moir

Buckner

et al. 2010

Blood

245

263

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IntroductionNumerous perturbations of B-cell phenotype and function have been described in HIV-infected individuals (reviewed in Cagigi et al 1 and Moir and Fauci 2 ). Phenotypic perturbations of B cells circulating in the peripheral blood include over-representation of activated, exhausted, and terminally differentiated B cells associated with HIV viremia 3-5 ; over-representation of immature/ transitional B cells associated with HIV-induced CD4 ϩ T-cell lymphopenia 6,7 ; and reduced representation of CD27 ϩ memory B cells associated with most stages of HIV infection. [8][9][10][11][12][13] Most of these studies, whether longitudinal or cross-sectional, have been conducted on chronically HIV-infected individuals, whereas only a few studies, generally with small sample sizes, have addressed the effect of duration of infection and initiation of antiretroviral therapy (ART) on perturbations of B-cell subpopulations in HIVinfected individuals. 9,14,15 Functional perturbations of B cells in HIV-infected individuals include hypergammaglobulinemia associated with polyclonal and HIV-specific activation of B cells induced by ongoing HIV replication, 15,16 as well as decreased B-cell responses to specific immunogens and non-HIV pathogens. 11,17,18 The latter is likely a reflection of both CD4 ϩ T-cell dependent and independent defects in B cells that arise in HIV-infected individuals, and especially in individuals with ongoing viral replication. Many of the functional B-cell defects described in HIV-viremic individuals can be improved with ART, although there is 1 important exception that has received relatively little attention. While B-cell responses against non-HIV antigens are either stabilized or increased after initiation of ART, 19-22 the reverse is often observed for B-cell responses against HIV antigens,15,23,24 suggesting that the humoral response against HIV is dependent on continuous HIV replication. In the most comprehensive study on B-cell responses after ART, Morris and colleagues described a rapid loss of HIV-specific B cells (actively secreting plasmablasts) during therapy, followed by a more gradual decrease in antibody titers against HIV in chronically infected individuals; the loss was even more rapid in early-treated individuals. 15 In a previous study of chronically HIV-infected individuals, we reported a reduction in B-cell numbers and the presence of perturbed B-cell subpopulations before initiation of ART followed by partial normalization 1 year after successful reduction in viremia by ART. 25 In a more recent study, 5 we identified a subpopulation of CD27 Ϫ tissue-like memory B cells within an abnormal CD21 lo B-cell compartment of the peripheral blood of chronically HIVviremic individuals; this subpopulation had been included within the activated B-cell compartment that we had previously described. 25 These CD27 Ϫ tissue-like memory B cells bore many features of exhausted cells, arising in the context of chronic immune activation, and with features that include expression of multiple inhibitory...

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Section: Lymphocyte Counts Before and After Artsupporting

confidence: 91%

Section: Lymphocyte Counts Before and After Artsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 55%

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B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy

Moir

Buckner

et al. 2010

Blood

245

263

View full text Add to dashboard Cite

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“…Intuitively, the earlier that intervention can be initiated following HIV acquisition, the more enhanced will be the anticipated effect on outcome. Although much of the early immunological work has focused on acute infection (Rosenberg et al 2000;Kaufmann et al 2004), a more recent study (Hecht et al 2006) comparing early intervention (<14 days) with later (2 weeks to 6 months) identified immunological benefit in both groups although enhanced outcome was only seen with earlier intervention. It is also of interest to note that while viral testing is an important tool for the detection of an acute HIV infection, it does not serve as the stand alone diagnostic assay and the recommendations are that when acute HIV infection is diagnosed by a positive viral test (such as HIV RNA or p24 antigen) coupled with a negative HIV antibody test, a confirmatory HIV antibody test should be performed over the next 3 months to confirm seroconversion (DHHS and OARAC 2011).…”

Section: Pregnant Women In the Wp A Missed Opportunity To Treat And mentioning

confidence: 99%

The HIV Seronegative Window Period: Diagnostic Challenges and Solutions

Jehuda-Cohen¹

2011

Recent Translational Research in HIV/AIDS

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“…Two recent studies showed that initiating treatment during acute HIV infection improves the CD4 þ T cell count. 29,30 Thus, patients with a high viral load set point, as well as patients with a low postseroconversion level of CD4 count, are likely to benefit from early treatment.…”

Section: Discussionmentioning

confidence: 99%

210 Low Post-Seroconversion CD4 Count and Rapid Decrease of CD4 Density Identify HIV+ Fast Progressors

Audigé

Taff

Rickenbach

et al. 2011

JAIDS Journal of Acquired Immune Deficiency Syndromes

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R (2010). Low postseroconversion CD4 count and rapid decrease of CD4 density identify HIV+ fast progressors. AIDS Research and Human Retroviruses, 26(9) CD4 expression in HIV replication is paradoxical: HIV entry requires high cell-surface CD4 densities, but replication requires CD4 down-modulation. However, is CD4 density in HIV þ patients affected over time? Do changes in CD4 density correlate with disease progression? Here, we examined the role of CD4 density for HIV disease progression by longitudinally quantifying CD4 densities on CD4þ T cells and monocytes of ARTnaive HIV þ patients with different disease progression rates. This was a retrospective study. We defined three groups of HIV þ patients by their rate of CD4 þ T cell loss, calculated by the time between infection and reaching a CD4 level of 200 cells/ml: fast (<7.5 years), intermediate (7.5-12 years), and slow progressors (>12 years). Mathematical modeling permitted us to determine the maximum CD4 þ T cell count after HIV seroconversion (defined as ''postseroconversion CD4 count'') and longitudinal profiles of CD4 count and density. CD4 densities were quantified on CD4 þ T cells and monocytes from these patients and from healthy individuals by flow cytometry. Fast progressors had significantly lower postseroconversion CD4 counts than other progressors. CD4 density on T cells was lower in HIV þ patients than in healthy individuals and decreased more rapidly in fast than in slow progressors. Antiretroviral therapy (ART) did not normalize CD4 density. Thus, postseroconversion CD4 counts define individual HIV disease progression rates that may help to identify patients who might benefit most from early ART. Early discrimination of slow and fast progressors suggests that critical events during primary infection define long-term outcome. A more rapid CD4 density decrease in fast progressors might contribute to progressive functional impairments of the immune response in advanced HIV infection. The lack of an effect of ART on CD4 density implies a persistent dysfunctional immune response by uncontrolled HIV infection.

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A Multicenter Observational Study of the Potential Benefits of Initiating Combination Antiretroviral Therapy during Acute HIV Infection

Cited by 156 publications

References 24 publications

B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy

B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy

The HIV Seronegative Window Period: Diagnostic Challenges and Solutions

210 Low Post-Seroconversion CD4 Count and Rapid Decrease of CD4 Density Identify HIV+ Fast Progressors

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