Blunted Response to Combination Antiretroviral Therapy in HIV Elite Controllers: An International HIV Controller Collaboration

Boufassa, Faroudy; Lechenadec, Jérome; Meyer, Laurence; Costagliola, Dominique; Hunt, Peter W.; Pereyra, Florencia; Deeks, Steven G.; Pancino, Gianfranco; Tauléra, Olivier; Lichterfeld, Mathias; Delobel, Pierre; Sáez‐Cirión, Asier; Lambotte, Olivier

doi:10.1371/journal.pone.0085516

Cited by 32 publications

(23 citation statements)

References 31 publications

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“…In this population, the etiology of CD4 + T cell decline may be multifactorial because T-cell activation has also been found to be associated with lower CD4 + cell counts [ 12 ]. It is interesting to note that although initiation of ART in HIV controllers has resulted in diminished HIV reservoir size [ 46 ], lower levels of residual viremia, and T-cell activation [ 38 ], it is only associated with a modest or no increase in CD4 + cell counts [ 38 , 47 ]. The etiology behind this blunted CD4 + cell response to ART remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Differential Levels of Soluble Inflammatory Markers by Human Immunodeficiency Virus Controller Status and Demographics

Arnold

et al. 2015

Open Forum Infectious Diseases

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Background. Human immunodeficiency virus (HIV)-1 elite controllers (ECs) represent an ideal population to study the effects of HIV persistence on chronic inflammation in the absence of antiretroviral therapy (ART).Methods. Twenty inflammatory markers measured in cohorts of ECs, HIV suppressed noncontrollers, and HIV-uninfected controls were compared using rank-based tests and partial least squares discriminant analysis (PLSDA). Spearman correlations were determined among the inflammatory markers, residual viremia by the single-copy assay, and CD4+ T cell slope.Results. Significant differences were seen between cohorts in 15 of the soluble inflammatory markers. Human immunodeficiency virus-1 ECs were found to have the highest levels for all of the markers with the exception of RANTES. In particular, median levels of 7 inflammatory markers (soluble CD14 [sCD14], interferon [IFN]-γ, IFN-γ-inducible protein [IP]-10, interleukin [IL]-4, IL-10, sCD40L, and granulocyte-macrophage colony-stimulating factor) were twice as high in the HIV-1 ECs compared with either of the HIV-suppressed or uninfected groups. Multivariate PLSDA analysis of inflammatory markers improved differentiation between the patient cohorts, discerning gender differences in inflammatory profile amongst individuals on suppressive ART. Soluble markers of inflammation in ECs were not associated with either levels of residual HIV-1 viremia or CD4+ T cell decline.Conclusions. Despite maintaining relatively low levels of viremia, HIV-1 ECs had elevated levels of a set of key inflammatory markers. Additional studies are needed to determine whether ECs may benefit from ART and to further evaluate the observed gender differences.

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Section: Discussionmentioning

confidence: 99%

Differential Levels of Soluble Inflammatory Markers by Human Immunodeficiency Virus Controller Status and Demographics

Arnold

et al. 2015

Open Forum Infectious Diseases

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“…These individuals, termed HIV controllers, represent a rare group whose HIV-specific immune responses enable them to control the virus without ART (Migueles and Connors 2015; Walker and Yu 2013). Despite evidence of ongoing virus replication in HIV controllers not receiving ART (Boufassa et al 2014; Chun et al 2013; Fukazawa et al 2015; Hatano et al 2013; Mens et al 2010; OConnell et al 2010; Salgado et al 2010), prior work has shown fewer CD4 T cells containing HIV DNA (Julg et al 2010) and replication-competent HIV (Blankson et al 2007) in HIV controllers than in non-controllers. We reasoned that this would allow us to sample more of the total virus population in these individuals and therefore obtain a comprehensive view of the infected CD4 T cell pool.…”

Section: Introductionmentioning

confidence: 99%

Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Boritz¹,

Darko²,

Swaszek³

et al. 2016

Cell

160

154

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SUMMARY Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.

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“…However, some HICs eventually exhibit a decline in their CD4+ T cell count during the period of HIV control and/or lose the ability to control HIV [ 11 , 12 ]. Using ultrasensitive techniques, low levels of HIV replication can be detected in HICs and might be correlated with the CD4+ T cell loss [ 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Immunologic and Virologic Progression in HIV Controllers: The Role of Viral “Blips” and Immune Activation in the ANRS CO21 CODEX Study

Noël¹,

Lerolle

Lécuroux³

et al. 2015

PLoS ONE

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Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm3 or more than 200/mm3 with a baseline count below 600/mm3. Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up.

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Blunted Response to Combination Antiretroviral Therapy in HIV Elite Controllers: An International HIV Controller Collaboration

Cited by 32 publications

References 31 publications

Differential Levels of Soluble Inflammatory Markers by Human Immunodeficiency Virus Controller Status and Demographics

Differential Levels of Soluble Inflammatory Markers by Human Immunodeficiency Virus Controller Status and Demographics

Multiple Origins of Virus Persistence during Natural Control of HIV Infection

Immunologic and Virologic Progression in HIV Controllers: The Role of Viral “Blips” and Immune Activation in the ANRS CO21 CODEX Study

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