Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial : AIDS

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Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA

a randomized trial

Katlama, Christine; Lambert-Niclot, Sidonie; Assoumou, Lambert; Papagno, Laura; Lecardonnel, François; Zoorob, Rima; Tambussi, Giuseppe; Clotet, Bonaventura; Youle, Mike; Achenbach, Chad J.; Murphy, Robert L.; Calvez, Vincent; Costagliola, Dominique; Autran, Brigitte on behalf of the EraMune-01 study team

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AIDS 30(2):p 221-230, January 2016. | DOI: 10.1097/QAD.0000000000000894



The concept of HIV remission is currently supported by the existence of few patient populations capable of controlling HIV replication in the absence of antiretroviral therapy (ART) such as the untreated elite-controllers and the post-treatment controllers initiating ART during primary infection [1,2]. All have low levels of cell-associated total HIV-DNA reservoir [1,3] suggesting total HIV DNA is one of the predictors in post-treatment control [4]. Thus, decreasing HIV DNA could be a step toward facilitating HIV eradication. Several mechanisms promote HIV persistence [5,6] including latency of integrated virus within quiescent long-lived memory cells and persistence of ongoing low-level replication particularly in tissues with poor drug penetrance due to cell to cell spread [7,8]. Initial attempts of raltegravir (RAL) ART intensification resulted in small increases in production of 2-long terminal repeat (2-LTR) circles and a modest impact on residual HIV replication [9–12]. These results prompted us to evaluate whether ART intensification with two anti-HIV compounds, RAL and maraviroc (MVC), from two new drug classes might have a greater impact on reservoir persistence.

Several agents have been proposed to reactivate HIV from latently infected cells including interleukin-7 (IL-7) and histone deacetylase inhibitors [5,6]. We focused on IL-7 because it triggers signalling pathways inducing HIV production [13–15] and it produces strong T-cell homeostatic proliferation. Indeed IL-7 had been shown in vitro to increase transcription and replication of HIV from CD4+ T cells and to induce transient ‘blips’ of plasma HIV-RNA among patients on suppressive ART [14–17]. Furthermore, IL-7 increases lymphocyte Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G and potentially causes G to A mutations in virus genomes leading to defective viruses [18].

The EraMune program designed two parallel, multicentre, randomized clinical trials (EraMune 01 and EraMune 02) where treatment intensification with RAL and MVC was followed by immune modulators: a cytokine (IL-7) in EraMune 01 and an HIV vaccine (DNA prime/adenovirus-5 boost) in EraMune 02 [19]. Here, we present the results of EraMune 01 in virally suppressed patients on ART.


Study design

The EraMune 01 study was a prospective, multicentre, randomized, open-label, noncomparative, phase II clinical trial of ART intensification alone or with IL-7. After a lead-in of RAL and MVC intensification for 8 weeks, participants were randomly assigned (1 : 1) to continue RAL/MVC intensification alone (RAL/MVC Arm) or RAL/MVC with recombinant-human-interleukin-7 (r-hIL-7) (RAL/MVC/IL-7 Arm) for a total of 56 weeks. The study protocol (EudraCT No. 2009-014406-34) was approved by the Investigational Review Board of Hôpital Pitié-Salpétrière (CPP Ile de France VI) and by IRBs/IECs at each study site. A written informed consent was obtained from all patients.

Eligibility criteria

We included chronically infected patients, 18 to 70 years of age, naive to integrase and CCR5 inhibitors, on stable ART with plasma HIV-RNA below 200 copies/ml for at least 3 years and below 50 copies/ml within the past year, with CD4+ T-cell count at least 350/μl and cell-associated HIV-DNA between 10 and 1000 copies/106 peripheral blood mononuclear cells (PBMCs). Main exclusion criteria were any immunotherapeutic intervention within the past year and active hepatitis B or C co-infection.

Randomization and masking

Randomization was computer-generated in permuted blocks of six and stratified by study site. All study participants and patients were aware of the treatment allocation throughout the study.

Treatment interventions

After enrolment, all patients remained on their baseline ART and received RAL 400 mg twice daily (provided by Merck & Co., USA) and MVC 150 mg twice daily (provided by Pfizer Inc. and ViiV Healthcare, USA) for 56 weeks.

Patients randomized to the RAL/MVC/IL-7 arm were administered 3 weekly subcutaneous injections of r-hIL-7 dosed 20 μg/kg (provided by Cytheris SA, France) at weeks 8, 9 and 10. In June 2011, considering the extremely large T-cell increase following the first cycle of r-hIL-7 injections and the absence of safety data on r-hIL-7 among patients with CD4+ cell counts over 1500 cells/μl, the DSMB recommended terminating the second cycle of 3 r-hIL-7 injections planned for week 28. At week 56, RAL/MVC intensification was discontinued and patients remained on their baseline ART.

Follow-up and sample collection

Clinical evaluations were performed and samples collected at screening, baseline and monthly to assess safety, cell-associated HIV DNA, plasma HIV RNA, standard biochemistry and CD4+/CD8+ cell analysis. An additional assessment was performed at W80. Safety was assessed according to the National Institute of Allergy and Infectious Diseases Division of AIDS table for grading the severity of clinical and biological events (version 1·0, December 2004, clarification August 2009).

PBMCs were cryopreserved locally and stored in liquid nitrogen. A subset of participants volunteered to undergo sigmoidoscopy to collect rectal tissue at baseline and week 56. Approximately 15–20 tissue samples were collected for virologic analyses on flash-frozen pieces stored at −80°C from all patients, and immunological analyses on seven fresh samples from the Pitié-Salpétrière centre, as previously described [20].


HIV-1 RNA plasma viral load was quantified locally using the COBAS TaqMan HIV-1 Test v2.0 with a 20 copies/ml limit of detection. Except for screening samples assessed locally, total cell HIV DNA was quantified in PBMCs and rectal tissue by ultrasensitive real-time PCR as previously described [20–22] at the Pitié-Salpétrière virology laboratory. Ultrasensitive plasma HIV-1 RNA was measured at screening, baseline (D0), weeks 8, 12,28, 36 and 56 with a limit of quantification of 1 copy/ml, as previously reported [23].

Additional HIV RNA measurements were performed in the RAL/MVC/IL-7 group at W9 and week 10 during the IL-7 administration period.

Genetic diversity of total cell-associated HIV DNA and the presence of stop codons in the context of G to A mutations were studied using Sanger sequencing of the reverse transcriptase gene [24]. Unspliced HIV transcripts were quantified in total CD4+ T cells purified from PBMCs at D0, weeks 8, 12 and 56 from 16 patients: five from the RAL/MVC arm and 11 from RAL/MVC+IL-7 arm, along with two healthy donors, as previously described [25].


Analyses were batched and performed centrally on cryopreserved PBMCs from all study patients and on fresh rectal mononuclear cells (RMCs) only from patients at the Pitié-Salpêtrière site. CD4+ and CD8+ T-cell subset analyses performed were as follows: naive (TN: CD45RA+CCR7+CD27+), central-memory (TCM: CD45RACCR7+CD27+), transitional-memory (TTM: CD45RACCR7CD27+), effector-memory (TEM: CD45RACCR7CD27) and terminal-effector TEMRA (CD45RA+CCR7CD27) cells were characterized using: anti-CD3, CD4+, CD27, HLA-DR, Ki67 and Bcl-2 (Becton Dickinson), CD45RA, CD57 and CD38 (Beckman Coulter), CD127 (Miltenyi-Biotech), CD8 and CD31 (eBioscience) monoclonal antibodies. Rectal cells were stained using a modified combination as previously described [22]. All flow-cytometry analyses were performed on a 5-laser beam LSR-Fortessa (Becton-Dickinson) on the CyPS platform (UPMC) using Live-Dead Fixable-Aqua (Life-Technologies) and the FlowJo software (Treestar).

Endpoints, sample size and analyses

The primary endpoint was a decrease in cell-associated HIV DNA of at least 0·5 log copies/106 PBMCs between baseline and week 56. We selected this magnitude of change based on variability of the HIV DNA assay and timing at week 56 considering the half-life of CD4+ TCM, the major cell of the HIV reservoir, is at least 6 months.

Secondary endpoints included the following: changes in cell-associated HIV DNA copies/106 CD4+ T cells [using the formula (HIV-DNA copies/106 PBMCs) × 90% x %CD4+ cells] or /ml of whole blood [(HIV-DNA copies/106 PBMCs) × (lymphocytes/μl + monocytes/μl)/1000]; changes in rectal tissue–associated HIV DNA copies/106 rectal cells; changes in CD4+, CD8+ cell counts, activation and differentiation markers; proportion of patients with ultrasensitive HIV RNA more than 1 copy/ml; and occurrence of serious adverse events.

In this proof of concept study, a sample size of 14 evaluable patients in each arm was required such that if no patient in the RAL/MVC/IL-7 arm reached the primary endpoint of at least 0.5 log copies/106 PBMCs decline in HIV DNA, there was a 95% likelihood that the success rate was lower than 20% and the strategy was not worth pursuing.

Categorical and continuous variables were described as number with percentage and median with interquartile range (IQR), respectively. The Wilcoxon paired test was used to compare changes in continuous variables and McNemar test to compare changes in categorical variables between baseline and key study time points (weeks 8, 20, 32, 36, W56 and 80) in each arm. We did not perform comparison analyses between RAL/MVC and RAL/MVC/IL-7 arms considering the noncomparative study design.

Analysis were done using IBM SPSS statistics version 22. All reported P-values are two sided with a significant level of 0.05.


Baseline characteristics

After screening 57 individuals, 29 were enrolled between September 2010 and May 2011 with 14 patients in the RAL/MVC arm and 15 patients in the RAL/MVC/IL-7 arm (Supplementary Figure 1, Patients had a median CD4+ T-cell count of 558 cells/μl (IQR 452, 726), median viral suppression duration of 2.3 years (IQR 2.1, 2.6) and total cell-associated HIV-DNA of 360 copies/106 PBMCs (IQR 228, 828) (Table 1). All patients remained in the study through the primary endpoint at week 56 and for an additional visit off all study interventions at week 80.

Table 1:
Patients baseline characteristics.

Virologic responses

No patient, in either arm, reached the primary endpoint of more than 0.5 log10 decrease in HIV DNA copies/106 PBMC between baseline and week 56 (Fig. 1a). In the RAL/MVC arm, no significant change from baseline was observed in total HIV DNA at week 56 (–0.02 log10 copies/106 PBMCs) (P = 0.875) or week 80 (–0.18 log10 copies/106 PBMCs) (P = 0.064). Similar results were obtained with HIV DNA expressed per 106 CD4+ T cells or per ml of whole blood (Table 2).

Fig. 1:
Median change from baseline in HIV-DNA in PBMC and rectal mucosa, and percentage of patients with plasma HIV-RNA >1 copy/ml overtime.(a) Median change from baseline in HIV-DNA, log10 copies per million PBMC. (b) Median change from baseline in rectal mucosa HIV-DNA at W56, log10 copies per million cells, C. Percentage of patients with plasma HIV-RNA >1 copy/ml overtime.
Table 2:
Median changes from baseline of HIV-DNA log10 copies in different blood compartments at week (W) 12, 56 and 80, and in total CD4+ T-cell count and CD4+ T-cell subpopulations at W12 and W56.

In the RAL/MVC/IL-7 arm, total cell-associated HIV DNA significantly increased at week 12 (change from baseline +0.28 log10 copies/106 PBMCs, P = 0.001) (Fig. 1a) paralleling an extremely large CD4+ T-cell count increase (see below). Then, HIV DNA levels significantly decreased from weeks 12 to 56 (–0.18 log10 copies/106 PBMC, P = 0.002) to a level slightly higher than baseline at week 56 with a return to baseline values by week 80. Similar results were observed with HIV DNA expressed per 106 CD4+ T cells (Table 2). Increases in HIV DNA expressed per ml of whole blood remained higher than baseline values throughout the study follow-up (Table 2).

A total of 18 patients (nine in each arm) participated in the rectal tissue substudy. We observed no significant change in rectal tissue HIV DNA levels between baseline and week 56 in either study arm (Fig. 1b). Importantly, PBMC and rectal tissue HIV DNA levels were strongly correlated at baseline (r = 0.699, P = 0.001) and week 56 (r = 0.786, P < 0.001).

Six patients experienced viral blips in HIV RNA during follow-up. Two patients from the RAL/MVC arm had single blips with 66 and 994 copies/ml at weeks 16 and 24, respectively. Four patients from the RAL/MVC/IL-7 arm had viral blips during rhIL-7 administration: one patient with 177 at week 9 and 159 copies/ml at week 10, one patient with 84 at week 9 and 124 copies/ml at week 10, one patient had blip with 85 copies/ml at week 9 and one patient with 83 copies/ml at week 10. All of them spontaneously returned to viral suppression less than 50 copies/ml at W12.

The proportion of patients with ultrasensitive HIV-RNA assay more than 1 copy/ml showed no significant change throughout the study follow-up in the RAL/MVC arm whereas in the RAL/MVC/IL-7 arm, this proportion changed from three of 15 (20%) to eight of 14 (57%) between weeks 8 and 12 during IL-7 administration (P = 0.07) (Fig. 1c). However we could not detect any significant increase in the numbers of unspliced HIV transcripts in purified CD4+ cells at weeks 12, 28 or 56 compared to baseline (data not shown). We conducted phylogenetic tree analysis from Sanger sequences of all patients in the two arms (using PhyML on Seaview software, with reference strain HXB2 as an out-group). This phylogenetic analysis and the calculation of matrices of genetic distance showed no increase in genetic variability of cell-associated HIV DNA between baseline and weeks 12 or 56 in either arm (data not shown). There was a trend to an increase in the number of patients with at least one stop codon between baseline (2/15, 13%) and week 56 (6/15, 40%) in the RAL/MVC/IL-7 arm (P = 0.219).

Changes in T-cell populations

In the RAL/MVC arm, peripheral blood CD4+ T cells significantly increased from baseline to week 56 by a median of +40 cells/μl (IQR +1, +174) (P = 0.017) (Fig. 2a, Table 2). This increase persisted to week 80 with a median of +136 CD4+ T cells (IQR –6, +245) (P = 0.035). In addition, CD4+/CD8+ T-cell ratio increases at week 56 (P = 0.056) became significant by week 80 [+0.07 (IQR +0.01, +0.29), P = 0.003].

Fig. 2:
Median change from baseline in CD4+ and CD8+ T-cell counts, in proportions of CD4+ T-cell subpopulations and activation.(a) Median change in CD4+ and CD8+ T-cell absolute counts. (b) Median change in the proportions of CD4+ T-cell subpopulations and activation (TN, TCM, TTM, TEM, TEMRA and HLA-DR).

In the RAL/MVC/IL-7 arm, median CD4+ T-cell count increased following IL-7 infusions by +1385 cells/μl (IQR +1226, +1847) at week 12 (P < 0.001), then gradually declined, though still higher than baseline at week 56 [+312 cells/μl (IQR +231, +465), P = 0.001] (Fig. 2a) with a persistent elevation of +267 cells/μl (IQR +98, +327) at week 80 (P = 0.015). The CD8+ T-cell counts showed similar kinetics with +1464 cells/μl at week 12 (IQR +1047, +2122, P < 0.001), +473 cells/μl at week 56 (IQR +274, +646, P = 0.001) (Fig. 2a) and +307 cells/μl at week 80 (IQR +135, +434, P = 0.002). There was no change in CD4+/CD8+ T-cell ratio at any time point.

The naive, TCM, TTM, TEM and TEMRA CD4+ or CD8+ T-cell subsets did not show significant changes in the RAL/MVC arm (Fig. 2b) except significant increases in CD4+ TTM (+18 cells/μl, P = 0.019) and TEMRA (+5 cells/μl, P = 0.009) absolute values at week 56 (Table 2). In contrast, in the RAL/MVC/IL-7 arm, the absolute CD4+ T-cell expansion at weeks 12 and 56 only involved proportions of TCM [+5% (IQR: +3, +7) and +5% (IQR: +3, +10) respectively, P = 0.001] whereas TTM and TEM proportions remained stable and TEMRA proportion decreased (–1.1%, IQR: –1.7, –0.1, P = 0.023) (Fig. 2b). Proportions of naive T cells also decreased from baseline to week 56 by –6% (IQR: –11, –4, P = 0.009) without changes in CD31high recent thymic emigrants (data not shown). Consequently, absolute values of all memory (+128 TCM, +66 TTM and +55 TEM/μl), but not of TN and TEMRA, subsets, increased from baseline to week 56 (Table 2). The CD4+ T-cell activation assessed by Ki67 did not change at week 12, whereas CD4+HLA-DR+ T cells decreased at week 56 (–2.3%, IQR: –5.6, –0.1, P = 0.016) with decrease in antiapoptotic Bcl-2 expression in both TN and TEMRA CD4+ T cells (–21%, IQR: –34, –8, P = 0.001) and (–29%, IQR: –39, –14, P < 0.001). Few changes occurred in CD8+ subsets and activation with the exception of reduced proportions of TEMRA (–4.4%, IQR: –15.7, –1.4, P = 0.023) and immune-senescent CD57+CD8+ T cells (–9%, IQR: –15, –6, P = 0.009) at week 56 and a transient CD8+CD38+ T-cell increase at week 12 (+14%, IQR: +9, +21, P = 0.001).

In rectal biopsies, the baseline T-cell distribution differed from PBMCs with no TN, low TCM (4.5%), massive predominance of TTM (63%), and high levels of activated (60% HLA-DR+) CD4+ T cells. At week 56, rectal CD4+ T cells tended to decrease in both arms (–9 and –8% in RAL/MVC and RAL/MVC/IL-7 arms, respectively) (Supplementary Fig. 2,


In the RAL/MVC arm, 27 adverse events with grade 2 or higher occurred in eight patients including three serious adverse events: abdominal pain and arterial hypotension, both considered not related to the study treatment, and diffuse joint pain leading to RAL discontinuation.

In the RAL/MVC/IL-7 arm, 19 adverse events with grade 2 or higher occurred during the course of the study in nine patients including one serious adverse event: phlebitis of the right lower limb probably related to the study treatment, which spontaneously resolved.


EraMune is a program investigating strategies to decrease the HIV reservoir in chronically infected patients with prolonged viral suppression on ART. We used the same proof of concept design to test the impact of ART intensification with RAL and MVC followed by immune modulation with either IL-7 (EraMune 01) or a DNA-prime recombinant adenovirus-5 boost HIV vaccine (EraMune 02) [19]. Interventional clinical trials evaluating HIV cure strategies are challenging in the modern day context of potent, effective and well-tolerated ART. Our primary endpoint measured total HIV DNA in PBMCs, an imperfect but strongly validated assay [20] correlating with tissue HIV DNA [4,20,21].

Overall, in this population of chronically infected patients with long-term HIV RNA suppression, dual ART intensification with RAL and MVC, alone or in combination with IL-7 did not lead to achieve the primary study endpoint of a 0.5 log decrease in total cell-associated HIV DNA. There was no significant change in the total cell-associated HIV DNA in the intensification alone arm. In contrast, in the intensification along with IL-7 arm, total cell-associated HIV DNA transiently but significantly increased at week 12. However HIV DNA expressed per million PBMC or per million CD4+ cells subsequently declined to baseline values. HIV DNA expressed per ml of whole blood remained higher throughout the study follow-up. The use of total HIV DNA to measure the reservoir might be a limitation of our therapeutic approach although it aligns with previous work in this area. In addition, if total cell-associated HIV DNA does not distinguish replication-competent integrated proviruses, it reflects proviruses integrated into cells from fully suppressed patients, and likely represents a mixture of both replication competent and defective proviruses [26–28]. We could confirm in an EraMune-01 substudy currently in progress, the peripheral blood HIV reservoir harboured in the various resting CD4+ subsets was fully replication-competent [29]. However we cannot exclude that the increase in HIV DNA may also reflect expansion of cells harbouring replication incompetent virus whereas cells harbouring replication competent virus could possibly be killed off through reactivation.

The addition of RAL and MVC alone to suppressive cART did not result in decreases or increases of either cell-associated HIV DNA or ultrasensitive HIV RNA, consistent with prior intensification studies using RAL or MVC [10,12,30]. We did not investigate the level of preintegration episomal DNA (2-LTR circles), but some studies did find transient accumulation of 2-LTR circles with RAL or MVC. Overall this suggests that residual viral replication, if any, is unlikely to occur in sites reached by current cART.

The addition of IL-7 to ART intensification induced a transient increase in plasma HIV RNA. The low levels of HIV RNA do not appear to have replenished HIV reservoirs as a lack of evolution in genetic variability among cell-associated HIV DNA suggests cell division (mainly central-memory T-cell expansion) as the primary driver of the observed HIV DNA increase the in RAL/MVC/IL-7 arm [13–15]. IL-7 also induced an increase in stop codons through acquisition of G to A mutations likely mediated by APOBEC as has been previously reported [18]. Potentially, this could lead to a shift in HIV DNA from replication competent to defective proviruses.

Long-term follow-up demonstrated that the transient increase in cell-associated total HIV DNA returned to baseline except for HIV DNA expressed per ml of whole blood whereas CD4+ cell counts remained elevated 68 weeks after IL-7 administration. These long term changes in both CD4+ T cells and HIV DNA appeared to be limited to the blood compartment, thus adding to the recent reports on the lack of mucosal CD4+ T-cells amplification with IL-7 [14–16]. Indeed no significant changes in HIV DNA levels in rectal tissue could be observed between baseline and week 56 in either study arm, although rectal tissue may not reflect other lymphoid tissues such as nodes or spleen.

The transient peak in HIV DNA coincided with a durable increase in absolute numbers of the two TCM and TTM memory CD4+ subsets which harbours the majority of the HIV reservoir [26,29]. Among CD4+ T cells, we found only the proportions of TCM increased, whereas those of naïve CD4+ T cells decreased. This contrasts from previous studies investigating IL-7 among HIV-infected patients with poor immunologic response to ART [14,16,17]. The decrease in proportions of activated, terminally differentiated, immunosenescent CD4+ and CD8+ T cells, and of cells displaying the antiapoptotic Bcl-2 molecule, suggests IL-7 primarily induced expansion of nonactivated long-lived memory T cells and does not lead to long-term deleterious immune activation.

Another limitation of our study design might be a lack of early blood sampling after IL-7 infusions limiting our ability to capture a transient increase in Ki67 expression of CD4+ T cells as previously reported [14], and could explain the lack of detection of HIV RNA transcripts in circulating CD4+ T cells at weeks 12 and 24 despite plasma HIV RNA blips.

Other HIV latency reactivation interventions, such as the histone deacetylase inhibitors vorinostat [31,32], panobinostat [33], or romidepsin [34], also did not decrease cell-associated total HIV DNA despite early in-vivo and ex-vivo increases in HIV transcripts measured or increased HIV RNA increased after romidepsin [34] or after IL-7 infusion such as observed in our study and others [14,16].

HIV cure is a challenging field for clinical investigations where efficacy and safety of interventions need to be carefully rationalized to expose a minimal number of patients to highly innovative strategies with potential deleterious effects with robust and conclusive findings. Our results, although disappointing, are conclusive enough to state that neither 56 weeks of dual intensification with RAL and MVC alone nor with IL-7 reduces the virus reservoir in patients with chronic HIV infection. In fact, IL-7 induced HIV reactivation but actually amplified HIV DNA as a result of central-memory CD4+ T-cell expansion, thus limiting IL-7 usage to purge HIV reservoirs. None of the HIV cure strategies tested so far have decreased the HIV reservoir. Achieving this challenging goal will require a combination of interventions with stronger HIV reactivation, improved delivery of ART to tissues, and novel therapeutic immunization.

Authorship contributions, disclosures and conflicts of interest

C.K., B.A., V.C., R.M., C.A. and D.C. designed the EraMune-01 study. Patients’ recruitment, enrolment and follow-up were performed by G.T. (San Raffaele Scientific Institute, Milan), C.K. (Groupe Hospitalier Pitié-Salpêtrière, Paris), B.C. (Fundacio irsiCaixa – Hospital Germans Trias i Pujol, Badalona), and M.Y. (Royal Free Hospital, London). Virologic assays were performed by S.L.N. under the guidance of V.C. at Pitié-Salpêtrière virology. Immunologic assays were performed by L.P. under the guidance of B.A. at Pitié-Salpêtrière immunology. L.A. performed primary endpoint and virologic statistical analyses under the guidance of D.C. The initial draft of the manuscript was written by C.K., L.A., D.C., R.M., C.A. and B.A. Throughout the study, all authors participated in discussions about the design, statistical analyses and interpretation of findings. All authors were also involved in the review and editing process of draft and eventual final manuscript for submission.

C.K. has received travel grants, consultancy fees, honoraria and study grants from Bristol-Myers-Squibb (BMS), Merck-Sharp & Dohme-Chibret and ViiV Healthcare. D.C. has received travel grants, consultancy fees, honoraria and study grants from various pharmaceutical companies including BMS, Gilead Sciences, Janssen-Cilag, Merck-Sharp & Dohme-Chibret and ViiV Healthcare. B.C. has acted during the past 2 years as a consultant, participated in advisory boards, received speaker fees and participated as an investigator for clinical trials for BMS, Abbott, Gilead, Janssen, Merck (MSD) and ViiV. B.A. has received speaker fees from Glead, BMS and ViiV.


These findings are presented on behalf of the EraMune-01 team.

We are grateful for the dedication and commitment of the patients who enthusiastically participated in this study and remain dedicated to research in Cure strategies.

We thank all the EraMune-01 investigators and study teams: San Raffaele Scientific Institute, Milan: Manuela Pogliaghi, Silvia Nozza, Stefania Chiappetta, Andrea Galli, Liviana Della Torre, Paola Cinque, Arabella Bestetti, Manuela Testa, Claudio Doglioni, Massimo Cernuschi; Pitié-Salpêtrière, Paris: Roland Tubiana, Marc Antoine Valantin, Yasmine Dudoit, Hind Stitou, Luminita Schneider, Benoit Mory, Anne-Geneviève Marcelin, CathiaSoulié, Frédéric Charlotte, Angélique Curjol, Yasmine Dudoit, Aurore Delobelle; Fundacio irsiCaixa – Hospital Germans Trias i Pujol, Badalona: Javier Martinez-Picado, Beatriz Mothe-Pujadas, Pep Coll, Eulalia Grau, Isabel Bravo, Patricia Cobarsi; Royal Free Hospital, London: Sabine Kinloch de Loes, Steven Leckie, Anne Carroll, Patrick Byrne; Hôpital Européen Georges Pompidou, Paris: Agnès Lillo Le Louët, Vincent Rouget-Quermalet, Virginie Fulda; We would also like to thank CYTHERIS (T. Croughs, M. Morre), ViiV Healthcare France (C. Lemarchand, L. Finkielsztejn), MSD France (L. Naït-Ighil, F. Durand) for their support and J.D. Daumont for technical assistance.

We thank Professor Gilles Brucker, ORVACS president, for his continuous support, the Foundation Bettencourt Schueller for their generous support in financing HIV Cure research.

Funding and support: Funding was provided by Objectif Recherche Vaccin SIDA (ORVACS) and the Fondation Bettencourt-Schueller. Study interventions were provided by Cytheris, Pfizer and Merck.

Conflicts of interest

There are no conflicts of interest.

Preliminary results of the EraMune-01 study were presented as a poster presentation (#170aLB) at the 20th Conference on Retroviruses and Opportunistic Infections (CROI), Atlanta, USA, March 2013.


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antiretroviral therapy intensification; HIV cure; HIV DNA; HIV eradication; immune modulation; interleukin-7; maraviroc; raltegravir

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