First-line Raltegravir/Emtricitabine/Tenofovir Combination in Human Immunodeficiency Virus Type 2 (HIV-2) Infection: A Phase 2, Noncomparative Trial (ANRS 159 HIV-2)

Sophie Matheron, Diane Descamps, Sebastien Gallien, Amel Besseghir, Pierre Sellier, Laurent Blum, Emmanuel Mortier, Charlotte Charpentier, Roland Tubiana, Florence Damond, Gilles Peytavin, Diane Ponscarme, Fideline Collin, Francoise Brun-Vezinet, Genevieve Chene, France REcherche Nord&Sud Sida-Hiv Hépatites (ANRS) 159 HIV-2 Trial Study Group, S Matheron, F Boue, C Goujard, L Weiss, A Rami, E Mortier, R Tubiana, P Campa, D Ponscarme, L Piroth, P Miailhes, J Reynes, L Blum, M-A Khuong, O Patey, B Elharrar, G Beck-Wirth, P Fialaire, I Amri, F Cardon, L Marchand, Sophie Matheron, Diane Descamps, Sebastien Gallien, Amel Besseghir, Pierre Sellier, Laurent Blum, Emmanuel Mortier, Charlotte Charpentier, Roland Tubiana, Florence Damond, Gilles Peytavin, Diane Ponscarme, Fideline Collin, Francoise Brun-Vezinet, Genevieve Chene, France REcherche Nord&Sud Sida-Hiv Hépatites (ANRS) 159 HIV-2 Trial Study Group, S Matheron, F Boue, C Goujard, L Weiss, A Rami, E Mortier, R Tubiana, P Campa, D Ponscarme, L Piroth, P Miailhes, J Reynes, L Blum, M-A Khuong, O Patey, B Elharrar, G Beck-Wirth, P Fialaire, I Amri, F Cardon, L Marchand

Abstract

Background: New options for first-line treatment of human immunodeficiency virus type 2 (HIV-2) infection are needed. We evaluated an integrase inhibitor (raltegravir)-containing regimen.

Methods: Antiretroviral therapy (ART)-naive adults with symptomatic infection by HIV-2 only, CD4 count <500 cells/μL or CD4 decrease >50 cells/μL/year over the past 3 years, or a confirmed plasma HIV-2 RNA (pVL) load ≥100 copies/mL were eligible for this noncomparative trial. The composite primary endpoint was survival at 48 weeks without any of the following: CD4 gain from baseline <100 cells/μL, confirmed pVL ≥40 copies/mL from week 24, raltegravir permanent discontinuation, or incident B or C event. HIV-2 ultrasensitive pVL (uspVL) and total DNA were assessed using in-house polymerase chain reaction (PCR) assays.

Results: Baseline median CD4 count of 30 enrolled individuals (67% women) was 436 cells/µL (interquartile range [IQR], 314-507 cells/µL); pVL was ≥40 copies/mL in 67% of them, uspVL was ≥5 copies/mL in 92%, and total DNA was >6 copies by PCR in 32%. At week 48, the composite endpoint of success was reached in 40% [95% confidence interval, 22.7%-59.4%]. Failure was mainly (50%) due to CD4 gain <100 cells/µL; uspVL was <5 copies/mL in 87% and total DNA >6 copies by PCR in 12% of participants. Median CD4 gain was 87 cells/µL (IQR, 38-213 cells/µL; n = 28). No serious adverse reactions were reported.

Conclusions: Raltegravir-containing ART is a safe option for first-line treatment of HIV-2 infection, yielding a comparable success rate to protease inhibitors.

Clinical trials registration: NCT 01605890.

Trial registration: ClinicalTrials.gov NCT01605890.

Figures

Figure 1.
Figure 1.
Flow diagram of the ANRS (France REcherche Nord&Sud Sida-Hiv Hépatites) 159 HIV-2 trial.
Figure 2.
Figure 2.
Median CD4 cell count from week (W) 0 to week 48, ANRS (France REcherche Nord&Sud Sida-Hiv Hépatites) 159 HIV-2 trial. Median CD4 change at W12 and W48: +73/µL (interquartile range [IQR], +2 to +143) (n = 30) and +87/µL (IQR, +38 to +213) (n = 28), respectively. At W48, median CD4 change: +115/µL and +70/µL in those with baseline plasma viral load ≥40 and

Figure 3.

Proportion of participants with plasma…

Figure 3.

Proportion of participants with plasma human immunodeficiency virus type 2 RNA

Figure 3.
Proportion of participants with plasma human immunodeficiency virus type 2 RNA
Similar articles
Cited by
References
    1. Marlink R, Kanki P, Thior I et al. . Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 1994; 265:1587–90. - PubMed
    1. Whittle H, Morris J, Todd J et al. . HIV-2-infected patients survive longer than HIV-1-infected patients. AIDS 1994; 8:1617–20. - PubMed
    1. Thiébaut R, Matheron S, Taieb A, Brun-Vezinet F, Chêne G, Autran B; Immunology Group of the ANRS CO5 HIV-2 Cohort Long-term nonprogressors and elite controllers in the ANRS CO5 HIV-2 cohort. AIDS 2011; 25:865–7. - PubMed
    1. Ekouévi DK, Avettand-Fènoël V, Tchounga BK et al. . IeDEA West Africa Collaboration Plasma HIV-2 RNA according to CD4 count strata among HIV-2-infected adults in the IeDEA West Africa Collaboration. PLoS One 2015; 10:e0129886. - PMC - PubMed
    1. MacNeil A, Sarr AD, Sankalé JL, Meloni ST, Mboup S, Kanki P. Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection. J Virol 2007; 81:5325–30. - PMC - PubMed
Show all 38 references
Publication types
MeSH terms
Associated data
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 3.
Figure 3.
Proportion of participants with plasma human immunodeficiency virus type 2 RNA

References

    1. Marlink R, Kanki P, Thior I et al. . Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 1994; 265:1587–90.
    1. Whittle H, Morris J, Todd J et al. . HIV-2-infected patients survive longer than HIV-1-infected patients. AIDS 1994; 8:1617–20.
    1. Thiébaut R, Matheron S, Taieb A, Brun-Vezinet F, Chêne G, Autran B; Immunology Group of the ANRS CO5 HIV-2 Cohort Long-term nonprogressors and elite controllers in the ANRS CO5 HIV-2 cohort. AIDS 2011; 25:865–7.
    1. Ekouévi DK, Avettand-Fènoël V, Tchounga BK et al. . IeDEA West Africa Collaboration Plasma HIV-2 RNA according to CD4 count strata among HIV-2-infected adults in the IeDEA West Africa Collaboration. PLoS One 2015; 10:e0129886.
    1. MacNeil A, Sarr AD, Sankalé JL, Meloni ST, Mboup S, Kanki P. Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection. J Virol 2007; 81:5325–30.
    1. Popper SJ, Sarr AD, Guèye-Ndiaye A, Mboup S, Essex ME, Kanki PJ. Low plasma human immunodeficiency virus type 2 viral load is independent of proviral load: low virus production in vivo. J Virol 2000; 74:1554–7.
    1. Simon F, Matheron S, Tamalet C et al. . Cellular and plasma viral load in patients infected with HIV-2. AIDS 1993; 7:1411–7.
    1. Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, Heneine W. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther 2004; 9:57–65.
    1. Desbois D, Roquebert B, Peytavin G et al. . French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2) In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother 2008; 52:1545–8.
    1. Campbell-Yesufu OT, Gandhi RT. Update on human immunodeficiency virus (HIV)-2 infection. Clin Infect Dis 2011; 52:780–7.
    1. Gottlieb GS, Hawes SE, Agne HD et al. . Lower levels of HIV RNA in semen in HIV-2 compared with HIV-1 infection: implications for differences in transmission. AIDS 2006; 20:895–900.
    1. Visseaux B, Damond F, Matheron S, Descamps D, Charpentier C. HIV-2 molecular epidemiology. Infect Genet Evol 2016; 46:233–40.
    1. Andersson S, Norrgren H, da Silva Z et al. . Plasma viral load in HIV-1 and HIV-2 singly and dually infected individuals in Guinea-Bissau, West Africa: significantly lower plasma virus set point in HIV-2 infection than in HIV-1 infection. Arch Intern Med 2000; 160:3286–93.
    1. Drylewicz J, Matheron S, Lazaro E et al. . Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France. AIDS 2008; 22:457–68.
    1. Popper SJ, Sarr AD, Travers KU et al. . Lower human immunodeficiency virus (HIV) type 2 viral load reflects the difference in pathogenicity of HIV-1 and HIV-2. J Infect Dis 1999; 180:1116–21.
    1. Matheron S. HIV-2 infection: a call for controlled trials. AIDS 2008; 22:2073–4.
    1. French HIV Experts Group. Prise en charge médicale des personnes vivant avec le VIH—recommandations du groupe d’experts. Sous la direction du Pr Philippe Morlat et sous l’égide du CNS et de l’ANRS Available at: . Accessed 8 April 2018.
    1. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. Geneva, Switzerland: WHO, 2013.
    1. Ekouevi DK, Tchounga BK, Coffie PA et al. . Antiretroviral therapy response among HIV-2 infected patients: a systematic review. BMC Infect Dis 2014; 14:461.
    1. Gilleece Y, Chadwick DR, Breuer J et al. . BHIVA Guidelines Subcommittee British HIV Association guidelines for antiretroviral treatment of HIV-2-positive individuals 2010. HIV Med 2010; 11:611–9.
    1. Markowitz M, Morales-Ramirez JO, Nguyen BY et al. . Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr 2006; 43:509–15.
    1. Balestre E, Ekouevi DK, Tchounga B et al. . International Epidemiological Database to Evaluate AIDS (IeDEA) West Africa Collaboration Immunologic response in treatment-naive HIV-2-infected patients: the IeDEA West Africa cohort. J Int AIDS Soc 2016; 19:20044.
    1. Bénard A, Damond F, Campa P et al. . ANRS CO5 HIV-2 Cohort Study Group Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naive HIV-2-infected patients. AIDS 2009; 23:1171–3.
    1. Benard A, van Sighem A, Taieb A et al. . ACHIEV2E Collaboration Study Group Immunovirological response to triple nucleotide reverse-transcriptase inhibitors and ritonavir-boosted protease inhibitors in treatment-naive HIV-2-infected patients: the ACHIEV2E Collaboration Study Group. Clin Infect Dis 2011; 52:1257–66.
    1. Matheron S, Damond F, Benard A et al. . ANRS CO5 HIV2 Cohort Study Group CD4 cell recovery in treated HIV-2-infected adults is lower than expected: results from the French ANRS CO5 HIV-2 cohort. AIDS 2006; 20:459–62.
    1. Wittkop L, Arsandaux J, Trevino A et al. . CD4 cell count response to first-line combination antiretroviral treatment in HIV-2 compared to HIV-1 positive patients: a multinational multicohort European study. J Antimicrob Chemother 2017; 72:2869–78.
    1. Roquebert B, Damond F, Collin G et al. . French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2) HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro. J Antimicrob Chemother 2008; 62:914–20.
    1. Damond F, Lariven S, Roquebert B et al. . Virological and immunological response to HAART regimen containing integrase inhibitors in HIV-2-infected patients. AIDS 2008; 22:665–6.
    1. Garrett N, Xu L, Smit E, Ferns B, El-Gadi S, Anderson J. Raltegravir treatment response in an HIV-2 infected patient: a case report. AIDS 2008; 22:1091–2.
    1. Peterson K, Rowland-Jones S. Novel agents for the treatment of HIV-2 infection. Antivir Ther 2012; 17:435–8.
    1. Peterson K, Ruelle J, Vekemans M, Siegal FP, Deayton JR, Colebunders R. The role of raltegravir in the treatment of HIV-2 infections: evidence from a case series. Antivir Ther 2012; 17:1097–100.
    1. Wandeler G, Furrer H, Rauch A. Sustained virological response to a raltegravir-containing salvage therapy in an HIV-2-infected patient. AIDS 2011; 25:2306–8.
    1. Avettand-Fenoel V, Damond F, Gueudin M et al. . ANRS-CO5 HIV-2 and the ANRS-AC11 Quantification Working Group New sensitive one-step real-time duplex PCR method for group A and B HIV-2 RNA load. J Clin Microbiol 2014; 52:3017–22.
    1. Bertine M, Gueudin M, Mélard A et al. . New highly sensitive real-time PCR assay for HIV-2 group A and group B DNA quantification. J Clin Microbiol 2017; 55:2850–7.
    1. Charpentier C, Camacho R, Ruelle J et al. . HIV-2EU: supporting standardized HIV-2 drug resistance interpretation in Europe. Clin Infect Dis 2013; 56:1654–8.
    1. Gottlieb GS, Eholie SP, Nkengasong JN et al. . A call for randomized controlled trials of antiretroviral therapy for HIV-2 infection in West Africa. AIDS 2008; 22:2069–72; discussion 73–4.
    1. Charpentier C, Camacho R, Ruelle J et al. . HIV-2EU-supporting standardized HIV-2 drug-resistance interpretation in Europe: an update. Clin Infect Dis 2015; 61:1346–7.
    1. Ba S, Raugi D, Smith RA et al. . A trial of fixed dose combination of elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate for the initial treatment of HIV-2 infection: 48 week results from Senegal, West Africa [abstract MOPEB0294]. In: Program and Abstracts of the Ninth International AIDS Society Conference, Paris, France, 23–27 July 2017.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir