Virological and immunological impact of integrase inhibitor-based regimens initiated during primary HIV-1 infection.
Adult
CD4 Lymphocyte Count
CD4-CD8 Ratio
Cohort Studies
Darunavir
/ therapeutic use
Female
HIV Infections
/ drug therapy
HIV Integrase Inhibitors
/ therapeutic use
HIV Protease Inhibitors
/ therapeutic use
Heterocyclic Compounds, 3-Ring
/ therapeutic use
Humans
Logistic Models
Male
Middle Aged
Oxazines
/ therapeutic use
Piperazines
/ therapeutic use
Pyridones
/ therapeutic use
Sustained Virologic Response
Viral Load
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
15 03 2020
15 03 2020
Historique:
pubmed:
26
11
2019
medline:
22
1
2021
entrez:
26
11
2019
Statut:
ppublish
Résumé
Current international guidelines recommend either boosted protease inhibitor (PI/r)-based or integrase inhibitors (INSTI)-based regimens during primary HIV infection (PHI), even though the latter have only demonstrated their superiority at the chronic stage. We compared the effectiveness of INSTI-based versus PI/r-based combined antiretroviral therapy (cART) initiated during PHI. This study was conducted among patients who initiated cART between 2013 and 2017, using data from the ANRS-PRIMO cohort and the Dat'AIDS study. Cumulative proportions of patients reaching viral suppression (HIV-1 RNA <50 copies/ml) were calculated using Turnbull's estimator for interval-censored data. CD4 cells and CD4/CD8 ratio increases were estimated using mixed linear models. Results were adjusted for the data source. Among the 712 study patients, 299 received an INSTI-based cART. Patients' baseline characteristics were similar between groups. Viral suppression was reached more rapidly in INSTI-treated versus PI/r-treated patients (P < 0.01), with cumulative proportions of 32 versus 6% at 4 weeks, 72 versus 31% at 12 weeks, 91 versus 78% at 24 weeks and about 95% in both groups at 48 weeks. At 4 weeks, INSTI-treated patients had gained on average 40 CD4 cells/μl (P = 0.05) over PI/r-treated ones; mean CD4 counts were similar in the two groups at 48 weeks. The CD4/CD8 ratio followed the same pattern. Results were similar when restricted to a comparison between dolutegravir-based versus darunavir-based cART. On the basis of this study and available literature, we recommend the use of INSTI-based cART for treatment initiation during PHI, as it leads to faster viral suppression and immune restoration.
Identifiants
pubmed: 31764069
doi: 10.1097/QAD.0000000000002447
pii: 00002030-202003150-00001
doi:
Substances chimiques
HIV Integrase Inhibitors
0
HIV Protease Inhibitors
0
Heterocyclic Compounds, 3-Ring
0
Oxazines
0
Piperazines
0
Pyridones
0
dolutegravir
DKO1W9H7M1
Darunavir
YO603Y8113
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
493-500Références
Baggaley RF, White RG, Hollingsworth TD, Boily M-C. Heterosexual HIV-1 infectiousness and antiretroviral use: systematic review of prospective studies of discordant couples. Epidemiology 2013; 24:110–121.
Morlat P, France, Conseil national du SIDA, France, Ministère des affaires sociales et de la santé, Agence nationale de recherches sur le sida (France). Prise en charge médicale des personnes vivant avec le VIH: rapport 2013 [pour le] Ministère des affaires sociales et de la santé: recommandations du groupe d’experts. Paris: la Documentation française; 2013.
Blanc A, Bonnet F, Brun-Vezinet F, Costagliola D, Dabis F, Delobel P, et al. Groupe d’experts pour la prise en charge du VIH. 2016. p. 16.
Acute and Recent (Early) HIV Infection Considerations for Antiretroviral Use in Special Patient Populations Adult and Adolescent ARV. AIDSinfo. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/20/acute-and-recent--early--hiv-infection. [Accessed 13 June 2019]
Phung B-C, Yeni P. Darunavir: an effective protease inhibitor for HIV-infected patients. Expert Rev Anti Infect Ther 2011; 9:631–643.
Deeks ED. Darunavir: a review of its use in the management of HIV-1 infection. Drugs 2014; 74:99–125.
Clotet B, Feinberg J, van Lunzen J, Khuong-Josses M-A, Antinori A, Dumitru I, et al. ING114915 Study Team. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet Lond Engl 2014; 383:2222–2231.
Kelley CF, Barbour JD, Hecht FM. The relation between symptoms, viral load, and viral load set point in primary HIV infection. J Acquir Immune Defic Syndr 1999 2007; 45:445–448.
Nozza S, Poli A, Ripa M, Galli L, Chiappetta S, Spagnuolo V, et al. Efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as treatment for primary or recent HIV infection. J Antimicrob Chemother 2017; 72:632–633.
Ngo Bell EC, Vandenhende M-A, Caldato S, Saunier A, Bellecave P, Tumiotto C, et al. High decay of blood HIV reservoir when tenofovir/emtricitabine/elvitegravir/cobicistat is initiated during the acute primary HIV infection. J Antimicrob Chemother 2017; 72:2681–2683.
Troude P, Chaix M-L, Tran L, Deveau C, Seng R, Delfraissy J-F, et al. ANRS Primo cohort. No evidence of a change in HIV-1 virulence since 1996 in France. AIDS Lond Engl 2009; 23:1261–1267.
Pochard L, Hauviller L, Cuzin L, Eyvrard F, Sommet A, Montastruc J-L, et al. Use of Nadis(®) software to improve adverse drug reaction reporting of antiretroviral drugs: experience in south west of France (midi-pyrénées). Therapie 2014; 69:149–155.
Turnbull BW. The empirical distribution function with arbitrarily grouped, censored and truncated data. J R Stat Soc Ser B Methodol 1976; 38:290–295.
Leroy F, Trinquart L. Extensions du test du logrank aux données censurées par intervalle.; 2010. Available at: https://hal.inria.fr/inria-00494727/document. [Accessed 13 June 2019]
Bennett S. Log-logistic regression models for survival data. J R Stat Soc Ser C Appl Stat 1983; 32:165–171.
Fitzmaurice GM, Laird NM, Ware JH. Alternative methods of adjusting for baseline response. In Applied longitudinal analysis. 2nd Edition. Hoboken, NJ: Wiley-Blackwell; 2011; 128–134.
Chéret A, Nembot G, Mélard A, Lascoux C, Slama L, Miailhes P, et al. OPTIPRIM ANRS Study Group. Intensive five-drug antiretroviral therapy regimen versus standard triple-drug therapy during primary HIV-1 infection (OPTIPRIM-ANRS 147): a randomised, open-label, phase 3 trial. Lancet Infect Dis 2015; 15:387–396.
Jacobson K, Ogbuagu O. Integrase inhibitor-based regimens result in more rapid virologic suppression rates among treatment-naïve human immunodeficiency virus-infected patients compared to nonnucleoside and protease inhibitor-based regimens in a real-world clinical setting: a retrospective cohort study. Medicine (Baltimore) 2018; 97:e13016.
Kityo C, Szubert AJ, Siika A, Heyderman R, Bwakura-Dangarembizi M, Lugemwa A, et al. REALITY trial team. Raltegravir-intensified initial antiretroviral therapy in advanced HIV disease in Africa: a randomised controlled trial. PLOS Med 2018; 15:e1002706.
Valcour V, Chalermchai T, Sailasuta N, Marovich M, Lerdlum S, Suttichom D, et al. RV254/SEARCH 010 Study Group. Central nervous system viral invasion and inflammation during acute HIV infection. J Infect Dis 2012; 206:275–282.
Crowell CS, Huo Y, Tassiopoulos K, Malee KM, Yogev R, Hazra R, et al. PACTG 219C Study Team and the Pediatric HIVAIDS Cohort Study (PHACS). Early viral suppression improves neurocognitive outcomes in HIV-infected children. AIDS Lond Engl 2015; 29:295–304.
Fisher M, Pao D, Brown AE, Sudarshi D, Gill ON, Cane P, et al. Determinants of HIV-1 transmission in men who have sex with men: a combined clinical, epidemiological and phylogenetic approach. AIDS Lond Engl 2010; 24:1739–1747.
Brenner BG, Roger M, Routy J-P, Moisi D, Ntemgwa M, Matte C, et al. Quebec Primary HIV Infection Study Group. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 2007; 195:951–959.
Pilcher CD, Tien HC, Eron JJ, Vernazza PL, Leu S-Y, Stewart PW, et al. Quest Study; Duke-UNC-Emory Acute HIV Consortium. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004; 189:1785–1792.
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med 2016; 375:830–839.
Novelli S, Lécuroux C, Avettand-Fenoel V, Seng R, Essat A, Morlat P, et al. Long-term therapeutic impact of the timing of antiretroviral therapy in patients diagnosed with primary human immunodeficiency virus type 1 infection. Clin Infect Dis 2018; 66:1519–1527.
Le T, Wright EJ, Smith DM, He W, Catano G, Okulicz JF, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013; 368:218–230.
Thornhill J, Inshaw J, Oomeer S, Kaleebu P, Cooper D, Ramjee G, et al. Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection. J Int AIDS Soc 2014; 17: (4 Suppl 3): 19480.
Oxenius A, Price DA, Easterbrook PJ, O’Callaghan CA, Kelleher AD, Whelan JA, et al. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes. Proc Natl Acad Sci U S A 2000; 97:3382–3387.
Bourgi K, Rebeiro PF, Turner M, Castilho JL, Hulgan T, Raffanti SP, et al. Greater weight gain in treatment naïve persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis 2019; Published Online First; doi: 10.1093/cid/ciz407.
doi: 10.1093/cid/ciz407