Association between markers of hepatitis B virus infection and risk of virological rebound in people with HIV receiving antiretroviral therapy.
ART
HBcAb
HIV rebound
HIV/HBV
occult hepatitis B infection
Journal
HIV medicine
ISSN: 1468-1293
Titre abrégé: HIV Med
Pays: England
ID NLM: 100897392
Informations de publication
Date de publication:
04 Jun 2024
04 Jun 2024
Historique:
received:
24
07
2023
accepted:
17
05
2024
medline:
5
6
2024
pubmed:
5
6
2024
entrez:
5
6
2024
Statut:
aheadofprint
Résumé
The aim of this analysis was to investigate the impact of hepatitis B virus (HBV) coinfection on the risk of HIV viral rebound (VR) after achieving suppression for the first time following initiation of antiretroviral therapy (ART) in the real-world setting. Patients living with HIV (PLWH) who were enrolled in the ICONA Foundation Study cohort and achieved viral suppression ≤50 copies/mL for the first time after starting ART were prospectively evaluated and divided in three exposure groups according to serology test results: (a) HIV-monoinfected; (b) HIV-positive/HBcAb-positive/HBsAg-negative; (c) HIV-positive/HBsAg-positive. The occurrence of VR, defined as two consecutive HIV-RNA values >50 copies/mL after achieving viral suppression for the first time (baseline), was investigated. Standard survival analysis by means of Kaplan-Meier curves and Cox regression analysis with the serology exposure fitted as a time-fixed covariate measured at baseline was employed after controlling for key confounding factors. Of a total of 5657 patients included, 4090 (72%) were HIV-monoinfected, 1342 (23.7%)were HBcAb-positive, and 225 (3.9%) were HbsAg-positive coinfected. Overall, 654 (11.5%) PLWH experienced VR > 50 copies/mL during follow-up. After controlling for all sources of measured confounding, coinfected PLWH showed an increased risk of experiencing VR compared with those who were HIV-monoinfected. In particular, the strongest associations were seen for the HIV/HBsAg-positive participants [adjusted hazard ratio (aHR) = 1.56, 95% confidence interval (CI): 1.03-2.38, p = 0.037] but an excess of risk was also seen in those who were HIV-positive/HBcAb-positive/HBsAg-negative (aHR = 1.25, 95% CI: 1.00-1.55, p = 0.047). Coinfection with HBV seems to have an impact on the probability of maintaining HIV viral suppression achieved for the first time after ART initiation. Of note, even PLWH positive for HBcAb, a marker of inactive HBV infection, appeared to be at higher risk of VR compared with those who were HIV-monoinfected and their HIV-RNA should be carefully monitored.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 British HIV Association.
Références
Barnabas RV, Webb EL, Weiss HA, Wasserheit JN. The role of coinfections in HIV epidemic trajectory and positive prevention: a systematic review and meta‐analysis. AIDS. 2011;25:1559‐1573.
Cai CW, Sereti I. Residual immune dysfunction under antiretroviral therapy. Semin Immunol. 2021;51:101471.
Hunt PW. HIV and inflammation: mechanisms and consequences. Curr HIV/AIDS Rep. 2012;9:139‐147.
Hatano H. Immune activation and HIV persistence: considerations for novel therapeutic interventions. Curr Opin HIV AIDS. 2013;8:211‐216.
Massanella M, Gianella S, Lada SM, Richman DD, Strain MC. Quantification of total and 2‐LTR (long terminal repeat) HIV DNA, HIV RNA and herpesvirus DNA in PBMCs. Bio Protoc. 2015;5:e1492.
Gonzalez VD, Falconer K, Blom KG, et al. High levels of chronic immune activation in the T‐cell compartments of patients coinfected with hepatitis C virus and human immunodeficiency virus type 1 and on highly active antiretroviral therapy are reverted by alpha interferon and ribavirin treatment. J Virol. 2009;83:11407‐11411.
Demosthenes JP, Fletcher GJ, Zachariah UG, et al. Chronic immune activation among treatment naïve HIV/ HBV coinfected individuals from southern India. Curr HIV Res. 2021;19:332‐341.
He Y, Cai W, Chen J, et al. Persistent chronic immune activation in HIV/HBV‐coinfected patients after antiretroviral therapy. J Viral Hepat. 2021;28:1355‐1361.
Chun HM, Roediger MP, Hullsiek KH, et al. Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters. J Infect Dis. 2012;205(2):185‐193.
Platt L, French CE, McGowan CR, et al. Prevalence and burden of HBV co‐infection among people living with HIV: a global systematic review and meta‐analysis. J Viral Hepat. 2020;27(3):294‐315.
Fasano M, Poliseno MC, Fiore JR, Lo Caputo S, d'Arminio Monforte A, Santantonio TA. Management of chronic hepatitis B in HIV‐coinfected patients. Viruses. 2022;14(9):2022.
Thio CL. Hepatitis B and human immunodeficiency virus coinfection. Hepatology. 2009;49(5 Suppl):S138‐S145.
Basnayake SK, Easterbrook PJ. Wide variation in estimates of global prevalence and burden of chronic hepatitis B and C infection cited in published literature. J Viral Hepat. 2016;23(7):545‐559.
Raimondo G, Locarnini S, Pollicino T, et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol. 2019;71(2):397‐408.
Soriano V, Aguilera A, Gonzalez R, et al. Occult hepatitis B and HIV infection. Eur J Gastroenterol Hepatol. 2019;31:1403‐1407.
Malagnino V, Cerva C, Teti E, et al. Poor CD4/CD8 ratio recovery in HBcAb‐positive HIV patients with worse immune status is associated with significantly higher CD8 cell numbers. Sci Rep. 2021;11:3965.
Salpini R, Malagnino V, Piermatteo L, et al. Cryptic HBV replicative activity is frequently revealed in anti‐HBc‐positive/HBsAg‐negative patients with HIV infection by highly sensitive molecular assays, and can Be predicted by integrating classical and novel serological HBV markers. Microorganisms. 2020;8(11):1819.
Malagnino V, Teti E, Compagno M, et al. HBcAb positivity is a risk factor for an increased detectability of HIV RNA after switching to a two‐drug regimen lamivudine‐based (2DR‐3TC‐based) treatment: analysis of a multicenter Italian cohort. Microorganisms. 2021;9:396.
Montaner JSG. Treatment as prevention—a double hat‐trick. Lancet. 2011;378:208‐209.
Montaner JSG, Lima VD, Barrios R, et al. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population‐based study. Lancet. 2010;376:532‐539.
Battegay M, Nüesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV‐1 infection. Lancet Infect Dis. 2006;6:280‐287.
Doyle T, Smith C, Vitiello P, et al. Plasma HIV‐1 RNA detection below 50 copies/ml and risk of virologic rebound in patients receiving highly active antiretroviral therapy. Clin Infect Dis. 2012;54:724‐732.
Maggiolo F, Callegaro A, Cologni G, et al. Ultrasensitive assessment of residual low‐level HIV viremia in HAART‐treated patients and risk of virological failure. J Acquir Immune Defic Syndr. 2012;60:473‐482.
Charpentier C, Landman R, Laouenan C, et al. Persistent low‐level HIV‐1 RNA between 20 and 50 copies/mL in antiretroviral‐treated patients: associated factors and virological outcome. J Antimicrob Chemother. 2012;67:2231‐2235.
Doyle T, Geretti AM. Low‐level viraemia on HAART: significance and management. Curr Opin Infect Dis. 2012;25:17‐25.
Henrich TJ, Wood BR, Kuritzkes DR. Increased risk of virologic rebound in patients on antiviral therapy with a detectable HIV load <48 copies/mL. PLoS One. 2012;7:e50065.
Modjarrad K, Vermund SH. Effect of treating co‐infections on HIV‐1 viral load: a systematic review. Lancet Infect Dis. 2010;10:455‐463.
Gianella S, Anderson CM, Var SR, et al. Replication of human herpesviruses is associated with higher HIV DNA levels during antiretroviral therapy started at early phases of HIV infection. J Virol. 2016;90:3944‐3952.
Chaillon A, Nakazawa M, Rawlings SA, et al. Subclinical Cytomegalovirus and Epstein‐Barr virus shedding is associated with increasing HIV DNA molecular diversity in peripheral blood during suppressive antiretroviral therapy. J Virol. 2020;94:e00927‐20.
Chun HM, Mesner O, Thio CL, et al. HIV outcomes in hepatitis B virus coinfected individuals on HAART. J Acquir Immune Defic Syndr. 2014;66(2):197‐205.
Kouamé GM, Boyd A, Moh R, et al. Higher mortality despite early antiretroviral therapy in human immunodeficiency virus and hepatitis B virus (HBV)‐coinfected patients with high HBV replication. Clin Infect Dis. 2018;66(1):112‐120.
Morsica G, Ancarani F, Bagaglio S, et al. Occult hepatitis B virus infection in a cohort of HIV‐positive patients: correlation with hepatitis C virus coinfection, virological and immunological features. Infection. 2009;37(5):445‐449.
Malagnino V, Cerva C, Maffongelli G, et al. HBcAb seropositivity is correlated with poor HIV viremia control in an Italian cohort of HIV/HBV‐coinfected patients on first‐line therapy. Sci Rep. 2019;9(1):11942.
Goletti D, Weissman D, Jackson RW, et al. Effect of mycobacterium tuberculosis on HIV replication. Role of immune activation. J Immunol. 1996;157:1271‐1278.
Lidofsky A, Holmes JA, Feeney ER, et al. Macrophage activation marker soluble CD163 is a dynamic marker of liver fibrogenesis in human immunodeficiency virus/hepatitis C virus coinfection. J Infect Dis. 2018;218:1394‐1403.
Malagnino V, Cerva C, Cingolani A, et al. HBcAb positivity increases the risk of severe hepatic fibrosis development in HIV/HCV‐positive subjects from the ICONA Italian cohort of HIV‐infected patients. Open Forum Infect Dis. 2020;8(1):ofaa566.