Skip to main content
Top
Published in: Virology Journal 1/2021

Open Access 01-12-2021 | Hepatitis B | Research

Prevalence and characteristics of hepatitis B and D virus infections among HIV-positive individuals in Southwestern Nigeria

Authors: Oluyinka Oladele Opaleye, Olusola Anuoluwapo Akanbi, Folakemi Abiodun Osundare, Bo Wang, Olufisayo Adesina, Adeolu Sunday Oluremi, Sola Thomas Sunday, Abiodun Akeem Akindele, Patrycja Klink, C. Thomas Bock

Published in: Virology Journal | Issue 1/2021

Login to get access

Abstract

Background

Coinfections of HIV-positive individuals with Hepatitis B and D virus (HBV and HDV) are common and can be associated with rapid liver damage. Several antiretroviral drugs for HIV exhibit anti-HBV effect; however, the selection of HBV drug resistance mutations (DRMs) in individuals under HIV antiretroviral therapy (ART) has been reported but rarely in Nigeria. In this study the HBV/HDV prevalence and HBV DRMs in HIV-positive individuals in Southwestern Nigeria were assessed.

Methods

Plasma samples collected from 310 HIV-positive individuals including 295 ART-experienced and 15 ART-naïve persons attending the HIV clinic in three south-western states of Nigeria between June 2017 and August 2017 were analysed by ELISA for HBsAg and anti-HDV. The presence of HDV RNA and HBV DNA was analysed by (RT)-PCR followed by sequencing and phylogenetic analyses for genotyping. The HBV reverse transcription (RT) region was amplified and sequenced for the analysis of drug resistance mutations.

Results

Overall, 16.1% (n = 50/310) of the HIV-positive individuals were positive for HBsAg, most of which were ART-experienced (94.0%; n = 47/50). From the 50 HBsAg-positive samples, 72.0% (n = 36/50) were positive for HBV DNA and 16.0% (n = 8/50) had detectable HDV RNA while 5.6% (n = 2/36) of the HBV-DNA positive samples had anti-HDV total antibodies. Sequences were available for 31/36 of the HBV DNA-positive and 3/8 HDV RNA-positive samples. HBV DNA-positive samples were characterised as HBV genotype E infections exclusively, while HDV genotype 1 was detected in the HDV RNA-positive samples. HBV DRMs V173L, L180M, S202I and M204V/I, which are associated with lamivudine resistance, were detected in 32.2% (n = 10/31) of the HBV DNA-positive samples. Most of these mutations (90.0%; n = 9/10) were present in the ART-experienced cohort.

Conclusions

This study indicates that HBV/HDV coinfections are common in HIV-positive individuals under ART in Nigeria. Furthermore, a high proportion of HBV DRMs which potentially compromise future treatment options were detected, underscoring the need for HBV screening prior to starting ART. Further studies should be performed to monitor a possible increase in the spread of HDV among populations at risk of HIV and HBV infections.
Literature
1.
go back to reference Singh KP, Crane M, Audsley J, Avihingsanon A, Sasadeusz J, Lewin SR. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. Aids. 2017;31(15):2035–52.CrossRef Singh KP, Crane M, Audsley J, Avihingsanon A, Sasadeusz J, Lewin SR. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. Aids. 2017;31(15):2035–52.CrossRef
2.
go back to reference Assih M, Ouattara AK, Diarra B, Yonli AT, Compaore TR, Obiri-Yeboah D, Djigma FW, Karou S, Simpore J. Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol. 2018;10(11):807–21.CrossRef Assih M, Ouattara AK, Diarra B, Yonli AT, Compaore TR, Obiri-Yeboah D, Djigma FW, Karou S, Simpore J. Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol. 2018;10(11):807–21.CrossRef
3.
go back to reference Chun HM, Mesner O, Thio CL, Bebu I, Macalino G, Agan BK, Bradley WP, Malia J, Peel SA, Jagodzinski LL, et al. HIV outcomes in Hepatitis B virus coinfected individuals on HAART. J Acquir Immune Defic Syndr. 2014;66(2):197–205.CrossRef Chun HM, Mesner O, Thio CL, Bebu I, Macalino G, Agan BK, Bradley WP, Malia J, Peel SA, Jagodzinski LL, et al. HIV outcomes in Hepatitis B virus coinfected individuals on HAART. J Acquir Immune Defic Syndr. 2014;66(2):197–205.CrossRef
4.
go back to reference Hønge BL, Jespersen S, Medina C, Té DS, da Silva ZJ, Lewin S, Østergaard L, Erikstrup C, Wejse C, Laursen AL, et al. Hepatitis B and delta virus are prevalent but often subclinical co-infections among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional study. PLoS ONE. 2014;9(6):e99971.CrossRef Hønge BL, Jespersen S, Medina C, Té DS, da Silva ZJ, Lewin S, Østergaard L, Erikstrup C, Wejse C, Laursen AL, et al. Hepatitis B and delta virus are prevalent but often subclinical co-infections among HIV infected patients in Guinea-Bissau, West Africa: a cross-sectional study. PLoS ONE. 2014;9(6):e99971.CrossRef
6.
go back to reference Opaleye OO, Japhet OM, Adewumi OM, Omoruyi EC, Akanbi OA, Oluremi AS, Wang B, Tong HV, Velavan TP, Bock CT. Molecular epidemiology of hepatitis D virus circulating in Southwestern Nigeria. Virol J. 2016;13:61.CrossRef Opaleye OO, Japhet OM, Adewumi OM, Omoruyi EC, Akanbi OA, Oluremi AS, Wang B, Tong HV, Velavan TP, Bock CT. Molecular epidemiology of hepatitis D virus circulating in Southwestern Nigeria. Virol J. 2016;13:61.CrossRef
7.
go back to reference Lunel-Fabiani F, Mansour W, Amar AO, Aye M, Le Gal F, Malick FZF, Baïdy L, Brichler S, Veillon P, Ducancelle A, et al. Impact of hepatitis B and delta virus co-infection on liver disease in Mauritania: a cross sectional study. J Infect. 2013;67(5):448–57.CrossRef Lunel-Fabiani F, Mansour W, Amar AO, Aye M, Le Gal F, Malick FZF, Baïdy L, Brichler S, Veillon P, Ducancelle A, et al. Impact of hepatitis B and delta virus co-infection on liver disease in Mauritania: a cross sectional study. J Infect. 2013;67(5):448–57.CrossRef
8.
go back to reference Katwesigye E, Seremba E, Semitala F, Ocama P. Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda. Afr Health Sci. 2016;16(4):1089–93.CrossRef Katwesigye E, Seremba E, Semitala F, Ocama P. Low sero-prevalence of hepatitis delta antibodies in HIV/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda. Afr Health Sci. 2016;16(4):1089–93.CrossRef
9.
go back to reference Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, Zoulim F, Tacke F. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.CrossRef Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, Zoulim F, Tacke F. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.CrossRef
10.
go back to reference Gunthard HF, Saag MS, Benson CA, del Rio C, Eron JJ, Gallant JE, Hoy JF, Mugavero MJ, Sax PE, Thompson MA, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2016 recommendations of the International Antiviral Society-USA Panel. JAMA. 2016;316(2):191–210.CrossRef Gunthard HF, Saag MS, Benson CA, del Rio C, Eron JJ, Gallant JE, Hoy JF, Mugavero MJ, Sax PE, Thompson MA, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2016 recommendations of the International Antiviral Society-USA Panel. JAMA. 2016;316(2):191–210.CrossRef
11.
go back to reference Warner N, Locarnini S. Mechanisms of hepatitis B virus resistance development. Intervirol. 2014;57(3–4):218–24.CrossRef Warner N, Locarnini S. Mechanisms of hepatitis B virus resistance development. Intervirol. 2014;57(3–4):218–24.CrossRef
13.
go back to reference Belyhun Y, Maier M, Liebert UG. HIV therapy with unknown HBV status is responsible for higher rate of HBV genome variability in Ethiopia. Antivir Ther. 2017;22(2):97–111.CrossRef Belyhun Y, Maier M, Liebert UG. HIV therapy with unknown HBV status is responsible for higher rate of HBV genome variability in Ethiopia. Antivir Ther. 2017;22(2):97–111.CrossRef
14.
go back to reference Chambal LM, Samo Gudo E, Carimo A, Corte Real R, Mabunda N, Maueia C, Vubil A, Zicai AF, Bhatt N, Antunes F. HBV infection in untreated HIV-infected adults in Maputo, Mozambique. PLoS ONE. 2017;12(7):e0181836.CrossRef Chambal LM, Samo Gudo E, Carimo A, Corte Real R, Mabunda N, Maueia C, Vubil A, Zicai AF, Bhatt N, Antunes F. HBV infection in untreated HIV-infected adults in Maputo, Mozambique. PLoS ONE. 2017;12(7):e0181836.CrossRef
15.
go back to reference Oreagba IA, Usman SO, Olayemi SO, Oshikoya KA, Opanuga O, Adeyemo TA, Lesi OA, Dodoo AN, Akanmu AS. Pharmacoepidemiology of antiretroviral drugs in a teaching hospital in Lagos. Nigeria Ghana Med J. 2014;48(4):194–203.CrossRef Oreagba IA, Usman SO, Olayemi SO, Oshikoya KA, Opanuga O, Adeyemo TA, Lesi OA, Dodoo AN, Akanmu AS. Pharmacoepidemiology of antiretroviral drugs in a teaching hospital in Lagos. Nigeria Ghana Med J. 2014;48(4):194–203.CrossRef
16.
go back to reference Selabe SG, Lukhwareni A, Song E, Leeuw YG, Burnett RJ, Mphahlele MJ. Mutations associated with lamivudine-resistance in therapy-naive hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients. J Med Virol. 2007;79(11):1650–4.CrossRef Selabe SG, Lukhwareni A, Song E, Leeuw YG, Burnett RJ, Mphahlele MJ. Mutations associated with lamivudine-resistance in therapy-naive hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients. J Med Virol. 2007;79(11):1650–4.CrossRef
17.
go back to reference Oluyinka OO, Tong HV, Bui Tien S, Fagbami AH, Adekanle O, Ojurongbe O, Bock CT, Kremsner PG, Velavan TP. Occult hepatitis B virus infection in nigerian blood donors and hepatitis B virus transmission risks. PLoS ONE. 2015;10(7):e0131912-e132012.CrossRef Oluyinka OO, Tong HV, Bui Tien S, Fagbami AH, Adekanle O, Ojurongbe O, Bock CT, Kremsner PG, Velavan TP. Occult hepatitis B virus infection in nigerian blood donors and hepatitis B virus transmission risks. PLoS ONE. 2015;10(7):e0131912-e132012.CrossRef
18.
go back to reference Sy BT, Ratsch BA, Toan NL, Song LH, Wollboldt C, Bryniok A, Nguyen HM, Luong HV, Velavan TP, Wedemeyer H, et al. High prevalence and significance of hepatitis D virus infection among treatment-naïve HBsAg-positive patients in Northern Vietnam. PLoS ONE. 2013;8(10):e78094–194.CrossRef Sy BT, Ratsch BA, Toan NL, Song LH, Wollboldt C, Bryniok A, Nguyen HM, Luong HV, Velavan TP, Wedemeyer H, et al. High prevalence and significance of hepatitis D virus infection among treatment-naïve HBsAg-positive patients in Northern Vietnam. PLoS ONE. 2013;8(10):e78094–194.CrossRef
19.
go back to reference Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol. 2016;33(7):1870–4.CrossRef Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol. 2016;33(7):1870–4.CrossRef
20.
go back to reference Rhee SY, Margeridon-Thermet S, Nguyen MH, Liu TF, Kagan RM, Beggel B, Verheyen J, Kaiser R, Shafer RW. Hepatitis B virus reverse transcriptase sequence variant database for sequence analysis and mutation discovery. Antiviral Res. 2010;88(3):269–75.CrossRef Rhee SY, Margeridon-Thermet S, Nguyen MH, Liu TF, Kagan RM, Beggel B, Verheyen J, Kaiser R, Shafer RW. Hepatitis B virus reverse transcriptase sequence variant database for sequence analysis and mutation discovery. Antiviral Res. 2010;88(3):269–75.CrossRef
21.
go back to reference Noubiap JJN, Nansseu JRN, Ndoula ST, Bigna JJR, Jingi AM, Fokom-Domgue J. Prevalence, infectivity and correlates of hepatitis B virus infection among pregnant women in a rural district of the Far North Region of Cameroon. BMC Public Health. 2015;15(1):454.CrossRef Noubiap JJN, Nansseu JRN, Ndoula ST, Bigna JJR, Jingi AM, Fokom-Domgue J. Prevalence, infectivity and correlates of hepatitis B virus infection among pregnant women in a rural district of the Far North Region of Cameroon. BMC Public Health. 2015;15(1):454.CrossRef
22.
go back to reference Nongo B, Agida T, Oghenebuk U, Yunusa T. Seroprevalence of hepatitis B virus among antenatal attendees at the University of Abuja Teaching Hospital, Nigeria. An Niger Med. 2016;10(2):58–62.CrossRef Nongo B, Agida T, Oghenebuk U, Yunusa T. Seroprevalence of hepatitis B virus among antenatal attendees at the University of Abuja Teaching Hospital, Nigeria. An Niger Med. 2016;10(2):58–62.CrossRef
23.
go back to reference Musa BM, Bussell S, Borodo MM, Samaila AA, Femi OL. Prevalence of hepatitis B virus infection in Nigeria, 2000–2013: a systematic review and meta-analysis. Niger J Clin Pract. 2015;18(2):163–72.CrossRef Musa BM, Bussell S, Borodo MM, Samaila AA, Femi OL. Prevalence of hepatitis B virus infection in Nigeria, 2000–2013: a systematic review and meta-analysis. Niger J Clin Pract. 2015;18(2):163–72.CrossRef
24.
go back to reference Gu L, Han Y, Li Y, Zhu T, Song X, Huang Y, Yang F, Guan S, Xie J, Gohda J, et al. Emergence of lamivudine-resistant HBV during antiretroviral therapy including lamivudine for patients coinfected with HIV and HBV in China. PLoS ONE. 2015;10(8):e0134539.CrossRef Gu L, Han Y, Li Y, Zhu T, Song X, Huang Y, Yang F, Guan S, Xie J, Gohda J, et al. Emergence of lamivudine-resistant HBV during antiretroviral therapy including lamivudine for patients coinfected with HIV and HBV in China. PLoS ONE. 2015;10(8):e0134539.CrossRef
26.
go back to reference King J, Hagemeister DT. Hepatitis B co-infection in HIV-infected patients receiving antiretroviral therapy at the TC Newman Anti Retroviral Treatment Clinic in Paarl, Western Cape. South Afr J HIV Med. 2016;17(1):336.CrossRef King J, Hagemeister DT. Hepatitis B co-infection in HIV-infected patients receiving antiretroviral therapy at the TC Newman Anti Retroviral Treatment Clinic in Paarl, Western Cape. South Afr J HIV Med. 2016;17(1):336.CrossRef
27.
go back to reference Tounkara A, Sarro YS, Kristensen S, Dao S, Diallo H, Diarra B, Noumsi TG, Guindo O. Seroprevalence of HIV/HBV coinfection in Malian blood donors. J Int Assoc Phys AIDS Care. 2009;8(1):47–51.CrossRef Tounkara A, Sarro YS, Kristensen S, Dao S, Diallo H, Diarra B, Noumsi TG, Guindo O. Seroprevalence of HIV/HBV coinfection in Malian blood donors. J Int Assoc Phys AIDS Care. 2009;8(1):47–51.CrossRef
28.
go back to reference Okeke TC, Obi SN, Okezie OA, Ugwu EO, Akogu SP, Ocheni S, Ezenyeaku CC. Coinfection with hepatitis B and C viruses among HIV positive pregnant women in Enugu south east. Nigeria Niger J Med. 2012;21(1):57–60.PubMed Okeke TC, Obi SN, Okezie OA, Ugwu EO, Akogu SP, Ocheni S, Ezenyeaku CC. Coinfection with hepatitis B and C viruses among HIV positive pregnant women in Enugu south east. Nigeria Niger J Med. 2012;21(1):57–60.PubMed
29.
go back to reference Balogun TM, Emmanuel S, Ojerinde EF. HIV, Hepatitis B and C viruses’ coinfection among patients in a Nigerian tertiary hospital. Pan Afr Med J. 2012;12:100.PubMedPubMedCentral Balogun TM, Emmanuel S, Ojerinde EF. HIV, Hepatitis B and C viruses’ coinfection among patients in a Nigerian tertiary hospital. Pan Afr Med J. 2012;12:100.PubMedPubMedCentral
30.
go back to reference Mbougua JBT, Laurent C, Kouanfack C, Bourgeois A, Ciaffi L, Calmy A, Gwet H, Koulla-Shiro S, Ducos J, Mpoudi-Ngolé E, et al. Hepatotoxicity and effectiveness of a Nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral hepatitis B or C infection in Cameroon. BMC public health. 2010;10:105.CrossRef Mbougua JBT, Laurent C, Kouanfack C, Bourgeois A, Ciaffi L, Calmy A, Gwet H, Koulla-Shiro S, Ducos J, Mpoudi-Ngolé E, et al. Hepatotoxicity and effectiveness of a Nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral hepatitis B or C infection in Cameroon. BMC public health. 2010;10:105.CrossRef
31.
go back to reference Mado S, Idris H, Abdullahi S, Musa S. Probable lamivudine-resistant hepatitis B infection in children: a case report involving two Nigerian siblings at Ahmadu Bello University Teaching Hospital, Shika, Zaria. Sub-Saharan Afric J Med. 2017;4(3):87–90.CrossRef Mado S, Idris H, Abdullahi S, Musa S. Probable lamivudine-resistant hepatitis B infection in children: a case report involving two Nigerian siblings at Ahmadu Bello University Teaching Hospital, Shika, Zaria. Sub-Saharan Afric J Med. 2017;4(3):87–90.CrossRef
32.
go back to reference Andernach IE, Leiss LV, Tarnagda ZS, Tahita MC, Otegbayo JA, Forbi JC, Omilabu S, Gouandjika-Vasilache I, Komas NP, Mbah OP, Muller CP. Characterization of hepatitis delta virus in sub-Saharan Africa. J Clin Microbiol. 2014;52(5):1629–36.CrossRef Andernach IE, Leiss LV, Tarnagda ZS, Tahita MC, Otegbayo JA, Forbi JC, Omilabu S, Gouandjika-Vasilache I, Komas NP, Mbah OP, Muller CP. Characterization of hepatitis delta virus in sub-Saharan Africa. J Clin Microbiol. 2014;52(5):1629–36.CrossRef
33.
go back to reference Castellares C, Barreiro P, Martin-Carbonero L, Labarga P, Vispo ME, Casado R, Galindo L, Garcia-Gasco P, Garcia-Samaniego J, Soriano V. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. J Viral Hepat. 2008;15(3):165–72.PubMed Castellares C, Barreiro P, Martin-Carbonero L, Labarga P, Vispo ME, Casado R, Galindo L, Garcia-Gasco P, Garcia-Samaniego J, Soriano V. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. J Viral Hepat. 2008;15(3):165–72.PubMed
34.
go back to reference Soriano V, Fernandez-Montero JV, Benitez-Gutierrez L, Mendoza CD, Arias A, Barreiro P, Peña JM, Labarga P. Dual antiretroviral therapy for HIV infection. Exp Opin Drug Saf. 2017;16(8):923–32.CrossRef Soriano V, Fernandez-Montero JV, Benitez-Gutierrez L, Mendoza CD, Arias A, Barreiro P, Peña JM, Labarga P. Dual antiretroviral therapy for HIV infection. Exp Opin Drug Saf. 2017;16(8):923–32.CrossRef
Metadata
Title
Prevalence and characteristics of hepatitis B and D virus infections among HIV-positive individuals in Southwestern Nigeria
Authors
Oluyinka Oladele Opaleye
Olusola Anuoluwapo Akanbi
Folakemi Abiodun Osundare
Bo Wang
Olufisayo Adesina
Adeolu Sunday Oluremi
Sola Thomas Sunday
Abiodun Akeem Akindele
Patrycja Klink
C. Thomas Bock
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2021
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-021-01493-4

Other articles of this Issue 1/2021

Virology Journal 1/2021 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.