Skip to main content
Top
Published in: BMC Infectious Diseases 1/2022

Open Access 01-12-2022 | Hepatitis B | Research

Long-term effect of chronic hepatitis B on mortality in HIV-infected persons in a differential HBV transmission setting

Authors: Justine Umutesi, Sabin Nsanzimana, Carol Yingkai Liu, Patrizio Vanella, Jördis J. Ott, Gérard Krause

Published in: BMC Infectious Diseases | Issue 1/2022

Login to get access

Abstract

Background

There remain gaps in quantifying mortality risk among individuals co-infected with chronic hepatitis B (HBV) and human immunodeficiency virus (HIV) in sub-Saharan African contexts. Among a cohort of HIV-positive individuals in Rwanda, we estimate the difference in time-to mortality between HBV-positive (HIV/HBV co-infected) and HBV-negative (HIV mono-infected) individuals.

Methods

Using a dataset of HIV-infected adults screened for hepatitis B surface antigen (HBsAg) from January to June 2016 in Rwanda, we performed time-to-event analysis from the date of HBsAg results until death or end of study (31 December 2019). We used the Kaplan–Meier method to estimate probability of survival over time and Cox proportional hazard models to adjust for other factors associated with mortality.

Results

Of 21,105 available entries, 18,459 (87.5%) met the inclusion criteria. Mean age was 42.3 years (SD = 11.4) and 394 (2.1%) died during follow-up (mortality rate = 45.7 per 100,000 person-months, 95% confidence interval (CI) 41.4–50.4) Mortality rate ratio for co-infection was 1.7, 95% CI 1.1–2.6, however, Cox regression analysis did not show any association with mortality between compared groups. The adjusted analysis of covariates stratified by co-infection status showed that males, residing outside of the capital Kigali, drinking alcohol, WHO-HIV-clinical stage 3 and 4 were associated with increased mortality in this HIV cohort.

Conclusions

HBV infection does not significantly influence mortality among HIV-infected individuals in Rwanda. The current cohort is likely to have survived a period of high-risk exposure to HBV and HIV mortality and limited health care until their diagnosis.
Appendix
Available only for authorised users
Literature
1.
go back to reference World Health Organization. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. Geneva: WHO Press; 2021. World Health Organization. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. Geneva: WHO Press; 2021.
2.
go back to reference Kourtis AP, et al. HIV-HBV coinfection-a global challenge. N Engl J Med. 2012;1:1–5. Kourtis AP, et al. HIV-HBV coinfection-a global challenge. N Engl J Med. 2012;1:1–5.
3.
go back to reference World Health Organization. HIV and hepatitis B co-infection. Geneva: World Health Organization; 2009. p. 1–43. World Health Organization. HIV and hepatitis B co-infection. Geneva: World Health Organization; 2009. p. 1–43.
4.
go back to reference Kafeero HM, Ndagire D, Ocama P, Kudamba A, Walusansa A, Sendagire H. Prevalence and predictors of hepatitis B virus (HBV) infection in east Africa: evidence from a systematic review and meta-analysis of epidemiological studies published from 2005 to 2020. Arch Public Health. 2021;79(1):1–19.CrossRef Kafeero HM, Ndagire D, Ocama P, Kudamba A, Walusansa A, Sendagire H. Prevalence and predictors of hepatitis B virus (HBV) infection in east Africa: evidence from a systematic review and meta-analysis of epidemiological studies published from 2005 to 2020. Arch Public Health. 2021;79(1):1–19.CrossRef
6.
go back to reference MacLachlan JH, Cowie BC. Hepatitis B virus epidemiology. Cold Spring Harb Perspect Med. 2015;5(5):1–12.CrossRef MacLachlan JH, Cowie BC. Hepatitis B virus epidemiology. Cold Spring Harb Perspect Med. 2015;5(5):1–12.CrossRef
7.
go back to reference Nikolopoulos GK, Paraskevis D, Hatzitheodorou E, Moschidis Z, Sypsa V, Zavitsanos X, et al. Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis. Clin Infect Dis. 2009;48(12):1763–71.PubMedCrossRef Nikolopoulos GK, Paraskevis D, Hatzitheodorou E, Moschidis Z, Sypsa V, Zavitsanos X, et al. Impact of hepatitis B virus infection on the progression of AIDS and mortality in HIV-infected individuals: a cohort study and meta-analysis. Clin Infect Dis. 2009;48(12):1763–71.PubMedCrossRef
8.
go back to reference McGovern BH. The epidemiology, natural history and prevention of hepatitis B: implications of HIV coinfection. Antivir Ther. 2007;12(Suppl 3):H3-13.PubMedCrossRef McGovern BH. The epidemiology, natural history and prevention of hepatitis B: implications of HIV coinfection. Antivir Ther. 2007;12(Suppl 3):H3-13.PubMedCrossRef
9.
go back to reference Kouamé GM, Gabillard D, Moh R, Badje A, Ntakpé JB, Emième A, et al. Higher risk of mortality in HIV-HBV co-infected patients from sub-Saharan Africa is observed at lower CD4+ cell counts. Antivir Ther. 2021;26:25–33.PubMedCrossRef Kouamé GM, Gabillard D, Moh R, Badje A, Ntakpé JB, Emième A, et al. Higher risk of mortality in HIV-HBV co-infected patients from sub-Saharan Africa is observed at lower CD4+ cell counts. Antivir Ther. 2021;26:25–33.PubMedCrossRef
10.
go back to reference Thornton AC, Jose S, Bhagani S, Chadwick D, Dunn D, Gilson R, et al. Hepatitis B, hepatitis C, and mortality among HIV-positive individuals. AIDS. 2017;31(18):2525–32.PubMedCrossRef Thornton AC, Jose S, Bhagani S, Chadwick D, Dunn D, Gilson R, et al. Hepatitis B, hepatitis C, and mortality among HIV-positive individuals. AIDS. 2017;31(18):2525–32.PubMedCrossRef
11.
go back to reference Zhang F, Zhu H, Wu Y, Dou Z, Zhang Y, Kleinman N, et al. HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010–12: a retrospective observational cohort study. HHS Public Access. 2018;14(11):1065–72. Zhang F, Zhu H, Wu Y, Dou Z, Zhang Y, Kleinman N, et al. HIV, hepatitis B virus, and hepatitis C virus co-infection in patients in the China National Free Antiretroviral Treatment Program, 2010–12: a retrospective observational cohort study. HHS Public Access. 2018;14(11):1065–72.
13.
go back to reference Chen M, Wong WW, Law MG, Kiertiburanakul S, Yunihastuti E, Merati TP, et al. Hepatitis B and C co-infection in HIV patients from the TREAT Asia HIV observational database: analysis of risk factors and survival. PLoS ONE. 2016;11(3):1–17. Chen M, Wong WW, Law MG, Kiertiburanakul S, Yunihastuti E, Merati TP, et al. Hepatitis B and C co-infection in HIV patients from the TREAT Asia HIV observational database: analysis of risk factors and survival. PLoS ONE. 2016;11(3):1–17.
15.
go back to reference RBC. Rwanda population-based HIV impact assessment RPHIA 2018–2019. 2019. RBC. Rwanda population-based HIV impact assessment RPHIA 2018–2019. 2019.
16.
go back to reference Rwanda M of health. National guidelines for prevention and management of HIV and STIs edition 2016. 2016. Rwanda M of health. National guidelines for prevention and management of HIV and STIs edition 2016. 2016.
17.
go back to reference Umutesi J, Simmons B, Makuza JD, Dushimiyimana D, Mbituyumuremyi A, Uwimana JM, et al. Prevalence of hepatitis B and C infection in persons living with HIV enrolled in care in Rwanda. BMC Infect Dis. 2017;17(1):1–7.CrossRef Umutesi J, Simmons B, Makuza JD, Dushimiyimana D, Mbituyumuremyi A, Uwimana JM, et al. Prevalence of hepatitis B and C infection in persons living with HIV enrolled in care in Rwanda. BMC Infect Dis. 2017;17(1):1–7.CrossRef
18.
go back to reference Nsanzimana S, Semakula M, Ndahindwa V, Remera E, Sebuhoro D, Uwizihiwe JP, et al. Retention in care and virological failure among adult HIV + patients on second-line ART in Rwanda : a national representative study. BMC Infect Dis. 2019;2:1–9. Nsanzimana S, Semakula M, Ndahindwa V, Remera E, Sebuhoro D, Uwizihiwe JP, et al. Retention in care and virological failure among adult HIV + patients on second-line ART in Rwanda : a national representative study. BMC Infect Dis. 2019;2:1–9.
19.
go back to reference Amoroso CL, Akimana B, Wise B, Sf H. Using electronic medical records for HIV care in rural Rwanda. In: Medinfo. 2010;337–41. Amoroso CL, Akimana B, Wise B, Sf H. Using electronic medical records for HIV care in rural Rwanda. In: Medinfo. 2010;337–41.
20.
go back to reference World Health Organization (WHO). Interim WHO clinical staging of HIV/AIDS and HIV/AIDS case definitions for surveillance, African region. Geneva: World Health Organization; 2005. p. 513–4. World Health Organization (WHO). Interim WHO clinical staging of HIV/AIDS and HIV/AIDS case definitions for surveillance, African region. Geneva: World Health Organization; 2005. p. 513–4.
21.
go back to reference Chalker J, Andualem T, Tadeg H, Gitau L, Ntaganira J, Obua C, et al. Developing standard methods to monitor adherence to antiretroviral medicines and treatment defaulting in resource-poor settings. Essent Med Monit. 2019;1:4–8. Chalker J, Andualem T, Tadeg H, Gitau L, Ntaganira J, Obua C, et al. Developing standard methods to monitor adherence to antiretroviral medicines and treatment defaulting in resource-poor settings. Essent Med Monit. 2019;1:4–8.
22.
go back to reference WHO. What’s new in treatment monitoring: viral load and CD4 testing. HIV Treat care. 2017;(update):8624–8. WHO. What’s new in treatment monitoring: viral load and CD4 testing. HIV Treat care. 2017;(update):8624–8.
23.
go back to reference Kleinbaum DG, Klein M. Statistics for biology and health. In: Survival analysis, a self-learning text. 3rd edition. Media. 2010. Kleinbaum DG, Klein M. Statistics for biology and health. In: Survival analysis, a self-learning text. 3rd edition. Media. 2010.
24.
go back to reference Sooriyarachchi WWMA, Sooriyarachchi MR, Abeysekera. Use of Schoenfeld’s global test to test the proportional hazards assumption in the Cox proportiona. J Nat Sci Found. 2009;37(1). Sooriyarachchi WWMA, Sooriyarachchi MR, Abeysekera. Use of Schoenfeld’s global test to test the proportional hazards assumption in the Cox proportiona. J Nat Sci Found. 2009;37(1).
25.
go back to reference Wooldridge JM. Introductory econometrics: a modern approach. 5th ed. Boston: Cengage Learning; 2012. p. 127–8. Wooldridge JM. Introductory econometrics: a modern approach. 5th ed. Boston: Cengage Learning; 2012. p. 127–8.
27.
go back to reference Huang AJ, Núñez M. Outcomes in HIV/HBV-coinfected patients in the tenofovir era are greatly affected by immune suppression. J Int Assoc Provid AIDS Care. 2015;14(4):360–8.PubMedCrossRef Huang AJ, Núñez M. Outcomes in HIV/HBV-coinfected patients in the tenofovir era are greatly affected by immune suppression. J Int Assoc Provid AIDS Care. 2015;14(4):360–8.PubMedCrossRef
28.
go back to reference Dore GJ, Cooper DA, Barrett C, Goh LE, Thakrar B, Atkins M. Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). J Infect Dis. 1999;180(3):607–13.PubMedCrossRef Dore GJ, Cooper DA, Barrett C, Goh LE, Thakrar B, Atkins M. Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized, controlled study (CAESAR). J Infect Dis. 1999;180(3):607–13.PubMedCrossRef
29.
go back to reference Zampino R, Boemio A, Sagnelli C, Alessio L, Adinolfi LE, Sagnelli E, et al. Hepatitis B virus burden in developing countries. World J Gastroenterol. 2015;21(42):11941–53.PubMedPubMedCentralCrossRef Zampino R, Boemio A, Sagnelli C, Alessio L, Adinolfi LE, Sagnelli E, et al. Hepatitis B virus burden in developing countries. World J Gastroenterol. 2015;21(42):11941–53.PubMedPubMedCentralCrossRef
30.
go back to reference Lee HW, Kim SU, Park JY, Baatarkhuu O, Kim DY, Ahn SH, et al. Prognosis of untreated minimally active chronic hepatitis B patients in comparison with virological responders by antivirals. Clin Transl Gastroenterol. 2019;10(6):1–6.CrossRef Lee HW, Kim SU, Park JY, Baatarkhuu O, Kim DY, Ahn SH, et al. Prognosis of untreated minimally active chronic hepatitis B patients in comparison with virological responders by antivirals. Clin Transl Gastroenterol. 2019;10(6):1–6.CrossRef
31.
go back to reference Desalegn H, Aberra H, Berhe N, Mekasha B, Stene-Johansen K, Krarup H, et al. Treatment of chronic hepatitis B in sub-Saharan Africa: 1-year results of a pilot program in Ethiopia. BMC Med. 2018;16(1):1–10.CrossRef Desalegn H, Aberra H, Berhe N, Mekasha B, Stene-Johansen K, Krarup H, et al. Treatment of chronic hepatitis B in sub-Saharan Africa: 1-year results of a pilot program in Ethiopia. BMC Med. 2018;16(1):1–10.CrossRef
32.
go back to reference Stabinski L, O’Connor S, Barnhart M, Kahn RJ, Hamm TE. Prevalence of HIV and hepatitis B virus co-infection in Sub-Saharan Africa and the potential impact and program feasibility of Hepatitis B surface antigen screening in resource-limited settings. J Acquir Immune Defic Syndr. 2015;68:S274–85.PubMedCrossRef Stabinski L, O’Connor S, Barnhart M, Kahn RJ, Hamm TE. Prevalence of HIV and hepatitis B virus co-infection in Sub-Saharan Africa and the potential impact and program feasibility of Hepatitis B surface antigen screening in resource-limited settings. J Acquir Immune Defic Syndr. 2015;68:S274–85.PubMedCrossRef
33.
go back to reference World Health Organization. HIV/AIDS in Europe. Moving from death sentence to chronic disease management. Geneva: WHO; 2006. p. 188. World Health Organization. HIV/AIDS in Europe. Moving from death sentence to chronic disease management. Geneva: WHO; 2006. p. 188.
34.
go back to reference Konopnicki D, Mocroft A, De Wit S, Antunes F, Ledergerber B, Katlama C, et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS. 2005;19(6):593–601.PubMedCrossRef Konopnicki D, Mocroft A, De Wit S, Antunes F, Ledergerber B, Katlama C, et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS. 2005;19(6):593–601.PubMedCrossRef
35.
go back to reference Burchell AN, Raboud J, Donelle J, Loutfy MR, Rourke SB, Rogers T, et al. Cause-specific mortality among HIV-infected people in Ontario, 1995–2014: a population-based retrospective cohort study. CMAJ Open. 2019;7(1):E1-7.PubMedPubMedCentralCrossRef Burchell AN, Raboud J, Donelle J, Loutfy MR, Rourke SB, Rogers T, et al. Cause-specific mortality among HIV-infected people in Ontario, 1995–2014: a population-based retrospective cohort study. CMAJ Open. 2019;7(1):E1-7.PubMedPubMedCentralCrossRef
36.
go back to reference Kerkhoff AD, Sikombe K, Eshun-Wilson I, Sikazwe I, Glidden DV, Pry JM, et al. Mortality estimates by age and sex among persons living with HIV after ART initiation in Zambia using electronic medical records supplemented with tracing a sample of lost patients: a cohort study. PLoS Med. 2020;17(5):1–21. https://doi.org/10.1371/journal.pmed.1003107.CrossRef Kerkhoff AD, Sikombe K, Eshun-Wilson I, Sikazwe I, Glidden DV, Pry JM, et al. Mortality estimates by age and sex among persons living with HIV after ART initiation in Zambia using electronic medical records supplemented with tracing a sample of lost patients: a cohort study. PLoS Med. 2020;17(5):1–21. https://​doi.​org/​10.​1371/​journal.​pmed.​1003107.CrossRef
37.
go back to reference Druyts E, Dybul M, Kanters S, Nachega J, Birungi J, Ford N, et al. Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: a systematic review and meta-analysis. AIDS. 2013;27(3):417–25.PubMedCrossRef Druyts E, Dybul M, Kanters S, Nachega J, Birungi J, Ford N, et al. Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: a systematic review and meta-analysis. AIDS. 2013;27(3):417–25.PubMedCrossRef
38.
go back to reference Tang H, Mao Y, Tang W, Han J, Xu J, Li J. “Late for testing, early for antiretroviral therapy, less likely to die”: results from a large HIV cohort study in China, 2006–2014. BMC Infect Dis. 2018;18(1):1–13.CrossRef Tang H, Mao Y, Tang W, Han J, Xu J, Li J. “Late for testing, early for antiretroviral therapy, less likely to die”: results from a large HIV cohort study in China, 2006–2014. BMC Infect Dis. 2018;18(1):1–13.CrossRef
39.
go back to reference Mills EJ, Beyrer C, Birungi J, Dybul MR. Engaging men in prevention and care for HIV/AIDS in Africa. PLoS Med. 2012;9(2):1–4.CrossRef Mills EJ, Beyrer C, Birungi J, Dybul MR. Engaging men in prevention and care for HIV/AIDS in Africa. PLoS Med. 2012;9(2):1–4.CrossRef
40.
go back to reference Konrad BP, DarleneTaylor JM, et al. Age-specific mortality patterns in HIV-infected individuals: a comparative analysis of African community study data. AIDS. 2007;21(SUPPL. 6):87–96. Konrad BP, DarleneTaylor JM, et al. Age-specific mortality patterns in HIV-infected individuals: a comparative analysis of African community study data. AIDS. 2007;21(SUPPL. 6):87–96.
41.
go back to reference Umutesi J, Klett-Tammen C, Nsanzimana S, Krause G, Ott JJ. Cross-sectional study of chronic hepatitis B virus infection in Rwandan high-risk groups: unexpected findings on prevalence and its determinants. BMJ Open. 2021;11(12):e054039.PubMedCentralCrossRef Umutesi J, Klett-Tammen C, Nsanzimana S, Krause G, Ott JJ. Cross-sectional study of chronic hepatitis B virus infection in Rwandan high-risk groups: unexpected findings on prevalence and its determinants. BMJ Open. 2021;11(12):e054039.PubMedCentralCrossRef
42.
go back to reference Sorenson SB. Gender disparities in injury mortality: consistent, persistent, and larger than you’d think. Am J Public Health. 2011;101(SUPPL. 1):353–8.CrossRef Sorenson SB. Gender disparities in injury mortality: consistent, persistent, and larger than you’d think. Am J Public Health. 2011;101(SUPPL. 1):353–8.CrossRef
43.
go back to reference Xi B, Veeranki SP, Zhao M, Ma C, Yan Y, Mi J. Relationship of alcohol consumption to all-cause, cardiovascular, and cancer-related mortality in U.S. adults. J Am Coll Cardiol. 2017;70(8):913–22.PubMedCrossRef Xi B, Veeranki SP, Zhao M, Ma C, Yan Y, Mi J. Relationship of alcohol consumption to all-cause, cardiovascular, and cancer-related mortality in U.S. adults. J Am Coll Cardiol. 2017;70(8):913–22.PubMedCrossRef
44.
go back to reference Nsanzimana S, Remera E, Kanters S, Chan K, Forrest JI, Ford N, et al. Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study. Lancet Glob Health. 2015;3(3):e169–77.PubMedCrossRef Nsanzimana S, Remera E, Kanters S, Chan K, Forrest JI, Ford N, et al. Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study. Lancet Glob Health. 2015;3(3):e169–77.PubMedCrossRef
45.
go back to reference Zhang P, Liu Q, Yuan M, Wang L. Tenofovir disoproxil fumarate reduce incidence of HCC development in CHB-patients with compensated cirrhosis. Infect Agent Cancer. 2018;13(1):1–5.CrossRef Zhang P, Liu Q, Yuan M, Wang L. Tenofovir disoproxil fumarate reduce incidence of HCC development in CHB-patients with compensated cirrhosis. Infect Agent Cancer. 2018;13(1):1–5.CrossRef
46.
go back to reference Kouame GM, Boyd A, Moh R, Badje A, Gabillard D, Ouattara E, 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):112–20.PubMedCrossRef Kouame GM, Boyd A, Moh R, Badje A, Gabillard D, Ouattara E, 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):112–20.PubMedCrossRef
47.
go back to reference Velen K, Charalambous S, Innes C. Chronic hepatitis B increases mortality and complexity among HIV-co-infected patients in South Africa: a cohort study. HIV Med. 2019;17(9):702–7.CrossRef Velen K, Charalambous S, Innes C. Chronic hepatitis B increases mortality and complexity among HIV-co-infected patients in South Africa: a cohort study. HIV Med. 2019;17(9):702–7.CrossRef
Metadata
Title
Long-term effect of chronic hepatitis B on mortality in HIV-infected persons in a differential HBV transmission setting
Authors
Justine Umutesi
Sabin Nsanzimana
Carol Yingkai Liu
Patrizio Vanella
Jördis J. Ott
Gérard Krause
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07477-1

Other articles of this Issue 1/2022

BMC Infectious Diseases 1/2022 Go to the issue