Lamivudine-Resistant HBV Infection in HIV-Positive Patients Receiving Antiretroviral Therapy in a Public Routine Clinic in Cameroon

Abstract

Background

In Africa, most HIV–HBV-coinfected patients on antiretroviral therapy (ART) receive an anti-HBV lamivudine monotherapy that has been shown in northern countries to lead to frequent emergence of drug resistance. We assessed the HBV prevalence and the rate and pattern of lamivudine-resistant HBV mutations in Cameroonian HIV-infected, ART-treated patients.

Methods

A cross-sectional survey was performed in 2006–2007 at the HIV/AIDS outpatient clinic of the Central Hospital in Yaoundé, Cameroon. Plasma samples were tested as appropriate for hepatitis B surface antigens, antibodies to hepatitis B core, HBV DNA, genotypes and lamivudine-resistant polymerase mutations.

Results

Of 552 adult patients (71% women, median age 38 years), 290 had received lamivudine-based ART for 12 months and 262 for 24 months. No patient had received tenofovir. The prevalence of hepatitis B surface antigen was 9.8%. Overall, 26% of seropositive patients had an HBV DNA level >40 IU/ml. Genotypes A and E were identified. Polymerase resistance mutations were detected in 14% and 60% of patients at months 12 and 24, respectively.

Conclusions

This study supports both WHO recommendations of screening for HBV before initiation of ART and of using ART containing tenofovir and either lamivudine or emtricitabine in HIV–HBV-coinfected patients in Africa.

References

Modi

A.A.

, Feld

J.J.

Viral hepatitis and HIV in Africa. AIDS Rev 2007; 9: 25–39.

UNAIDS. Global report: UNAIDS report on the global AIDS epidemic 2010. (Accessed 1 December 2010). Available from: http://www.unaids.org/documents/20101123_GlobalReport_em.pdf.

Hoffmann

C.J.

, Thio

C.L.

Clinical implications of HIV and hepatitis B co-infection in Asia and Africa. Lancet Infect Dis 2007; 7: 402–409.

Barth

R.E.

, Huijgen

, Taljaard

, Hoepelman

A.I.

Hepatitis B/C and HIV in sub-Saharan Africa: an association between highly prevalent infectious diseases. A systematic review and meta-analysis. Int J Infect Dis 2010; 14: e1024–e1031.

World Health Organization. Towards universal access. Scaling up priority HIV/AIDS interventions in the health sector. Progress report 2010. (Accessed 13 October 2010). Available from http://whqlibdoc.who.int/publications/2010/9789241500395_eng.pdf.

World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents. Recommendations for a public health approach. 2010 revision. (Accessed 12 October 2010). Available from http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf.

Ford

, Calmy

Improving first-line antiretroviral therapy in resource-limited settings. Curr Opin HIV AIDS 2010; 5: 38–47.

De Beaudrap

, Diallo

M.B.

, Landman

Changes in the renal function after tenofovir-containing antiretroviral therapy initiation in a senegalese cohort (ANRS 1215). AIDS Res Hum Retroviruses 2010; 26: 1221–1227.

Matthews

G.V.

, Bartholomeusz

, Locarnini

Characteristics of drug resistant HBV in an international collaborative study of HIV-HBV-infected individuals on extended lamivudine therapy. AIDS 2006; 20: 863–870.

10.

Sulkowski

M.S.

Viral hepatitis and HIV coinfection. J Hepatol 2008; 48: 353–367.

11.

Kouanfack

, Montavon

, Laurent

Low levels of antiretroviral-resistant HIV infection in a routine clinic in Cameroon that uses the World Health Organization (WHO) public health approach to monitor antiretroviral treatment and adequacy with the WHO recommendation for second-line treatment. Clin Infect Dis 2009; 48: 1318–1322.

12.

Rouet

, Chaix

M.L.

, Nerrienet

Impact of HIV-1 genetic diversity on plasma HIV-1 RNA quantification: usefulness of the Agence Nationale de Recherches sur le SIDA second-generation long terminal repeat-based realtime reverse transcriptase polymerase chain reaction test. J Acquir Immune Defic Syndr 2007; 45: 380–388.

13.

Lauritsen

J.M.

, & Bruus

EpiData (version 3). A comprehensive tool for validated entry and documentation of data. Odense, Denmark: The EpiData Association 2003–2004.

14.

Laurent

, Bourgeois

, Mpoudi-Ngole

High rates of active hepatitis B and C co-infections in HIV-1 infected Cameroonian adults initiating antiretroviral therapy. HIV Med 2010; 11: 85–89.

15.

Alter

M.J.

Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006; 44 Suppl: S6–S9.

16.

Geretti

A.M.

, Patel

, Sarfo

F.S.

Detection of highly prevalent hepatitis B virus coinfection among HIV-seropositive persons in Ghana. J Clin Microbiol 2010; 48: 3223–3230.

17.

Mendes-Correa

M.C.

, Pinho

J.R.

, Locarnini

High frequency of lamivudine resistance mutations in Brazilian patients co-infected with HIV and hepatitis B. J Med Virol 2010; 82: 1481–1488.

18.

Wongprasit

, Manosuthi

, Kiertiburanakul

, Sungkanuparph

Hepatitis B virus drug resistance in HIV-1-infected patients taking lamivudine-containing antiretroviral therapy. AIDS Patient Care STDS 2010; 24: 205–209.

19.

Benhamou

, Bochet

, Thibault

Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology 1999; 30: 1302–1306.

20.

Ramos

, Nunez

, Martin-Carbonero

Hepatitis B virus genotypes and lamivudine resistance mutations in HIV/hepatitis B virus-coinfected patients. J Acquir Immune Defic Syndr 2007; 44: 557–561.

21.

Damerow

, Yuen

, Wiegand

Mutation pattern of lamivudine resistance in relation to hepatitis B genotypes: hepatitis B genotypes differ in their lamivudine resistance associated mutation pattern. J Med Virol 2010; 82: 1850–1858.

22.

European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 2009; 50: 227–242.

23.

McMahon

M.A.

, Jilek

B.L.

, Brennan

T.P.

The HBV drug entecavir – effects on HIV-1 replication and resistance. N Engl J Med 2007; 356: 2614–2621.

24.

Sasadeusz

, Audsley

, Mijch

The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients. AIDS 2008; 22: 947–955.

25.

Soriano

, Puoti

, Peters

Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. AIDS 2008; 22: 1399–1410.

26.

Valsamakis

Molecular testing in the diagnosis and management of chronic hepatitis B. Clin Microbiol Rev 2007; 20: 426–439.

27.

Mphahlele

M.J.

, Lukhwareni

, Burnett

R.J.

, Moropeng

L.M.

, Ngobeni

J.M.

High risk of occult hepatitis B virus infection in HIV-positive patients from South Africa. J Clin Virol 2006; 35: 14–20.

28.

Selabe

S.G.

, Lukhwareni

, Song

, Leeuw

Y.G.

, Burnett

R.J.

, Mphahlele

M.J.

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: 1650–1654.