The impact of HBV or HCV infection in a cohort of HIV-infected pregnant women receiving a nevirapine-based antiretroviral regimen in Malawi

BMC Infectious Diseases

Sandro Mancinelli⁵  Leonardo Palombi⁵  Marina Giuliano³  Stefano Vella³  Maria Cristina Marazzi⁴  Elisabetta Gennaro⁵  Maria Grazia Mancini³  Roberta Amici³  Richard Luhanga²  Jean-Baptiste Sagno²  Martin Maulidi¹  Haswell Jere²  Giuseppe Liotta⁵  Maria Franca Pirillo³  Mauro Andreotti³ 

[1] DREAM Program, Community of S. Egidio, Mthengo Wa Ntengo Hospital, Lilongwe, Lumbadzi, Malawi;DREAM Program, Community of S. Egidio, P.O. Box 30355, Blantyre, Malawi;Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;LUMSA University, Via Transpontina 21, 00193 Rome, Italy;DREAM Program, Community of S. Egidio, Piazza Sant’Egidio, 00153 Rome, Italy

关键词: Mother-to-child HIV transmission;    Pregnancy;    Nevirapine;    HCV;    HBV;    Hepatotoxicity;    Antiretroviral therapy;   

Others  :  1134215
DOI  :  10.1186/1471-2334-14-180

 received in 2013-06-06, accepted in 2014-03-31,  发布年份 2014

【 摘 要 】

Background

Coinfection with the hepatitis viruses is common in the HIV population in sub-Saharan Africa. The aim of this study was to assess, in a cohort of HIV-infected pregnant women receiving antiretroviral drugs (ARVs), the prevalence of HBV and HCV infections and to determine the impact of these infections on the occurrence of liver toxicity and on the viro-immunological response.

Methods

Women were screened for HBsAg and HCV-RNA before starting, at week 25 of gestational age, an antiretroviral regimen consisting of lamivudine and nevirapine plus either stavudine or zidovudine. Women with CD4+ < 350/mm³ continued ARVs indefinitely, while the other women interrupted treatment 6 months postpartum (end of breastfeeding period). Both groups were followed for 2 years after delivery. Liver function was monitored by alanine aminotransferase (ALT) measurement. The Cox proportional hazards model was used to identify factors associated with the emergence of liver toxicity.

Results

A total of 28 women out of the 309 enrolled in the study (9.1%) were coinfected with HBV (n. 27), or HCV (n. 1). During follow-up 125 women (40.4%) developed a grade ≥ 1 ALT elevation, 28 (9.1%) a grade ≥ 2 and 6 (1.9%) an elevation defining grade 3 toxicity. In a multivariate model including age, baseline CD4+ count and hemoglobin level, the presence of either HBV or HCV infection was significantly associated with the development of an ALT increase of any grade (P = 0.035). Moderate or severe liver laboratory toxicity (grade ≥ 2) was more frequent among women with baseline CD4+ > 250/mm³ (P = 0.030). In HBV-infected women a baseline HBV-DNA level above 10,000 IU/ml was significantly associated to the development of liver toxicity of grade ≥ 1 (P = 0.040). Coinfections had no impact on the immunological and virological response to antiretroviral drugs up to 2 years after delivery.

Conclusions

In this cohort of nevirapine-treated women the presence of HBV or HCV was associated only to the development of mild liver toxicity, while the occurrence of moderate or severe hepatoxicity was correlated to a baseline CD4+ count > 250/mm³. No statistically significant effect of the coinfections was observed on the efficacy of antiretroviral therapy.

【 授权许可】

   
2014 Andreotti et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Koziel MJ, Peteres MG: Viral hepatitis in HIV infection. New Engl J Med 2007, 356:1445-1454.
• [2]Shen YZ, Wang ZY, Qi TK, Jiang XY, Song W, Tang Y, Wang JR, Liu L, Zhang RF, Zheng YF, Dai ZS, Lu HZ: Serological survey of viral hepatitis markers among newly diagnosed patients with HIV/AIDS in China. HIV Med 2013, 14:167-175.
• [3]Thio CL, Smeaton L, Saulynas M, Hwang H, Saravan S, Kilkarni S, Hakim J, Nyirenda M, Igbal HS, Lalloo UG, Mehta AS, Hollabaugh K, Campbell TB, Lockman S, Currier JS: Characterization of HIV-HBV coinfection in a multinational HIV-infected cohort. AIDS 2013, 27:191-201.
• [4]Hawkins C, Christian B, Ye J, Nagu T, Aris E, Chalamilla G, Spiegelman D, Mugusi F, Mehta S, Fawzi W: Prevalence of Hepatitis B co-infection and response to antiretroviral therapy among HIV-infected patients in urban Tanzania. AIDS 2013, 27:919-927.
• [5]Hoffmann CJ, Charalambous S, Martin DJ, Innes C, Churchyard GJ, Chaisson RE, Grant AD, Fielding KL, Thio CL: Hepatitis B virus infection and response to antiretroviral therapy (ART) in a South African ART program. Clin Infect Dis 2008, 47:1479-1485.
• [6]Idoko J, Meloni S, Muazu M, Nimzing L, Badung B, Hawjins C, Sankalé JL, Ekong E, Murphy R, Kanki P, Thio CL: Impact of hepatitis B virus infection on human immunodeficiency virus response to antiretroviral therapy in Nigeria. Clin Infect Dis 2009, 49:1268-1273.
• [7]Mbougua JBT, Laurent C, Kouanfack C, Bourgeois A, Ciaffi L, Calmy A, Gwet H, Koulla-Shiro S, Ducos J, Mpoudi-Ngolé E, Molinari N, Delaporte E: Hepatotoxicity and effectiveness of a nevirapine-based antiretroviral therapy in HIV-infected patients with or without viral heptitis B or C infection in Cameroon. BMC Public Health 2010, 10:105. BioMed Central Full Text
• [8]Ouyang DW, Shapiro DE, Lu M, Brogly SB, French AL, Leighty RM, Thompson B, Tuomala RE, Hershow RC: Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure. AIDS 2009, 23:2425-2430.
• [9]Palombi L, Pirillo MF, Andreotti M, Liotta G, Erba F, Sagno JB, Maulidi M, Ceffa S, Jere H, Marchei E, Pichini S, Galluzzo CM, Marazzi MC, Vella S, Giuliano M: Antiretroviral prophylaxis for breastfeeding transmission in Malawi: drug concentrations, virological efficacy and safety. Antivir Ther 2012, 17:1511-1519.
• [10]Division of AIDS: Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004. Bethesda, Maryland, USA: National Institute of Health; 2004. http://rsc.tech-res.com/Document/safetyandpharmacovigilance/Table_for_Grading_Severity_of_Adult_Pediatric_Adverse_Events.pdf webcite
• [11]Rouet F, Chaix ML, Inwoley A, Msellati P, Viho I, Combe P, Leroy V, Dabis F, Rouzioux C: HBV and HCV prevalence and viraemia in HIV-positive and HIV-negative pregnant women in Abidjan, Côte d’Ivoire: the ANRS 1236 study. J Med Virol 2004, 74:34-40.
• [12]WHO: Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. 2013. [Recommendations for a Public Health Approach] http://www.who.int/hiv/pub/guidelines/arv2013/download/en/ webcite
• [13]Baylor MS, Johann-Liang R: Hepatoxicity associated with nevirapine use. J Acquir Immune Defic Syndr 2004, 35:538-539.
• [14]Marazzi MC, Germano P, Liotta G, Guidotti G, Loureiro S, de Crus Gomes A, Valls Blazquez MC, Narciso P, Perno CF, Mancinelli S, Palombi L: Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. HIV Med 2006, 7:338-344.
• [15]Ford N, Calmy A, Andrieux-Meyer I, Hargreaves S, Mills EJ, Shubber Z: Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis. AIDS 2013, 24:1135-1143.
• [16]Chadwick D, Ankcorn M, Sarfo F, Phillips R, Fox Z, Garcia A, Appiah L, Bedu-Addo G, Geretti AM: Outcomes of starting first-line antiretroviral therapy in hepatitis B virus/HIV-coinfected patients in Ghana. J Antimicrob Chemother 2012, 67:2939-42.
• [17]Moore E, Beadsworth MB, Chaponda M, Mhango B, Faragher B, Njala J, Hofland HWC, Davies J, Hart IJ, Beeching NJ, Zijlstra EE, van Oosterhout JJ: Favourable one-year ART outcomes in adult Malawians with hepatitis B and C co-infection. J Infect 2010, 61:155-63.
• [18]Chasela CS, Wall P, Drobeniuc J, King CC, Teshale E, Hosseinipour MC, Ellington SR, Codd M, Jamieson DJ, Knight RJ, Fitzpatrick P, Kourtis AP, Hoffman IF, Kayira D, Mumba N, Kamwendo DD, Martisnon F, Powderly W, van der Horst C, Kamili S, the BAN team: Prevalence of hepatitis C virus infection among human immunodeficiency virus-1-infected pregnant women in Malawi: the BAN study. J Clin Virol 2012, 54:318-20.
• [19]Galluzzo C, Liotta G, Andreotti M, Luhanga R, Jere H, Mancinelli S, Maulidi M, Sagno JB, Pirillo MF, Erba F, Amici R, Ceffa S, Marazzi MC, Vella S, Palombi L, Giuliano M: Emergence of lamivudine resistance hepatitis B virus mutations in pregnant women infected with HBV and HIV receiving antiretroviral prophylaxis for the prevention of mother-to-infant transmission in Malawi. J Med Virol 2012, 84:1553-1557.