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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Cytomegalovirus infection in HIV-infected versus non-infected infants and HIV disease progression in Cytomegalovirus infected versus non infected infants early treated with cART in the ANRS 12140—Pediacam study in Cameroon

Authors: Anfumbom K. W. Kfutwah, Paul Alain T. Ngoupo, Casimir Ledoux Sofeu, Francis Ateba Ndongo, Georgette Guemkam, Suzie Tetang Ndiang, Félicité Owona, Ida Calixte Penda, Patrice Tchendjou, Christine Rouzioux, Josiane Warszawski, Albert Faye, Mathurin Cyrille Tejiokem

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

The outcome of CMV/HIV co-infection in infants treated early with combined antiretroviral therapy (cART) in resource-limited settings has not been described.
We aimed to estimate the prevalence and identify factors associated with early CMV infection in HIV-infected and non-infected infants included in a study in Cameroon, and to compare HIV disease progression and survival after 1 year of early cART, following infants’ CMV status.

Methods

HIV-infected infants followed from birth or from HIV diagnosis before 7 months old and HIV-uninfected infants born to HIV-infected or uninfected mothers were tested for CMV at a median age of 4.0 months [Interquartile range (IQR): 3.4–4.9]. Multivariable logistic regression was performed to identify factors associated with CMV infection. Early cART was offered to HIV-infected infants: mortality, immunological and virological outcomes were assessed.

Results

Three hundred and sixty-nine infants were tested. The proportion of infants infected with CMV at baseline was significantly higher in HIV-infected than in HIV-uninfected groups (58.9% (86/146) vs 30.0% (67/223), p < 0.001). At baseline, median CMV viral load was higher in HIV-infected (3.7 log copies/ml [IQR; 3.1–4.3]) than in HIV-uninfected infants (2.8 log copies [IQR; 2.1–3.4], p < 0.001). cART was initiated in 90% of HIV-infected infants (132/146) at a median age of 4.0 months (IQR; 3.2–5.9); in this sub-group CMV infection was independently associated with being followed from the time of HIV diagnosis rather than from birth (aOR = 3.1, 95%CI [1.2–8.0]), born to a non-single mother (aOR = 3.4[1.4–8.1]), and breastfeeding (aOR = 7.3 [2.7–19.4]). HIV-infected infants were retested after a median of 7.1 months [4.8–9.5]: CMV was undetectable in 37 of the 61 (60.7%) initially CMV-infected cases and became detectable in 8 of the 38 (21.1%) initially CMV-negative cases. After 1 year of cART, the probability of death (0.185 vs 0.203; p = 0.75), the proportion of cases with HIV RNA viral load <400 copies/ml (75.5% vs 61.5%; p = 0.17) and the mean CD4 percentage increase (10.97% vs 6.88%; p = 0.15) did not differ between CMV+ and CMV- infants.

Conclusions

We observed a high prevalence of CMV infection among HIV-infected infants. Early initiation of cART may have limited the negative impact of CMV even in the absence of specific anti-CMV treatment.
Literature
1.
go back to reference van der Sande MA, Kaye S, Miles DJ, Waight P, Jeffries DJ, Ojuola OO, et al. Risk factors for and clinical outcome of congenital cytomegalovirus infection in a peri-urban West-African birth cohort. PLoS One. 2007;2:e492.CrossRefPubMedPubMedCentral van der Sande MA, Kaye S, Miles DJ, Waight P, Jeffries DJ, Ojuola OO, et al. Risk factors for and clinical outcome of congenital cytomegalovirus infection in a peri-urban West-African birth cohort. PLoS One. 2007;2:e492.CrossRefPubMedPubMedCentral
2.
go back to reference Bowen EF, Sabin CA, Wilson P, Griffiths PD, Davey CC, Johnson MA, et al. Cytomegalovirus (CMV) viraemia detected by polymerase chain reaction identifies a group of HIV-positive patients at high risk of CMV disease. AIDS. 1997;11:889–93.CrossRefPubMed Bowen EF, Sabin CA, Wilson P, Griffiths PD, Davey CC, Johnson MA, et al. Cytomegalovirus (CMV) viraemia detected by polymerase chain reaction identifies a group of HIV-positive patients at high risk of CMV disease. AIDS. 1997;11:889–93.CrossRefPubMed
3.
go back to reference de Vries JJ, Vossen AC, Kroes AC, van der Zeijst BA. Implementing neonatal screening for congenital cytomegalovirus: addressing the deafness of policy makers. Rev Med Virol. 2011;21:54–61.CrossRefPubMed de Vries JJ, Vossen AC, Kroes AC, van der Zeijst BA. Implementing neonatal screening for congenital cytomegalovirus: addressing the deafness of policy makers. Rev Med Virol. 2011;21:54–61.CrossRefPubMed
5.
go back to reference Doyle M, Atkins JT, Rivera-Matos IR. Congenital cytomegalovirus infection in infants infected with human immunodeficiency virus type 1. Pediatr Infect Dis J. 1996;15:1102–6.CrossRefPubMed Doyle M, Atkins JT, Rivera-Matos IR. Congenital cytomegalovirus infection in infants infected with human immunodeficiency virus type 1. Pediatr Infect Dis J. 1996;15:1102–6.CrossRefPubMed
6.
go back to reference Kovacs A, Schluchter M, Easley K, Demmler G, Shearer W, La Russa P, et al. Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group. N Engl J Med. 1999;341:77–84.CrossRefPubMedPubMedCentral Kovacs A, Schluchter M, Easley K, Demmler G, Shearer W, La Russa P, et al. Cytomegalovirus infection and HIV-1 disease progression in infants born to HIV-1-infected women. Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group. N Engl J Med. 1999;341:77–84.CrossRefPubMedPubMedCentral
7.
go back to reference Guibert G, Warszawski J, Le Chenadec J, Blanche S, Benmebarek Y, Mandelbrot L, et al. Decreased risk of congenital cytomegalovirus infection in children born to HIV-1-infected mothers in the era of highly active antiretroviral therapy. Clin Infect Dis. 2009;48:1516–25.CrossRefPubMed Guibert G, Warszawski J, Le Chenadec J, Blanche S, Benmebarek Y, Mandelbrot L, et al. Decreased risk of congenital cytomegalovirus infection in children born to HIV-1-infected mothers in the era of highly active antiretroviral therapy. Clin Infect Dis. 2009;48:1516–25.CrossRefPubMed
8.
go back to reference Frederick T, Homans J, Spencer L, Kramer F, Stek A, Operskalski E, et al. The effect of prenatal highly active antiretroviral therapy on the transmission of congenital and perinatal/early postnatal cytomegalovirus among HIV-infected and HIV-exposed infants. Clin Infect Dis. 2012;55:877–84.CrossRefPubMed Frederick T, Homans J, Spencer L, Kramer F, Stek A, Operskalski E, et al. The effect of prenatal highly active antiretroviral therapy on the transmission of congenital and perinatal/early postnatal cytomegalovirus among HIV-infected and HIV-exposed infants. Clin Infect Dis. 2012;55:877–84.CrossRefPubMed
9.
go back to reference Slyker JA, Lohman-Payne BL, John-Stewart GC, Maleche-Obimbo E, Emery S, Richardson B, et al. Acute cytomegalovirus infection in Kenyan HIV-infected infants. AIDS. 2009;23:2173–81.CrossRefPubMedPubMedCentral Slyker JA, Lohman-Payne BL, John-Stewart GC, Maleche-Obimbo E, Emery S, Richardson B, et al. Acute cytomegalovirus infection in Kenyan HIV-infected infants. AIDS. 2009;23:2173–81.CrossRefPubMedPubMedCentral
10.
go back to reference Mwaanza N, Chilukutu L, Tembo J, Kabwe M, Musonda K, Kapasa M, et al. High rates of congenital cytomegalovirus infection linked with maternal HIV infection among neonatal admissions at a large referral center in sub-Saharan Africa. Clin Infect Dis. 2014;58:728–35.CrossRefPubMed Mwaanza N, Chilukutu L, Tembo J, Kabwe M, Musonda K, Kapasa M, et al. High rates of congenital cytomegalovirus infection linked with maternal HIV infection among neonatal admissions at a large referral center in sub-Saharan Africa. Clin Infect Dis. 2014;58:728–35.CrossRefPubMed
11.
go back to reference Manicklal S, van Niekerk AM, Kroon SM, Hutto C, Novak Z, Pati SK, et al. Birth prevalence of congenital cytomegalovirus among infants of HIV-infected women on prenatal antiretroviral prophylaxis in South Africa. Clin Infect Dis. 2014;58:1467–72.CrossRefPubMed Manicklal S, van Niekerk AM, Kroon SM, Hutto C, Novak Z, Pati SK, et al. Birth prevalence of congenital cytomegalovirus among infants of HIV-infected women on prenatal antiretroviral prophylaxis in South Africa. Clin Infect Dis. 2014;58:1467–72.CrossRefPubMed
12.
go back to reference Leruez-Ville M, Ouachee M, Delarue R, Sauget AS, Blanche S, Buzyn A, et al. Monitoring cytomegalovirus infection in adult and pediatric bone marrow transplant recipients by a real-time PCR assay performed with blood plasma. J Clin Microbiol. 2003;41:2040–6.CrossRefPubMedPubMedCentral Leruez-Ville M, Ouachee M, Delarue R, Sauget AS, Blanche S, Buzyn A, et al. Monitoring cytomegalovirus infection in adult and pediatric bone marrow transplant recipients by a real-time PCR assay performed with blood plasma. J Clin Microbiol. 2003;41:2040–6.CrossRefPubMedPubMedCentral
13.
go back to reference Leruez-Ville M, Ngin S, Guilleminot T, Kfutwah A, Moussa S, Tran T, et al. Detection of cytomegalovirus DNA on dried blood spots collected from infants infected with HIV: an in-house method adaptable in resource-limited settings. J Virol Methods. 2013;193:503–7.CrossRefPubMed Leruez-Ville M, Ngin S, Guilleminot T, Kfutwah A, Moussa S, Tran T, et al. Detection of cytomegalovirus DNA on dried blood spots collected from infants infected with HIV: an in-house method adaptable in resource-limited settings. J Virol Methods. 2013;193:503–7.CrossRefPubMed
14.
go back to reference Lohman-Payne B, Slyker JA, Richardson BA, Farquhar C, Majiwa M, Maleche-Obimbo E, et al. Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition. Clin Exp Immunol. 2009;156:511–7.CrossRefPubMedPubMedCentral Lohman-Payne B, Slyker JA, Richardson BA, Farquhar C, Majiwa M, Maleche-Obimbo E, et al. Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition. Clin Exp Immunol. 2009;156:511–7.CrossRefPubMedPubMedCentral
15.
go back to reference Hsiao NY, Zampoli M, Morrow B, Zar HJ, Hardie D. Cytomegalovirus viraemia in HIV exposed and infected infants: prevalence and clinical utility for diagnosing CMV pneumonia. J Clin Virol. 2013;58:74–8.CrossRefPubMed Hsiao NY, Zampoli M, Morrow B, Zar HJ, Hardie D. Cytomegalovirus viraemia in HIV exposed and infected infants: prevalence and clinical utility for diagnosing CMV pneumonia. J Clin Virol. 2013;58:74–8.CrossRefPubMed
16.
go back to reference EDS-MICS. Institut National de la statistique. Rapport préliminaire de la quatrième enquête démographique et de santé au Cameroun (EDS-MICS IV). 2011. EDS-MICS. Institut National de la statistique. Rapport préliminaire de la quatrième enquête démographique et de santé au Cameroun (EDS-MICS IV). 2011.
17.
go back to reference Vollmer B, Seibold-Weiger K, Schmitz-Salue C, Hamprecht K, Goelz R, Krageloh-Mann I, et al. Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants. Pediatr Infect Dis J. 2004;23:322–7.CrossRefPubMed Vollmer B, Seibold-Weiger K, Schmitz-Salue C, Hamprecht K, Goelz R, Krageloh-Mann I, et al. Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants. Pediatr Infect Dis J. 2004;23:322–7.CrossRefPubMed
18.
go back to reference Croly-Labourdette S, Vallet S, Gagneur A, Gremmo-Feger G, Legrand-Quillien MC, Ansquer H, et al. Pilot epidemiologic study of transmission of cytomegalovirus from mother to preterm infant by breastfeeding. Arch Pediatr. 2006;13:1015–21.CrossRefPubMed Croly-Labourdette S, Vallet S, Gagneur A, Gremmo-Feger G, Legrand-Quillien MC, Ansquer H, et al. Pilot epidemiologic study of transmission of cytomegalovirus from mother to preterm infant by breastfeeding. Arch Pediatr. 2006;13:1015–21.CrossRefPubMed
19.
go back to reference Chang TS, Wiener J, Dollard SC, Amin MM, Ellington S, Chasela C, et al. Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers. AIDS. 2015;29:831–6.CrossRefPubMedPubMedCentral Chang TS, Wiener J, Dollard SC, Amin MM, Ellington S, Chasela C, et al. Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers. AIDS. 2015;29:831–6.CrossRefPubMedPubMedCentral
20.
go back to reference Fowler KB, Pass RF. Sexually transmitted diseases in mothers of neonates with congenital cytomegalovirus infection. J Infect Dis. 1991;164:259–64.CrossRefPubMed Fowler KB, Pass RF. Sexually transmitted diseases in mothers of neonates with congenital cytomegalovirus infection. J Infect Dis. 1991;164:259–64.CrossRefPubMed
21.
go back to reference Sheevani, Jindal N, Aggarwal A. A pilot seroepidemiological study of cytomegalovirus infection in women of child bearing age. Indian J Med Microbiol. 2005;23:34–6.CrossRefPubMed Sheevani, Jindal N, Aggarwal A. A pilot seroepidemiological study of cytomegalovirus infection in women of child bearing age. Indian J Med Microbiol. 2005;23:34–6.CrossRefPubMed
22.
go back to reference Reitter A, Buxmann H, Haberl AE, Schlosser R, Kreibich M, Keppler OT, et al. Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study. Med Microbiol Immunol. 2016;205:63–71.CrossRefPubMed Reitter A, Buxmann H, Haberl AE, Schlosser R, Kreibich M, Keppler OT, et al. Incidence of CMV co-infection in HIV-positive women and their neonates in a tertiary referral centre: a cohort study. Med Microbiol Immunol. 2016;205:63–71.CrossRefPubMed
23.
go back to reference Gantt S, Leister E, Jacobsen DL, Boucoiran I, Huang ML, Jerome KR, et al. Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy. J Med Virol. 2016;88:1051–8.CrossRefPubMed Gantt S, Leister E, Jacobsen DL, Boucoiran I, Huang ML, Jerome KR, et al. Risk of congenital cytomegalovirus infection among HIV-exposed uninfected infants is not decreased by maternal nelfinavir use during pregnancy. J Med Virol. 2016;88:1051–8.CrossRefPubMed
24.
go back to reference Wada NI, Jacobson LP, Margolick JB, Breen EC, Macatangay B, Penugonda S, et al. The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS. 2015;29:463–71.CrossRefPubMedPubMedCentral Wada NI, Jacobson LP, Margolick JB, Breen EC, Macatangay B, Penugonda S, et al. The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS. 2015;29:463–71.CrossRefPubMedPubMedCentral
25.
go back to reference Jimenez A, Molero L, Castanon S, Subira D, De Gorgolas M, Fedz-Guerrero M, et al. Role of antiretroviral regimes in HIV-1 patients in reducing immune activation. Immunology. 2002;106:80–6.CrossRefPubMedPubMedCentral Jimenez A, Molero L, Castanon S, Subira D, De Gorgolas M, Fedz-Guerrero M, et al. Role of antiretroviral regimes in HIV-1 patients in reducing immune activation. Immunology. 2002;106:80–6.CrossRefPubMedPubMedCentral
26.
go back to reference Marin Gabriel MA, Ramos Amador JT, Gonzalez Tome M, Rojo Conejo P, Saavedra Lozano J, de la Cruz Bertolo J. Cytomegalovirus infection in the first year of life in human immunodeficiency virus-infected children: impact on survival and progression of the HIV disease. Med Sci Monit. 2007;13:CR177–181.PubMed Marin Gabriel MA, Ramos Amador JT, Gonzalez Tome M, Rojo Conejo P, Saavedra Lozano J, de la Cruz Bertolo J. Cytomegalovirus infection in the first year of life in human immunodeficiency virus-infected children: impact on survival and progression of the HIV disease. Med Sci Monit. 2007;13:CR177–181.PubMed
27.
go back to reference Mussi-Pinhata MM, Yamamoto AY, Figueiredo LT, Cervi MC, Duarte G. Congenital and perinatal cytomegalovirus infection in infants born to mothers infected with human immunodeficiency virus. J Pediatr. 1998;132:285–90.CrossRefPubMed Mussi-Pinhata MM, Yamamoto AY, Figueiredo LT, Cervi MC, Duarte G. Congenital and perinatal cytomegalovirus infection in infants born to mothers infected with human immunodeficiency virus. J Pediatr. 1998;132:285–90.CrossRefPubMed
28.
go back to reference Nigro G, Krzysztofiak A, Gattinara GC, Mango T, Mazzocco M, Porcaro MA, et al. Rapid progression of HIV disease in children with cytomegalovirus DNAemia. AIDS. 1996;10:1127–33.PubMed Nigro G, Krzysztofiak A, Gattinara GC, Mango T, Mazzocco M, Porcaro MA, et al. Rapid progression of HIV disease in children with cytomegalovirus DNAemia. AIDS. 1996;10:1127–33.PubMed
29.
go back to reference Para MF, Kalish LA, Collier AC, Murphy EL, Drew WL. Correlates of change in cytomegalovirus viremia in patients with advanced human immunodeficiency virus infection who require transfusion. J Infect Dis. 2001;183:1673–7.CrossRefPubMed Para MF, Kalish LA, Collier AC, Murphy EL, Drew WL. Correlates of change in cytomegalovirus viremia in patients with advanced human immunodeficiency virus infection who require transfusion. J Infect Dis. 2001;183:1673–7.CrossRefPubMed
30.
go back to reference O’Sullivan CE, Drew WL, McMullen DJ, Miner R, Lee JY, Kaslow RA, et al. Decrease of cytomegalovirus replication in human immunodeficiency virus infected-patients after treatment with highly active antiretroviral therapy. J Infect Dis. 1999;180:847–9.CrossRefPubMed O’Sullivan CE, Drew WL, McMullen DJ, Miner R, Lee JY, Kaslow RA, et al. Decrease of cytomegalovirus replication in human immunodeficiency virus infected-patients after treatment with highly active antiretroviral therapy. J Infect Dis. 1999;180:847–9.CrossRefPubMed
Metadata
Title
Cytomegalovirus infection in HIV-infected versus non-infected infants and HIV disease progression in Cytomegalovirus infected versus non infected infants early treated with cART in the ANRS 12140—Pediacam study in Cameroon
Authors
Anfumbom K. W. Kfutwah
Paul Alain T. Ngoupo
Casimir Ledoux Sofeu
Francis Ateba Ndongo
Georgette Guemkam
Suzie Tetang Ndiang
Félicité Owona
Ida Calixte Penda
Patrice Tchendjou
Christine Rouzioux
Josiane Warszawski
Albert Faye
Mathurin Cyrille Tejiokem
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2308-x

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