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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency

Authors: Fatima Kakkar, Valerie Lamarre, Thierry Ducruet, Marc Boucher, Silvie Valois, Hugo Soudeyns, Normand Lapointe

Published in: BMC Infectious Diseases | Issue 1/2014

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Abstract

Background

Reports of increased morbidity and mortality from infectious diseases among HIV Exposed Uninfected (HEU) infants have raised concern about a possible underlying immunodeficiency among them. The objective of this study was to assess the immunological profile of HEU infants born to mothers exhibiting different levels of HIV-1 viremia at the time of delivery.

Methods

Study subjects were enrolled in the Centre maternel et infantile sur le SIDA (CMIS) mother-child cohort between 1997 and 2010 (n =585). Infant CD4+ T cell, CD8+ T cell and CD19+ B cell counts were assessed at 2 and 6 months of age, and compared among HEU infants in groups defined by maternal viral load (VL) at the time of delivery (VL < 50 copies/ml, VL 50–1000 copies/ml, and VL > 1000 copies/ml) in a multivariable analysis.

Results

At 2 months of age, infants born to mothers with VL > 1000 copies/ml had lower CD4+ T cell counts compared to those born to mothers with VL < 50 copies/ml at the time of delivery (44.3% versus 48.3%, p = 0.007, and 2884 vs. 2432 cells/mm3, p = 0.02). These differences remained significant after adjusting for maternal and infant antiretroviral drug use, gender, race and gestational age, and persisted at 6 months of age. There were no differences in CD8+ T cell count or absolute CD19+ B cell count between groups, though higher CD19+ B cell percentage was seen among infants born to mothers with VL > 1000 copies/ml.

Conclusions

These results suggest that exposure to high levels of HIV-1 viremia in utero, even in the absence of perinatal transmission, may affect the infant’s developing immune system. While further work needs to be done to confirm these findings, they reinforce the need for optimal treatment of HIV infected pregnant women, and careful follow-up of HEU infants.
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Literature
1.
Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, Berrebi A, Bénifla JL, Burgard M, Lachassine E, Barret B, Chaix ML, Bongain A, Ciraru-Vigneron N, Crenn-Hébert C, Delfraissy JF, Rouzioux C, Mayaux MJ, Blanche S, Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study Group: Lamivudine-Zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA. 2001, 285: 2083-2093. 10.1001/jama.285.16.2083.CrossRefPubMed
2.
European Collaborative Study: Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005, 40: 458-465.CrossRef
3.
Forbes JC, Alimenti AM, Singer J, Brophy JC, Bitnun A, Samson LM, Money DM, Lee TC, Lapointe ND, Read SE: A national review of vertical HIV transmission. AIDS. 2012, 26: 757-763. 10.1097/QAD.0b013e328350995c.CrossRefPubMed
4.
Filteau S: The HIV-exposed, uninfected African child. Trop Med Int Health. 2009, 14: 276-287. 10.1111/j.1365-3156.2009.02220.x.CrossRefPubMed
5.
Marinda E, Humphrey JH, Iliff PJ, Mutasa K, Nathoo KJ, Piwoz EG, Moulton LH, Salama P, Ward BJ, ZVITAMBO Study Group: Child Mortality according to maternal and infant HIV status in Zimbabwe. Pediatric Infec Dis J. 2006, 26: 519-526.CrossRef
6.
Shapiro RL, Lockman S, Kim S, Smeaton L, Rahkola JT, Thior I, Wester C, Moffat C, Arimi P, Ndase P, Asmelash A, Stevens L, Montano M, Makhema J, Essex M, Janoff EN: Infant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and uninfected women in Botswana. J Infect Dis. 2007, 196: 562-569. 10.1086/519847.CrossRefPubMed
7.
Mussi-Pinhata MM, Freimanis L, Yamamoto AY, Korelitz J, Pinto JA, Cruz ML, Losso MH, Read JS: Infectious disease morbidity among young HIV-1-exposed but uninfected infants in Lain America and Caribbean Countries: The National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study. Pediatrics. 2007, 119: e694-e704. 10.1542/peds.2006-1856.CrossRefPubMed
8.
Fulforf T-A, Pierre R, Lewis K, Palmer P, Walters C, Christie CDC: Infectious Disease Morbidity and Growth Pattern of HIV Exposed Uninfected Infants in Jamaica: An Epidemiological Cohort Study. 2012, Washington D.C: AIDS, Abstract # MOPE115
9.
Thorne C, Newell ML, Dunn D, Peckham C, Giaquinto C, Ruga E, Cozzani S, DeRossi A, Delia R, GroschWorner I, Mok J, Omenaca F, GarciaRodriguez MC, Bates I, DeJose I, Hawkins F, Zapico RM, AsensiBotet F, Otero MC, PerezTamarit D, Molina AG, Canosa C, Scherpbier H, Bohlin AB, Belfrage E, Levy J, Alimenti A, Ferrazin A, DeMaria A, Gotta C, et al: Hospitalization of children born to human immunodeficiency virus-infected women in Europe. Pediatric Infect Dis J. 1997, 16: 1151-1156. 10.1097/00006454-199712000-00010.CrossRef
10.
Singh HK, Gupte N, Kinikar A, Bharadwaj R, Sastry J, Suryavanshi N, Nayak U, Tripathy S, Paranjape R, Jamkar A, Bollinger RC, Gupta A, SWEN India Study Team: High rates of all-cause and gastroenteritis-related hospitalization morbidity and mortality among HIV-exposed Indian infants. BMC Infect Dis. 2011, 11: 193-10.1186/1471-2334-11-193.CrossRefPubMedPubMedCentral
11.
Taha TE, Graham SM, Kumwenda NI, Broadhead RL, Hoover DR, Markakis D, van Der Hoeven L, Liomba GN, Chiphangwi JD, Miotti PG: Morbidity among human immunodeficiency virus-1 infected and uninfected African Children. Pediatrics. 2000, 106: E77-10.1542/peds.106.6.e77.CrossRefPubMed
12.
Epalza C, Goetghebuer T, Hainaut M, Prayez F, Barlow P, Dediste A, Marchant A, Levy J: High Incidence of Group B Streptococcal Infections in HIV-Exposed Uninfected Infants. Pediatrics. 2010, 126: e631-e638. 10.1542/peds.2010-0183.CrossRefPubMed
13.
Karpelowsky JS, Millar AJ, van der Graaf N, van Bogerijen G, Zar HJ: Outcome of HIV-exposed uninfected children undergoing surgery. BMC Pediatr. 2011, 11: 69-10.1186/1471-2431-11-69.CrossRefPubMedPubMedCentral
14.
McNally LM, Jeena PM, Gajee K, Thula SA, Sturm AW, Cassol S, Tomkins AM, Coovadia HM, Goldblatt D: Effect of age, polymicrobial disease, and maternal HIV status on treatment response and cause of severe pneumonia in South African Children; a prospective descriptive study. Lancet. 2007, 369: 1440-1451. 10.1016/S0140-6736(07)60670-9.CrossRefPubMed
15.
Slogrove A, Reije B, Nadoo S, De Beer C, Ho K, Cotton M, Bettinger J, Speert D, Esser M, Kollmann T: HIV-exposed uninfected infants are at increased risk of severe infections in the first year of life. J Trop Pediatr. 2012, 58: 505-508. 10.1093/tropej/fms019.CrossRefPubMedPubMedCentral
16.
Brahmbhatt H, Kigozi G, Wabwire-Mangen F, Serwadda D, Lutalo T, Nalugoda F, Sewankambo N, Kiduggavu M, Wawer M, Gray R: Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr. 2006, 41: 504-508. 10.1097/01.qai.0000188122.15493.0a.CrossRefPubMed
17.
Landes M, van Lettow M, Chan AK, Mayuni I, Schouten EJ, Bedell RA: Mortality and health outcomes of HIV-exposed and unexposed children in a PMTCT cohort in Malawi. PLoS One. 2012, 7: e47338-10.1371/journal.pone.0047338.CrossRef
18.
Heresi GP, Caceres E, Reuben J, Doyle M: Pneumocystis carinii pneumonia in infants who were exposed to human immunodeficiency virus but were not infected: an exception to the AIDS surveillance case definition. Clin Infec Dis. 1997, 25: 739-740. 10.1086/516938.CrossRef
19.
Morrow BM, Hsaio NY, Zampoli M, Whitelaw A, Zar HJ: Pneumocystis pneumonia in South African children with and without human immunodeficiency virus infection in the era of highly active antiretroviral therapy. Pediatric Infect Dis J. 2010, 29: 535-539.
20.
Slogrove AL, Cotton MF, Esser M,M: Severe infections in HIV-exposed uninfected infants; clinical evidence of immunodeficiency. J Tropical Pediatrics. 2010, 56: 75-81. 10.1093/tropej/fmp057.CrossRef
21.
Afran L, Garcia Knight M, Nduati E, Urban B, Heyderman RS, Rowland-Jones SL: HIV-exposed uninfected children: a growing population with a vulnerable immune system?. Clin Exp Immunol. 2013, Epub ahead of print
22.
Clerici M, Saresella M, Colombo F, Fossati S, Sala N, Bricalli D, Villa ML, Ferrante P, Dally L, Vigano’ A: T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV. Blood. 2000, 96: 3866-3871.PubMed
23.
Ono E, Sanots AM N d, de Menezes Succi RC, Machado DM, de Angelis DS, Salomão R, Kallás EG, de Moraes-Pinto MI: Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1 infected mothers on HAART. Braz J Med Biol. 2008, 41: 700-708.
24.
Chougnet C, Kovacs A, Baker R, Mueller BU, Luban NL, Liewehr DJ, Steinberg SM, Thomas EK, Shearer GM: Influence of human immunodeficiency virus-infected mater- nal environment on development of infant inter- leukin-12 production. J Infect Dis. 2000, 181: 590-597.CrossRef
25.
Vigano A, Saresella M, Schenal M, Erba P, Piacentini L, Tornaghi R, Naddeo V, Giacomet V, Borelli M, Trabattoni D, Clerici M: Immune activation and normal levels of endogenous antivirals are seen in healthy adolescents born of HIV-infected mothers. AIDS. 2007, 21: 245-248. 10.1097/QAD.0b013e328011d7d3.CrossRefPubMed
26.
Romano MF, Buffolano W, Bisogni R, Russo R, Liuzzi R, Bunders M, Newell ML, Giarrusso PC: Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis. Viral Immunol. 2006, 19: 363-372. 10.1089/vim.2006.19.363.CrossRefPubMed
27.
Miyamoto M, Pessoa SD, Ono E, Machado DM, Salomão R, Succi RC, Pahwa S, de Moraes-Pinto MI: Lower CD4+ T-cell levels and B-cell apoptosis in vertically HIV-exposed noninfected children and adolescents. J Trop Pediatr. 2010, 56: 427-432. 10.1093/tropej/fmq024.CrossRefPubMedPubMedCentral
28.
Neilsen SD, Jeppesen DL, Kolte L, Clark DR, Sørensen TU, Dreves AM, Ersbøll AK, Ryder LP, Valerius NH, Nielsen JO: Impaired progenitor cell function in HIV-negative infants of HIV positive mothers results in decreased thymic output and low CD4 counts. Blood. 2001, 2001 (98): 398-404.CrossRef
29.
Le Chenadec J, Mayaux MJ, Guihenneuc-Jouyaux C, Blanche S, Enquête Périnatale Française Study Group: Perinatal antiretroviral treatment and hematopoiesis in HIV-uninfected infants. AIDS. 2003, 17: 2053-2061. 10.1097/00002030-200309260-00006.CrossRefPubMed
30.
Pachero SE, McIntosh K, Lu M, Mofenson LM, Diaz C, Foca M, Frederick M, Handelsman E, Hayani K, Shearer WT: Effect of perinatal antiretroviral drug exposure on hematological values in HIV-uninfected children: an analysis of the women and infants transmission study. JID. 2006, 194: 1089-1097. 10.1086/507645.CrossRef
31.
Neu N, Leighty R, Adeniyi-Jones S, Diaz C, Handelsman E, Kaufman G, Paul ME, Rich K, Mofenson L, Pitt J, Women and Infants Transmission Study: Immune parameters and morbidity in hard drug and human immunodeficiency virus-exposed but uninfected infants. Pediatrics. 2004, 113: 1260-1266. 10.1542/peds.113.5.1260.CrossRefPubMed
32.
Dauby N, Goetghebuer T, Kollmann TR, Levy J, Marchant A: Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections. Lancet Infect Dis. 2012, 12: 330-340. 10.1016/S1473-3099(11)70341-3.CrossRefPubMed
33.
Pit DS, Polderman AM, Schulz-Key H, Soboslay PT: Prenatal immune priming with helminth infections: parasite-specific cellular reactivity and Th1 and Th2 cytokine responses in neonates. Allergy. 2000, 55: 732-739. 10.1034/j.1398-9995.2000.00477.x.CrossRefPubMed
34.
Malhotra I, Mungai P, Muchiri E, Ouma J, Sharma S, Kazura JW, King CL: Distinct Th1- and Th2-Type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands. Infect Immun. 2005, 73: 3462-3470. 10.1128/IAI.73.6.3462-3470.2005.CrossRefPubMedPubMedCentral
35.
Dauby N, Alonso-Vega C, Suarez E, Flores A, Hermann E, Córdova M, Tellez T, Torrico F, Truyens C, Carlier Y: Maternal infection with Trypanosoma cruzi and congenital Chagas disease induce a trend to a type 1 polarization of infant immune responses to vaccines. PLoS Negl Trop Dis. 2009, 22: e571-CrossRef
36.
Legrand FA, Nixon DF, Loo CP, Ono E, Chapman JM, Miyamoto M, Diaz RS, Santos AM, Succi RC, Abadi J, Rosenberg MG, de Moraes-Pinto MI, Kallas EG: Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal. PLoS One. 2006, 1: e102-10.1371/journal.pone.0000102.CrossRefPubMedPubMedCentral
37.
Rowland-Jones SL, Nixon DF, Aldhous MC, Gotch F, Ariyoshi K, Hallam N, Kroll JS, Froebel K, McMichael A: HIV-specific cytotoxic T-cell activity in an HIV-exposed but uninfected infant. Lancet. 1993, 341: 860-861. 10.1016/0140-6736(93)93063-7.CrossRefPubMed
38.
Cheynier R, Langlade-Demoyen P, Marescot M-R, Blanche S, Blondin G, Wain-Hobson S, Griscelli C, Vilmer E, Plata F: Cytotoxic T lymphocyte responses in the peripheral blood of children born to HIV-1 infected mothers. Eur J Immunol. 1992, 22: 2211-2217. 10.1002/eji.1830220905.CrossRefPubMed
39.
Kuhn L, Coutsoudis A, Moodley D, Trabattoni D, Mngqundaniso N, Shearer GM, Clerici M, Coovadia HM, Stein Z: T-helper cell responses to HIV-envelope peptides in cord blood: protection against intrapartum and breast-feeding transmission. AIDS. 2001, 15: 1-9. 10.1097/00002030-200101050-00003.CrossRefPubMed
40.
Moraleda C, de Deus N, Serna-Bolea C, Renom M, Quinto L, Macete E, Menendez C, Naniche D: Impact of HIV-exposure on health outcomes in HIV-negative infants born to HIV-positive mothers in Sub-Saharan Africa. J Acquir Immune Defic Syndr. 2014, 66: 182-189.CrossRef
41.
Kuhn L, Meddows-Taylor S, Gray G, Tiemessen C: Human Immunodeficiency Virus (HIV)–specific cellular immune responses in newborns exposed to HIV in utero. Clin Infect Dis. 2002, 34: 267-276. 10.1086/338153.CrossRefPubMed
42.
Faye A, Pornpraset S, Mary JY, Dolcini G, Derrien M, Barré-Sinoussi F, Chaouat G, Menu E: Characterization of the main placental cytokine profiles from HIV-1 infected pregnant women treated with anti-retroviral drugs in France. Clin Exp Immunol. 2007, 149: 430-439. 10.1111/j.1365-2249.2007.03411.x.CrossRefPubMedPubMedCentral
43.
Economides A, Schmid I, Anisman-Posner DJ, Plaeger S, Bryson YJ, Uittenbogaart CH: Apoptosis in cord blood T lymphocytes from infants of human immunodeficiency virus-infected mothers. Clin Diagn Lab Immunol. 1998, 5: 230-234.PubMedPubMedCentral
44.
Jones CE, Naidoo S, De Beer C, Esser M, Kampmann B, Hesseling AC: Maternal HIV infection and antibody responses against vaccine-preventable diseases in uninfected infants. JAMA. 2011, 305: 576-584. 10.1001/jama.2011.100.CrossRefPubMed
45.
Reike BA, Naidoo S, Ruck CE, Slogrove AL, de Beer C, la Grange H, Adams RC, Ho K, Smolen K, Speert DP, Cotton MF, Preiser W, Esser M, Kollmann TR: Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first two years of life. Clin Vaccine Immunol. 2013, 20: 33-38. 10.1128/CVI.00557-12.CrossRef
46.
Bunders M, Pembrey L, Kuijpers T, Newell ML: Evidence of impact of maternal HIV infection on immunoglobulin levels in HIV-exposed uninfected children. AIDS Res Hum Retroviruses. 2010, 26: 967-975. 10.1089/aid.2009.0241.CrossRefPubMed
47.
Sanz-Ramos M, Manno D, Kapambwe M, Ndumba I, Musonda KG, Bates M, Chibumbya J, Siame J, Monze M, Filteau S, Gompels UA: Reduced Poliovirus vaccine neutralizing antibody titres in infants with maternal HIV exposure. Vaccine. 2013, 31: 2042-2049. 10.1016/j.vaccine.2013.02.044.CrossRefPubMed
48.
Abramczuk BM, Mazzola TN, Moreno YM, Zorzeto TQ, Quintilio W, Wolf PS, Blotta MH, Morcillo AM, da Silva MT, Dos Santos Vilela MM: Impaired Humoral response to vaccines among HIV-exposed uninfected infants. Clin Vaccine Immunol. 2011, 18: 1406-1409. 10.1128/CVI.05065-11.CrossRefPubMedPubMedCentral
49.
Cutland CL, Schrag SJ, Zell ER, Kuwanda L, Buchmann E, Velaphi SC, Groome MJ, Adrian PV, Madhi SA, PoPS trial team: Maternal HIV infectionx and vertical transmission of pathogenic bacteria. Pediatrics. 2012, 130: e581-e590. 10.1542/peds.2011-1548.CrossRefPubMed
50.
Wiener JB, Kayira D, Chasela C, King CC, Ellington SR, Hosseinipour M, Jamieson DJ, Van der Horst C, Kourtis AP, BAN Study Team: Morbidity and Mortality Among HIV-1-Exposed Uninfected Infants Enrolled in the Breastfeeding, Antiretrovirals and Nutrition (BAN) Trial in Malawi. 2012, Washington D.C: XIX International AIDS Conference, Abstract no WEPE178
Metadata
Title
Impact of maternal HIV-1 viremia on lymphocyte subsets among HIV-exposed uninfected infants: protective mechanism or immunodeficiency
Authors
Fatima Kakkar
Valerie Lamarre
Thierry Ducruet
Marc Boucher
Silvie Valois
Hugo Soudeyns
Normand Lapointe
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-236

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