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RÉSUMÉ
Introduction. L’objectif de cette étude était de mettre rechercher la présence d’un déficit en cellules T chez le nourrisson exposé non infectés (ENI), l’hypothèse étant que le déficit serait plus marqué lorsque la charge virale maternelle est élevée. Matériels et méthodes. Il s’agit d’une étude transversale analytique menée du 1er décembre 2015 au 08 juin 2016. En phase rétrospective, les données ont été collectées à base d’un questionnaire préétabli. En phase prospective les prélèvements sanguins ont été effectués et les profils immunologiques ont été établis. Les facteurs de transmission du VIH de la mère à l'enfant ont été évalués par régression logistique multi variée. Le test de Hosmer et Lemeshow ont été utilisés pour vérifier l'ajustement du modèle. Résultats. 153 patients répartis en trois groupes dont 60 enfants exposés non infectés, 60 enfants non exposés (NE) et 33 enfants exposés infectés (EI) ont été enrôlés. Les profils immunologiques des enfants NE et ENI ont montré une différence statistiquement significative (P=0,007) pour les taux de CD4. Les profils immunologiques des enfants de la tranche d’âge de 12 à 59 mois d’une part EI et ENI ont montré des différences significatives pour les CD45 (P=0,003), les CD4 (P=0,01), les CD8 (P=0,02). Conclusion. Chez les nourrissons non infectés nés de mères séropositives, plusieurs anomalies immunologiques peuvent être détectées. Ces anomalies pourraient être une conséquence de l’exposition au VIH in utero et en début de vie, et/ou à l’exposition aux médicaments antirétroviraux, ou à la transmission précoce des infections virales persistantes telles que CMV.
ABSTRACT
Introduction. The objective of the study was to assess the presence of age-dependent T-cell deficiency in the exposed uninfected infant (EUI) and to test the hypothesis that it should be more marked when the maternal viral load is high. Materials and methods. This was a cross-sectional analytical study carried out from 1st December 2015 to 08 June 2016. In retrospect, the data were collected on the basis of a pre-established questionnaire. In the prospective phase the blood samples were taken and the immunological profiles were established. The factors relating to mother-to-child transmission of HIV were assessed by multi-varied logistic regression. The Hosmer and Lemeshow test were used to check the fit of the model. Results. A total of 153 patients were enrolled in three groups, including 60 ENI children, 60 unexposed children (NE) and 33 exposed infected children (EI). Immunological profiles of NE and ENI children showed a statistically significant difference (P = 0.007) for CD4 levels. Immunological profiles of children in the 12 to 59 month age group on the one hand EI and ENI showed significant differences for CD45 (P = 0.003), CD4 (P = 0.01), CD8 (P = 0.02). Conclusion. Several immunological abnormalities can be detected in the blood of uninfected infants born to seropositive mothers; These abnormalities could be a consequence of exposure to HIV in utero and early life, and / or exposure to antiretroviral drugs, as well as the early transmission of persistent viral infections such as CMV.
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References
- Horne C, Semenenko I, Pilipenko T, Malyuta R. Ukraine European Collaborative Study Group: Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study. BMC Infect Dis, 2009; 9:40.
- Albrecht, S., K. Semrau, P. Kasonde, M. Sinkala, C. Kankasa, C. Vwalika, G. M. Aldrovandi, D. M. Thea, and L. Kuhn. "Predictors of non-adherence to single-dose nevirapine therapy for the prevention of mother-to-child HIV transmission." J Acquir Immune Defic Syndr, 2006; 41(1):114-8.
- Boateng D, Kwapong GD, Agyei-Baffour P. Knowledge, perception about antiretroviral therapy (ART) and prevention of mother-to-child-transmission (PMTCT) and adherence to ART among HIV positive women in the Ashanti Region, Ghana: a cross-sectional study. BMC Women’s Health. 2013;13:2.
- Anoje C, Aiyenigba B, Suzuki C, Badru T, Akpoigbe K, Odo M, et al. Reducing mother-to-child transmission of HIV: findings from an early infant diagnosis program in south-south region of Nigeria. BMC Public Health, 2012; 12:184.
- Feola DJ, Garvy BA: Combination exposure to zidovudine plus sulfamethoxazole-trimethoprim diminishes B lymphocyte immune responses to Pneumocystis murina infection in healthy mice. Clin Vaccine Immunol. 2006, 13: 193-201.
- Fiore S, Newell ML, Trabattoni D, Thorne C, Gray L, Savasi V, Tibaldi C, Ferrazzi E, Clerici M: Antiretroviral therapy-associated modulation of Th1 and Th2 immune responses in HIV-infected pregnant women. J Reprod Immunol. 2006, 70: 143-150.
- Kidzeru EB, Hesseling AC, Passmore JA, Myer L, Gamieldien H, Tchakoute CT, et al. In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants. Aids, 2014;28(10):1421–30.
- Olivero OA, Torres LR, Gorjifard S, et al. Perinatal exposure of Patas monkeys to antiretroviral nucleoside reverse-transcriptase inhibitors induces genotoxicity persistent for up to 3 years of age. J Infect Dis. 2013;208:244–248.
- Slyker JA, Rowland-Jones SL, Dong T, et al. Acute cytomegalovirus infection is associated with increased frequencies of activated and apoptosis-vulnerable T cells in HIV-1-infected infants. J Virol. 2012;86:11373–11379.
- Sanz-Ramos M, Manno D, Kapambwe M, et al. Reduced poliovirus vaccine neutralising-antibody titres in infants with maternal HIV-exposure. Vaccine. 2013;31:2042–2049.
- Evans C, Humphrey JH, Ntozini R, Prendergast AJ. HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era. Front Immunol. 2016; 7: 190
- De Deus N, Moraleda C, Serna-Bolea C, Renom M, Menendez C, Naniche D.
- Impact of high maternal HIV viral load on delivery to T lymphocyte populations in HIV exposed non-infected infants in Mozambique. BMC Infectious Diseases, 2015 ; 15, : 37.
- Kakkar F, Lamarre V, Ducruet T, Boucher M, Valois S, Soudeyns H, Lapointe N. Impact of mother HIV-1 viremia on subsets of lymphocytes in uninfected infants exposed to HIV: protection mechanism Or immunodeficiency. BMC Infectious Diseases, 2014;14:236.
- Desai A, Smith LE, Mbuya MN, Chigumira A, Fundira D, Tavengwa NV, et al. The SHINE trial infant feeding intervention: pilot study of effects on maternal learning and infant diet quality in rural Zimbabwe. Clin Infect Dis, 2015 ;61(Suppl 7):S710–5.10.
- Morden E, Technau KG, Giddy J, Maxwell N, O Keizer, Davies MA. The growth of uninfected infants exposed to HIV in the first 6 months of life in South Africa: The IeDEA-SA Collaboration. Nixon DF, ed. PLoS ONE. 2016; 11 (4): e0151762. Doi: 10.1371 / journal.pone.0151762.
- De Deus N, Moraleda C, Serna-Bolea C, Renom M, Menendez C, Naniche D.Impact of high HIV viral load from mother to childbirth on T lymphocyte populations in HIV exposed uninfected infants in Mozambique. BMC Infectious Diseases. 2015; 15: 37.
- Kafulafula G , Hoover DR , Taha TE , Thigpen M , Li Q , Fowler MG et al. Frequency of gastroenteritis and gastroenteritis-associated mortality with early weaning in HIV-1-uninfected children born to HIV-infected women in Malawi. J Acquir Immune Defic Syndr, 2010;53(1):6–13.
- Kidzeru EB, Hesseling AC, JA Passmore, Myer L, Gamieldien H, Tchakoute CT, et al. In utero exposure to maternal HIV infection alters the immune response of T cells to vaccination in HIV - negative infants. AIDS. 2014; 28 (10): 1421-30.
- Moraleda C, deus N, Serna-Bolea C, Renom M, L Quinto, Macete E, et al. 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; 65 (2): 182-9.
- Hygino J, Lima PG, Filho RGS, Silva AAL, Saramago CSM, Andrade RM, Andrade DM, Andrade AF, Brindeiro R, Tanuri A, Bento CA. Altered immunological reactivity of HIV-1 exposed to uninfected infants. Clin Immunol. 2008; 127: 340-347.
- Slogrove AL, Goetghebuer T, Cotton MF, Singer J, Judge Bettinger. Reason for Infectious Diseases Morbidity in HIV-infected infants and uninfected children. Frontiers in Immunology. 2016; 7: 164.
- Longwe H, Phiri KS, Mbeye NM, Gondwe T, Jambo KC, Mandala WL. Proportions of CD4 +, CD8 + and B - cell subsets are not affected by exposure to HIV or cotrimoxazole prophylaxis in Malawian children who are HIV - negative but exposed. BMC Immunology. 2015; 16:50.
- Clerici M, Saresella M, Colombo F, Fossati S, Sala N, Bricalli D, et al. T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV. Blood. 2000;96(12):3866–71
- Ono E, Santos AM N d, de Menezes Succi RC, Machado DM, de Angelis DS, Salomao R, et al. 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 Res. 2008;41(8):700–8.
- Nielsen SD, Jeppesen DL, Kolte L, Clark DR, Sorensen TU, Dreves AM, et al. Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts. Blood. 2001;98(2):398–404.
- Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, Scott N, et al. Does the severity of HIV disease in HIV-infected mothers affect mortality and morbidity in their uninfected infants? Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America, 2005;41 (11): 1654-1661.
- Taron-Brocard C, Le Chenadec J , Faye A , Dollfus C , Goetghebuer T , Gajdos V et al. Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014;59(9):1332–1345.
- Afran L, Garcia Chevalier M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL. Exposés au VIH des enfants non infectés: une population croissante avec un système immunitaire vulnérable? Clinical and Experimental Immunology. 2014; 176 (1): 11-22.
- Zinkernagel RM. Les anticorps maternels, les infections infantiles et les maladies auto - immunes. N Engl J Med. 2001; 345 : 1331-1335.
- Bunders M, Pembrey L, Kuijpers T, Newell ML. Preuve de l’impact de l’infection maternelle du VIH sur les taux d'immunoglobulines chez les enfants non infectés exposés au VIH. AIDS Res Hum Retroviruses. 2010; 26 : 967-975.
- Cumberland P, Shulman CE, Maple PA, et al. Maternal HIV infection and placental malaria reduced transfer of transplacental antibodies and tetanus antibody levels in newborns in Kenya. J Infect Dis. 2007; 196: 550-557.
- Scott S, Moss WJ, Cousens S, et al. The influence of HIV-1 exposure and infection on passively acquired antibody levels to measles virus in Zambian infants. Clin Infect Dis. 2007; 45: 1417-1424.
- Kuhn L, Kim HY, L Hsiao et al. Oligosaccharide Breast milk composition Influences Survival of uninfected Children born to HIV-positive mothers in Lusaka, Zambia. The Journal of Nutrition. 2015; 145 (1): 66-72.
- Slogrove AL, Goetghebuer T, Cotton MF, Singer J, JA Bettinger. Pattern of Infectious Morbidity in HIV - Exposed uninfected Infants and children. Immunol, 2016; 7: 164-9.
- Madhi S, Izu A, Violari A, Cotton MF, Panchia R, Dobbels E, et al. Immunogenicity following the first and second doses of 7-valent pneumococcal conjugate vaccine in HIV-infected and uninfected infants. Vaccine, 2013 ;31(5):777–83.
- Simani O, Izu A, Violari A, Cotton MF, van Niekerk N, Adrian PV, et al. Effect of HIV-1 exposure and antiretroviral treatment strategies in HIV-infected children on immunogenicity of vaccines during infancy. AIDS, 2014 ;28(4):531–41.
References
Horne C, Semenenko I, Pilipenko T, Malyuta R. Ukraine European Collaborative Study Group: Progress in prevention of mother-to-child transmission of HIV infection in Ukraine: results from a birth cohort study. BMC Infect Dis, 2009; 9:40.
Albrecht, S., K. Semrau, P. Kasonde, M. Sinkala, C. Kankasa, C. Vwalika, G. M. Aldrovandi, D. M. Thea, and L. Kuhn. "Predictors of non-adherence to single-dose nevirapine therapy for the prevention of mother-to-child HIV transmission." J Acquir Immune Defic Syndr, 2006; 41(1):114-8.
Boateng D, Kwapong GD, Agyei-Baffour P. Knowledge, perception about antiretroviral therapy (ART) and prevention of mother-to-child-transmission (PMTCT) and adherence to ART among HIV positive women in the Ashanti Region, Ghana: a cross-sectional study. BMC Women’s Health. 2013;13:2.
Anoje C, Aiyenigba B, Suzuki C, Badru T, Akpoigbe K, Odo M, et al. Reducing mother-to-child transmission of HIV: findings from an early infant diagnosis program in south-south region of Nigeria. BMC Public Health, 2012; 12:184.
Feola DJ, Garvy BA: Combination exposure to zidovudine plus sulfamethoxazole-trimethoprim diminishes B lymphocyte immune responses to Pneumocystis murina infection in healthy mice. Clin Vaccine Immunol. 2006, 13: 193-201.
Fiore S, Newell ML, Trabattoni D, Thorne C, Gray L, Savasi V, Tibaldi C, Ferrazzi E, Clerici M: Antiretroviral therapy-associated modulation of Th1 and Th2 immune responses in HIV-infected pregnant women. J Reprod Immunol. 2006, 70: 143-150.
Kidzeru EB, Hesseling AC, Passmore JA, Myer L, Gamieldien H, Tchakoute CT, et al. In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants. Aids, 2014;28(10):1421–30.
Olivero OA, Torres LR, Gorjifard S, et al. Perinatal exposure of Patas monkeys to antiretroviral nucleoside reverse-transcriptase inhibitors induces genotoxicity persistent for up to 3 years of age. J Infect Dis. 2013;208:244–248.
Slyker JA, Rowland-Jones SL, Dong T, et al. Acute cytomegalovirus infection is associated with increased frequencies of activated and apoptosis-vulnerable T cells in HIV-1-infected infants. J Virol. 2012;86:11373–11379.
Sanz-Ramos M, Manno D, Kapambwe M, et al. Reduced poliovirus vaccine neutralising-antibody titres in infants with maternal HIV-exposure. Vaccine. 2013;31:2042–2049.
Evans C, Humphrey JH, Ntozini R, Prendergast AJ. HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era. Front Immunol. 2016; 7: 190
De Deus N, Moraleda C, Serna-Bolea C, Renom M, Menendez C, Naniche D.
Impact of high maternal HIV viral load on delivery to T lymphocyte populations in HIV exposed non-infected infants in Mozambique. BMC Infectious Diseases, 2015 ; 15, : 37.
Kakkar F, Lamarre V, Ducruet T, Boucher M, Valois S, Soudeyns H, Lapointe N. Impact of mother HIV-1 viremia on subsets of lymphocytes in uninfected infants exposed to HIV: protection mechanism Or immunodeficiency. BMC Infectious Diseases, 2014;14:236.
Desai A, Smith LE, Mbuya MN, Chigumira A, Fundira D, Tavengwa NV, et al. The SHINE trial infant feeding intervention: pilot study of effects on maternal learning and infant diet quality in rural Zimbabwe. Clin Infect Dis, 2015 ;61(Suppl 7):S710–5.10.
Morden E, Technau KG, Giddy J, Maxwell N, O Keizer, Davies MA. The growth of uninfected infants exposed to HIV in the first 6 months of life in South Africa: The IeDEA-SA Collaboration. Nixon DF, ed. PLoS ONE. 2016; 11 (4): e0151762. Doi: 10.1371 / journal.pone.0151762.
De Deus N, Moraleda C, Serna-Bolea C, Renom M, Menendez C, Naniche D.Impact of high HIV viral load from mother to childbirth on T lymphocyte populations in HIV exposed uninfected infants in Mozambique. BMC Infectious Diseases. 2015; 15: 37.
Kafulafula G , Hoover DR , Taha TE , Thigpen M , Li Q , Fowler MG et al. Frequency of gastroenteritis and gastroenteritis-associated mortality with early weaning in HIV-1-uninfected children born to HIV-infected women in Malawi. J Acquir Immune Defic Syndr, 2010;53(1):6–13.
Kidzeru EB, Hesseling AC, JA Passmore, Myer L, Gamieldien H, Tchakoute CT, et al. In utero exposure to maternal HIV infection alters the immune response of T cells to vaccination in HIV - negative infants. AIDS. 2014; 28 (10): 1421-30.
Moraleda C, deus N, Serna-Bolea C, Renom M, L Quinto, Macete E, et al. 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; 65 (2): 182-9.
Hygino J, Lima PG, Filho RGS, Silva AAL, Saramago CSM, Andrade RM, Andrade DM, Andrade AF, Brindeiro R, Tanuri A, Bento CA. Altered immunological reactivity of HIV-1 exposed to uninfected infants. Clin Immunol. 2008; 127: 340-347.
Slogrove AL, Goetghebuer T, Cotton MF, Singer J, Judge Bettinger. Reason for Infectious Diseases Morbidity in HIV-infected infants and uninfected children. Frontiers in Immunology. 2016; 7: 164.
Longwe H, Phiri KS, Mbeye NM, Gondwe T, Jambo KC, Mandala WL. Proportions of CD4 +, CD8 + and B - cell subsets are not affected by exposure to HIV or cotrimoxazole prophylaxis in Malawian children who are HIV - negative but exposed. BMC Immunology. 2015; 16:50.
Clerici M, Saresella M, Colombo F, Fossati S, Sala N, Bricalli D, et al. T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV. Blood. 2000;96(12):3866–71
Ono E, Santos AM N d, de Menezes Succi RC, Machado DM, de Angelis DS, Salomao R, et al. 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 Res. 2008;41(8):700–8.
Nielsen SD, Jeppesen DL, Kolte L, Clark DR, Sorensen TU, Dreves AM, et al. Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts. Blood. 2001;98(2):398–404.
Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, Scott N, et al. Does the severity of HIV disease in HIV-infected mothers affect mortality and morbidity in their uninfected infants? Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America, 2005;41 (11): 1654-1661.
Taron-Brocard C, Le Chenadec J , Faye A , Dollfus C , Goetghebuer T , Gajdos V et al. Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014;59(9):1332–1345.
Afran L, Garcia Chevalier M, Nduati E, Urban BC, Heyderman RS, Rowland-Jones SL. Exposés au VIH des enfants non infectés: une population croissante avec un système immunitaire vulnérable? Clinical and Experimental Immunology. 2014; 176 (1): 11-22.
Zinkernagel RM. Les anticorps maternels, les infections infantiles et les maladies auto - immunes. N Engl J Med. 2001; 345 : 1331-1335.
Bunders M, Pembrey L, Kuijpers T, Newell ML. Preuve de l’impact de l’infection maternelle du VIH sur les taux d'immunoglobulines chez les enfants non infectés exposés au VIH. AIDS Res Hum Retroviruses. 2010; 26 : 967-975.
Cumberland P, Shulman CE, Maple PA, et al. Maternal HIV infection and placental malaria reduced transfer of transplacental antibodies and tetanus antibody levels in newborns in Kenya. J Infect Dis. 2007; 196: 550-557.
Scott S, Moss WJ, Cousens S, et al. The influence of HIV-1 exposure and infection on passively acquired antibody levels to measles virus in Zambian infants. Clin Infect Dis. 2007; 45: 1417-1424.
Kuhn L, Kim HY, L Hsiao et al. Oligosaccharide Breast milk composition Influences Survival of uninfected Children born to HIV-positive mothers in Lusaka, Zambia. The Journal of Nutrition. 2015; 145 (1): 66-72.
Slogrove AL, Goetghebuer T, Cotton MF, Singer J, JA Bettinger. Pattern of Infectious Morbidity in HIV - Exposed uninfected Infants and children. Immunol, 2016; 7: 164-9.
Madhi S, Izu A, Violari A, Cotton MF, Panchia R, Dobbels E, et al. Immunogenicity following the first and second doses of 7-valent pneumococcal conjugate vaccine in HIV-infected and uninfected infants. Vaccine, 2013 ;31(5):777–83.
Simani O, Izu A, Violari A, Cotton MF, van Niekerk N, Adrian PV, et al. Effect of HIV-1 exposure and antiretroviral treatment strategies in HIV-infected children on immunogenicity of vaccines during infancy. AIDS, 2014 ;28(4):531–41.