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1. The landscape of selection in 551 Esophageal Adenocarcinomas defines genomic biomarkers for the clinic

Author

Frankell, AM, Jammula, S, Li, X, Contino, G, Killcoyne, S, Abbas, S, Perner, J, Bower, L, Devonshire, G, Cocks, E, Grehan, N, Mok, J, O'Donovan, M, MacRae, S, Eldridge, MD, Tavare, S, Fitzgerald, RC, Noorani, A, Edwards, PAW, Grehanl, N, Nutzinger, B, Hughes, CI, Fidziukiewicz, E, Northrop, A, De la Rue, R, Katz-Summercorn, A, Loureda, D, Miremadi, A, Malhotra, S, Tripathi, M, Lynch, AG, Eldridge, M, Secrier, M, Davies, J, Crichton, C, Carro, N, Safranek, P, Hindmarsh, A, Sujendran, V, Hayes, SJ, Ang, Y, Sharrocks, A, Preston, SR, Oakes, S, Bagwan, I, Save, V, Skipworth, RJE, Hupp, TR, ONeill, JR, Tucker, O, Beggs, A, Taniere, P, Puig, S, Underwood, T, Walker, RC, Grace, BL, Barr, H, Shepherd, N, Old, O, Lagergren, J, Gossage, J, Davies, A, Chang, F, Zylstra, J, Mahadeva, U, Goh, V, Ciccarelli, FD, Sanders, G, Berrisford, R, Harden, C, Lewis, M, Cheong, E, Kumar, B, Parsons, SL, Soomro, I, Kaye, P, Saunders, J, Lovat, L, Haidry, R, Igali, L, Scott, M, Sothi, S, Suortamo, S, Lishman, S, Hanna, GB, Moorthy, K, Peters, CJ, Grabowska, A, Turkington, R, McManus, D, Coleman, H, Khoo, D, and Fickling, W

Subjects
Male, Oncology, Mutation rate, Esophageal Neoplasms, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Exome, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Mutation, GATA4, Incidence (epidemiology), Genomics, CANCER, Cell Cycle Gene, Gene Expression Regulation, Neoplastic, Cohort, Adenocarcinoma, Female, Life Sciences & Biomedicine, Silent mutation, medicine.medical_specialty, CARCINOMA, DNA Copy Number Variations, Biology, Article, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, Genetics, Carcinoma, medicine, Humans, Gene, SIGNATURES, 030304 developmental biology, Science & Technology, Gene Expression Profiling, PATHWAYS, Cancer, SOMATIC MUTATIONS, 06 Biological Sciences, medicine.disease, COMPREHENSIVE MOLECULAR CHARACTERIZATION, PD-1 BLOCKADE, Gene expression profiling, PATTERNS, DRIVER, Cancer research, Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, 030217 neurology & neurosurgery, ACQUIRED-RESISTANCE, Developmental Biology
Abstract

Esophageal Adenocarcinoma (EAC) is a poor prognosis cancer type with rapidly rising incidence. Our understanding of genetic events which drive EAC development is limited and there are few molecular biomarkers for prognostication or therapeutics. We have accumulated a cohort of 551 genomically characterised EACs (73% WGS and 27% WES) with clinical annotation and matched RNA-seq. Using a variety of driver gene detection methods, we discover 77 EAC driver genes (73% novel) and 21 non-coding driver elements (95% novel), and describe mutation and CNV types with specific functional impact. We identify a mean of 4.4 driver events per case derived from both copy number events and mutations. We compare driver mutation rates to the exome-wide mutational excess calculated using Non-synonymous vs Synonymous mutation rates (dNdS). We observe mutual exclusivity or co-occurrence of events within and between a number of EAC pathways (GATA factors, Core Cell cycle genes, TP53 regulators and the SWI/SNF complex) suggestive of important functional relationships. These driver variants correlate with tumour differentiation, sex and prognosis. Poor prognostic indicators (SMAD4, GATA4) are verified in independent cohorts with significant predictive value. Over 50% of EACs contain sensitising events for CDK4/6 inhibitors which are highly correlated with clinically relevant sensitivity in a panel EAC cell lines and organoids.

Published
2018

2. Duration of ruptured membranes and vertical transmission of HIV-1: a meta-analysis from 15 prospective cohort studies

Author

Bulterys, M. B., Fowler, M. G., Hanson, I. C., Lemay, M., Mayaux, M. J., Mofenson, L., Newell, M. -L., Peavy, H., Peckham, C., Read, J. S., Rother, C., Simpson, B. J., Van Dyke, R. B., Harris, D. R., Peavy, H. H., Easley, K., Khammy, A., Nugent, R. P., Mitchell, R., Owen, W., Van Dyke, R., Widmayer, S., Bardeguez, A., Hanson, C., Wiznia, A., Luzuriaga, K., Viscarello, R., Ho, D., Koup, R., Chen, I., Krogstad, P., Mullins, J., Wolinsky, S., Korber, B., Walker, B., Ammann, A., Clapp, S., Mcdonald, D., Lapointe, N., Boucher, M., Fauvel, M., Hankins, C., Samson, J., Newell, M. L., Peckham, C. S., Thorne, C. N., Giaquinto, C., Ruga, E., De Rossi, A., Truscia, D., Grosch-Worner, I., Schafer, A., Mok, J., Johnstone, F., Jiminez, J., de Alba, C., Garcia Rodriguez, M. C., Bates, I., de Josee, I., Hawkins, F., Martinez Zapico, R., Pena, J. M., Gonzalez Garcia, J., Arribas Lopez, J. R., Asensi-Botet, F., Otero, M. C., Peerez-Tamarit, D., Moya, A., Galbis, M. J., Scherpbier, H., Boer, K., Bohlin, A. B., Lindgren, S., Anzen, B., Belfrage, E., Lidin-Jansson, G., Levy, J., Barlow, P., Hainaut, M., Peltier, A., Ferrazin, A., De Maria, A., Gotta, C., Mur, A., Vinolas, M., Paya, A., Loepez-Vilchez, M. A., Coll, O., Fortuny, C., Boguna, J., Casellas Caro, M., Canet, Y., Pardi, G., Ravizza, M., Semprini, E., Castagna, C., Fiore, S., Guerra, B., Lanari, M., Bianchi, S., Bovicelli, L., Prati, E., Zanelli, S., Duse, M., Soresina, A., Scaravelli, G., Stegagno, M., De Santis, M., Muggiasca, M. L., Vigano, A., Spinillo, A., Ravagni Probizer, F., Bucceri, A., Rancilio, L., Taylor, G. P., Lyall, H., Penn, Z., Blott, M., Valerius, N. H., Martinelli, P., Buffolano, W., Tibaldi, C., Ziarati, N., Semprini, A., Della Torre, M., Parazzini, F., Dallacasa, P., Bianchi, U., Pachi, A., Mancuso, S., Villa, P., Conti, M., Principi, N., Muggiasca, M., Marchisio, P., Zara, C., Ravagni, F., Vignali, M., Rossi, G., Selvaggi, L., Greco, P., Vimercati, A., Massi, G., Innocenti, T., Fiscella, A., Sansone, M., Benedetto, C., Tadrist, B., Thevenieau, D., Gondry, J., Paulard, B., Alisy, C., Brault, D., Tordjeman, N., Mamou, J., Rozan, M., Colombani, D., Pincemaille, O., Salvetti, A., Chabanier, C., Hernandorena, X., Leroy, J., Schaal, J., Balde, P., Faucher, P., Lachassinne, E., Benoit, S., Douard, D., Hocke, C., Barjot, P., Brouard, J., Delattre, P., Stien, L., Audibert, F., Labrune, P., Vial, M., Mazy, F., Sitbon, D., Crenn-Hebert, C., Floch-Tudal, C., Akakpo, R., Daveau, C., Leblanc, A., Cesbron, P., Duval-Arnould, M., Huraux-Rendu, C., Lemerle, S., Touboul, C., Guerin, M., Maingueneau, C., Reynaud, I., Rousseau, T., Ercoil, V., Lanza, M., Denavit, M., Garnier, J., Lahsinat, K., Pia, P., Allouche, C., Nardou, M., Grall, F., May, A., Dallot, M., Lhuillier, P., Cecile, W., Mezin, R., Bech, A., Lobut, J., Algava, G., Chalvon Dermesay, A., Busuttil, R., Jacquemot, M., Bader-Meunier, B., Fridman, S., Codaccioni, X., Maxingue, F., Thomas, D., Alain, J., De Lumley, L., Tabaste, J., Bailly Salin, P., Seaume, H., Guichard, A., Kebaill, K., Roussouly, C., Botto, C., De Lanete, A., Wipff, P., Cravello, L., De Boisse, P., Leclaire, M., Michel, G., Crumiere, C., Lefevre, V., Le Lorier, B., Pauly, I., Robichez, B., Seguy, D., Delhinger, M., Rideau, F., Talon, P., Benos, P., Huret, C., Nicolas, J., Heller-Roussin, B., Saint-Leger, S., Delaporte, M., Hubert, C., De Sarcus, B., Karoubi, P., Mechinaud, F., Bertcrottiere, D., Bongain, A., Monpoux, F., De Gennes, C., Devianne, F., Nisand, I., Rousset, M., Mouchnino, G., Muray, J., Munzer, M., Quereux, C., Brossard, V., Clavier, B., Allemon, M., Rotten, D., Stephan, J., Varlet, M., Guyot, B., Narcy, P., Bardinet, F., De Caunes, F., Jeny, R., Robin, M., Raison Boulley, A., Savey, L., Berrebi, A., Tricoire, J., Borderon, J., Fignon, A., Guillot, F., Maria, B., Broyard, A., Chitrit, Y., Firtion, G., Mandelbrot, L., Lafay Pillet, M., Parat, S., Boissinot, C., Garec, N., Levine, M., Ottenwalter, A., Schaller, F., Vilmer, E., Courpotin, C., Brunner, C., Ciraru-Vigneron, N., Hatem-Gantzer, G., Fritel, X., Wallet, A., Bouille, J., Milliez, J., Bensaid Mrejen, D., Dermer, E., Noseda, G., Bardou, D., Cressaty, J., Francoual, C., Carlus Moncomble, C., Cohen, H., Blanche, S., Bastion, H., Benifla, J., Benkhatar, F., Berkane, N., Hervee, F., Ronzier, M., Mayaux, Mj., de Martino, M., Tovo, P. -A., Galli, L., Gabiano, C., Ferraris, G., Garetto, S., Palomba, E., Riva, C., Vierucci, A., de Luca, M., Farina, S., Fundaro, C., Genovese, O., Mereu, G., Forni, G. L., Casadei, A., Zuccotti, G. V., Riva, E., Cellini, M., Baraldi, C., Consolini, R., Palla, G., Ruggeri, M., Ciccimarra, F., Guarino, A., Osimani, P., Benaglia, G., Romano, A., De Mattia, D., Caselli, D., Boni, S., Dell'Erba, G., Bassanetti, F., Sticca, M., Timpano, C., Magnani, C., Salvatore, C., Lipreri, R., Tornaghi, R., Pinzani, R., Cecchi, M. T., Bezzi, T., Battisti, L., Bresciani, E., Castelli Gattinara, G., Nasi, C., Pellegatta, A., Mazza, A., Baldi, F., Altobelli, R., Deiana, M., Colnaghi, C., Tarallo, L., Tondo, U., Anastasio, E., Chiriaco, P. G., Ruggeri, C., Scott, G., Hutto, C., O'Sullivan, M., Malmsberry, A., Willoughby, A., Burns, D., Goedert, J., Landesman, S., Minkoff, H., Mendez, H., Holman, S., Rubinstein, A., Durako, S., Muenz, L., Goodwin, S., Bryson, Y., Dillon, M., Nielsen, K., Boyer, P., Liao, D., Keller, M., Deveikis, A., Nesheim, S., Lindsay, M., Lee, F., Nahmias, A., Sawyer, M., Vink, P., Farley, J., Alger, L., Abrams, E., Bamji, M., Lambert, G., Schoenbaum, E., Thomas, P., Weedon, J., Palumbo, P., Denny, T., Oleske, J., Bulterys, M., Simonds, R., Ethier-Ives, J., Rogers, M., Schluchter, M., Kutner, M., Kaplan, S., Kattan, M., Lipshultz, S., Mellins, R., Shearer, W., Sopko, G., Sloand, E., Wu, M., Kind, C., Nadal, D., Rudin, C., Siegrist, C. -A., Wyler, C. -A., Cheseaux, J. -J., Aebi, C., Gnehm, H., Schubiger, G., Klingler, J., Hunziker, U., Kuchler, H., Gianinazzi, M., Buhlmann, U., Biedermann, K., Lauper, U., Irion, O., Brunelli, A., Spoletini, G., Schreyer, A., Hosli, I., Saurenmann, E., Drack, G., Isenschmid, M., Poorbeik, M., Schupbach, J., Perrin, L., Erb, P., Joller, H., Kovacs, A., Stek, A., Chan, L., Khoury, M., Diaz, C., Pacheco-Acosta, E., Tuomala, R., Cooper, E., Mesthene, D., Pitt, J., Higgins, A., Moroso, G., Rich, K., Turpin, D., Cooper, N., Davenny, K., Thompson, B., Andiman, W., Simpson, J., THE INTERNATIONAL PERINATAL HIV, Group, Martinelli, Pasquale, Bulterys M.B., Fowler M.G., Hanson I.C., Lemay M., Mayaux M.J., Mofenson L., Newell M.-L., Peavy H., Peckham C., Read J.S., Rother C., Simpson B.J., Van Dyke R.B., Harris D.R., Peavy H.H., Easley K., Khammy A., Nugent R.P., Mitchell R., Owen W., Van Dyke R., Widmayer S., Bardeguez A., Hanson C., Wiznia A., Luzuriaga K., Viscarello R., Ho D., Koup R., Chen I., Krogstad P., Mullins J., Wolinsky S., Korber B., Walker B., Ammann A., Clapp S., McDonald D., Lapointe N., Boucher M., Fauvel M., Hankins C., Samson J., Newell M.L., Peckham C.S., Thorne C.N., Giaquinto C., Ruga E., De Rossi A., Truscia D., Grosch-Worner I., Schafer A., Mok J., Johnstone F., Jiminez J., de Alba C., Garcia Rodriguez M.C., Bates I., de Josee I., Hawkins F., Martinez Zapico R., Pena J.M., Gonzalez Garcia J., Arribas Lopez J.R., Asensi-Botet F., Otero M.C., Peerez-Tamarit D., Moya A., Galbis M.J., Scherpbier H., Boer K., Bohlin A.B., Lindgren S., Anzen B., Belfrage E., Lidin-Jansson G., Levy J., Barlow P., Hainaut M., Peltier A., Ferrazin A., De Maria A., Gotta C., Mur A., Vinolas M., Paya A., Loepez-Vilchez M.A., Coll O., Fortuny C., Boguna J., Casellas Caro M., Canet Y., Pardi G., Ravizza M., Semprini E., Castagna C., Fiore S., Guerra B., Lanari M., Bianchi S., Bovicelli L., Prati E., Zanelli S., Duse M., Soresina A., Scaravelli G., Stegagno M., De Santis M., Muggiasca M.L., Vigano A., Spinillo A., Ravagni Probizer F., Bucceri A., Rancilio L., Taylor G.P., Lyall H., Penn Z., Blott M., Valerius N.H., Martinelli P., Buffolano W., Tibaldi C., Ziarati N., Semprini A., Della Torre M., Parazzini F., Dallacasa P., Bianchi U., Pachi A., Mancuso S., Villa P., Conti M., Principi N., Muggiasca M., Marchisio P., Zara C., Ravagni F., Vignali M., Rossi G., Selvaggi L., Greco P., Vimercati A., Massi G., Innocenti T., Fiscella A., Sansone M., Benedetto C., Tadrist B., Thevenieau D., Gondry J., Paulard B., Alisy C., Brault D., Tordjeman N., Mamou J., Rozan M., Colombani D., Pincemaille O., Salvetti A., Chabanier C., Hernandorena X., Leroy J., Schaal J., Balde P., Faucher P., Lachassinne E., Benoit S., Douard D., Hocke C., Barjot P., Brouard J., Delattre P., Stien L., Audibert F., Labrune P., Vial M., Mazy F., Sitbon D., Crenn-Hebert C., Floch-Tudal C., Akakpo R., Daveau C., Leblanc A., Cesbron P., Duval-Arnould M., Huraux-Rendu C., Lemerle S., Touboul C., Guerin M., Maingueneau C., Reynaud I., Rousseau T., Ercoil V., Lanza M., Denavit M., Garnier J., Lahsinat K., Pia P., Allouche C., Nardou M., Grall F., May A., Dallot M., Lhuillier P., Cecile W., Mezin R., Bech A., Lobut J., Algava G., Chalvon Dermesay A., Busuttil R., Jacquemot M., Bader-Meunier B., Fridman S., Codaccioni X., Maxingue F., Thomas D., Alain J., De Lumley L., Tabaste J., Bailly Salin P., Seaume H., Guichard A., Kebaill K., Roussouly C., Botto C., De Lanete A., Wipff P., Cravello L., De Boisse P., Leclaire M., Michel G., Crumiere C., Lefevre V., Le Lorier B., Pauly I., Robichez B., Seguy D., Delhinger M., Rideau F., Talon P., Benos P., Huret C., Nicolas J., Heller-Roussin B., Saint-Leger S., Delaporte M., Hubert C., De Sarcus B., Karoubi P., Mechinaud F., Bertcrottiere D., Bongain A., Monpoux F., De Gennes C., Devianne F., Nisand I., Rousset M., Mouchnino G., Muray J., Munzer M., Quereux C., Brossard V., Clavier B., Allemon M., Rotten D., Stephan J., Varlet M., Guyot B., Narcy P., Bardinet F., De Caunes F., Jeny R., Robin M., Raison Boulley A., Savey L., Berrebi A., Tricoire J., Borderon J., Fignon A., Guillot F., Maria B., Broyard A., Chitrit Y., Firtion G., Mandelbrot L., Lafay Pillet M., Parat S., Boissinot C., Garec N., Levine M., Ottenwalter A., Schaller F., Vilmer E., Courpotin C., Brunner C., Ciraru-Vigneron N., Hatem-Gantzer G., Fritel X., Wallet A., Bouille J., Milliez J., Bensaid Mrejen D., Dermer E., Noseda G., Bardou D., Cressaty J., Francoual C., Carlus Moncomble C., Cohen H., Blanche S., Bastion H., Benifla J., Benkhatar F., Berkane N., Hervee F., Ronzier M., Mayaux MJ., de Martino M., Tovo P.-A., Galli L., Gabiano C., Ferraris G., Garetto S., Palomba E., Riva C., Vierucci A., de Luca M., Farina S., Fundaro C., Genovese O., Mereu G., Forni G.L., Casadei A., Zuccotti G.V., Riva E., Cellini M., Baraldi C., Consolini R., Palla G., Ruggeri M., Ciccimarra F., Guarino A., Osimani P., Benaglia G., Romano A., De Mattia D., Caselli D., Boni S., Dell'Erba G., Bassanetti F., Sticca M., Timpano C., Magnani C., Salvatore C., Lipreri R., Tornaghi R., Pinzani R., Cecchi M.T., Bezzi T., Battisti L., Bresciani E., Castelli Gattinara G., Nasi C., Pellegatta A., Mazza A., Baldi F., Altobelli R., Deiana M., Colnaghi C., Tarallo L., Tondo U., Anastasio E., Chiriaco P.G., Ruggeri C., Scott G., Hutto C., O'Sullivan M., Malmsberry A., Willoughby A., Burns D., Goedert J., Landesman S., Minkoff H., Mendez H., Holman S., Rubinstein A., Durako S., Muenz L., Goodwin S., Bryson Y., Dillon M., Nielsen K., Boyer P., Liao D., Keller M., Deveikis A., Nesheim S., Lindsay M., Lee F., Nahmias A., Sawyer M., Vink P., Farley J., Alger L., Abrams E., Bamji M., Lambert G., Schoenbaum E., Thomas P., Weedon J., Palumbo P., Denny T., Oleske J., Bulterys M., Simonds R., Ethier-Ives J., Rogers M., Schluchter M., Kutner M., Kaplan S., Kattan M., Lipshultz S., Mellins R., Shearer W., Sopko G., Sloand E., Wu M., Kind C., Nadal D., Rudin C., Siegrist C.-A., Wyler C.-A., Cheseaux J.-J., Aebi C., Gnehm H., Schubiger G., Klingler J., Hunziker U., Kuchler H., Gianinazzi M., Buhlmann U., Biedermann K., Lauper U., Irion O., Brunelli A., Spoletini G., Schreyer A., Hosli I., Saurenmann E., Drack G., Isenschmid M., Poorbeik M., Schupbach J., Perrin L., Erb P., Joller H., Kovacs A., Stek A., Chan L., Khoury M., Diaz C., Pacheco-Acosta E., Tuomala R., Cooper E., Mesthene D., Pitt J., Higgins A., Moroso G., Rich K., Turpin D., Cooper N., Davenny K., Thompson B., Andiman W., and Simpson J.

Subjects
Time Factors, Epidemiology, Infectious Disease Transmission, Prevention of perinatal transmission, Extraembryonic Membranes, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Cohort Studies, Pregnancy, Risk Factors, INFECTION, Vertical, Immunology and Allergy, HIV Infection, MOTHER-TO-CHILD, Pregnancy Complications, Infectious, Prospective cohort study, prevention of perinatal transmission, vertical transmission, obstetrics/gynaecology, epidemiology, Obstetrics, Transmission (medicine), Infectious, HUMAN-IMMUNODEFICIENCY-VIRUS, MOTHER-TO-CHILD, ZIDOVUDINE PROPHYLAXIS, RISK-FACTORS, TYPE-1, PREGNANCY, INFECTION, TRIAL, PREVENTION, Breast Feeding, Infectious Diseases, Meta-analysis, HUMAN-IMMUNODEFICIENCY-VIRUS, Vertical transmission, Regression Analysis, TRIAL, Female, Delivery, Obstetrics gynaecology, Human, medicine.medical_specialty, Time Factor, Ruptured membranes, Immunology, Regression Analysi, NO, ZIDOVUDINE PROPHYLAXIS, Extraembryonic Membrane, medicine, Humans, TYPE-1, business.industry, Risk Factor, Infant, Newborn, Infant, Obstetric, Delivery, Obstetric, Newborn, PREVENTION, Infectious Disease Transmission, Vertical, Pregnancy Complications, Obstetrics/gynaecology, RISK-FACTORS, Cohort Studie, business
Abstract

Objective: To test the a priori hypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV. Design: The relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis. Methods: Eligible studies were prospective cohort studies including at least 100 mother-child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded. Results: The primary analysis included 4721 deliveries with duration of ruptured membranes ≤ 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P < 0.01). Conclusions: These results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membranes. © 2001 Lippincott Williams & Wilkins.

Published
2001

3. Combination antiretroviral therapy and duration of pregnancy

Author

Aebi, C, Battegay, M, Bernasconi, E, Biedermann, K, Cheseaux, JJ, Drack, G, Erb, P, Flepp, M, Francioli, P, Furrer, HJ, Gianinazzi, MP, Gyr, T, Hirschel, B, Hosli, I, Hug, I, Irion, O, Keller, K, Kind, C, Laubereau, B, Lauper, U, Lorenzi, P, Matter, L, Nadal, D, Perrin, L, Rickenbach, M, Rudin, C, Schreyer, A, Schupbach, J, Telenti, A, Vernazza, P, Wolf, K, Wunder, D, Wyler, CA, Giaquinto, C, Ruga, E, De Rossi, A, Grosch-Worner, I, Seel, K, Schafer, A, Mok, J, Johnstone, F, Jimenez, J, Garcia-Rodriguez, MC, Bates, I, de Jose, I, Hawkins, F, de Gevara, CL, Pena, JM, Garcia, JG, Lopez, JRA, Asensi-Botet, F, Otero, MC, Perez-Tamarit, D, Ridaura, S, Gregori, P, de la Torre, R, Scherpbier, H, Kreyenbroek, M, Boer, K, Bohlin, AB, Lindgren, S, Ehrnst, A, Belfrage, E, Lidman, K, Christensson, B, Levy, J, Hainaut, M, Peltier, A, Barlow, P, Wibaut, S, Lecroart, MC, Ferrazin, A, Bassetti, D, De Maria, A, Gotta, C, Mur, A, Paya, A, Vinolas, M, Lopez-Vilchez, MA, Martinez-Gomez, P, Carreras, R, Coll, O, Fortuny-Guasch C, Boguna, J, Caro, MC, Canet, Y, Pardi, G, Ravizza, M, Guerra, B, Lanari, M, Bianchi, S, Bovicelli, L, Prati, E, Duse, M, Scaravelli, G, Stegagno, M, De Santis, M, Semprini, AE, Savasi, V, Vigano, A, Probizer, FR, Maccabruni, A, Bucceri, A, Rancilio, L, Taylor, GP, Lyall, H, Penn, Z, Valerius, NH, Martinelli, P, Buffolano, W, Sansone, M, Tibaldi, C, Ziarati, N, Benedetto, C, Niemiec, T, Horban, A, Newell M.-L., Aebi C., Battegay M., Bernasconi E., Biedermann K., Cheseaux J.-J., Drack G., Erb P., Flepp M., Francioli P., Furrer H.J., Gianinazzi M.-P., Gyr T., Hirschel B., Hosli I., Hug I., Irion O., Keller K., Kind C., Laubereau B., Lauper U., Lorenzi P., Matter L., Naddal D., Perrin L., Rickenbach M., Rudin C., Schreyer A., Schupbach J., Telenti A., Vernazza P., Wolf K., Wunder D., Wyler C.-A., Giaquinto C., Ruga E., De Rossi A., Grosh-Worner I., Seel K., Schafer A., Mok J., Johnstone F., Jimenez J., Garcia-Rodriguez M.C., Bates I., De Jose I., Hawkins F., Ladron de Gevara C., Ma Pena J., Gonzalez Garcia J., Arribas Lopez J.R., Asensi-Botet F., Otero M.C., Perez-Tamarit D., Ridaura S., Gregori P., De la Torre R., Scherpbier H., Kreyenbroek M., Boer K., Bohlin A.B., Lindgren S., Ehrnst A., Belfrage E., Lidman K., Christensson B., Levy J., Hainaut M., Peltier A., Barlow P., Wibaut S., Lecroart M.C., Ferrazin A., Bassetti D., De Maria A., Gotta C., Mur A., Paya A., Vinolas M., Lopez-Vilchez M.A., Martinez-Gomez P., Carreras R., Coll O., Fortuny C., Boguna J., Casellas Caro M., Canet Y., Pardi G., Ravizza M., Guerra B., Lanari M., Bianchi S., Bovicelli L., Prati E., Duse M., Scaravelli G., Stegagno M., De Santis M., and Semprini A.E.

Subjects
Epidemiology, HIV Infections, Substance Abuse, Intravenou, Cohort Studies, Pregnancy, Immunology and Allergy, Medicine, HIV Infection, Prospective Studies, Pregnancy Complications, Infectious, Substance Abuse, Intravenous, Prospective cohort study, Obstetrics, Infectious, Substance Abuse, Pregnancy Outcome, Gestational age, Viral Load, Antiretroviral therapy, Reverse Transcriptase Inhibitor, Infectious Diseases, Combination, Reverse Transcriptase Inhibitors, Drug Therapy, Combination, Female, Intravenous, Prematurity, Delivery, Zidovudine, Viral load, Infant, Premature, Human, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Combination therapy, Anti-HIV Agents, Immunology, CD4 Lymphocyte Count, Delivery, Obstetric, Gestational Age, HIV-1, Humans, Infant, Newborn, Drug Therapy, antiretroviral therapy, combination therapy, epidemiology, pregnancy, prematurity, Premature, business.industry, Infant, Anti-HIV Agent, Obstetric, Odds ratio, Newborn, medicine.disease, Surgery, Pregnancy Complications, Prospective Studie, Pregnancy Complications, Infectiou, Cohort Studie, business
Abstract

Objective: To assess the association between type and timing of initiation of antiretroviral therapy in pregnancy and duration of pregnancy. Design: Prospective study. Methods: Data on 3920 mother child pairs were examined (3015 mother-child pairs from the European Collaborative Study and 905 from the Swiss Mother + Child HIV Cohort Study). Factors examined included gestational age, antiretroviral therapy during pregnancy, maternal CD4 count, viral load, illicit drug use (IDU) and mode of delivery. Deliveries at less than 37 weeks were defined as premature. Results: The prematurity rate was 17% and median gestational age 39 weeks. Twenty-three per cent (896 of 3920) of women received antiretroviral therapy during pregnancy: 64% (573 of 896) zidovudine monotherapy, 24% (215) combination therapy without protease inhibitors (PI) and 12% (108) combination therapy with PI. In multivariate analysis, adjusted for maternal CD4 count and IDU, odds ratio (OR) of prematurity was 2.60 195% confidence interval (CI), 1.43-4.751 and 1.82 (95% CI, 1.13-2.92) for infants exposed to combination therapy with and without a Pl, respectively, compared to no treatment. Exposure to monotherapy was not associated with prematurity, but severe immunosuppression and IDU in pregnancy were. Women on combination therapy from before pregnancy were twice as likely to deliver prematurely as those starting therapy in the third trimester (OR, 2.17 95% CI, 1.03-4.58). Conclusions: Pregnancy issues should be discussed when making decisions about initiation of combination antiretroviral therapy for HIV-infected women. Elective caesarean section to reduce vertical transmission at 36 weeks rather than 38 weeks may be advisable in women on combination therapy with PI. © 2000 Lippincott Williams & Wilkins.

Published
2000

4. Age-Related Standards for Total Lymphocyte, CD4+ and CD8+ T Cell Counts in Children Born in Europe

Author

Giaquinto, Carlo, Rampon, O, Giacomet, V, DE ROSSI, Anita, GROSCH WORNER, I, Mok, J, Bates, I, DE JOSE, I, Hawkins, F, GARCIA RODRIGUEZ MC, DE GUEVARA, L, Pena, Jm, Garcia, Jg, Lopez, Jra, ASENSI BOTET, F, Otero, Mc, PEREZ TAMARIT, D, Orti, A, SAN MIGUEL MJ, Scherpbier, H, Kreyenbroek, M, Boer, K, Bohlin, Ab, Belfrage, E, Naver, L, Levy, J, Hainaut, M, Peltier, A, Goetghebuer, T, Barlow, P, Ferrazin, A, DE MARIA, A, Gotta, C, Mur, A, LOPEZ VILCHEZ MA, Paya, A, Carreras, R, Valerius, Nh, Niemec, T, and Marczynska, M.

Subjects
lymphocytes, Microbiology (medical), Lymphocyte, Human immunodeficiency virus (HIV), Black People, HIV Infections, lymphocytes, CD4(+) cells, CD8(+) cells, human immunodeficiency virus, CD8-Positive T-Lymphocytes, medicine.disease_cause, White People, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Age related, medicine, Humans, Cytotoxic T cell, Lymphocyte Count, Pregnancy Complications, Infectious, Child, Prospective cohort study, Total Lymphocyte Counts, human immunodeficiency virus, business.industry, Age Factors, Infant, Newborn, Infant, CD8(+) cells, medicine.disease, CD4 Lymphocyte Count, Europe, CD4(+) cells, Infectious Diseases, medicine.anatomical_structure, Child, Preschool, Pediatrics, Perinatology and Child Health, Immunology, HIV-1, Female, business, Demography
Abstract

Objective Currently used reference values for immunologic markers in children are largely derived from cross-sectional data from historic, small sample size studies in predominantly white children. There is a lack of reliable age-related standards for immunologic markers, such as CD4+ cell counts, in particular in black children whose values according to recent reports may differ from those in white children. Standards are essential for diagnosing and monitoring childhood diseases such as pediatric human immunodeficiency virus (HIV) infection. Design Prospective cohort study with data on 1781 uninfected children born to HIV-infected mothers in the European Collaborative Study. Methods Age-related standards (centiles) for immunologic markers (CD4+ and CD8+ cell counts and total lymphocyte counts) up to 5 years in black and up to 10 years in white children were constructed using Generalized Additive Models for Location, Scale and Shape method, which allows for variability and skewness of the data. The optimal model was chosen according to the Akaike Information Criterion. Results Patterns and values of total lymphocyte, CD4+ and CD8+ cell counts varied with age, especially in the first 3 years of life, but less so thereafter. Values of all 3 immunologic markers were substantially and significantly lower in black than in white children of the same age. Conclusions We present age-related standards separately for black and white children to aid clinicians in the monitoring of childhood diseases. These standards may also contribute to the decision on an accurate cutoff for CD4+ cell counts for initiating treatment of HIV-infected children.

Published
2005

5. Five year follow up of vertically HIV infected children in a randomised double blind controlled trial of immediate versus deferred zidovudine: the PENTA 1 trial

Author

Aboulker, J. P., Babiker, A., Darbyshire, J. H., Debre, M., Giaquinto, C., Gibb, D. M., Harper, L., Newberry, A., Saidi, Y., Levy, J., Della Negra, M., Forbes, J., Vaudry, W., Mechinaud, F., Nicolas, J., Wahn, V., Dammann, C., Notheis, G., Hinkelmann, B., Butler, K., De Manzini, A., Mazza, A., Duse, Marzia, Loy, A., Plebani, A., Castelli Gattinara, G., Cellini, M., Palomba, E., Caselli, D., Guarino, A., Osimani, P., Scherpbier, H., Delgado, A., Gomez, I. D., Lecuona, J. E., Pena, M. J. M., Baselga, C., Leal, J. A. L., Amador, J. T. R., Canosa, C., Sierra, A. M., Calavia, L. C., Rodrigo, C., Guasch, C. F., Bohlin, A., Nadal, D., Mok, J., Lyall, H., Novelli, V., Sharland, M., Sloper, K., J., Levy, M., Della Negra, J., Forbe, W., Vaudry, F., Mechinaud, J. Nicolas V., Wahn, C., Dammann, G., Nothei, B., Hinkelmann, K., Butler, C., Giaquinto, A., De Manzini, A., Mazza, M., Duse, A., Loy, A., Plebani, G., Castelli Gattinara, M., Cellini, E., Palomba, D., Caselli, Guarino, Alfredo, P., Osimani, H., Scherpbier, A., Delgado, I., De José Gomez, J., Echeverria Lecuona, MJ Mellado, Pena, C., Baselga, J. A., Leon Leal, J. T., Ramos Amador, C., Canosa, A., Mur Sierra, L., Ciria Calavia, C., Rodrigo, C., Fortuny Guasch, A., Bohlin, D., Nadal, J., Mok, H., Lyall, V., Novelli, M., Sharland, and K. S. l. o. p. e., R.

Subjects
Male, medicine.medical_specialty, Pediatrics, Adolescent, Anti-HIV Agents, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Statistics, Nonparametric, aids, hiv, penta, placebo-controlled, randomised, zidovudine, law.invention, Double blind, Zidovudine, Double-Blind Method, Randomized controlled trial, Acquired immunodeficiency syndrome (AIDS), law, Humans, Medicine, Child, Proportional Hazards Models, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Five year follow up, Infant, Viral Load, Flow Cytometry, medicine.disease, Infectious Disease Transmission, Vertical, CD4 Lymphocyte Count, Surgery, Area Under Curve, Child, Preschool, Pediatrics, Perinatology and Child Health, Disease Progression, HIV-1, General and Specialist Paediatrics, Female, business, Follow-Up Studies, medicine.drug
Abstract

A total of 195 children were randomised to zidovudine (immediate) or matching placebo (deferred) in a multicentre double blind trial in vertically HIV infected children with early disease (the PENTA 1 trial). Median follow up in the blinded phase was 1.9 years. Thereafter, individual children were unblinded following the results of adult trials showing a benefit of combination antiretroviral therapy (ART) over monotherapy, but follow up continued and is reported here until December 1998 (total follow up 4.6 years). Median time to starting ART in the deferred group was 2.7 years; 19% of deferred children had not started ART by 1999. Throughout follow up, the percentage of time spent on no ART, monotherapy, dual, and triple ART was 21%, 44%, 29%, and 6% respectively for immediate and 62%, 12%, 18%, and 8% for deferred groups. During the blinded phase eight (7.8%) immediate and 12 (13.3%) deferred children developed AIDS or died (log rank p = 0.24); overall 21 immediate and 20 deferred children progressed. In an analysis including all children regardless of original allocation, the risk of progression to AIDS or death, adjusting for age and time since trial entry was significantly lower during 1997-98 (2.4 per 100 child years) than during 1992-96 (6.6 per 100 child years), most likely a result of increased use of combination ART.

Published
2001

6. The Mode of Delivery and the Risk of Vertical Transmission of Human Immunodeficiency Virus Type 1 — A Meta-Analysis of 15 Prospective Cohort Studies

Author

Andiman, W., Boucher, M., Burns, D., Bryson, Y., Farley, J., Fowler, H., Gabiano, C., Galli, L., Hutto, C., Kind, C., Korber, B., Kovacs, A., Krogstad, P., Landesman, S., Lapointe, N., Lemay, M., Lew, J., Mandelbrot, L., Mayaux, Mj, Mellins, R., Minkoff, H., Mofenson, L., Nielsen, K., Newell, Ml, Pardi, G., Peavy, H., Peckham, C., Read, J., Rother, C., Rudin, C., Scott, G., Semprini, A., Shearer, W., Simonds, R., Simpson, B., Stek, A., Tovo, Pa, Tuomala, R., Dyke, R., Weedon, J., Martino, M., Lindsay, M., Belair, S., Chan, L., Harris, D., Kalish, L., Muenz, L., Nugent, R., Schluchter, M., Durako, S., Goodwin, S., Mitchell, R., Nourjah, P., Owen, W., Widmayer, S., Bardeguez, A., Hanson, C., Wiznia, A., Luzuriaga, K., Viscarello, R., Ho, D., Koup, R., Chen, I., Mullins, J., Wolinsky, S., Walker, B., Ammann, A., Clapp, S., Mcdonald, D., Fauvel, M., Hankins, C., Samson, J., Bailey, A., Giaquinto, C., Ruga, E., Rossi, A., Truscia, D., Grosch-Worner, I., Schafer, A., Mok, J., Johnstone, F., Jiminez, J., Alba, C., Garcia-Rodriguez, M., Bates, I., Jose, I., Hawkins, F., Zapico, Rm, Asensi-Botet, F., Otero, M., Perez-Tamarit, D., Moya, A., Galbis, M., Scherpbier, H., Boer, K., Bohlin, A., Lindgren, S., Ehrnst, A., Anzen, B., Belfrage, E., Levy, J., Alimenti, A., Barlow, P., Ferrazin, A., Maria, A., Gotta, C., Maritati, V., Mur, A., Rovira, M., Paya, A., Coll, O., Fortuny, C., Boguna, J., Caro, Mc, Canet, Y., Ravizza, M., Castagna, C., Fiore, S., Guerra, B., Lanari, M., Bianchi, S., Bovicelli, L., Prati, E., Duse, M., Soresina, A., Scaravelli, G., Santis, M., Muggiasca, M., Vigano, A., Marchisio, P., Iasci, A., Spinillo, A., Bucceri, A., Grossi, E., Rancilio, L., Della Torre, M., Dallacasa, P., Pachi, A., Principi, N., Zara, C., Vignali, M., Rossi, G., Selvaggi, L., Greco, P., Vimercati, A., Massi, G., Innocenti, T., Fiscella, A., Sansone, M., Benedetto, C., Tibaldi, C., Ziarati, N., Tadrist, B., Thevenicau, D., Gondry, J., Paulard, B., Alisy, C., Brault, D., Tordjeman, P., Mamou, J., Rozan, M., Colombani, D., Pincemaille, O., Salvetti, A., Chabanier, C., Hernandorena, X., Leroy, J., Schaal, J., Balde, P., Faucher, P., Lachassinne, E., Benoit, S., Douard, D., Hocke, C., Barjot, P., Brouard, J., Delattre, P., Stien, L., Audibert, F., Labrune, P., Vial, M., Mazy, F., Sitbon, D., Crenn-Hebert, C., Floch-Tudal, C., Akakpo, R., Daveau, C., Leblanc, A., Cesbron, P., Duval-Arnould, H., Huraux-Rendu, C., Lemerle, S., Touboul, C., Guerin, M., Maingueneau, C., Reynaud, I., Rousseau, T., Ercoil, V., Lanza, M., Denavit, M., Garnier, J., Lahsinat, K., Pia, R., Allouche, C., Nardou, M., Grall, F., May, A., Dallot, M., Lhuillier, P., Cecile, W., Mezin, R., Bech, A., Lobut, J., Algava, G., Dermesay, Ac, Busuttil, R., Jacquemot, M., Bader-Meunier, B., Fridman, S., Codaccioni, X., Maxingue, F., Thomas, D., Alain, J., Lumley, L., Tabaste, J., Salin, Pb, Seaume, H., Guichard, A., Kebaili, K., Roussouly, C., Botto, C., Lanete, A., Wipff, P., Cravello, L., Boisse, P., Leclaire, M., Michel, G., Crumiere, C., Lefevre, V., Le Lorier, B., Pauly, I., Robichez, B., Seguy, D., Dehlinger, M., Rideau, F., Talon, P., Benos, P., Huret, C., Nicolas, J., Heller-Roussin, B., Saint-Leger, S., Delaporte, M., Hubert, C., Sarcus, B., Karoubi, P., Mechinaud, F., Bertcrottiere, D., Bongain, A., Monpoux, F., Gennes, C., Devianne, F., Nisand, I., Rousset, M., Mouchnino, G., Muray, J., Munzer, M., Quereux, C., Brossard, V., Clavier, B., Allemon, M., Rotten, D., Stephan, J., Varlet, M., Guyot, B., Narey, P., Bardinet, F., Caunes, F., Jeny, R., Robin, M., Bouley, Ar, Savey, L., Berrebi, A., Tricoire, J., Borderon, J., Fignon, A., Guillot, F., Maria, B., Broyard, A., Chitrit, Y., Firtion, G., Pillet, Ml, Parat, S., Boissinot, C., Garec, N., Levine, M., Ottenwalter, A., Schaller, F., Vilmer, B., Courpotin, C., Brunner, C., Ciraru-Vigneron, N., Hatem-Gantzer, G., Xavier FRITEL, Wallet, A., Bouille, J., Milliez, J., Mrejen, Db, Dermer, E., Noseda, G., Bardou, D., Cressaty, J., Francoual, C., Moncomble, Cc, Cohen, H., Blanche, S., Bastion, H., Benifla, J., Benkhatar, F., Berkane, N., Herve, F., Ronzier, M., Ferraris, G., Rancillo, L., Tulisso, S., Scolfaro, C., Riva, C., Vierucci, A., Luca, M., Farina, S., Fundaro, C., Genovese, O., Mercu, G., Forni, G., Stegagno, M., Falconieri, P., Zuccotti, G., Riva, E., Cellini, M., Baraldi, C., Consolini, R., Palla, G., Ruggeri, M., Pignata, C., Guarino, A., Osimani, P., Metri, A., Antonellini, A., Benaglia, G., Romano, A., Mattia, D., Caselli, D., Boni, S., Erba, G., Bassanetti, F., Sticca, M., Timpano, C., Magnani, C., Salvatore, C., Gambaretto, G., Lipreri, R., Tornaghi, R., Pinzani, R., Cecchi, M., Bezzi, T., Battisti, L., Bresciani, E., Gattinara, G., Berrino, R., Pellegatta, A., Mazza, A., Baldi, F., Micheletti, E., Altobelli, R., Deiana, M., Colnaghi, C., Tarallo, L., Tondo, U., Anastasio, E., Chiriaco, P., Contardi, I., Ruggeri, C., Ibba, P., O Sullivan, M., Malmsberry, A., Willoughby, A., Goedert, J., Mendez, H., Holman, S., Rubinstein, A., Nesheim, S., Clark, S., Lee, F., Nahmias, A., Sawyer, M., Vink, P., Alger, L., Abrams, E., Bamji, M., Lambert, G., Schoenbaum, E., Thea, D., Thomas, P., Palumbo, P., Denny, T., Oleske, J., Orloff, S., Ethier-Ives, J., Rogers, M., Kutner, M., Kaplan, S., Kattan, M., Lipshultz, S., Sopko, G., Sloand, E., Wu, M., Nadal, D., Siegrist, Ca, Wyler, Ca, Cheseaux, Jj, Aebi, C., Gnehm, H., Schubiger, G., Klingler, J., Hunziker, U., Kuchler, H., Gianinazzi, M., Buhlmann, U., Biedermann, K., Lauper, U., Irion, O., Brunelli, A., Spoletini, G., Schreyer, A., Hosli, I., Saurenmann, E., Drack, G., Isenschmid, M., Poorbeik, M., Schupbach, J., Perrin, L., Erb, P., Joller, H., Dillon, M., Nielsen, R., Boyer, P., Liao, D., Keller, M., Deveikis, A., Khoury, M., Diaz, C., Pacheco-Acosta, E., Cooper, E., Mesthene, D., Pitt, J., Higgins, A., Moroso, G., Rich, K., Turpin, D., Cooper, N., Fowler, M., Smeriglio, V., Mckinlay, S., and Ellis, S.

Subjects
Male, medicine.medical_specialty, Multivariate analysis, Anti-HIV Agents, Birth weight, HIV Infections, Cohort Studies, Pregnancy, Risk Factors, medicine, Birth Weight, Humans, Rupture of membranes, Pregnancy Complications, Infectious, Prospective cohort study, Cesarean Section, Obstetrics, business.industry, Infant, Newborn, General Medicine, Odds ratio, Delivery, Obstetric, medicine.disease, Infectious Disease Transmission, Vertical, Confidence interval, Logistic Models, Multivariate Analysis, Immunology, HIV-1, Female, business, Zidovudine, Cohort study
Abstract

Background To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. Methods North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. Results The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. Conclusions The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine.

Published
1999

7. Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery

Author

Aebi Popp, K, Mulcahy, F, Glass, Tr, Rudin, C, Martinez de Tejada, B, Bertisch, B, Fehr, J, Grawe, C, Scheibner, K, Rickenbach, M, Hoesli, I, Thorne, C, European Collaborative Study in EuroCoord, Swiss, Mother, Child HIV Cohort Study Collaborators: Thorne, C, Bailey, H, Giaquinto, C, Rampon, O, Mazza, A, De Rossi, A, Wörner, I, Mok, J, de José MI, Martínez, B, Peña, J, Garcia, J, Lopez, Jr, Rodriguez, Mc, Asensi Botet, F, Otero, Mc, Pérez Tamarit, D, Scherpbier, Hj, Kreyenbroek, M, Godfried, Mh, Nellen, Fj, Boer, K, Navér, L, Bohlin, Ab, Lindgren, S, Kaldma, A, Belfrage, E, Levy, J, Barlow, P, Manigart, Y, Hainaut, M, Goetghebuer, T, Brichard, B, De Camps, J, Thiry, N, Deboone, G, Waterloos, H, Viscoli, C, De Maria, A, Bentivoglio, G, Ferrero, S, Gotta, C, Mûr, A, Payà, A, López Vilchez MA, Carreras, R, Valerius, Nh, Rosenfeldt, V, Coll, O, Suy, A, Perez, J, Fortuny, C, Boguña, J, Savasi, V, Fiore, S, Crivelli, M, Viganò, A, Giacomet, V, Cerini, C, Raimondi, C, Zuccotti, G, Alberico, S, Maso, G, Tropea, M, Barresi, V, Taylor, G, Lyall, Eg, Penn, Z, Buffolano, W, Tiseo, R, Martinelli, P, Sansone, M, Maruotti, G, Agangi, A, Tibaldi, C, Marini, S, Masuelli, G, Benedetto, Chiara, Niemieç, T, Marczynska, M, Dobosz, S, Popielska, J, Oldakowska, A, Aubert, V, Barth, J, Battegay, M, Bernasconi, E, Böni, J, Brazzola, P, Bucher, Hc, Burton Jeangros, C, Calmy, A, Cavassini, M, Cheseaux, Jj, Drack, G, Duppenthaler, A, Egger, M, Elzi, L, Fellay, J, Francini, K, Furrer, H, Fux, Ca, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, Hh, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B, Metzner, K, Müller, N, Nadal, D, Pantaleo, G, Polli, Ch, Posfay Barbe, K, Rauch, A, Regenass, S, Schmid, P, Schultze, D, Schöni Affolter, F, Schüpbach, J, Speck, R, Taffé, P, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Wyler, Ca, Yerly, S., Posfay Barbe, Klara, Wyler, Claire-Anne, University of Zurich, Aebi-Popp, Karoline, Aebi Popp, K, Mulcahy, F, Glass, Tr, Rudin, C, Martinez de Tejada, B, Bertisch, B, Fehr, J, Grawe, C, Scheibner, K, Rickenbach, M, Hoesli, I, Buffolano, Wilma, Thorne, C, European Collaborative Study in, Eurocoord, Swiss, Mother, and Child HIV Cohort, S. t. u. d. y.

Subjects
mode of delivery, medicine.medical_treatment, HIV Infections, Delivery, Obstetric/statistics & numerical data, Virus Replication, 10234 Clinic for Infectious Diseases, Cohort Studies, HIV Infections/drug therapy/prevention & control/transmission, Pregnancy, Antiretroviral Therapy, Highly Active, 2736 Pharmacology (medical), Pharmacology (medical), Surgical Procedures, Elective/statistics & numerical data, Pregnancy Complications, Infectious, Europe, HIV, Mode of delivery, Adult, Anti-HIV Agents, Cesarean Section, Delivery, Obstetric, Drug Therapy, Combination, Elective Surgical Procedures, Female, Guidelines as Topic, Health Policy, Humans, Infant, Newborn, Infectious Disease Transmission, Vertical, Viral Load, Infectious Diseases, ddc:618, Obstetrics, Vaginal delivery, Transmission (medicine), Cesarean Section/statistics & numerical data, Meta-analysis, provvedimento amministrativo - nullità - domanda riconvenzionale, Viral load, Cohort study, medicine.medical_specialty, Pregnancy Complications, Infectious/drug therapy/epidemiology/prevention & control, 610 Medicine & health, Europe/epidemiology, Pharmacotherapy, medicine, Caesarean section, business.industry, 2725 Infectious Diseases, medicine.disease, Viral Load/drug effects, HIV, pregnancy, mode of delivery, Anti-HIV Agents/therapeutic use, Settore MED/40 - Ginecologia e Ostetricia, business, Infectious Disease Transmission, Vertical/prevention & control/statistics & numerical data
Abstract

INTRODUCTION: Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe. METHODS: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre- or postpublication of national guidelines recommending vaginal delivery. RESULTS: Overall, 2663 women with 3013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2354) before to 7% (42/599) after the change in guidelines (P < 0.001). CONCLUSION: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

Published
2013

8. Insufficient antiretroviral therapy in pregnancy: missed opportunities for prevention of mother-to-child transmission of HIV in Europe

Author

Bayley, H, Townsend, C, Cortina Borja, M, Thorne, C, Newell, Ml, Giaquinto, Carlo, Rampon, O, Mazza, A, DE ROSSI, Anita, Grosch Wörner, I, Mok, J, de José MI, Larrú Martínez, B, Ma Peña, J, Gonzalez Garcia, J, Arribas Lopez JR, Garcia Rodriguez MC, Asensi Botet, F, Otero, Mc, Pérez Tamarit, D, Scherpbier, Hj, Kreyenbroek, M, Godfried, Mh, Nellen, Fj, Boer, K, Navér, L, Bohlin, Ab, Belfrage, E, Lindgren, S, Levy, J, Barlow, P, Manigart, Y, Hainaut, M, Goetghebuer, T, Brichard, B, De Camps, J, Thiry, N, Deboone, G, Waterloos, H, Viscoli, C, De Maria, A, Bentivoglio, G, Ferrero, S, Gotta, C, Mûr, A, Pàya, A, López Vilchez MA, Carreras, R, Valerius, Nh, Rosenfeldt, V, Coll, O, Suy, A, Perez, Jm, Fortuny, C, Boguña, J, Savasi, V, Fiore, S, Crivelli, M, Viganò, A, Giacomet, V, Cerini, C, Raimondi, C, Zuccotti, G, Alberico, S, Tropea, M, Businelli, C, Taylor, Gp, Lyall, Eg, Penn, Z, Buffolano, W, Tiseo, R, Martinelli, P, Sansone, M, Maruotti, G, Agangi, A, Tibaldi, C, Marini, S, Masuelli, G, Benedetto, C, Niemieç, T, Marczynska, M, Dobosz, S, Popielska, J, Oldakowska, A, Malyuta, R, Semenenko, I, Pilipenko, T., European Collaborative Study in, Eurocoord, Buffolano, Wilma, Bailey, H, Townsend, C, Cortina Borja, M, Thorne, C., European Collaborative, Study, Martinelli, Pasquale, AII - Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Infectious diseases, Other Research, and Obstetrics and Gynaecology

Subjects
Adult, medicine.medical_specialty, Acquired Immunodeficiency Syndrome, HIV, Pregnancy, Antiviral Agents, antiretroviral therapy, Human immunodeficiency virus (HIV), HIV-1 infected women, mother-to-child transmission, risk factors, HIV Infections, medicine.disease_cause, Medical care, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Antiretroviral Therapy, Highly Active, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Disengagement theory, Pregnancy Complications, Infectious, Pharmacology, 030219 obstetrics & reproductive medicine, business.industry, mother-to-child transmission, Prevention of mother to child transmission, medicine.disease, Antiretroviral therapy, Infectious Disease Transmission, Vertical, 3. Good health, Europe, Infectious Diseases, Family medicine, Immunology, HIV-1, Female, business, HIV-1 infected women, Viral load
Abstract

Background Although mother-to-child transmission (MTCT) rates are at an all-time low in Western Europe, potentially preventable transmissions continue to occur. Duration of antenatal combination antiretroviral therapy (ART) is strongly associated with MTCT risk. Methods Data on pregnant HIV-infected women enrolled in the Western and Central European sites of the European Collaborative Study between January 2000 and July 2009 were analysed. The proportion of women receiving no antenatal ART or 1–13 days of treatment was investigated, and associated factors explored using logistic regression models. Results Of 2,148 women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000–2003 to 5% in 2004– 2009 (χ2=8.73; PConclusions Over the last 10 years, around one in 11 women in this study received insufficient antenatal ART, accounting for 40% of MTCTs. One-half of these women were diagnosed before conception, suggesting disengagement from care.

Published
2011

9. Use of neonatal antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV is decreasing in Western Europe

Author

England, K., Thorne, C., Giaquinto, C., Rampon, O., D’Elia, R., De Rossi, A., Grosch Wörner, I., Mok, J., de José, I., Laaru ́, A., Bates, I., Salas, A., Ma Peña, J., Gonzalez Garcia, J., Arribas Lo pez, J. R., Garcia Rodriguez, M. C., Asensi Botet, F., Otero, M. C., Pérez Tamarit, D., Scherpbier, H. J., Kreyenbroek, M., Godfried, M. H., Nellen, F. J. B., Boer, K., Bohlin, A. B., Lindgren, S., Anzén, B., Lidman, K., Elfgren, K., Gyllensten, K., Pehrson, P. O., Levy, J., Barlow, P., Manigart, Y., Hainaut, M., Peltier, A., Goetghebuer, T., Ferrazin, A., DE MARIA, Andrea, Bentivoglio, Giorgio, Ferrero, Simone, Gotta, C., Mur, A., Paya, A., López Vilchez, M. A., Carreras, R., Valerius, N. H., Rosenfeldt, V., Jimenez, J., Coll, O., Suy, A., Perez, J. M., Fortuny, C., Boguña, J., Canet, Y., Pardi, G., Ravizza, M., Guerra, B., Lanari, M., Bianchi, S., Bovicelli, L., Prati, E., Duse, M., Scaravelli, G., Stegagno, M., De Santis, M., Savasi, V., Fiore, S., Cri velli, M., Ferrazzi, E., Vigano`, A., Giacomet, V., Frasca, D., Zuccotti, G., Ravagni Probizer, F., Maccabruni, A., Bucceri, A., Rancilio, L., Alberico, S., Rabusin, M., Bernardon, M., Taylor, G. P., Lyall, E. G. H., Penn, Z., Buffolano, W., Tiseo, R., Martinelli, P., Sansone, M., Maruotti, G., Agangi, A., Tibaldi, C., Marini, S., Masuelli, G., Benedetto, C., Marczynska, T. Niemiec ̧ M., Dobosz, S., Popielska, J., and Oldakowska, A.

Subjects
Microbiology (medical), Cart, Pediatrics, medicine.medical_specialty, antiretroviral therapy, HIV Infections, Chemoprevention, Article, Zidovudine, Pregnancy, Medicine, Humans, HIV, pregnancy, Maternal Transmission, business.industry, Infant, Newborn, medicine.disease, Infectious Disease Transmission, Vertical, Europe, Infectious Diseases, Chemoprophylaxis, Cohort, Observational study, Female, business, Viral load, medicine.drug
Abstract

To the Editor: Since the ACTG076 trial results were published in 1994 [1], antiretroviral prophylaxis for the neonate as well as during pregnancy and delivery has been the cornerstone of prevention of mother-to-child transmission (MTCT) of HIV. In the second decade of the combination antiretroviral therapy (cART) era, around 90% of pregnant HIV-infected women in Western Europe receive antenatal cART, for their own health and/or for prevention of MTCT (PMTCT) [2-4]. The rationale for including neonatal prophylaxis in the ACTG076 trial included uncertainty regarding timing of MTCT and the desire to boost the infant’s in utero and intrapartum antiretroviral drug exposure with 6 weeks zidovudine prophylaxis, as a post-exposure prophylaxis (PEP) for newborns not infected with HIV in utero. Observational studies and trials subsequently demonstrated effectiveness of neonatal PEP for infants whose mothers received no antiretroviral drugs [5-7]. No trial data exist comparing the efficacy of different neonatal prophylaxis regimens for infants of women on cART. We investigated trends in neonatal prophylaxis use in the cART era in Western European sites of the European Collaborative Study, a cohort of HIV-infected pregnant women and their children; full methods are described elsewhere [4]. Logistic regression was used to investigate factors associated with receipt of neonatal prophylaxis. Variables considered in the multivariable model were antenatal antiretroviral use, mode of delivery, country and year of delivery, prematurity (

Published
2009

10. The management of HCV infected pregnant women and their children European paediatric HCV network

Author

Pembrey, Lucy, Newell, Marie Louise, Tovo, Pier Angelo, Amoroso, A., Bevilaqua, E., Asensi Botet, F., Pereda, A., Balossini, V., Bona, G., Zaffaroni, M., Bandelloni, A., Coscia, A., Fabris, C., Aime, S., Belloni, C., Bossi, G., Salati, B., Boucher, C., Buffolano, W., Butler, K., Roura, L. Cabero, Sanges, J. M. Bertran, Cigna, P., Ciria, L. M., Ginard, C. Servera, Teruel, G. Claret, Fortuny, C., Coll, O., Corrias, A., Ledda, R., Floris, S., De Maria, A., Echeverria, J., Cilla, G., LANARI, MARCELLO, Tridapalli, E., Venturi, V., Fischler, B., Bohlin, A. B., Lindgren, S., Lindh, G., Giacomet, V., Merlo, M., Figini, C., Erba, P., Viganò, A., Hannam, S., Mieli Vergani, G., Hatzakis, A., Inchley, C., Fjaerli, H. O., Maccabruni, A., Marcellini, M., Sartorelli, M. R., Fontelos, P. Martin, Mazza, A., Mok, J. Y. Q., Mûr, A., Viñolas, M., Paternoster, D. M., Grella, P., Polywka, S., Quinti, I., Casadei, A. M., Rojahn, A., Berg, A., Rosso, R., Ferrando, S., Bassetti, D., Contreras, J. Ruiz, Manzanares, A., Extremera, A. Ruiz, Salvini, F., Zuccotti, G. V., Schmitz, T., Grosch Wörner, I., Sperling, C. Feiterna, Piening, T., Vegnente, A., Iorio, R., Versace, A., Lazier, L., Palomba, E., Gabiano, C., Balbo, L., Zanetti, A., Tanzi, E., FALDELLA, GIACOMO, Pembrey, L., Newell, M. L., Tovo, P. A., Amoroso, A., Bevilacqua, E., Asensi Botet, F., Pereda, A., Balossini, V., Bona, G., Zaffaroni, M., Bandelloni, A., Coscia, A., Fabris, C., Iorio, Raffaele, Vegnente, Angela, Pembrey, Lucy, Newell, Marie-Louise, Tovo, Pier-Angelo, Bevilaqua, E., Asensi-Botet, F., Aime, S., Belloni, C., Bossi, G., Salati, B., Boucher, C., Buffolano, W., Butler, K., Roura, L. Cabero, Sanges, J.M. Bertran, Cigna, P., Ciria, L.M., Ginard, C. Servera, Teruel, G. Claret, Fortuny, C., Coll, O., Corrias, A., Ledda, R., Floris, S., De Maria, A., Echeverria, J., Cilla, G., Faldella, Giacomo, Lanari, M., Tridapalli, E., Venturi, V., Fischler, B., Bohlin, A.-B., Lindgren, S., Lindh, G., Giacomet, V., Merlo, M., Figini, C., Erba, P., Viganò, A., Hannam, S., Mieli-Vergani, G., Hatzakis, A., Inchley, C., Fjaerli, H.O., Maccabruni, A., Marcellini, M., Sartorelli, M.R., Fontelos, P. Martin, Mazza, A., Mok, J.Y.Q., Mûr, A., Viñolas, M., Paternoster, D.M., Grella, P., Polywka, S., Quinti, I., Casadei, A.M., Rojahn, A., Berg, A., Rosso, R., Ferrando, S., Bassetti, D., Contreras, J. Ruiz, Manzanares, A., Extremera, A. Ruiz, Salvini, F., Zuccotti, G.V., Schmitz, T., Grosch-Wörner, I., Sperling, C. Feiterna, Piening, T., Vegnente, A., Iorio, R., Versace, A., Lazier, L., Palomba, E., Gabiano, C., Balbo, L., Zanetti, A., and Tanzi, E.

Subjects
Pediatrics, medicine.medical_specialty, Psychological intervention, Breastfeeding, Pregnancy, Prenatal Diagnosis, Diagnosis, medicine, Humans, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, Hepatitis C, Clinical management, Mother-to-child transmission, Paediatric, Follow-up, Hepatology, business.industry, Transmission (medicine), Gastroenterology, Infant, Newborn, virus diseases, Evidence-based medicine, medicine.disease, digestive system diseases, Infectious Disease Transmission, Vertical, Europe, Immunology, Female, Viral disease, business, Diagnosi
Abstract

Background/Aims: As evidence accumulates relating to mother-to-child (vertical) transmission of hepatitis C virus (HCV), it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children. Methods: A review of evidence from the European Paediatric HCV Network (EPHN) prospective study of HCV infected women and their children and other published studies. Meeting of EPHN clinical experts to reach a consensus on recommendations for management. Each recommendation was graded according to the level of evidence. Results/conclusions: Although several risk factors for mother-to-child transmission have been identified, none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV. Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women. Based on the current evidence, routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV. HCV/HIV co-infected women should follow existing HIV guidelines. © 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Published
2005

11. Combination antiretroviral therapy and duration of pregnancy

Author

Aebi, C, Battegay, M, Bernasconi, E, Biedermann, K, Cheseaux, JJ, Drack, G, Erb, P, Flepp, M, Francioli, P, Furrer, HJ, Gianinazzi, MP, Gyr, T, Hirschel, B, Hosli, I, Hug, I, Irion, O, Keller, K, Kind, C, Laubereau, B, Lauper, U, Lorenzi, P, Matter, L, Nadal, D, Perrin, L, Rickenbach, M, Rudin, C, Schreyer, A, Schupbach, J, Telenti, A, Vernazza, P, Wolf, K, Wunder, D, Wyler, CA, Giaquinto, C, Ruga, E, De Rossi, A, Grosch-Worner, I, Seel, K, Schafer, A, Mok, J, Johnstone, F, Jimenez, J, Garcia-Rodriguez, MC, Bates, I, de Jose, I, Hawkins, F, de Gevara, CL, Pena, JM, Garcia, JG, Lopez, JRA, Asensi-Botet, F, Otero, MC, Perez-Tamarit, D, Ridaura, S, Gregori, P, de la Torre, R, Scherpbier, H, Kreyenbroek, M, Boer, K, Bohlin, AB, Lindgren, S, Ehrnst, A, Belfrage, E, Lidman, K, Christensson, B, Levy, J, Hainaut, M, Peltier, A, Barlow, P, Wibaut, S, Lecroart, MC, Ferrazin, A, Bassetti, D, De Maria, A, Gotta, C, Mur, A, Paya, A, Vinolas, M, Lopez-Vilchez, MA, Martinez-Gomez, P, Carreras, R, Coll, O, Fortuny-Guasch C, Boguna, J, Caro, MC, Canet, Y, Pardi, G, Ravizza, M, Guerra, B, Lanari, M, Bianchi, S, Bovicelli, L, Prati, E, Duse, M, Scaravelli, G, Stegagno, M, De Santis, M, Semprini, AE, Savasi, V, Vigano, A, Probizer, FR, Maccabruni, A, Bucceri, A, Rancilio, L, Taylor, GP, Lyall, H, Penn, Z, Valerius, NH, Martinelli, P, Buffolano, W, Sansone, M, Tibaldi, C, Ziarati, N, Benedetto, C, Niemiec, T, Horban, A, and European Collaborative Study Swiss

Published
2000

12. Vertical transmission of HIV-1: maternal immune status and obstetric factors. The European Collaborative Study

Author

Newell, ML, Dunn, DT, Peckham, CS, Semprini, AE, Pardi, G, Giaquinto, C, Ruga, E, DeRossi, A, Truscia, D, GroschWorner, I, Shafer, A, Mok, J, Johnstone, F, Teres, FO, Jiminez, J, deAlba, C, GarciaRodriguez, MC, Bates, I, deJose, I, Hawkins, F, Zapico, RM, Canosa, CA, Galbis, G, Scherpbier, H, Boer, K, Bohlin, AB, Lindgren, S, Ehrnst, A, Anzen, B, Belfrage, E, Levy, J, Alimenti, A, Barlow, P, Ferrazin, A, DeMaria, A, Gotta, C, Maritati, Mur, A, Gris, J, Puges, MTR, Coll, O, Fortuny-Guasch C, Boguna, J, Caro, MC, Canet, Y, Ravizza, M, Castagna, C, Fiore, S, Guerra, B, Dallacasa, P, Bianchi, S, Bovicelli, L, Prati, E, Zanelli, S, Duse, M, Soresina, A, Scaravelli, G, Stegagno, M, DeSantis, M, Muggiasca, ML, Marchisio, P, Iasci, A, Spinillo, A, Bucceri, A, Grossi, E, and Rancilio, L

Abstract

To estimate the effect of maternal factors and events around the time of delivery on HIV-1 vertical transmission risk.

Published
1996

13. WEIGHT, HEIGHT AND HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION IN; YOUNG-CHILDREN OF INFECTED MOTHERS

Author

NEWELL, ML, DUNN, D, ADES, T, PECKHAM, C, ALIMENTI, A, LEVY, J, GIAQUINTO, C, DEROSSI, A, CHIECOBIANCHI, L, ZACCHELLO, F, GROSCHWORNER, I, LANGHOF, M, MOK, J, TERES, FO, GARCIARODRIGUEZ, MC, ZAPICO, RM, DEJOSE, MI, HAWKINS, F, CANOSA, CA, ASENSI, F, OTERO, MC, TAMARIT, AP, SCHERPBIER, H, BOHLIN, AB, BELFRAGE, E, EHRNST, A, FORSGREN, M, FERRAZIN, A, DEMARIA, A, GOTTA, C, MUR, A, YAZBECK, H, LLORENS, J, Fortuny-Guasch C, DETEJADA, BM, and ZAMORA, L

Published
1995

14. Psychologic adjustment of the family with a member who has cystic fibrosis

Author

Cowen L, Mok J, Corey M, Harriet MacMillan, Simmons R, and Levison H

Subjects
Adult, Male, Psychological Tests, Self-Assessment, Adolescent, Cystic Fibrosis, Mothers, Child Behavior Disorders, Middle Aged, Self Concept, Fathers, Child, Preschool, Surveys and Questionnaires, Pediatrics, Perinatology and Child Health, Adaptation, Psychological, Humans, Sibling Relations, Family, Female, Child
Abstract

Seventy-eight percent of the 384 patients 2 years of age and older who were enrolled in the Cystic Fibrosis Clinic at the Hospital for Sick Children participated in this study of family adjustment to cystic fibrosis. Residence with at least one parent at the time of the survey was a condition for inclusion in the study. The effect of the disease on the family was assessed using three questionnaires: an inventory of family problems as perceived by the parents and two standardized measures of family interaction. Measures of behavior and selfconcept in each patient and sibling, physical disease parameters for each patient, and demographic characteristics of the families were examined and analyzed in relation to the responses to the questionnaires on family interaction. Families of patients with cystic fibrosis were found to function very well, with normal mean scores on both standardized profiles. Children with cystic fibrosis showed more behavior problems than expected from the test norms, and healthy siblings of children with cystic fibrosis had behavior problem scores midway between those with the disease and norm scores. Measures of self-concept were remarkably similar for patients and siblings and showed levels at or above those for children and young adults in the general population. Parents psychosocial scores were influenced by the patients' physical parameters, but the severity of the disease generally was unrelated to psychosocial scores of patients and siblings. A notable exception was the correlation of emotional disturbance with amount of hospitalization in patients older than 12 years of age.

Published
1986

15. Levels and patterns of neutrophil cell counts over the first 8 years of life in children of HIV-1-infected mothers

Author

European Collaborative Study, Giaquinto, C., Rampon, O., Giacomet, V., Rossi, A., Grosch-Worner, I., Mok, J., Bates, I., Jos, I., Hawkins, F., Garcia-Rodriguez, Mc, Guevara, Cl, Pena, Jm, Garcia, Jdg, Lopez, Jra, Asensi-Botet, F., Otero, Mc, Perez-Tamarit, D., Orti, A., San Miguel, Mj, Scherpbier, H., Kreyenbroek, M., Boer, K., Bohlin, Ab, Belfrage, E., Lars Naver, Levy, J., Hainaut, M., Peltier, A., Goetghebuer, T., Barlow, P., Ferrazin, A., Bassetti, D., Maria, A., Gotta, C., Mur, A., Lopez-Vilchez, Ma, Paya, A., Carreras, B., Valerius, Nh, AII - Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology, and Obstetrics and Gynaecology

Subjects
Male, medicine.medical_specialty, Neutrophils, Lymphocyte, Immunology, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, antiretroviral medication, Cohort Studies, Zidovudine, Leukocyte Count, Pharmacokinetics, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Internal medicine, medicine, gender, Immunology and Allergy, Humans, Clinical significance, Longitudinal Studies, Pregnancy Complications, Infectious, Child, Transmission (medicine), business.industry, Infant, Newborn, virus diseases, Infant, haematopoiesis, medicine.disease, CD4 Lymphocyte Count, HIV-1, haematopoiesis, antiretroviral medication, gender, Infectious Diseases, medicine.anatomical_structure, Child, Preschool, Absolute neutrophil count, HIV-1, Female, business, medicine.drug
Abstract

Background: Antiretroviral drugs (ARV) as prophylaxis to prevent mother-to-child transmission of HIV results in decreased haematological parameters during and shortly after exposure, with recent data suggesting a more prolonged inhibition of haematopoiesis until at least 18 months. Design: Data on 156 HIV-infected and 1533 uninfected children in the European Collaborative Study followed from birth until at least 8 years of age. Methods: Smoothers and splines were used to elucidate patterns over age; linear mixed effects allowed for repeated measurements. Covariates included the child's HIV-1 infection status, prematurity, gender, race, drug withdrawal symptoms at birth and ARV exposure; effects on neutrophil count were quantified in regression analyses using z-scores (SD from mean) of neutrophil counts obtained after modelling untransformed values using the LMS method. For HIV-infected children, progression to AIDS and ARV therapy were also included. Results: After approximately 4 months of age, neutrophil counts were consistently and substantially lower in HIV-infected children than in uninfected children; in both groups, black children had significantly lower counts than white children across the whole age range. In uninfected children, male gender and ARV exposure were associated with reduced neutrophil count until at least 8 years of age. In HIV-infected children, advanced disease and ARV treatment were significantly associated with neutrophil count. Conclusion: A considerably longer effect of exposure to ARV was shown in uninfected children than previously thought and significant associations were shown between race and gender and neutrophil count, as previously observed for lymphocyte counts. The clinical relevance of these reduced levels of neutrophils requires further investigation. (C) 2004 Lippincott Williams Wilkins

18. Morbidity and mortality in European children vertically infected by HIV- 1: The French pediatric HIV infection study group and European collaborative study

Author

Blanche, S., Marie-Louise Newell, Mayaux, M. -J, Dunn, D. T., Teglas, J. P., Rouzioux, C., Peckham, C. S., Allisy, C., Brault, D., Mamou, A., Broyart, A., Lachassine, E., Vial, E., Labrune, P., Meier, F., Floch, C., Arnould, M. D., Lemerle, S., Rendu, C. H., Nardou, M., Leblanc, A., May, A., Dallot, M. C., Vedrenne, J., Tardieu, M., Seaume, H., Botto, C., Wipff, T., Crumiere, C., Lelorier, B., Seguy, D., Talon, C., Karoubi, P., Berterottiere, D., Rousset, E., Mouchino, G., Retbi, J. M., Allemon, M. C., Narcy, P., Robin, M., Filou, F. L., Boulley, A. M. R., Busuttil, R., Guillot, F., Coutry, A. L., Pautard, B., Hernandorena, J. X., Douard, D., Masquelier, B., Brouard, J., Lanza, M., Denavit, M. F., Michel, G., Tamalet, C., Vallee, D., Deboisse, P., Nicolas, J., Deville, A., Cottalorda, J., Monpoux, F., Brossard, V., Tricoire, J., Puel, J., Borderon, J. C., Mazi, F., Crepy, A., Simon, F., Gantzer, A., Aufrant, C., Parat, S. M., Ronzier, A., Moncomble, C. C., Ciraru-Vigneron, N., Brunner, M., Heller-Roussin, B., Noseda, G., Dermer, E., Firtion, G., Vilmer, E., Levine, M., Wallet, A., Brossard, Y., Matthieu, F. P., Francoual, C., Krivine, A., Herve, F., Courpotin, C., Dolfus, C., Veber, F., Burgard, M., Giaquinto, C., Ruga, E., Rossi, A., Grosch-Worner, I., Mok, J., Johnstone, F., and Teres, F. O.

19. Perinatal findings in children born to HIV-infected mothers

Author

Newell, M. -L, Dunn, D., Ades, A. E., Peckham, C., Pardi, G., AUGUSTO ENRICO SEMPRINI, Giaquinto, C., Truscia, D., Rossi, A., Chieco-Bianchi, L., Zachello, F., Grosch-Worner, I., Vocks-Hauck, M., Langhof, M., Mok, J., Johnstone, F. D., Teres, F. O., Bates, I., and Garcia-Rodriguez, M. C.

21. Mother-to-child transmission of HIV inspection

Author

Peckham, C. S., Senturia, Y. D., Ades, A. E., Newell, M. L., Giaquinto, C., Anita De Rossi, Chieco-Bianchi, L., Zacchello, F., Mok, J. Y. Q., Hague, R., Grosch-Worner, I., Koch, S., Canosa, C. A., Omenaca Teres, F., Garcia Rodriguez, M. C., Scherpbier, H. J., Bohlin, A. B., Maria, A., Gotta, C., and Terragna, A.

22. A significan sex—but not elective cesarean section—effect on mother-to-child transmission of hepatitis C virus infection

Author

Amoroso, A., Asensi-Botet, F., Pereda, A., Balossini, V., Bona, G., Zaffaroni, M., Bandelloni, A., Coscia, A., Fabris, C., Aime, S., Belloni, C., Bossi, G., Salati, B., Boucher, C., Buffolano, W., Butler, K., Cabero Roura, L., Bertran Sanges, J. M., Cigna, P., Ciria, L. M., Servera Ginard, C., Claret Teruel, G., Fortuny, C., Coll, O., Corrias, A., Ledda, R., Floris, S., Maria, A., Echeverria, J., Cilla, G., Lanari, M., Tridapalli, E., Venturi, V., Faldella, G., Fischler, B., Bohlin, A. -B, Lindgren, S., Lindh, G., Giacomet, V., Merlo, M., Figini, C., Erba, P., Viganò, A., Hannam, S., Mieli-Vergani, G., Hatzakis, A., Inchley, C., Fjaerli, H. O., Maccabruni, A., Marcellini, M., Sartorelli, M. R., Martin Fontelos, P., Mazza, A., Mok, J. Y. Q., Mûr, A., Viñolas, M., Paternoster, D. M., Grella, P., Polywka, S., Quinti, I., Casadei, A. M., Rojahn, A., Berg, A., Rosso, R., Ferrando, S., Bassetti, D., Ruiz Contreras, J., Manzanares, A., Ruiz Extremera, A., Salvini, F., Gianvincenzo Zuccotti, Schmitz, T., Grosch-Wörner, I., Feiterna Sperling, C., Piening, T., Vegnente, A., Iorio, R., Versace, A., Garetto, S., Lazier, L., Bressio, S., Riva, C., Alfarano, A., Wejstal, R., Norkrans, G., Zanetti, A., Tanzi, E., Tovo, P. -A, Pembrey, L., and Newell, M. -L

23. The mother-to-child HIV transmission epidemic in Europe: evolving in the East and established in the West

Author

Giaquinto, C., Rampon, O., D Elia, R., Anita De Rossi, Grosch-Woerner, I., Feiterna-Sperling, C., Schmitz, T., Casteleyn, S., Mok, J., Jose, I., Bates, I., Larru, B., Pena, J. M., Garcia, J. Gonzalez, Lopez, J. R. Arribas, Garcia-Rodriguez, M. C., Asensi-Botet, F., Otero, M. C., Perez-Tamarit, D., Suarez, G., Scherpbier, H., Kreyenbroek, M., Godfried, M. H., Nellen, F. J., Boer, K., Bohlin, A. B., Lindgren, S., Belfrage, E., Naver, L., Anzen, B., Lidman, K., Levy, J., Hainaut, M., Goetghebuer, T., Manigart, Y., Barlow, P., Ferrazin, A., Bassetti, D., Maria, A., Bentivoglio, G., Ferrero, S., Gotta, C., Mur, A., Paya, A., Lopez-Vilchez, M. A., Carreras, R., Valerius, N. H., Jimenez, J., Coll, O., Suy, A., Perez, J. M., Fortuny, C., Boguna, J., Caro, M. Casellas, Canet, Y., Pardi, G., Ravizza, M., Guerra, B., Lanari, M., Bianchi, S., Bovicelli, L., Prati, E., Duse, M., Scaravelli, G., Stegagno, M., Santis, M., Savasi, V., Ferrazzi, E., Vigano, A., Giacomet, V., Probizer, F. Ravagni, Maccabruni, A., Bucceri, A., Rancilio, L., Alberico, S., Rabusin, M., Bernardon, M., Taylor, G. P., Lyall, E. G. H., Penn, Z., Buffolano, W., Tiseo, R., Martinelli, P., Sansone, M., Agangi, A., Tibaldi, C., Marini, S., Masuelli, G., Benedetto, C., Niemiec, T., Marczynska, M., Oldakowska, A., Kaflik, M., Posokhova, S., Kaleeva, T., Stelmah, A., Kiseleva, G., and European Collaborative, Study

24. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy

Author

Giaquinto, C., Ruga, E., Anita De Rossi, Grosch-Worner, I., Mok, J., Jose, I., Bates, I., Hawkins, F., Guevara, C. L., Pena, J. M., Garcia, J. G., Lopez, J. R. A., Garcia-Rodriguez, M. C., Asensi-Botet, F., Otero, M. C., Perez-Tamarit, D. P., Suarez, G., Scherpbier, H., Kreyenbroek, M., Boer, K., Bohlin, A. B., Lindgren, S., Ehrnst, A., Belfrage, E., Naver, L., Lidman, K., Anzen, B., Levy, J., Barlow, P., Hainaut, M., Peltier, A., Goetghebuer, T., Ferrazin, A., Bassetti, D., Maria, A., Gotta, C., Mur, A., Paya, A., Vinolas, M., Lopez-Vilchez, M. A., Rovira, Carreras, R., Valerius, N. H., Jimenez, J., Coll, O., Suy, A., Perez, J. M., Fortuny, C., Caro, M. C., Canet, Y., Savasi, V., Vigano, A., Ferrazi, E., Alberico, S., Rabusin, M., Bernardon, M., Taylor, G. P., Lyall, E. G. H., Penn, Z., Buffolano, W., Tiseo, R., Martinelli, P., Agangi, A., Sansone, M., Tibaldi, C., Marini, S., Masuelli, G., Benedetto, C., Niemiec, T., Marczynska, M., Horban, A., and European Collaborative, Study

28. Management of vertically HIV-infected children in Europe

Author

Thorne, C., Gray, L., Marie-Louise Newell, Giaquinto, C., Ruga, E., Rossi, A., Grosch-Würner, I., Mok, J., Johnstone, F., José, I., Bates, I., Hawkins, F., Ladrón Guevara, C., Peña, J. M., Gonzalez Garcia, J., Arribas Lopez, J. R., Garcia-Rodriguez, M. C., Asensi-Botet, F., Otero, M. C., Pérez-Tamarit, D., Ridaura, S., Gregori, P., La Torre, R., Scherpbier, H., Kreyenbroek, M., Boer, K., Bohlin, A. -B, Belfrage, E., Navér, L., Levy, J., Barlow, P., Hainaut, M., Peltier, A., Wibaut, S., Ferrazin, A., Bassetti, D., Maria, A., Gotta, C., Mûr, A., Payà, A., Viñolas, M., López-Vilchez, M. A., Rovira, and Carreras, R.

30. Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women

Author

European Collaborative Study, Newell, Ml, Giaquinto, C., Ruga, E., Rossi, A., Grosch-Worner, I., Mok, J., Johnstone, F., Jose, I., Bates, I., Salas, S., Guevara, Cl, Pena, Jm, Garcia, Jg, Lopez, Jra, Garcia-Rodriguez, Mc, Asensi-Botet, F., Otero, Mc, Perez-Tamarit, D., Ridaura, S., Gregori, P., La Torre, R., Scherpbier, H., Kreyenbroek, M., Boer, K., Bohlin, Ab, Lindgren, S., Ehrnst, A., Belfrage, E., Lars Naver, Levy, J., Barlow, P., Hainaut, M., Peltier, A., Wibaut, S., Ferrazin, A., Bassetti, D., Maria, A., Gotta, C., Mur, A., Paya, A., Vinolas, M., Lopez-Vilchez, Ma, Rovira, Ma, Carreras, R., Valerius, Nh, Coll, O., Vidal, R., Perez, Jm, Boguna, J., Fortuny, C., Pardi, G., Ravizza, M., Guerra, B., Lanari, M., Bianchi, S., Bovicelli, L., Savasi, V., Vigano, A., Ferrazzi, E., Brambilla, T., Bianchi, L., Maccabruni, A., Taylor, Gp, Lyall, Egh, Penn, Z., Buffolano, W., Martinelli, P., Sansone, M., Tibaldi, C., Marini, C., Masuelli, G., Benedetto, C., Niemiec, T., and Marczynska, M.

32. The role of ventromedial prefrontal cortex in reward valuation and future thinking during intertemporal choice

Author

R. Shayna Rosenbaum, Joel Myerson, Violetta Knyagnytska, Carl F. Craver, Flavia De Luca, Francesca Bianconi, Donna Kwan, Leonard Green, Elisa Ciaramelli, Jenkin Mok, and Ciaramelli E, De Luca F, Kwan D, Mok J, Bianconi F, Knyagnytska V, Craver C, Green L, Myerson J, Rosenbaum RS.

Subjects
Male, Time Factors, QH301-705.5, Science, Ventromedial prefrontal cortex, Prefrontal Cortex, episodic future thinking, ventromedial prefrontal cortex, Intertemporal choice, Choice Behavior, decision making, 050105 experimental psychology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Reward, medicine, Humans, 0501 psychology and cognitive sciences, Biology (General), Aged, delay discounting, Discounting, General Immunology and Microbiology, Delay discounting, General Neuroscience, 05 social sciences, General Medicine, Middle Aged, Valuation (logic), medicine.anatomical_structure, Imagination, Medicine, Female, Psychology, psychological phenomena and processes, 030217 neurology & neurosurgery, Research Article, Neuroscience, Human, Cognitive psychology
Abstract

Intertemporal choices require trade-offs between short-term and long-term outcomes. Ventromedial prefrontal cortex (vmPFC) damage causes steep discounting of future rewards (delay discounting; DD) and impoverished episodic future thinking (EFT). The role of vmPFC in reward valuation, EFT, and their interaction during intertemporal choice is still unclear. Here, twelve patients with lesions to vmPFC and forty-one healthy controls chose between smaller-immediate and larger-delayed hypothetical monetary rewards while we manipulated reward magnitude and the availability of EFT cues. In the EFT condition, participants imagined personal events to occur at the delays associated with the larger-delayed rewards. We found that DD was steeper in vmPFC patients compared to controls, and not modulated by reward magnitude. However, EFT cues downregulated DD in vmPFC patients as well as controls. These findings indicate that vmPFC integrity is critical for the valuation of (future) rewards, but not to instill EFT in intertemporal choice.

Published
2021

33. Comparison of dual nucleoside-analogue reverse-transcriptase inhibitor regimens with HIV-1 who have not previously been treated: the PENTA 5 randomized trial

Author

J. P. Aboulker, A. Babiker, A. Compagnucci, J. H. Darbyshire, M. Debré, C. Giaquinto, D. M. Gibb, L. Harper, Y. Saidi, AS Walker, J. Darbyshire, D. Johnson, P. Kelleher, L. McGee, A Newberry, A. Poland, A. S. Walker, J P. Aboulker, I. Carrière, V. Eliette, S. Leonardo, M. Gersten, A. Jones, S. Blanche, A. B. Bohlin, K Butler, G. Castelli Gattinara, P. Clayden, R De Groot, A. Faye, C. Griscelli, I Grosch Wörner, C. Kind, H. Lyall, J. Levy, M. Mellado Pena, D. Nadal, C Peckham, J. T. Ramos Amador, L. Rosado, C. Rudin, H. Scherpbier, M Sharland, P. A. Tovo, G. Tudor Williams, N. Valerius, A. Volny Anne, U Wintergerst, V. Wahn, C. Hill, P Lepage, A. Pozniak, S. Vella, M. Hainaut, A. Peltier, S. Carlier, G. Zissis, M. Della Negra, W. Queiroz, L. P. Feitosa, D Oliveira, F. Mechinaud, F. Ballerau, A. Lepelletier, S. Billaudel, V. Ferre, I. Grosch Wörner, R. Weigel, K. Seel, C. Feiterna Sperling, D. Ohlendorf, G. Riße, C. Müller, T. Niehues, J. Ndagijimana, G. Horneff, N. Vente, R. Ganschow, T. Simon, R. Vossen, H Pfister, U. Wintergerst, G. Notheis, G. Strotmann, S Schlieben, K. Butler, E. Hayes, M. O’Mara, J. Fanning, F. Goggins, S. Moriarty, M. Byrne, L. Battisti, M. Duse, S. Timpano, E. Uberti, P. Crispino, P. Carrara, F. Fomia, A. Manca, L. Galli, M. de Martino, F. Fioredda, E. Pontali, M. Cellini, C. Baraldi, M. Portolani, M. Meacci, P. Pietrosemoli, R. Berni Canani, P. Laccetti, M. Gobbo, V. Giacomet, R. D’Elia, O. Rampon, E. Ruga, A. de Rossi, M. Zanchetta, D. Caselli, A. Maccabruni, E. Cattaneo, V Landini, S. Bernardi, A. Krzysztofiak, C. Tancredi, P. Rossi, L. Pansani, E. Palomba, C. Gabiano, A. Mazza, G. Rossetti, R. Nicolin, A. Timillero, F. Candeias, G Santos, M. L. Ramos Ribeiro, M. C. Almeida, M. H. Lourenço, R. Antunes, M. J. Mellado Pena, M L. Carillo de Albornoz, P. Martinez Santos, L. Ciria Calavia, J. Serra Devecchi, O. Delgado, N. Matamoros, A. Foot, H. Kershaw, C. Kelly, O. Caul, W. Tarnow Mordi, J. Petrie, A. McDowell, P. McIntyre, K. Appleyard, K. Sloper, V. Shah, K. Cheema, A. Aali, J. Mok, R. Russell, A. Brewster, N. Richardson, S. Burns, D. Gibb, V. Novelli, N. Klein, S. Ewen, V. Yeung, C. Ball, K. Himid, D. Nayagam, D. Graham, A. Barrie, K. Stringer, S. Jones, N. Weerasooriya, M. Zuckerman, P. Bracken, E. Cooper, T. Fisher, R. Barrie, U. Patel, V. Van Someren, K. Moshal, L. Perry, T. Gundlach, J. Norman, M. Sharland, M. Richardson, S. Donaghy, Z. Mitchla, C. Wells, J. Booth, A. Shipp, J. White, S. Head, S. Lambers, K. O’Hara, C. Stainsby, G. Du Mont, T. Solanki, S. Swanton, S. O’Shea, A. Tilsey, S. Kaye, A. Finn, S. Choo, R. Lakshman, L. Barr, G. Bell, A. Siddens, GUARINO, ALFREDO, SPAGNUOLO, MARIA IMMACOLATA, Aboulker, J. P., Babiker, A., Compagnucci, A., Darbyshire, J. H., Debré, M., Giaquinto, C., Gibb, D. M., Harper, L., Saidi, Y., Walker, A, Darbyshire, J., Johnson, D., Kelleher, P., Mcgee, L., Newberry, A, Poland, A., Walker, A. S., Aboulker, J P., Carrière, I., Eliette, V., Leonardo, S., Gersten, M., Jones, A., Blanche, S., Bohlin, A. B., Butler, K, Castelli Gattinara, G., Clayden, P., R De Groot, Faye, A., Griscelli, C., I Grosch Wörner, Kind, C., Lyall, H., Levy, J., Mellado Pena, M., Nadal, D., Peckham, C, Ramos Amador, J. T., Rosado, L., Rudin, C., Scherpbier, H., Sharland, M, Tovo, P. A., Tudor Williams, G., Valerius, N., Volny Anne, A., Wintergerst, U, Wahn, V., Hill, C., Lepage, P, Pozniak, A., Vella, S., Hainaut, M., Peltier, A., Carlier, S., Zissis, G., Della Negra, M., Queiroz, W., Feitosa, L. P., Oliveira, D, Mechinaud, F., Ballerau, F., Lepelletier, A., Billaudel, S., Ferre, V., Grosch Wörner, I., Weigel, R., Seel, K., Feiterna Sperling, C., Ohlendorf, D., Riße, G., Müller, C., Niehues, T., Ndagijimana, J., Horneff, G., Vente, N., Ganschow, R., Simon, T., Vossen, R., Pfister, H, Wintergerst, U., Notheis, G., Strotmann, G., Schlieben, S, Butler, K., Hayes, E., O’Mara, M., Fanning, J., Goggins, F., Moriarty, S., Byrne, M., Battisti, L., Duse, M., Timpano, S., Uberti, E., Crispino, P., Carrara, P., Fomia, F., Manca, A., Galli, L., de Martino, M., Fioredda, F., Pontali, E., Cellini, M., Baraldi, C., Portolani, M., Meacci, M., Pietrosemoli, P., Guarino, Alfredo, Spagnuolo, MARIA IMMACOLATA, Berni Canani, R., Laccetti, P., Gobbo, M., Giacomet, V., D’Elia, R., Rampon, O., Ruga, E., de Rossi, A., Zanchetta, M., Caselli, D., Maccabruni, A., Cattaneo, E., Landini, V, Bernardi, S., Krzysztofiak, A., Tancredi, C., Rossi, P., Pansani, L., Palomba, E., Gabiano, C., Mazza, A., Rossetti, G., Nicolin, R., Timillero, A., Candeias, F., Santos, G, Ramos Ribeiro, M. L., Almeida, M. C., Lourenço, M. H., Antunes, R., Mellado Pena, M. J., Carillo de Albornoz, M L., Martinez Santos, P., Ciria Calavia, L., Serra Devecchi, J., Delgado, O., Matamoros, N., Foot, A., Kershaw, H., Kelly, C., Caul, O., Tarnow Mordi, W., Petrie, J., Mcdowell, A., Mcintyre, P., Appleyard, K., Sloper, K., Shah, V., Cheema, K., Aali, A., Mok, J., Russell, R., Brewster, A., Richardson, N., Burns, S., Gibb, D., Novelli, V., Klein, N., Ewen, S., Yeung, V., Ball, C., Himid, K., Nayagam, D., Graham, D., Barrie, A., Stringer, K., Jones, S., Weerasooriya, N., Zuckerman, M., Bracken, P., Cooper, E., Fisher, T., Barrie, R., Patel, U., Van Someren, V., Moshal, K., Perry, L., Gundlach, T., Norman, J., Sharland, M., Richardson, M., Donaghy, S., Mitchla, Z., Wells, C., Booth, J., Shipp, A., White, J., Head, S., Lambers, S., O’Hara, K., Stainsby, C., Du Mont, G., Solanki, T., Swanton, S., O’Shea, S., Tilsey, A., Kaye, S., Finn, A., Choo, S., Lakshman, R., Barr, L., Bell, G., and Siddens, A.

Abstract

Introduction Treatment options for children with HIV-1 are limited. We aimed to compare activity and safety of three dualnucleoside analogue reverse-transcriptase inhibitor (NRTI) regimens with or without a protease inhibitor in previously untreated children with HIV-1. Methods In our multicentre trial, we randomly assigned 36 children to zidovudine and lamivudine, 45 to zidovudine and abacavir, and 47 to lamivudine and abacavir. Children who were symptomfree (n=55) were also randomly assigned to receive nelfinavir or placebo. Children with more advanced disease received open-label nelfinavir (73). Primary endpoints were change in plasma HIV-1 RNA at 24 and 48 weeks for the NRTI comparison and occurrence of serious adverse events for both randomised comparisons. Analyses were by intention to treat. Findings Children had a median CD4 percentage of 22% (IQR 15–29) and a mean HIV-1 RNA concentration of 5·0 log copies/mL (SD 0·8). One child was lost to follow-up and one died of sepsis. At 48 weeks, in the zidovudine/lamivudine, zidovudine/abacavir, and lamivudine/abacavir groups, mean HIV-1 RNA had decreased by 1·71, 2·19, and 2·63 log copies/mL, respectively (estimated in absence of nelfinavir) (p=0·02 after adjustment for baseline factors). One child had a hypersensitivity reaction to abacavir; and three with possible reactions stopped abacavir. There were 24 serious adverse events—six in the symptom-free children (all on nelfinavir), but none were attributed to nelfinavir. Interpretation Regimens containing abacavir were more effective than zidovudine/lamivudine. Such regimens could be combined with protease inhibitors and non-nucleoside reverse transcriptase inhibitors for safe and effective treatment of previously untreated children with HIV-1.

Published
2002

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