Oct, 2013

The Immunological and Virological Consequences of Planned Treatment Interruptions in Children with HIV Infection.


Authors: Klein N, Sefe D, Mosconi I, et al; on Behalf of the Paediatric European Network for Treatment of AIDS (PENTA) 11 Trial Team

Published in: PLoS One. 2013;8(10):e76582.

Objective To evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV.

Design This was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children.

Methods HIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks.

Results In the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naïve and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA.

Conclusions PTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naïve CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.


Aug, 2013

A comparison of the pharmacokinetics of maraviroc during pregnancy and postpartum


Authors:  Colbers A, Brookie B, Wang J, Stek A, Hidalgo-Tenorio C, Hawkins D, Taylor G, Capparelli E, Burger D, Mirochnick M; on behalf of the PANNA network

Published: 20th Conference on Retroviruses and Opportunistic Infections, March 3rd-6th 2013, Atlanta. P_931




Jul, 2013

HCV treatment in children and young adults with HIV/HCV co-infection in Europe


Authors: Turkova A, Thorne C, Galli L, Goetghebuer T, de Martino M, Oprea C, Ramos Amador JT, Giaquinto C; for the European Pregnancy and Paediatric HIV Cohort Collaboration in EuroCoord.

Published in: 7th International AIDS Society Conference (IAS 2013), Kuala Lumpur, 30th June – 3rd July 2013


Jul, 2013

Missed opportunities for prevention of hepatitis B infection in childbearing women with HIV in Ukraine


Authors: Thorne C, Bailey H, Semenenko I, Tereschenko R, Adeyanova I, Kulakovskaya E, Ostrovskaya L, Malyuta R

Published in: 7th International AIDS Society Conference (IAS 2013), Kuala Lumpur, 30th June – 3rd July 2013


May, 2013

Pharmacokinetics of paediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands.


Authors: D Bastiaans, S Forcat, H Lyall, T Cressey, S Chalermpantmetagul, Y Saïdi, C Koenigs,  D Nayagam, A Compagnucci, S Montero, L Harper, C Giaquinto, E Colbers, D Burger.

Published in: 31st Annual Meeting of the ESPID- May 28 – June 1, 2013, Milan: Poster discussion Abstract A-534-0018-00429. 


Apr, 2013

Vaginal delivery as an option for HIV-infected women: decreasing late preterm delivery rates in a European cohort collaboration.


Authors: Aebi-Popp K, Mulcahy F, Glass T, Rudin C, Martinez de Tejada B, Bertisch B, Grawe C, Rickenbach M, Scheibner K, Hösli I and Thorne C  for the European Collaborative Study in EuroCoord and the Swiss Mother & Child HIV Cohort Study.

Published in: 5th International HIV Pediatrics Workshop, Kuala Lumpur, 28-29 June 2013.




Apr, 2013

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


Authors: Aebi-Popp K, Mulcahy F, Glass TR, et al.; for the European Collaborative Study in EuroCoord and the Swiss Mother & Child HIV Cohort Study.

Published in: J Acquir Immune Defic Syndr. 2013;64(1):58-65

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.


Apr, 2013

Improvements in virological control among women conceiving on cART in Western Europe


Authors: Bailey H, Townsend CL, Cortina-Borja M, Thorne C; for the European Collaborative Study in EuroCoord.

Published in: AIDS 2013; 27:2312-2315

Abstract Among 396 HIV-infected women conceiving on combination antiretroviral therapy and enrolled in the European Collaborative Study in 2000–2011, the proportion with virological failure (>200 copies/ml after ≥24 weeks of treatment) declined substantially from 34% in 2000–2001 to 3% in 2010–2011. In adjusted analyses, younger women and those with at least two children were at increased risk of virological failure, highlighting the importance of close monitoring and adherence support.




Mar, 2013

Use of combination neonatal prophylaxis for the prevention of mother-to-child transmission of HIV infection in European high-risk infants. 


Authors: Chiappini E, Galli L, Giaquinto C, et al. European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.

Published in: AIDS 2013; 27(6): 991-1000

Objectives To evaluate use of combination neonatal prophylaxis (CNP) in infants at high risk for mother-to-child transmission(MTCT) of HIV in Europe and investigate whether CNP is more effective in preventing MTCT than single drug neonatal prophylaxis (SNP).

Design Individual patient-data meta-analysis across eight observational studies.

Methods Factors associated with CNP receipt and with MTCT were explored by logistic regression using data from non-breastfed infants, born between 1996 and 2010 and at high risk for MTCT.

Results In 5285 mother-infant pairs, 1463 (27.7%) had no antenatal or intrapartum antiretroviral prophylaxis, 915 (17.3%) had only intrapartum prophylaxis and 2907 (55.0%) mothers had detectable delivery viral load despite receiving antenatal antiretroviral therapy. Any neonatal prophylaxis was administered to 4623 (87.5%) infants altogether; 1105 (23.9%) received CNP. Factors significantly associated with the receipt of CNP were later calendar birth year, no elective caesarean section, maternal CD4 cell count less than 200 cells/μl, maternal delivery viral load more than 1000 copies/ml, no antenatal antiretroviral therapy, receipt of intrapartum single-dose nevirapine and cohort. After adjustment, absence of neonatal prophylaxis was associated with higher risk of MTCT compared to neonatal prophylaxis [adjusted odds ratio (aOR) 2.29; 95% confidence interval (95% CI) 1.46-2.59; P < 0.0001]. Further, there was no association between CNP and MTCT compared to SNP (aOR 1.41; 95% CI 0.97-2.5; P = 0.07).

Conclusion In this European population, CNP use is increasing and associated with presence of MTCT risk factors. The finding of no observed difference in MTCT risk between one drug and CNP may reflect residual confounding or the fact that CNP may be effective only in a subgroup of infants rather than the whole population of high-risk infants.



Mar, 2013

The pharmacokinetics, safety and efficacy of tenofovir and emtricitabine in HIV-1-infected pregnant women


Authors: Colbers AP, Hawkins DA, Gingelmaier A, et al.

Published in: Aids. 2013; 27(5):739-748.

Objective To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum.

Design A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe.

Methods HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovirdisoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. Twenty-four-hour pharmacokinetic curves were recorded in the third trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0.

Results Thirty-four women were included in the analysis. Geometric mean ratios of third trimester vs. postpartum [90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area under the curve (AUC0-24 h); 0.81 (0.68-0.96) for TDF Cmax and 0.79 (0.70-0.90) for TDF C24 h and 0.75 (0.68-0.82) for FTC AUC0-24 h; and 0.87 (0.77-0.99) for FTC Cmax and 0.77 (0.52-1.12) for FTC C24 h. The viral load close to delivery was less than 200  copies/ml in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported.

Conclusion Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother-to-child transmission.


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