Mar, 2022

Birth outcomes following prenatal exposure to dolutegravir: the DOLOMITE-EPPICC study


Authors: C Thorne, K Aebi-Popp, L Ene, M Floridia, AM Gamell, M Illan, H Peters, A Samarina, L Ragone, C Giaquinto, V Vannappagari

Presented at: CROI 2022



Dolutegravir (DTG) is recommended and widely used during pregnancy for maternal viral suppression and preventing perinatal transmission of HIV. Our objective is to assess pregnancy and neonatal outcomes including birth defects following prenatal DTG use using real-world European data.

Dolomite-EPPICC is a multi-cohort European observational study of DTG use in pregnant women living with HIV and their infants. An analysis of prospectively collected data on all pregnancies with any prenatal DTG exposure and with birth outcomes was conducted among participating cohorts from Italy, Romania, the Russian Federation, Spain, Switzerland and UK/Ireland. Periconception exposure was defined as being within the first 6 weeks of gestation.

Overall, 550 pregnancies (540 singleton, 10 twin pregnancies) from 7 cohorts were included in the analysis resulting in 508 liveborn infants (491 singletons and 17 twins). Overall, 72.1% (365/506) pregnancies were in parous women. A total of 27 pregnancies ended in spontaneous abortion, 18 pregnancies were terminated and five ended in still birth. One termination was for neuronal migration disorder and severe microcephaly, with periconception DTG exposure. All stillbirths were exposed to periconception DTG, none with birth defects. Among the 508 liveborn infants, earliest DTG exposure was periconception for 326 (64.9%) infants, later in trimester 1 for 36 (7.2%) and in trimester 2/3 for 140 (27.9%); 6 had unknown timing of exposure. There were 21 infants with birth defects (4.1%, 95% CI 2.6, 6.2); one infant had 2 defects. The 22 defects were in the following systems: genitourinary (7), heart (4), limb (4 [polydactyly, 3]), gastrointestinal (2), chromosomal (1), other (4); no CNS defects were reported.

The prevalence rate for overall birth defects here is the same as recently reported from the Antiretroviral Pregnancy Registry for periconception exposure to DTG. Dolomite-EPPICC will continue to monitor use and safety of DTG-based regimens in pregnancy, noting that our sample size of periconception exposures is currently too small to exclude potential associations with rare birth defects like NTDs.

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Dec, 2020

Cascade of care in children and adolescents with HIV in Russian Federation

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Author: Anna Turkova, Evgeny Voronin, Yulia Plotnikova, Anna Samarina, Edith Milanzi, Vladimir Rozenberg, Liubov Okhonskaia, Inga Latysheva, Aleksey Plynsky, Elena Fertikh, Siobhan Crichton, Charlotte Jackson, Ali Judd, Intira J Collins, on behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Published in: 12th International Workshop on HIV Pediatrics

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The cascade of care summarises the 90-90-90 UNAIDS targets, of 90% of HIV+ people knowing their status, of whom 90% receive antiretroviral treatment (ART), of whom 90% are virally suppressed

By 2019, there were 1,068,839 people diagnosed with HIV in Russia, of whom 50% were on ART, and of those 76% were virally suppressed1.

However, there is less data on the HIV care continuum in children and adolescents with HIV in Russia



To summarise the cascade of care in children and adolescents living with HIV in three Russian clinics.



We included data on children/adolescents aged <18 years at HIV diagnosis from three Russian clinics within the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC).

Follow-up data from first presentation to HIV care until death, loss to follow-up, transfer to adult care or last visit (data cut-off 1/10/2016) were included.

As all patients were already diagnosed with HIV, we adapted the cascade of care as follows: (a) initiated ART, (b) virally suppressed (VS) ≤1000 copies/ml and (c) having good WHO immune status* at last visit.  The analysis was restricted to patients in active paediatric follow-up (FU) in 2015-2016 and had ≥12 months of FU.

Characteristics of patients and cascade results were stratified by age of HIV diagnosis:

i.Diagnosed during “childhood” (age <10) and

ii.Diagnosed during “adolescence” (age ≥10)

The proportion with VS and good immune status* at 12(±3) months after ART start was also summarized overall and by calendar year of ART start.



  • Of 922 patients followed in the 3 centres, 703 had ≥12 months FU and were in care in 2015/16 and included in this analysis. Of these:
  • 655 (93%) were diagnosed in childhood, of whom 94% had perinatally acquired HIV (Table 1)
  • 48 (7%) were diagnosed in adolescence, of whom 27% had perinatally acquired HIV, 25% sexually-acquired, and 48% had other or unknown mode of transmission
  • 94% (618/655) in the childhood group initiated ART compared to 81% (39/48) in the adolescent group.
  • At ART initiation, the median age was 2.2 years and 16.1 years in the childhood and adolescence group, respectively. 52% and 58% had advanced or severe WHO immunosuppression at ART start, respectively (Table 1).


Mar, 2020

Global variations in pubertal growth in adolescents living with perinatal HIV


Authors: Crichton S, Jesson J, Aké-Assi MH, Belfrage E, Davies MA, Pinto J, Teasdale C, Van Lam N, Vreeman R, Wanless S, Williams P, Yotebieng M, Leroy V, Goodall R on behalf of the CIPHER Global Cohort Collaboration

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.



Mar, 2020

Abacavir dosing, effectiveness, and safety in young infants living with HIV in Europe


Authors: Crichton S , Collins  IJ, Turkova A, Ene L, Galli L, Marczynska M, Navarro M, Naver L, Noguera-Julian A, Plotnikova Y, Scherpbier H, Volokha A, Voronin E, Judd A; on behalf of the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC)

Published in: 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.



Background: The World Health Organization (WHO) recommends abacavir as the preferred/alternative backbone for 1st line regimens in children with HIV from age 28 days. There are limited data available on safety and tolerability of abacavir in young infants aged <3 months.

Methods: We describe infant and regimen characteristics at the start of abacavir (including drug combinations and dosing) and outcomes up to 12 months after first use of abacavir. Outcomes include:

  • drug discontinuations (defined as interruption of abacavir for >30 days),
  • clinical adverse events (AE, reported from start of abacavir, and up to 30 days after discontinuation of abacavir) and
  • viral load at 6 and 12 (±3) months after start of abacavir

Conclusions: Across children initiating abacavir in early life in Europe, it was safe and well tolerated, and discontinuations for safety concerns were rare. • Viral suppression was below the UN-AIDS 90% target which may reflect challenges of treatment in infancy.


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Mar, 2020

Outcomes following prenatal exposure to dolutegravir: the Dolomite-EPPICC study


Authors: Thorne C, Rasi V, Aebi-Popp K, Ene L, Floridia M, Mendoza-Palomar N, Prieto L, Ragone L, Sconza R, CGiaquinto C, Vannappagari V; for the Dolomite-EPPICC study group

Published in: Oral presentation at 27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.



BACKGROUND • In 2018, the Tsepamo Study, Botswana reported significant increased risk of NTD in women conceiving on DTG (0.94%) 1 leading to a safety alert • Updated analysis of NTD prevalence (08/2014 – 03/2019)2 • 5 NTDs/1,683 deliveries in women on DTG at conception (0.30%, 95% CI 0.13-0.69 vs 0.10%, 95% CI 0.06-0.17 for non-DTG ART at conception • The Antiretroviral Pregnancy Registry recently reported 1 NTD in 312 periconception DTG exposures (0.3%) 3 • The Dolomite Study was set up in 2017 to address use & safety of DTG in pregnancy and exposed infants in Europe and Canada; conducted within the NEAT-ID network and EPPICC (the European Pregnancy and Paediatric Infections Cohort Collaboration)

Aim: To assess pregnancy and neonatal outcomes following DTG use during pregnancy in real-world European settings • Objectives were to describe: • characteristics of pregnant women receiving DTG-based regimens • frequency of adverse pregnancy and birth outcomes, by earliest timing of DTG exposure

Method: Dolomite-EPPICC involves pooled analyses of prospectively collected individual patient data on DTG-exposed pregnancies from participating studies • Data specification based on a modified HIV Data Exchange Protocol (www.hicdep.org) • Data merger included • All pregnancies with any prenatal DTG exposure • With birth outcomes reported by Feb 2019 • Periconception DTG exposure was defined as initial exposure at ≤6 weeks of estimated gestational age (EGA)

Results: 453 pregnancies in 428 women included (Figure) • Pregnancies reported from six countries • 347 (76.6%) UK and Ireland, 45 (9.9%) Spain, 29 (6.4%) Switzerland, 29 (6.4%) Italy, 3 (0.7%) Romania


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Mar, 2020

Long-term non-progression in children with perinatally acquired HIV


Authors: Jackson C, Bamford A, Crichton S, Goodall R,Goulder P, Klein N, Marques L, Paioni P, Riordan A, Spoulou V, Vieira VA, Collins IJ. On behalf of The European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Published in:  27th Conference on Retroviruses and Opportunistic Infections, March 8th –11th, 2020 – Boston.



Apr, 2019

Severe haematologic toxicity is rare in high risk HIV-exposed infants receiving combination neonatal prophylaxis.


Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord

Published in: HIV Med. 2019;20(5):291-307

Objectives Combination neonatal prophylaxis (CNP) is recommended in high‐risk situations for the prevention of mother‐to‐child HIV transmission, although data on its safety are limited. The aim of the study was to identify whether neonatal prophylaxis (NP) type is associated with the risk of severe anaemia or neutropaenia.

Methods An individual patient data meta‐analysis was conducted within six European cohorts, in infants at high risk for acquiring HIV infection. Adjusted logistic regression models were used to assess the risk of National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) grade 3–4 anaemia/neutropaenia at ages 0–6 months. Mixture models of haemoglobin (Hb) level and log10‐transformed neutrophil count (NC) were used to explore associations with NP type at ages 0–18 months.

Results Of 1836 infants, 25% were preterm, 1149 (63%) had antenatal combination antiretroviral therapy (cART) exposure and 395 (22%) received NP (125 received CNP with three drugs). Overall, 117 (6.7%) infants had grade 3–4 anaemia at age 0–6 months and 140 (9.1%) had grade 3–4 neutropaenia. The presence of grade 3–4 anaemia or neutropaenia was not associated with NP type [adjusted odds ratio (aOR) 1.04 for one‐drug NP and 1.60 for three‐drug NP versus two‐drug NP (P = 0.879 and P = 0.277, respectively) for anaemia; aOR 1.33 for one‐drug NP and 1.98 for three‐drug NP versus two‐drug NP (=0.330 and =0.113, respectively) for neutropaenia], but was associated with preterm delivery. Overall, 7746 Hb and NC results were available for 1836 infants up to age 18 months; no significant differences in predicted Hb level or NC were apparent by NP type.

Conclusions A small proportion of infants experienced grade 3–4 haematological adverse events; risk of anaemia or netropenia was not associated with type of NP.


Apr, 2019

Prevalence and clinical outcomes of poor immune response despite virologically suppressive antiretroviral therapy among children and adolescents with HIV in Europe and Thailand: cohort study


Authors: Collins IJ; European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord

Published in: Clin Infect Dis. 2019; 28. pii: ciz253. doi: 10.1093/cid/ciz253. [Epub ahead of print]

Background In HIV-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children on suppressive ART.

Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children aged<18 years at ART initiation, with sustained viral suppression (VS) (≤400copies/mL) for ≥1 year were included. The prevalence of PIR (defined as WHO advanced/severe immunosuppression for age: CD4%<30% in children aged<12 months, CD4%<25% in 12-35 months, CD4%<20% in 36-59 months; CD4%<15%/CD4<350 cells/mm3 in ≥5-years) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of AIDS or death on suppressive ART were calculated by PIR status.

Results Of 2318 children included, median age was 6.4 [IQR, 2.1, 10.4] years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis-B coinfection and residing in Thailand (all p≤0.03). Rates of AIDS/death (95% CI) per 100,000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92), p<0.001.

Conclusions One in eight children in our cohort experienced PIR despite sustained viral suppression. While the overall rate of AIDS/death was low, children with PIR had four-fold increase in risk of event as compared to immune responders.


Mar, 2019

Nucleoside reverse transcriptase inhibitor backbones and pregnancy outcomes


Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group

Published in: Aids. 2019;33(2):295-304.

Objectives The aim of this study was to investigate whether specific nucleoside reverse transcriptase inhibitor (NRTI) backbones are associated with risk of adverse pregnancy outcomes among pregnant women starting antiretroviral therapy (ART).

Design Seven observational studies across eight European countries of pregnancies in HIV-positive women.

Methods Individual-level data were pooled on singleton pregnancies conceived off-ART in which a single combination ART regimen was initiated at least 2 weeks before delivery, and ending in a live birth in 2008-2014. Preterm delivery (PTD) was defined as less than 37 gestational weeks and small-for-gestational-age (SGA) as less than 10th percentile according to INTERGROWTH standards. Poisson regression models were fitted to investigate associations between NRTI backbones and PTD/SGA.

Results Out of 7193 pregnancies, 45% (3207) were in UK/Ireland, 44% (3134) in Ukraine. 10% (722/7193) of deliveries were preterm and 11.1% (785/7089) of newborns SGA. The most common NRTI backbones were zidovudine (ZDV)-lamivudine (3TC) (71%), tenofovir (TDF)-XTC (16%) and abacavir (ABC)-3TC (10%) with TDF-containing backbone use increasing over time. Overall, 77% of regimens contained ritonavir-boosted lopinavir (LPV/r). There was no association between NRTI backbone and PTD in main adjusted analyses [adjusted prevalence ratios (aPRs) 0.97 (95% confidence interval, 95% CI 0.73-1.28] for ABC-3TC and aPR 1.06 (95% CI 0.83-1.35) for TDF-XTC, both vs. ZDV-3TC) or in 4720 pregnancies on LPV/r [aPR 1.03 (95% CI 0.74-1.43) for ABC-3TC and aPR 1.16 [0.85-1.57] for TDF-XTC, both vs. ZDV-3TC]. Infants exposed to ABC-3TC or TDF-XTC in utero were less likely to be SGA than those exposed to ZDV-3TC [aPR 0.72 (95% CI 0.53-0.97) and aPR 0.70 (95% CI 0.53-0.93), respectively].

Conclusion Results support the safety of TDF-XTC backbones initiated in pregnancy with respect to gestation length and birthweight.


Mar, 2019

Birth Defects After Exposure to Efavirenz-Based Antiretroviral Therapy at Conception/First Trimester of Pregnancy A Multicohort Analysis


Authors: Martinez de Tejada B; European Pregnancy and Paediatric HIV Cohort Collaboration Study Group.

Published in: J Acquir Immune Defic Syndr. 2019;80(3):316-324


Background To investigate the association between efavirenz (EFV) use during conception or first trimester (T1) of pregnancy and the occurrence of birth defects.

Setting Seven observational studies of pregnant HIV-positive women across 13 European countries and Thailand.

Methods Individual-level data were pooled on singleton pregnancies included in participating cohorts in 2002-2015. Birth defects were coded according to ICD-10 and the EUROCAT classification. We performed mixed-effects logistic regression models to assess the association between EFV exposure in utero and likelihood of birth defects.

Results We included 24,963 live births from 21,093 women. At conception, 30.2% (7537) women were on a non-EFV-based regimen, 4.8% (1200) on EFV, and 65% (16,226) were unexposed to antiretroviral therapy (ART). There were 412 infants with ≥1 birth defect, a prevalence of 1.65% (95% confidence interval: 1.50 to 1.82). Limb/musculoskeletal and congenital heart defects were the most common defects reported. Birth defects were present in 2.4%, 1.6%, and 1.3% of infants exposed to non-EFV, EFV, and unexposed to ART during conception/T1 (P = 0.135), respectively. The association between exposure to ART during conception/T1 and birth defects remained nonsignificant in adjusted analyses, as did exposure to EFV versus non-EFV (adjusted odds ratio 0.61; 95% confidence interval: 0.36 to 1.03, P = 0.067). Among the 21 birth defects in 19 infants on EFV, no neural tube defects were reported.

Conclusions Prevalence of birth defects after exposure to EFV-based compared with non-EFV-based ART in conception/T1 was not statistically different in this multicohort study, and even lower. EFV is at least as safe as other ART drugs currently recommended for antenatal use.


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