HIV | Eppicc

Authors: Turkova A, Giacomet V, Goetghebuer T, et al.

Published in: J Virus Erad. 2015;1(3):179-184

Methods HCV treatment data on children and young people aged <25 years with HIV/HCV co-infection were collected in a cohort collaboration of 11 European paediatric HIV cohorts. Factors associated with receipt of HCV treatment and with sustained virological response 24 weeks after treatment completion (SVR24) were explored.

Results Of 229 HIV/HCV co-infected patients, 22% had a history of AIDS and of 55 who were treated for HCV, 47 (85%) were receiving combined antiretroviral therapy. The overall HCV treatment rate was 24% (n=55) but it varied substantially between countries, with the highest rate being in Russia at 61% (30/49). Other factors associated with treatment receipt were older age [adjusted odds ratio (AOR) 5.24, 95% confidence interval (CI) 1.9–14.4, for 18–24-year-olds vs 11–17-year-olds, P=0.001] and advanced fibrosis (AOR 5.5, 95% CI 1.3–23.7; for ≥9.6 vs ≤7.2 kPa, P=0.02). Of 50 patients with known treatment outcomes, 50% attained SVR24. Of these, 16 (80%) had genotype (GT) 2,3 and 8 (29%) had GT 1,4 (P<0.001). After adjusting for genotype (GT 1,4 vs GT 2,3), females (P=0.003), patients with non-vertical HCV acquisition (P=0.002) and those with shorter duration of HCV (P=0.009) were more likely to have successful treatment outcomes.

Authors: Bailey H, Townsend C, Semenenko I, Malyuta R, Cortina-Borja, Thorne C; for the Ukraine European Collaborative Study in EuroCoord

Published in: BMC Public Health. 2014; 24(14):993

Background Poor adherence to antiretroviral therapy (ART) is associated with HIV disease progression and, during

pregnancy, increased mother-to-child transmission risk. In Ukraine, access to combination ART is expanding but data

on adherence are scarce.

Methods Cross-sectional surveys of HIV-positive women were conducted i) at delivery (on antenatal ART adherence)

and ii) during the first year postpartum (on ART adherence in the preceding four weeks). Factors associated with a

score ≤11 on the self-report Case Adherence Support Evaluation (CASE) index or ≥1 self-reported missed dose were

assessed using Fisher’s exact test.

Results Of 185 antenatal participants and 102 postnatal participants, median ages were 27.5 and 29.5 years

respectively: 28% (50/180) and 27% (26/98) reported an unplanned pregnancy, and 13% (24/179) and 17% (17/98) an

illicit drug-use history (excluding marijuana). One quarter (49/180 antenatally, 27/101 postnatally) screened positive for

depression. The proportion reporting ‘low’ ART-related self-efficacy (i.e. unable to do ≥1/5 ART-taking activities) was

20% (28/141) antenatally and 17% (11/66) postnatally. Antenatally, 14% (95% CI 10-21%) had a CASE score ≤11 and

35% (95% CI 28-42%) reported missing ≥1 dose. Factors associated with a CASE score ≤11 were unplanned pregnancy

(25% (12/48) vs. 11% (13/120) where planned, p = 0.03) and living with extended family (23% (13/57) vs. 10% (12/125)

living with partner/alone, p = 0.04). Self-report of ≥1 missed dose antenatally was additionally associated with

younger age (p = 0.03) and lower self-efficacy (50% (14/28) reported ≥1 missed dose vs. 28% (30/108) of those

with high self-efficacy, p = 0.04). Of 102 postnatal participants, 8% (95% CI 4-15%) had a CASE score ≤11 and 31%

(95% CI 22-41%) reported ≥1 missed dose. Of 11 women with low self-efficacy, 3 (27%) had a CASE score ≤11

compared with 3/55 (5%) of those with high self-efficacy (p = 0.05). Current smokers more commonly reported ≥1

missed dose postnatally (50% (13/26) vs. 25% (18/72) of non-smokers, p = 0.03).

Conclusions Our results highlight unmet needs for counselling and support. We identify some groups at risk of

poor ART adherence, including women with markers of social vulnerability and those with low ART-related

self-efficacy, who may benefit from targeted interventions.

Authors: Turkova A; for the European Paediatric HIV/HCV Co-infection Study Group in the European Pregnancy and Paediatric HIV Cohort Collaboration in EuroCoord.

Published in: 20th International AIDS Conference (AIDS 2014), July 20th-25th 2014, Melbourne, Australia.

Authors: Bagkeris E, Bailey H, Malyuta R, Volokha A, Thorne C

Published in: 6^th International Workshop on HIV Pediatrics, July 18th-19th  2014, Melbourne, Australia.

Authors: Judd A, Duong T, Galli L, et al; on behalf of the European Pregnancy and Paediatric HIV Cohort Collaboration study group in EuroCoord.

Published in: Pharmacoepidemiol  Drug Saf. 2014;23(3):321-5

Methods Retrospective analysis of individual patient data for all children aged 6–18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity.

Results Ninety-two HIV-infected children aged 6–18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1–11 years), and median age at start of FPV/r was 15 years (12–17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported.

Authors: Judd A, Collins J, Lodi S, Olson A, Pantazis N, Gibb DM; on behalf of the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) in EuroCoord

Published in: 18th International Workshop on HIV Observational Databases, March 27th-29th 2014, Sitges, Spain.

Authors: Judd A, Childs T, Collins J, Dodonov K, Galli L, Goetghebuer T, Konigs C, Noguera-Julian A, Rojo Conejo P, Naver L, Tookey P, Giaquinto C; on behalf of the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) in EuroCoord.

Published in: 18th International Workshop on HIV Observational Databases, March 27th-29th 2014, Sitges, Spain.

Authors: Bailey H, Thorne C, Giaquinto C, Tookey P; for the UK and Ireland National Study of HIV in Pregnancy and Childhood and the European Collaborative Study in EuroCoord.

Published in: 18th International Workshop on HIV Observational Databases, March 27th-29th  2014, Sitges, Spain.

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

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

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

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.

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.

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.

Authors: Goetghebuer T, Le Chenadec J, Haelterman E, et al.

Published in: Clinical Infectious Diseases 2012; 54(6): 878-881

Abstract The clinical benefit of antiretroviral therapy in infants is established. In this cohort collaboration, we compare immunological and virological response to treatment started before or after 3 months of age. Early initiation provides a better short-term response, although evolution after 12 months of age is similar in both groups.

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

Published in: AIDS 2011; 25(18): 2279-2287

Background Durable and tolerable first-line antiretroviral therapy (ART) regimens are needed for HIV-infected infants who may need life-long treatment. We investigated virological and immunological response to ART, and predictors of switching and interrupting treatment among infants starting ART in the European Pregnancy and Paediatric HIV Cohort Collaboration.

Methods 9 cohorts from 13 European countries contributed data on HIV-infected infants born 1996-2008 and starting ART before age 12 months. Logistic and linear regression, and competing risks methods were used to assess predictors of virological (viral load <400c/mL) and immunological (change in CD4 Z-score) response, switching to second-line ART and treatment interruptions with viral load <400c/mL.

Findings 437 infants were followed for median 5.9 (interquartile range 2.3-7.6) years after starting ART; 30% had an AIDS diagnosis prior to ART initiation. Virological response improved with calendar year of ART initiation; 53% had suppressed viral load <400c/mL at 12 months in 1996-1999, increasing to 77% in 2004-2008. Virological and immunological responses at 12 months varied by initial ART type (p<0.001 and p=0.03 respectively), with 4-drug NNRTI-based regimens being superior (virological response <400c/mL adjusted OR 3.00, 95%CI 1.24-7.23; mean increase in CD4 Z-score coefficient 0.64, 95%CI 0.10-1.17) to both 3-drug NNRTI-based (reference) and boosted PI regimens which were similar. Rates of switching to second-line ART were lower among children starting 4-drug NNRTI-based and boosted PI-based regimens compared to 3-drug NNRTI regimens (p=0.03). 65% of infants remained on first-line ART without treatment interruption after five years.

Interpretation Effective and prolonged responses to first-line ART can now be achieved in infants starting early ART outside trial settings. Superior responses to 4-drug NNRTI compared

Authors: Wittkop L, Günthard HF, de Wolf F, et al. EuroCoord-CHAIN study group.

Published in: Lancet Infectious Diseases 2011; 11(5): 363-71

Background The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration.

Methods HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy.

Findings Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8–4·7) for patients in the no TDR group, 4·7% (2·9–7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9–19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33–4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19–2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9–4·7, p=0·093).

Interpretation These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients.

Authors: Castro H, Judd A, Gibb DM, et al. Pursuing Later Treatment Options II (PLATO II) project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).

Published in: Lancet 2011; 377(9777): 1580-1587

Background: In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children.

Methods: In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation.

Findings: Of 1007 children followed up for a median of 4·2 (IQR 2·4–6·5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI 9·4–14·6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2·2 [95% CI 1·6–3·0, p<0·0001]).

Interpretation: Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression.

Authors: Lodwick R, Costagliola D, Reiss P, et al. Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).

Published in: Archives of Internal Medicine. 2010; 170(5):410-419

Background: Life expectancy in people with HIV is now estimated to approach that in the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades.

Methods: We studied the rate of triple class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) with an NNRTI- or PI/r-containing regimen from 1998 onwards. We also focussed on TCVF in patients who started a PI/r-containing regimen after virologically failing a first-line NNRTI-containing regimen.

Results: Of 45937 patients followed for a median (IQR) 3.0 (1.5-5.0) years, 980 (2.1%) developed TCVF. By 5 and 9 years after starting ART, an estimated 3.4% (95% CI:3.1%-3.6%) and 8.6% (95% CI:7.5%-9.8%) of patients had developed TCVF. The incidence of TCVF rose during the first 3-4 years on ART, but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI- or PI/r-based (p=0.11). By 5 years after starting a PI/r as second-line, 46% of patients had developed TCVF.

Conclusions: The rate of virologic failure of the three original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from start of a PI/r after NNRTI failure provides a comparator for studies of response to secondline regimens in resource-limited settings.

Authors: Goetghebuer T, Haelterman E, Le Chenadec J, et al. for the European infant collaboration group.

Published in: AIDS 2009;23:597-604

Objective: In the absence of treatment, rapid progression to AIDS occurs in approximately 20% of HIV-1-infected infants over the first year of life. The prognosis of these children has considerably improved with highly active antiretroviral therapy. As data from well resourced countries are lacking, the objective of this collaborative study was to evaluate the impact of early treatment in vertically infected infants.

Design: Children born to HIV-infected mothers between 1 September 1996 and 31 December 2004, who were diagnosed with HIV and free of AIDS before 3 months, were eligible. Demographics and pregnancy data, details of antiretroviral therapy, and clinical outcome were collected from 11 European countries.Methods:The risk of AIDS or death, by whether or not an infant started treatment before 3 months of age, was estimated by Kaplan–Meier survival analysis and Cox proportional hazards models.

Results: Among 210 children, 21 developed AIDS and three died. Baseline characteristics of the 124 infants treated before 3 months were similar to those of the 86 infants treated later. The risk of developing AIDS/death at 1 year was 1.6 and 11.7% in the two groups, respectively (P < 0.001). Deferring treatment was associated with increased risk of progression [crude hazard ratio 5.0; 95% confidence interval (CI) 2.0–12.6; P = 0.001] that persisted after adjusting for cohort in multivariate models (adjusted hazard ratio 3.0; 95% CI 1.2–7.9; P = 0.021).

Conclusion: In HIV-1 vertically infected infants, starting antiretroviral therapy before the age of 3 months is associated with a significant reduction in progression to AIDS and death.