Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Coinfection with HIV and hepatitis C virus in 229 children and young adults living in Europe

[Objective] To characterize children, adolescents and young adults infected with HIV/hepatitis C virus (HCV) vertically or before age of 18 years and living in Europe regarding mode of acquisition, HCV genotype, clinical status and treatment.[Design] Retrospective, cross-sectional study using pooled data from 11 European paediatric HIV cohorts.[Methods] Patients aged more than 18 months and less than 25 years, with HIV/HCV acquired vertically or in childhood, were included. Anonymized individual patient data were collected using a standard protocol and modified HIV Cohorts Data Exchange Protocol.[Results] Of 229 patients included, 142 (62%) had vertically acquired infection. Median age at last follow-up was 16.2 years. Most children had HCV genotype 1 (101/184, 55%) or 3 (57/184, 31%). One-fifth (46/214) had a previous AIDS diagnosis (data missing on prior AIDS diagnoses for 15). At their last clinic visit, 70% (145/208) had no/mild immunosuppression (Centers for Disease Control and Prevention stage 1), and 131 of 179 on antiretroviral therapy had undetectable HIV RNA (assay thresholds varied from <20 to <150 copies/ml). Overall, 42% (86/204) had hepatomegaly in the previous year, and 55% (116/213) had alanine aminotransferase more than 40 IU/l at their last test. Of 97 patients with transient elastography, 12 had results more than 9 kPa; this was associated with duration of HCV infection (P = 0.033), but not with CD4+ cell count, antiretroviral therapy use or sex in univariable analysis. Of 17 patients with liver biopsies, six had bridging fibrosis and one had cirrhosis. Twenty-five (11%) had been treated successfully for HCV.[Conclusion] The high proportion of patients with progressive liver disease underscores the need for close monitoring and earlier and more effective HCV treatment.This work was supported by funding from the EU Seventh Framework Programme (FP7/2007–2013) under EuroCoord grant agreement [no. 260694] and additional funding from Janssen.Peer reviewe

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

OBJECTIVES: To carry out an epidemiological analysis of the emerging epidemic in an Eastern European country and to compare the approach to prevention of mother-to-child transmission (MTCT) with that in Western Europe. DESIGN: Prospective cohort study established in 1985 in Western Europe and extended to Ukraine in 2000. METHODS: Data on 5967 HIV-infected pregnant women and their infants (1251 from Ukraine and 4716 from Western/Central Europe) was analysed. Factors associated with transmission were identified with logistic regression. RESULTS: HIV-infection among pregnant women enrolled in Western European centres has shifted from being largely injecting drug use (IDU)-related to heterosexually-acquired; in Ukraine IDU also gradually declined with women increasingly identified without specific risk factors. In Ukraine in 2000-2004 most (80%) women received single dose nevirapine (sdNVP) and/or short-course zidovudine prophylaxis [MTCT rate 4.2%; 95% confidence interval (CI), 1.8-8.0 for sdNVP with short-course zidovudine]; 2% (n = 27) received antenatal HAART and 33% (n = 418) delivered by elective caesarean section (CS); in Western European centres 72% of women received HAART (MTCT rate 1.0%; 95% CI, 0.4-1.9) and 66% delivered by elective CS during the same period. CONCLUSIONS: Our findings indicate distinct differences in the epidemics in pregnant women across Europe. The evolution of the MTCT epidemic in Ukraine does not appear to be following the same pattern as that in Western Europe in the 1980s and 1990s. Although uptake of preventive MTCT prophylaxis has been rapid in both Western Europe and Ukraine, substantial challenges remain in the more resource-constrained setting in Eastern Europe

Levels and patterns of HIV RNA viral load in untreated pregnant women.

none101OBJECTIVE: To assess pregnancy levels and patterns of HIV RNA in the absence of antiretroviral therapy, while appropriately adjusting for potential confounders, including maternal immune status and race. METHODS: Data on > or = 1 antenatal HIV RNA measurements were available for 333 untreated HIV-infected pregnant women enrolled in the European Collaborative Study. CD4 counts and HIV RNA measurements were routinely collected from 1992 and 1998, respectively. Linear mixed effects models based on 246 women for whom complete data were available examined changes in HIV RNA levels over pregnancy, with a nested random effects term accounting for measurement variability within women and period of sample collection. RESULTS: The change in HIV RNA over pregnancy varied significantly by race (p=0.005): from the second trimester until delivery, HIV RNA decreased significantly by an estimated 0.019 log(10) copies/ml/week in white women (95% CI -0.03, -0.007); in black women the estimated 0.016 log(10) copies/ml/week increase (95% CI -0.005, 0.037) was not statistically significant. At delivery, HIV RNA levels in black women were 0.45 log(10) copies/ml higher (95% CI 0.08, 0.83) than in white women. CONCLUSIONS: Our findings suggest that HIV RNA dynamics over pregnancy differ by race, although other interpretations cannot be excluded, due to potential for unmeasured confounding.mixedGIAQUINTO C; RAMPON O; D'ELIA R; DE ROSSI A; GROSCH-WÖRNER I; MOK J; DE JOSÉ MI; LARRÚ MARTÍNEZ B; PEÑA JM; 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; EHRNST A; BOHLIN AB; LINDGREN S; ANZÉN B; LIDMAN K; LEVY J; BARLOW P; MANIGART Y; HAINAUT M; GOETGHEBUER T; FERRAZIN A; VISCOLI C; DEMARIA A; BENTIVOGLIO G; S. FERRERO; GOTTA C; MÛR A; PAYÀ A; LÓPEZ-VILCHEZ MA; CARRERAS R; VALERIUS NH; ROSENFELDT V; JIMENEZ J; COLL O; SUY A; PEREZ JM; FORTUNY C; BOGUÑA J; CASELLAS CARO M; CANET Y; 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; CRIVELLI M; FERRAZZI E; VIGANÒ A; GIACOMET V; CERINI C; RAIMONDI C; ZUCCOTTI G; RAVAGNI PROBIZER F; MACCABRUNI A; BUCCERI A; RANCILIO L; ALBERICO S; RABUSIN M; BERNARDON M; 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; POSOKHOVA S; KALEEVA T; STELMAH A; KISELEVA GGiaquinto, C; Rampon, O; D'Elia, R; DE ROSSI, A; GROSCH WÖRNER, I; Mok, J; DE JOSÉ, Mi; LARRÚ MARTÍNEZ, B; Peña, Jm; 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; Ehrnst, A; Bohlin, Ab; Lindgren, S; Anzén, B; Lidman, K; Levy, J; Barlow, P; Manigart, Y; Hainaut, M; Goetghebuer, T; Ferrazin, A; Viscoli, Claudio; DE MARIA, Andrea; Bentivoglio, Giorgio; Ferrero, Simone; Gotta, C; Mûr, A; Payà, A; LÓPEZ VILCHEZ, Ma; Carreras, R; Valerius, Nh; Rosenfeldt, V; Jimenez, J; Coll, O; Suy, A; Perez, Jm; Fortuny, C; Boguña, J; CASELLAS CARO, M; Canet, Y; 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; Crivelli, M; Ferrazzi, E; Viganò, A; Giacomet, V; Cerini, C; Raimondi, C; Zuccotti, G; RAVAGNI PROBIZER, F; Maccabruni, A; Bucceri, A; Rancilio, L; Alberico, S; Rabusin, M; Bernardon, M; 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; Posokhova, S; Kaleeva, T; Stelmah, A; Kiseleva, G

Levels and patterns of HIV RNA viral load in untreated pregnant women

Objective: To assess pregnancy levels and patterns of HIV RNA in the absence of antiretroviral therapy, while appropriately adjusting for potential confounders, including maternal immune status and race. Methods: Data on >= 1 antenatal HIV RNA measurements were available for 333 untreated HIV-infected pregnant women enrolled in the European Collaborative Study. CD4 counts and HIV RNA measurements were routinely collected from 1992 and 1998, respectively. Linear mixed effects models based on 246 women for whom complete data were available examined changes in HIV RNA levels over pregnancy, with a nested random effects term accounting for measurement variability within women and period of sample collection. Results: The change in HIV RNA over pregnancy varied significantly by race (p = 0.005): from the second trimester until delivery, HIV RNA decreased significantly by an estimated 0.019 log(10) copies/ml/week in white women (95% Cl -0.03, -0.007); in black women the estimated 0.016 log(10) copies/ml/week increase (95% Cl -0.005, 0.037) was not statistically significant. At delivery, HIV RNA levels in black women were 0.45 log(10) copies/ml higher (95% Cl 0.08, 0.83) than in white women. Conclusions: Our findings suggest that HIV RNA dynamics over pregnancy differ by race, although other interpretations cannot be excluded, due to potential for unmeasured confounding. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Malignancies among children and young people with HIV in Western and Eastern Europe and Thailand the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Objectives: Investigate trends over time and predictors of malignancies among children and young people with HIV. Design: Pooled data from 17 cohorts in 15 countries across Europe and Thailand. Methods: Individuals diagnosed with HIV and presenting to paediatric care less than 18 years of age were included. Time at risk began at birth for children with documented vertically acquired HIV, and from first HIV-care visit for others. Children were followed until death, loss-to-follow-up, or last visit in paediatric or adult care (where data after transfer to adult care were available). Rates of reported malignancies were calculated overall and for AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (NADM) separately. Risk factors for any malignancy were explored using Poisson regression, and for mortality following a malignancy diagnosis using Cox regression. Results: Among 9632 individuals included, 140 (1.5%) were ever diagnosed with a malignancy, of which 112 (80%) were ADM. Overall, the rate of any malignancy was 1.18 per 1000 person-years; the rate of ADM decreased over time whereas the rate of NADM increased. Male sex, being from a European cohort, vertically acquired HIV, current severe immunosuppression, current viral load greater than 400 copies/ml, older age, and, for those not on treatment, earlier calendar year, were risk factors for a malignancy diagnosis. Fifty-eight (41%) individuals with a malignancy died, a median 2.4 months (IQR 0.6-8.8) after malignancy diagnosis. Conclusion: The rate of ADM has declined since widespread availability of combination ART, although of NADM, there was a small increase. Mortality following a malignancy was high, warranting further investigation

Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

BACKGROUND: In human immunodeficiency virus (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 receiving suppressive ART. METHODS: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children &lt;18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. RESULTS: Of 2318 children included, median age was 6.4 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 ≤ .03). Rates of AIDS/death (95% confidence interval) 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 &lt; .001). CONCLUSIONS: One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders