2017
Authors: Sáfadi MA, Nascimento-Carvalho CM
Published in: Pediatr Infect Dis J.2017;36(3):333-336
Abstract After remaining related to few sporadic cases in limited regions for more than half century since its discovery, Zika virus (ZIKV) was recently introduced into the Western Hemisphere, first in Brazil and then spreading very rapidly in the Americas. Unexpectedly, an increased incidence of microcephaly and other neurologic malformations in fetuses born to mothers infected with ZIKV during pregnancy was reported in Brazil, leading the World Health Organization to declare this situation a Public Health Emergency of International Concern
2017
Authors: Garcez PP, Nascimento JM, de Vasconcelos JM, et al.
Published in: Sci Rep. 2017 Jan 23;7:40780
Abstract Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.
2017
Authors: Sacramento CQ, de Melo GR, de Freitas CS, et al.
Published in: Sci Rep.2017 Jan 18;7: 40920
Abstract Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.
2017
Authors: Gaskell KM, Houlihan C, Nastouli E, Checkly AM
Published in: Emerg Infect Dis.2017;23(1):137-139
Abstract Zika virus is normally transmitted by mosquitos, but cases of sexual transmission have been reported. We describe a patient with symptomatic Zika virus infection in whom the virus was detected in semen for 92 days. Our findings support recommendations for 6 months of barrier contraceptive use after symptomatic Zika virus infection.
2017
Authors: Melbourne-Chambers R., Christie CD, Greenaway E., Bullock R
Published in: West Indian Med J.2016;65(3):425-430
Abstract Dengue, Chikungunya Fever (CHIKV) and Zika virus (ZIKV) are all transmitted by the Aedes aegypti mosquito and are currently circulating in Jamaica. Jamaica has been experiencing a ZIKV epidemic since February 2016. At the University Hospital of the West Indies (UHWI), Kingston, Jamaica, a cluster of five cases of paralysis attributed to neuro-inflammation was noted amongst adolescents admitted to the institution. Three were diagnosed with acute myelitis and one each with acute disseminated encephalomyelitis (ADEM) and guillain barre syndrome (GBS). In these patients, there were common presenting symptoms, characteristic findings of peripheral nerve involvement and a history of contact with persons with symptoms of possible ZIKV in the majority. In only one case was a viral association, Dengue infection, confirmed. This case series suggests a unique clinical pattern of neuro-inflammation in Jamaican adolescents occurring during the ZIKV epidemic and questions the role of the three circulating arboviruses in the pathogenesis.
2017
Authors: Iovine NM, Lednicky J, Cherabuddi K, et al.
Published in: Clin Infect Dis. 2017;64(1): 72–75.
Abstract Zika virus and dengue virus serotype 2 were isolated from a patient with travel to Haiti who developed fever, rash, arthralgias, and conjunctivitis. The infecting Zika virus was related to Venezuelan and Brazilian strains but evolved along a lineage originating from strains isolated in 2014 in the same region of Haiti.
2017
Authors: Fuller TL, Calvet G, Genaro Estevam C, et al.
Published in: PLoS One. 2017;12(11):e0188002
Abstract: The burden of arboviruses in the Americas is high and may result in long-term sequelae with infants disabled by Zika virus infection (ZIKV) and arthritis caused by infection with Chikungunya virus (CHIKV). We aimed to identify environmental drivers of arbovirus epidemics to predict where the next epidemics will occur and prioritize municipalities for vector control and eventual vaccination. We screened sera and urine samples (n = 10,459) from residents of 48 municipalities in the state of Rio de Janeiro for CHIKV, dengue virus (DENV), and ZIKV by molecular PCR diagnostics. Further, we assessed the spatial pattern of arbovirus incidence at the municipal and neighborhood scales and the timing of epidemics and major rainfall events. Lab-confirmed cases included 1,717 infections with ZIKV (43.8%) and 2,170 with CHIKV (55.4%) and only 29 (<1%) with DENV. ZIKV incidence was greater in neighborhoods with little access to municipal water infrastructure (r = -0.47, p = 1.2×10-8). CHIKV incidence was weakly correlated with urbanization (r = 0.2, p = 0.02). Rains began in October 2015 and were followed one month later by the largest wave of ZIKV epidemic. ZIKV cases markedly declined in February 2016, which coincided with the start of a CHIKV outbreak. Rainfall predicted ZIKV and CHIKV with a lead time of 3 weeks each time. The association between rainfall and epidemics reflects vector ecology as the larval stages of Aedes aegypti require pools of water to develop. The temporal dynamics of ZIKV and CHIKV may be explained by the shorter incubation period of the viruses in the mosquito vector; 2 days for CHIKV versus 10 days for ZIKV.
2017
Authors: Donà D, Luise D, Da Dalt L, Giaquinto C.
Published in: Int J Pediatr; 2017: 4239268.
Abstract: Background. Pneumonia represents an important threat to children’s health in both developed and developing countries. In the last 10 years, many national and international guidelines on the treatment of pediatric CAP have been published, in order to optimize the prescription of antibiotics and limit their cost and side effects. However, the practical implementation of these guidelines is still limited. Main Text. We analyzed the current recommendations for the therapy of pediatric community-acquired pneumonia (CAP) that all converge on the identification of aminopenicillins and beta-lactams as the optimal treatment for CAP. We also conducted a review of the current literature on antibiotic regimens used for pediatric CAP to identify the current state of guidelines implementation in different settings. We selected 37 studies published from 2010 to 2016, including both retrospective and prospective studies, mainly cross-sectional and hospital based. The results show a global heterogeneity in the antibiotics prescription for pediatric CAP, with application of guidelines varying from 0% to more than 91% and with important differences even within the same country. Conclusions. Our review has demonstrated that the implementation of the guidelines is still limited but also that achieving the optimal prescription is possible and can be done in both developed and developing countries.
2017
Authors: Schalkwijk S, Colbers A, Konopnicki D, et al.
Published in: Clin Infect Dis. 2017; 65(8):1335-1341.
2017
Authors: Judd A, Lodwick R, Noguera-Julian A, et al.. Pursuing Later Treatment Options II (PLATO II) Project Team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord.
Published in: HIV Med. 2017;18(3):171-180
Objectives The aim of the study was to determine the time to, and risk factors for, triple‐class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection.
Methods We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV‐1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI.
Results The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre‐ART AIDS, NNRTI‐based initial regimens, higher pre‐ART viral load and lower pre‐ART CD4.
Conclusions The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development
2017
Authors: Nelson B, Melbourne-Chambers R, Christie CDC
Published in: West Indian Med J. Published Online: December 20, 2017
Abstract Zika Virus is neurotropic. We report two children from the Caribbean island of Grenada, a three-year-old with acute neuro-inflammation who had intractable seizures, meningo-encephalitis, CSF pleocytosis and Zika IgM positive acute serology and a four-year-old with acute demyelinating encephalomyelitis manifesting as generalized seizures, optic neuritis, diffuse cerebral dysfunction, encephalopathy, impaired speech and ataxia who also had CSF pleocytosis as well as Zika IgM and dengue IgM positive acute serologies. Both cases occurred during the 2016 Zika and Dengue fever epidemic in Grenada. Both children recovered completely. The etiologic role of the Zika and Dengue arboviruses is discussed.
2017
Authors: Schwarz ER
Published in: Curr Opin Virol. 2017;27:71-77
Abstract Measles, mumps, and rubella have recently taken the stage as re-emerging diseases of public health importance-particularly in regards to the consequences seen with perinatal infections. Effective vaccination strategies have successfully reduced the spread of measles, mumps, and rubella in the United States, but a current trend of increased vaccination hesitancy, fear of vaccine safety, and spread of misconceptions surrounding the science of vaccines have led to a relative resurgence of these diseases in the developed world. This article aims to explore why measles, mumps, and rubella should continue to be on the radar of medical professionals, and why the study of these diseases is important for understanding other teratogenic viruses of public health importance.
2017
Authors: da Silva IRF, Frontera JA, Bispo de Filippis AM, Nascimento OJMD
Published in: JAMA Neurol.2017;74(10):1190-1198
Importance There are no prospective cohort studies assessing the incidence and spectrum of neurologic manifestations secondary to Zika virus (ZIKV) infection in adults.
Objective To evaluate the rates of acute ZIKV infection among patients hospitalized with Guillain-Barré syndrome (GBS), meningoencephalitis, or transverse myelitis.
Design, Setting, and Participants A prospective, observational cohort study was conducted at a tertiary referral center for neurological diseases in Rio de Janeiro, Brazil, between December 5, 2015, and May 10, 2016, among consecutive hospitalized adults (>18 years of age) with new-onset acute parainfectious or neuroinflammatory disease. All participants were tested for a series of arbovirosis. Three-month functional outcome was assessed.
Interventions Samples of serum and cerebrospinal fluid were tested for ZIKV using real-time reverse-transcriptase–polymerase chain reaction and an IgM antibody-capture enzyme-linked immunosorbent assay. Clinical, radiographic (magnetic resonance imaging), electrophysiological, and 3-month functional outcome data were collected.
Main Outcomes and Measures The detection of neurologic complications secondary to ZIKV infection.
Results Forty patients (15 women and 25 men; median age, 44 years [range, 22-72 years]) were enrolled, including 29 patients (73%) with GBS (90% Brighton level 1 certainty), 7 (18%) with encephalitis, 3 (8%) with transverse myelitis, and 1 (3%) with newly diagnosed chronic inflammatory demyelinating polyneuropathy. Of these, 35 patients (88%) had molecular and/or serologic evidence of recent ZIKV infection in the serum and/or cerebrospinal fluid. Of the patients positive for ZIKV infection, 27 had GBS (18 demyelinating, 8 axonal, and 1 Miller Fisher syndrome), 5 had encephalitis (3 with concomitant acute neuromuscular disease), 2 had transverse myelitis, and 1 had chronic inflammatory demyelinating polyneuropathy. Admission to the intensive care unit was required for 9 patients positive for ZIKV infection (26%), and 5 (14%) required mechanical ventilation. Compared with admission during the period from December 5, 2013, to May 10, 2014 (before the Brazilian outbreak of ZIKV), admissions for GBS increased from a mean of 1.0 per month to 5.6 per month, admissions for encephalitis increased from 0.4 per month to 1.4 per month, and admissions for transverse myelitis remained constant at 0.6 per month. At 3 months, 2 patients positive for ZIKV infection (6%) died (1 with GBS and 1 with encephalitis), 18 (51%) had chronic pain, and the median modified Rankin score among survivors was 2 (range, 0-5).
Conclusions and Relevance In this single-center Brazilian cohort, ZIKV infection was associated with an increase in the incidence of a diverse spectrum of serious neurologic syndromes. The data also suggest that serologic and molecular testing using blood and cerebrospinal fluid samples can serve as a less expensive, alternative diagnostic strategy in developing countries, where plaque reduction neutralization testing is impractical.
2017
Authors: Bosch I, de Puig H, Hiley M, et al.
Published in: Sci Transl Med. 2017 Sep 27;9(409)
Abstract The recent Zika virus (ZIKV) outbreak demonstrates that cost-effective clinical diagnostics are urgently needed to detect and distinguish viral infections to improve patient care. Unlike dengue virus (DENV), ZIKV infections during pregnancy correlate with severe birth defects, including microcephaly and neurological disorders. Because ZIKV and DENV are related flaviviruses, their homologous proteins and nucleic acids can cause cross-reactions and false-positive results in molecular, antigenic, and serologic diagnostics. We report the characterization of monoclonal antibody pairs that have been translated into rapid immunochromatography tests to specifically detect the viral nonstructural 1 (NS1) protein antigen and distinguish the four DENV serotypes (DENV1–4) and ZIKV without cross-reaction. To complement visual test analysis and remove user subjectivity in reading test results, we used image processing and data analysis for data capture and test result quantification. Using a 30-μl serum sample, the sensitivity and specificity values of the DENV1–4 tests and the pan-DENV test, which detects all four dengue serotypes, ranged from 0.76 to 1.00. Sensitivity/specificity for the ZIKV rapid test was 0.81/0.86, respectively, using a 150-μl serum input. Serum ZIKV NS1 protein concentrations were about 10-fold lower than corresponding DENV NS1 concentrations in infected patients; moreover, ZIKV NS1 protein was not detected in polymerase chain reaction–positive patient urine samples. Our rapid immunochromatography approach and reagents have immediate application in differential clinical diagnosis of acute ZIKV and DENV cases, and the platform can be applied toward developing rapid antigen diagnostics for emerging viruses.
2017
Authors: Barreto-Vieira DF, Jacome FC, da Silva MAN, et al.
Published in: PLoS One. 2017;12(9):e0184397
Abstract Zika virus (ZIKV) is a member of the flavivirus genus, and its genome is approximately 10.8 kilobases of positive-strand RNA enclosed in a capsid and surrounded by a membrane. Studies on the replication dynamics of ZIKV are scarce, which limits the development of antiviral agents and vaccines directed against ZIKV. In this study, Aedes albopictus mosquito lineage cells (C6/36 cells) and African green monkey kidney epithelial cells (Vero cells) were inoculated with a ZIKV sample isolated from a Brazilian patient, and the infection was characterized by immunofluorescence staining, phase contrast light microscopy, transmission electron microscopy and real-time RT-PCR. The infection was observed in both cell lineages, and ZIKV particles were observed inside lysosomes, the rough endoplasmic reticulum and viroplasm-like structures. The susceptibility of C6/36 and Vero cells to ZIKV infection was demonstrated. Moreover, this study showed that part of the replicative cycle may occur within viroplasm-like structures, which has not been previously demonstrated in other flaviviruses.
2017
Authors: Balmaseda A, Stettler K, Medialdea-Carrera R, et al.
Published in: Proc Natl Acad Sci U S A. 2017;114(31):8384-8389
Abstract Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged recently as a global health threat, causing a pandemic in the Americas. ZIKV infection mostly causes mild disease, but is linked to devastating congenital birth defects and Guillain-Barré syndrome in adults. The high level of cross-reactivity among flaviviruses and their cocirculation has complicated serological approaches to differentially detect ZIKV and dengue virus (DENV) infections, accentuating the urgent need for a specific and sensitive serological test. We previously generated a ZIKV nonstructural protein 1 (NS1)-specific human monoclonal antibody, which we used to develop an NS1-based competition ELISA. Well-characterized samples from RT-PCR-confirmed patients with Zika and individuals exposed to other flavivirus infections or vaccination were used in a comprehensive analysis to determine the sensitivity and specificity of the NS1 blockade-of-binding (BOB) assay, which was established in laboratories in five countries (Nicaragua, Brazil, Italy, United Kingdom, and Switzerland). Of 158 sera/ plasma from RT-PCR-confirmed ZIKV infections, 145 (91.8%) yielded greater than 50% inhibition. Of 171 patients with primary or secondary DENV infections, 152 (88.9%) scored negative. When the control group was extended to patients infected by other flaviviruses, other viruses, or healthy donors (n = 540), the specificity was 95.9%. We also analyzed longitudinal samples from DENV-immune and DENVnaive ZIKV infections and found inhibition was achieved within 10 d postonset of illness and maintained over time. Thus, the Zika NS1 BOB assay is sensitive, specific, robust, simple, low-cost, and accessible, and can detect recent and past ZIKV infections for surveillance, seroprevalence studies, and intervention trials.
2017
Authors: Braga JU, Bressan C, Dalvi APR, et al.
Published in: PLoS One.2017;12(6):e0179725.
Background Zika is a new disease in the American continent and its surveillance is of utmost importance, especially because of its ability to cause neurological manifestations as Guillain-Barrésyndrome and serious congenital malformations through vertical transmission. The detection of suspected cases by the surveillance system depends on the case definition adopted. As the laboratory diagnosis of Zika infection still relies on the use of expensive and complex molecular techniques with low sensitivity due to a narrow window of detection, most suspected cases are not confirmed by laboratory tests, mainly reserved for pregnant women and newborns. In this context, an accurate definition of a suspected Zika case is crucial in order for the surveillance system to gauge the magnitude of an epidemic.
Methodology We evaluated the accuracy of various Zika case definitions in a scenario where Dengue and Chikungunya viruses co-circulate. Signs and symptoms that best discriminated PCR confirmed Zika from other laboratory confirmed febrile or exanthematic diseases were identified to propose and test predictive models for Zika infection based on these clinical features.
Results and discussion Our derived score prediction model had the best performance because it demonstrated the highest sensitivity and specificity, 86·6% and 78·3%, respectively. This Zika case definition also had the highest values for auROC (0·903) and R2 (0·417), and the lowest Brier score 0·096.
Conclusions In areas where multiple arboviruses circulate, the presence of rash with pruritus or conjunctival hyperemia, without any other general clinical manifestations such as fever, petechia or anorexia is the best Zika case definition.
2017
Authors: Nascimento OJM, Frontera JA, Amitrano DA, Bispo de Filippis AM, Da Silva IRF; RIO-GBS-ZIKV Research Group
Published in: Neurology 2017;88(24):2330-2332
2017
Authors: Palma P, Chan M, Goodall R, Judd A, Gibb D, Babiker A, Rojo P.
Published: 35th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID), May 23rd-27th May, 2017, Madrid
Background A major obstacle to curing HIV infection is persistence of virus as integrated proviral DNA in long-lived cells even after many years on ART. ART-free HIV remission is more likely to occur if viral suppression is achieved very early in infection. We investigated factors associated with time to virological suppression in early ART treated children from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC).
2017
Authors: Palma P, Zangari P, Cotugno N, Rocca S, Nastouli E, McCoy LE, Ferns RB, Pahwa S, Rossi P
Published: 24th Conference on Retroviruses and Opportunistic Infections, February 13th – 16th, 2017, Seattle. P_1975.
Background It is still unknown whether the paucity of HIV-specific immune responses in early-treated (treated within 6 months of age; ET) HIV-infected children may represent a limitation or an advantage in the perspective of immune therapeutic studies. In ET patients, the failure to develop an immune response is attributed to the lack of antigen (Ag) stimulation, possibly indicating shrinking HIV reservoirs (Luzuriaga, JID 2014). Analysis of HIV antibodies (Ab) can reveal important insights to characterizing host immune profiles associated with HIV remission which appears to be linked with different serological profiles (Burbelo, JID 2014). Recent findings showed a functional plasticity of memory B-cell compartment, suggesting that IgM memory B-cells during a primary stage of infection share specific memory characteristics with IgG memory B-cells. The role of IgM memory responses in humans is debated (Seifert, PNAS 2015). Their generation, in the context of short-term Ag persistence such as in ET HIV-infected children, has been poorly investigated. Our aim was to further dissect Bcell responses in ET patients with different HIV Ab profiles and relate those to the predicted size of HIV reservoir (Total HIV-DNA) and to immune memory B-cell response.
2017
Authors: Colbers A, Schalkwijk S, Konopnicki D, Gingelmaier A, Lambert J, van der Ende I, Moltó J, Burger D.
Published: 24th Conference on Retroviruses and Opportunistic Infections, February 13th – 16th, 2017 – Seattle. Abstract number 754.
2017
Authors: Bernays S, Paparini S, Seeley J, Rhodes T.
Published in: Med Anthropol. 2017;36(5):485-499.
Abstract: Global health priorities are being set to address questions on adherence to HIV antiretroviral therapy in adolescence. Few studies have explored young people’s perspectives on the complex host of social and relational challenges they face in dealing with their treatment in secret and their condition in silence. In redressing this, we present findings from a longitudinal qualitative study with young people living with HIV in the UK, Ireland, US, and Uganda, embedded within the BREATHER international clinical trial. Drawing from Goffman’s notion of stigma, we analyze relational dynamics in HIV clinics, as rare spaces where HIV is “known,” and how young people’s relationships may be threatened by non-adherence to treatment. Young people’s reflections on and strategies for maintaining their reputation as patients raise questions about particular forms of medicalization of HIV and the moralization of treatment adherence that affect them, and how these may restrict opportunities for care across the epidemic.
2017
Authors: Hinkula J, Petkov S, Ljungberg K, Hallengärd D, Bråve A, Isaguliants M, Falkeborn T, Sharma S, Liakina V, Robb M, Eller M, Moss B, Biberfeld G, Sandström E, Nilsson C, Markland K, Blomberg P, Wahren B.
Published in: Heliyon
2017
Authors: Schomaker M, Leroy V, Wolfs T, et al. On behalf of theIeDEA West and Southern Africa regional collaborations and COHERE in EuroCoord.
Published in: Int J Epidemiol. 2017;46(2):453-465.
Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents.
Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula.
Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm3(394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes.
Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
2017
Authors: Volynets G, Skyortsowa TA, Ptapov AS, et al.
Published in: EASL, 19th – 23rd April 2017, Amsterdam
2017
Authors: Thorne C, Turkova A, Indolfi G, Venturini E, Giaquinto C
Published in: AIDS. 2017;31(1):127-135.
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.
2017
Authors: Majekodunmi AO, Thorne C, Malyuta R, et al.
Published in: Pediatr Infect Dis J. 2017;36(5):e123-e129
Objective To compare CD4 T cell recovery in HIV/HCV coinfected children with recovery in HIV monoinfected children.
Method We studied 355 HIV monoinfected and 46 HIV/HCV coinfected children receiving antiretroviral therapy (ART) during a median follow-up period of 4.2 years (interquartile range: 2.7-5.3 years). Our dataset came from the Ukraine pediatric HIV Cohort and the HIV/HCV coinfection study within the European Pregnancy and Paediatric HIV Cohort Collaboration. We fitted an asymptotic nonlinear mixed-effects model of CD4 T cell reconstitution to age-standardized CD4 counts in all 401 children and investigated factors predicting the speed and extent of recovery.
Results We found no significant impact of HCV coinfection on either pre-ART or long-term age-adjusted CD4 counts (z scores). However, the rate of increase in CD4 z score was slower in HIV/HCV coinfected children when compared with their monoinfected counterparts (P < 0.001). Both monoinfected and coinfected children starting ART at younger ages had higher pre-ART (P < 0.001) and long-term (P < 0.001) CD4 z scores than those who started when they were older.
Conclusions HIV/HCV coinfected children receiving ART had slower CD4 T cell recovery than HIV monoinfected children. HIV/HCV coinfection had no impact on pre-ART or long-term CD4 z scores. Early treatment of HIV/HCV coinfected children with ART should be encouraged.
2017
Authors: Indolfi G, Thorne C, El-Sayed MH, Giaquinto C, Gonzalez-Peralta RP.
Published in: J Pediatr Gastroenterol Nutr. 2017;64(6):851-854
Abstract The development of oral hepatitis C virus (HCV) direct-acting antivirals (DAAs) has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time genuinely raise the prospects of eradicating HCV. Many challenges, however, remain from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children.
2017
Authors:
Published in: Pediatr Infect Dis J. 2017 May;36(5):e123-e129. doi: 10.1097/INF.0000000000001478. PMID: 28403051; PMCID: PMC5380220.
2016
Authors: Colbers A, Best B, Schalkwijk S, et al. PANNA Network and the IMPAACT 1026 Study Team.
Published in: Clin Pharmacokinet. 2016;55(3):381-96
Abstract Pregnant women are usually excluded from clinical trials. Physiologically based pharmacokinetic (PBPK) modelling may provide a method to predict pharmacokinetics in pregnant women, without the need to perform extensive in vivo clinical trials. Here, we used mechanistic modelling to delineate the potential impact of drug transporters on darunavir pharmacokinetics and to identify current knowledge gaps that limit accurate PBPK modelling of darunavir/ritonavir (darunavir/r) exposure in pregnancy. Simcyp (version 13.2) was used for PBPK modelling, using physicochemical and in vitro pharmacokinetic parameters of darunavir and ritonavir from the literature. The Michaelis-Menten constant (K m) and the maximum rate of metabolite formation (V max) for cytochrome P450 3A4-mediated darunavir biotransformation and inhibition by ritonavir were determined experimentally, while the contributions of hepatocyte influx and efflux transporters were assessed by sensitivity analysis. The simulations were compared with previously published clinical pharmacokinetic data. We found that use of a well-stirred liver model overestimated darunavir exposure substantially. A permeability-limited liver model, including hepatic uptake and efflux transporters and an efficient enterohepatic circulation step, resulted in an acceptable description of darunavir/r exposure. For the 600/100 mg darunavir/r twice-daily dose and the 800/100 mg once-daily dose, the estimated pharmacokinetic parameters were within a 2-fold range of the reported data. The predicted decreases in the area under the concentration-time curve (AUC) values during pregnancy for the twice- and once-daily doses were 27 and 41%, respectively, which were in line with the observed decreases of 17-22 and 33%. In conclusion, our data support a clinically relevant role of hepatic transporters in darunavir pharmacokinetics. By including them in our model, we successfully approximated the increase in darunavir exposure mediated by ritonavir co-administration and the decrease in darunavir exposure observed during pregnancy.
2016
Authors: Ramos-Martin R , Johnson A, Livermore J, et al.
Published in: J Antimicrob Ther 2016;71(4):992-1002
2016
Authors: Bailey H, Malyuta R, Townsend C, Cortina Borja M, Thorne C for the Ukraine European Collaborative Study in EuroCoord.
Published in: Reprod Health. 2016;22(3):13-27.
Background Perinatal depression among HIV-positive women has negative implications for HIV-related and other maternal and infant outcomes. The aim of this study was to investigate the burden and correlates of perinatal depression among HIV-positive women in Ukraine, a lower middle income country with one of the largest HIV-positive populations in Europe.
Methods Cross-sectional surveys nested within the Ukraine European Collaborative Study were conducted of HIV-positive women at delivery and between 1 and 12 months postpartum. Depressive symptoms in the previous month were assessed using a self-report screening tool. Other data collected included demographics, antiretroviral therapy (ART)-related self-efficacy, and perceptions of risks/benefits of interventions to prevent mother-to-child transmission (PMTCT). Characteristics of women with and without a positive depression screening test result were compared using Fisher’s exact test and χ2 test for categorical variables.
Results A quarter (27% (49/180) antenatally and 25% (57/228) postnatally) of participants screened positive for depressive symptoms. Antenatal risk factors were living alone (58% (7/12) vs. 25% (42/167) p = 0.02), being somewhat/terribly bothered by ART side effects (40% (17/43) vs. 23% (30/129) not /only slightly bothered, p = 0.05) and having lower ART-related self-efficacy (43% (12/28) vs. 23% (25/110) with higher self-efficacy, p = 0.05). Postnatally, single mothers were more likely to screen positive (44% (20/45) vs. 21% (18/84) of cohabiting and 19% (19/99) of married women, p < 0.01) as were those unsure of the effectiveness of neonatal prophylaxis (40% (20/45) vs. 18% (28/154) sure of effectiveness, p < 0.01), those worried that neonatal prophylaxis could harm the baby (30% (44/146) vs. 14% (10/73) not worried p < 0.01) and those not confident to ask for help with taking ART (48% (11/23) vs. 27% (10/37) fairly confident and 15 % (4/26) confident that they could do this). Of women who reported wanting help for their depressive symptoms, 82% (37/45) postnatally but only 31% (12/39) antenatally were already accessing peer counselling, treatment adherence programmes, support groups or social services.
Conclusions A quarter of women screened positive for depression. Results highlight the need for proactive strategies to identify depressive symptoms, and an unmet need for provision of mental health support in the perinatal period for HIV-positive women in Ukraine.
2016
Authors: Safadi MA
Published in: Amer J Perinatol.2016; 33(11): 1029-1031
Abstract Zika virus (ZIKV) is an emerging arthropod-borne, enveloped RNA virus of the Flaviviridae family, which belongs to the genus Flavivirus, related to dengue, yellow fever, Japanese encephalitis, and West Nile viruses. Two major lineages, African and Asian, have been identified through phylogenetic analyses.
2016
Authors: Davidson T., Vickers I., Christie CD
Published in: West Indian Med J 2016;65(3);442-449
Background Dengue fever is hyper-endemic in Jamaica with exponential rates of infection in successive outbreaks. The absence of local data and the potential for massive outbreaks in a country where a third of the population are children formed the basis for this study.
Methods We evaluated the outcome of dengue in children hospitalized at the University Hospital of the West Indies (UHWI), Mona, Jamaica, during the island-wide dengue fever epidemic of 2012. This retrospective study reports all physician-diagnosed cases of dengue in hospitalized children aged less than 15 years.
Results A total of 134 hospitalized children with physician-diagnosed dengue were included. One hundred and eighteen (88%) had a confirmatory dengue laboratory test. One hundred and twenty (90%) were uncomplicated and 14 (10%) had severe dengue. Severe disease was significantly associated with a longer duration between disease onset and hospital admission (p = 0.0076). Main co-morbidities were sickle cell disease (14%) and asthma (13%), however neither was associated with increased mortality. Duration of hospitalization was longer for patients with sickle cell disease. Children with short stature were significantly more likely to have severe dengue [Z-score height-for-age < 2.0; OR 6.46(1.61, 25.88), p = 0.016]. There were five deaths with a case fatality rate of 3.73%. Prior use of Non-steroidal Anti-inflammatory Drugs was documented in four deaths.
Conclusion Delayed presentation and short stature were significantly associated with severe dengue. Children with sickle cell disease had longer hospital stay. The case fatality rate was 3.73%. Use of safe and efficacious dengue vaccines should mitigate the effects of dengue-attributable childhood morbidity and mortality.
2016
Authors: Christie CD, Melbourne-Chambers R, Ennevor J, et al.
Published in: West Indian Med J 2016;65(3);431-437
Background Chikungunya virus entered the Caribbean for the first time in 2013 and Jamaica experienced its maiden epidemic with Chikungunya Fever in 2014. We aimed to describe the public health effects and describe the clinical features in children and adolescents in Jamaica.
Methods This study reviewed the public health effects of the illness in Jamaica by reviewing available data sources and the clinical features in 210 children and adolescents meeting the case definition at two hospitals, Bustamante Hospital for Children and University Hospital of the West Indies between August 23 and October 31, 2014 by chart review. Descriptive analyses and comparisons between groups using the Mann-Whitney U test were performed with SPSS version 22.
Results The majority of households were affected by the illness which caused widespread absenteeism from school and work, loss of productivity and economic losses estimated at 60 billion dollars. The health sector was impacted by increased numbers seen in clinics and emergency departments, increased need for bed space and pharmaceuticals. Ninety-nine per cent of cases were febrile with a median maximal temperature of 102.4 F. Ninety-three per cent had household contacts of 0–20 persons. In addition to fever, maculopapular rash and joint pains, infants six months and younger presented with irritability and groaning (p = 0.00) and those between six months and six years presented with febrile seizures (p = 0.00). Neurologic involvement was noted in 24%. Apart from anaemia, few had other laboratory derangements. Few had severe organ dysfunction and there were no deaths.
Conclusion The Chikungunya Fever epidemic had significant public health and economic impact in Jamaica. In children, there were characteristic presentations in neonates and young infants and in children six months to six years. Neurologic involvement was common but other organ dysfunction was rare. These findings underscore the need to prevent further epidemics and the quest for a vaccine.
2016
Authors: Webster-Kerr K, Christie CDC, Grant A, et al.
Published in: West Indian Med J. 2016;65(1):243-249
Background Jamaica, along with the Americas, experienced major epidemics of arboviral diseases transmitted by the Aedes aegypti mosquito in recent years. These include dengue fever in 2012, chikungunya fever in 2014 and Zika virus infection (ZIKV) in 2016. We present the emergence of the ZIKV epidemic in Jamaica and outline the national response.
Methods The Ministry of Health’s preparedness included: heightened surveillance, clinical management guidance, vector control and management, laboratory capacity strengthening, training and staffing, risk communication and public education, social mobilization, inter-sectoral collaboration, resource mobilization and international cooperation.
Results The first case of ZIKV was confirmed on 29 January 2016 with date of onset of 17 January 2016. From 3 January to 30 July 2016 (Epidemiological Week (EW) 1-30), 4648 cases of ZIKV were recorded (4576 suspected, 72 laboratory-confirmed). Leading symptoms were similar among suspected and confirmed cases: rash (71% and 88%), fever (65% and 53%) and joint pains (47% and 38%). There were 17 suspected cases of Guillain-Barre Syndrome. Three hundred and eighty-three were reported in pregnant women, with no reports of microcephaly to date. Zika and dengue viruses were circulating predominantly in 2016. At EW30, 1744 cases of dengue were recorded (1661 suspected and 83 confirmed). Dengue serotypes 3 and 4 circulating with 121 reports of dengue haemorrhagic fever.
2016
Authors: Oliveira DB, Almeida FJ, Durigon EL, et al.
Published in: N Engl J Med. 2016. 22;375(12):1202-4
The presence of Zika virus (ZIKV) infection has been associated with microcephaly in multiple studies, although little is known about ZIKV shedding in congenitally infected infants. We report a case of a newborn who had continued viremia with ZIKV for at least 67 days after birth.
2016
Authors: Christie CD, Giaquinto C
Published in: West Indian Med J.2016;65(1):239-242
Abstract Zika virus epidemic now involves 72 countries, worldwide. Transmission is multimodal through mosquito bites and blood and body fluids. Zika virus causes Guillain Barre Syndrome syndrome and pregnancy complications including perinatal microcephaly. Diagnosis is complicated by subclinical infection in 80%, co-circulation with dengue and chikungunya fevers with similar presentations and cross-reactivity in serological tests. There is no cure, or preventive vaccine. Large population-based studies will help to elucidate ZIKV epidemiology, vertical transmission, risks to the fetus of maternal ZIKV infection and natural history of congenital and non-congenital ZIKV infection as provided by the activities in the “ZIKAction” research consortium in Latin America, Europe and the Caribbean, which was recently funded by the European Commission.
2016
Authors: Bocanegra C, Sulleiro E, Soriano-Arandes A, et al.
Published in: Clin Microbiol Infect. 2016;22(7):648-50
This case series of two pregnant women infected with the Zika virus in Barcelona, Spain and provides an algorithm for diagnosing pregnant women with suspected ZIKV infection in non-endemic areas.
2016
Authors: Capua I
Published in: Nature. 2016;16;534(7607):326
This correspondence urges Brazil to speed up reforms to current biosecurity legislation, enabling sharing of vital Zika virus samples and information.
2016
Authors: Kednicky J, Beau De Rochars VM, El Badry M, et al.
Published in: PLoS Negl Trop Dis. 2016;10(4):e0004687
Background Zika virus (ZIKV), first isolated in Uganda in 1947, is currently spreading rapidly through South America and the Caribbean. In Brazil, infection has been linked with microcephaly and other serious complications, leading to declaration of a public health emergency of international concern; however, there currently are only limited data on the virus (and its possible sources and manifestations) in the Caribbean.
Methods From May, 2014-February, 2015, in conjunction with studies of chikungunya (CHIKV) and dengue (DENV) virus infections, blood samples were collected from children in the Gressier/Leogane region of Haiti who presented to a school clinic with undifferentiated febrile illness. Samples were initially screened by RT-PCR for CHIKV and DENV, with samples negative in these assays further screened by viral culture.
Findings Of 177 samples screened, three were positive for ZIKV, confirmed by viral sequencing; DENV-1 was also identified in culture from one of the three positive case patients. Patients were from two different schools and 3 different towns, with all three cases occurring within a single week, consistent with the occurrence of an outbreak in the region. Phylogenetic analysis of known full genome viral sequences demonstrated a close relationship with ZIKV from Brazil; additional analysis of the NS5 gene, for which more sequences are currently available, showed the Haitian strains clustering within a monophyletic clade distinct from Brazilian, Puerto Rican and Guatemalan sequences, with all part of a larger clade including isolates from Easter Island. Phylogeography also clarified that at least three major African sub-lineages exist, and confirmed that the South American epidemic is most likely to have originated from an initial ZIKV introduction from French Polynesia into Easter Island, and then to the remainder of the Americas.
Conclusions ZIKV epidemics in South America, as well as in Africa, show complex dissemination patterns. The virus appears to have been circulating in Haiti prior to the first reported cases in Brazil. Factors contributing to transmission and the possible linkage of this early Haitian outbreak with microcephaly remain to be determined.
2016
Authors: Solomon T, Baylis M, Brown D.
Published in: Lancet Infect Dis. 2016;16(4):402-404
This article comments on the origins and consequences of recent Zika virus outbreaks, highlighting the urgent need to address several key gaps in knowledge regarding this virus.
2016
Author: Bispo A
Published in: Bull World Health Organ. 2016;94:165–166
In this interview, Anna Bispo describes the history of Zika virus in Brazil, including its potential links to an increase in microcephaly cases, and describes groundbreaking work in Zika virus diagnostics and virology at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil.
2016
Authors: Turkova A, Chappell E, Chalermpantmetagul S, et al.
Published in: Int J Tuberc Lung Dis 2016;20(11):1448-1456.
Setting Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil.
Objective To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children.
Design Observational study of TB diagnosed in HIV-infected children in 2011–2013.
Results Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0–11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes.
Conclusion Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.
2016
Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) study group in EuroCoord.
Published in: Antivir Ther. 2016; 21(4): 353-8
Background Surveillance for mid- and long-term antiretroviral therapy (ART) toxicity in children is important for informing treatment guidelines. We assessed the safety of darunavir (DRV) and atazanavir (ATV), commonly used as second-line protease inhibitors following lopinavir/ritonavir, in Europe and Thailand.
Methods Cohorts contributed individual patient data on adverse events (AE) in those aged <18 years taking DRV and ATV, respectively, to 02/2014. Rates of Division of AIDS (DAIDS) grade ≥3 laboratory AEs were calculated.
Results Of 431 patients on DRV and 372 on ATV, 317 (74%) and 301 (81%), respectively, had weight and dose data available, of whom 56 (18%) and 33 (9%) took the drugs at a non-approved age or dose. Median age at DRV and ATV start was 14.8 years (IQR 12.8-16.1) and 13.5 years (11.4-15.2); 43% and 26% had received ≥8 ART drugs previously. Overall rates of grade ≥3 AEs for absolute neutrophils, total cholesterol, triglycerides, pancreatic amylase, lipase and alanine aminotransferase (ALT) were ≤3/100 person-years (PY) on approved doses of both drugs, but 66/100 PY (95% CI 52, 84) for bilirubin after <12 months on ATV declining to 32/100 PY (95% CI 23, 44) after >24 months. Five serious drug-related clinical AEs were reported in four patients on ATV (one discontinued) and three in three patients on DRV (all discontinued), and did not substantially differ in those on approved compared to non-approved doses. Proportions on the drugs at last follow-up were 89% (383/431) for DRV and 81% (301/372) for ATV (including 73/92 with grade ≥3 hyperbilirubinaemia).
Conclusions AEs were few in number and comparable for the two drugs, with the exception of high rates of hyperbilirubinaemia for ATV; few patients discontinued due to toxicity.
2016
Authors: Judd A, Sohn A, Collins J.
Published in: Curr Opin HIV AIDS 2016;11(5):477-486.
Purpose of review There is an increasing number of deaths among adult survivors of perinatal HIV. Multiple and complex factors drive this mortality, including problems with retention in care and adherence during adolescence, coupled with the critical period of transition from paediatric to adult care, increasing their risk of treatment failure and severe immunosuppression. We reviewed studies that evaluated the impact of service delivery interventions to improve the health of perinatally infected adolescents living with HIV (P-ALHIV) to gain insight into what might help them survive the vulnerable period of adolescence.
Recent findings Youth-focused health services and individual-level interventions may improve P-ALHIV adherence and retention in care. However, there have been few studies, many with small sample sizes and with short durations of follow-up that end before the transition period. Studies from other childhood-onset chronic diseases are similarly limited.
Summary Further studies are urgently needed to identify optimal intervention strategies to reduce mortality and poor outcomes as the adolescent population expands and ages into adult care. Until we have a more robust evidence base, programmes can develop transition plans based on best practice recommendations to optimize the health and longevity of ALHIV in adulthood.
2016
Authors: Ngo-Giang-Huong N, Wittkop L, Judd A, et al. For EuroCoord-CHAIN-EPPICC joint project study group.
Published in: BMC Infect Dis. 2016;16(1):654.
Background Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children.
Methods HIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen.
Results Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1–10.1), CD4 cell count 297 cells/mm3(98–639), and HIV-RNA 5.2 log10copies/mL (4.7–5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5–10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4–23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2–54.8) versus 19.4 % (15.9–23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82–0.95; P < 0.001).
Conclusions PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.
2016
2016
Authors: Schalkwijk S, ter Heine R, Colbers A, Huitema A, Denti P, Dooley K, Capparelli E, Best B, Cressey T, Greupink R, Russel F, Mirochnick M, Burger D.
Published: 17th edition of the International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy, June 8th-10th 2016, Washington DC. P_26
2016
Authors: Colbers A, Schalkwijk S, Konopnicki D, Hawkins D, Hidalgo Tenorio C, Moltò J, Taylor G, Weizsacker K, van der Ende M, Burger D
Published: Oral presentation at 17th edition of the International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy, June 8th-10th 2016, Washington DC