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BackgroundCurrent guidelines recommend that infants born to women with hepatitis C (HCV) viremia are screened for HCV antibody at age 18 months, and if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based in part on analyses suggesting 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years.MethodsData on 179 infants with RNA and/or anti-HCV evidence of vertically acquired viraemia (single PCR+) or confirmed infection (2 PCR+ or anti-HCV beyond 18 months) in three prospective European cohorts were investigated. Ages at clearance of viremia and confirmed infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in infants in whom RNA was not detectable until after 6 weeks.ResultsClearance rates decline rapidly over the first 6 months. An estimated 90.6% (95%CrI: 83.5-95.9) of viremia cleared by 5 years, most within 3 months, and 65.9% (50.1-81.6) of confirmed infection cleared by 5 years, at a median 12.4 (7.1-18.9) months. If treatment began at age 6 months, 18 months or 3 years, at least 59.0% (42.0-76.9), 39.7 (17.9-65.9), and 20.9 (4.6-44.8) of those treated would clear without treatment. In seven (6.6%) confirmed infections, RNA was not detectable until after 6 weeks, and in 2 (1.9%) not until after 6 months. However, all such cases subsequently cleared.ConclusionsMost viraemia clears within 3 months, and most confirmed infection by 3 years. Delaying treatment avoids but does not eliminate over-treatment and should be balanced against loss to follow-up.Key pointsBased on a re-analysis of the largest purely prospective dataset assembled so far, 66% (50-82) of confirmed vertically acquired HCV clears spontaneously by age 5 years, rather than the 25-40% assumed in guidelines.

Background: The risk of vertical transmission of hepatitis C virus (HCV) is ≈6%, and evidence suggests HCV negatively affects pregnancy and infant outcomes. Despite this, universal antenatal HCV screening is not available in most settings, and direct acting antivirals (DAA) are yet to be approved for use in pregnancy or breastfeeding period. Larger safety and efficacy trials are needed. At current there is limited understanding of the acceptability of routine HCV screening and use of DAAs in pregnancy but only among women in high HCV burden countries. Methods: We conducted a cross-sectional survey of pregnant or post-partum (

BackgroundIt is widely accepted that the risk of HCV vertical transmission (VT) is 5-6% in mono-infected women, and that 25-40% of HCV infection clears spontaneously within 5 years. However, VT and clearance rates have not been estimated from the same datasets, and there is a lack of information on VT rates “net” of clearance.MethodsWe re-analysed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates “net” of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero and at delivery was estimated from data on the proportion of RNA positives in samples tested within three days of birth, and differences between elective caesarean and non-elective caesarean deliveries.FindingsOverall VT rates were 7.2% (95% credible interval 5.6-8.9) in mothers who were HIV negative and 12.1% (8.6-16.8) in HIV-co-infected women. The corresponding rates net of clearance at 5 years were 2.4% (1.1-4.1) and 4.1% (1.7-7.3). We estimated that 24.8% (12.1-40.8) of infections occur early in utero, 66.0% (42.5-83.3) later in utero, and 9.3% (0.5-30.6) during delivery.ConclusionOverall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.Key pointsTaking account of infections that would have cleared spontaneously before detection, the rate of HCV vertical transmission is 7.2% (95%CrI 5.6-8.9) in mono-infected women, but transmission “net” of clearance is 3.1% (1.8-4.4) at 3 years, and 2.4% (1.1-4.1) at 5.

Background Early infant HIV diagnosis (EID) is critical to ensuring timely diagnosis of HIV-exposed infants, and treatment in those found to be infected. However estimates of coverage vary considerably, depending on data sources used. We used 4 methods to estimate coverage among a historical cohort of HIV-exposed infants in rural South Africa, between 2010–2016. Methods We estimated the proportion of infants ever tested (methods 1–3) and tested by 7 weeks of age (1–4) as follows: (1) infants born to women identified as HIV-positive in demographic surveillance were linked to those with ≥1 EID result in routine laboratory surveillance; (2) the number of infants with ≥1 EID result in laboratory surveillance divided by the estimated number of HIV-exposed infants, calculated as total live births multiplied by antenatal HIV seroprevalence; (3) the number of infants with ≥1 EID result in routine laboratory surveillance, divided by the number of HIV-exposed infants as estimated by the district health service; (4) from documentation in infants’ Road-to-Health-booklets. Results The proportion ever tested was 43%, 88% and 138% for methods 1–3, and by 7 weeks of age was 25%, 49%, 86% and 46% for methods 1–4 respectively. Conclusions The four methods, applied to a range of routine data sources, resulted in estimates varying considerably, and the true coverage of EID remains unclear. Our findings highlight the importance of developing unique patient identifiers, improving training of healthcare providers using reporting systems, and ensuring the accuracy of healthcare records, to ensure the best possible health outcomes for HIV-exposed infants.

Contains fulltext : 208830.pdf (Publisher’s version ) (Open Access) BACKGROUND: With the global efforts to eradicate hepatitis C virus (HCV), treatment during pregnancy is becoming a priority for research as this, and maternal cure should reduce vertical transmission. However, as information on the efficacy and safety of direct-acting antivirals (DAAs) in pregnancy is generally lacking, treatment of HCV infection during pregnancy is not currently recommended. AIM: To provide an overview of current knowledge regarding maternal exposure, placental handling and safety of DAAs during pregnancy and lactation METHODS: A literature search was performed focusing on the effect of pregnancy on maternal exposure to DAAs, the placental handling of DAAs, the safety of DAAs for mother and child during pregnancy and the safety of DAAs during lactation. RESULTS: Exposure to all DAAs studied is likely to be altered during pregnancy, mostly related to pregnancy-induced effects on drug absorption and metabolism. Although animal studies show that most DAAs are reported to cross the placenta and transfer into breast milk, most DAA combinations show a favourable safety profile. Because of the rapid viral decline after treatment initiation, and to avoid the critical period of organogenesis, treatment may be started at the end of the second trimester or early third trimester. CONCLUSIONS: Treatment of HCV infection during pregnancy is realistic, as DAAs are highly effective and treatment duration is relatively short. There is an urgent need to study DAAs during pregnancy and lactation to contribute to the goal of HCV elimination.

Introduction As adolescents and young people living with HIV (AYLH) age, they face a “transition cascade,” a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high‐income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub‐Saharan Africa, paediatric HIV care is mostly provided in decentralized, non‐specialist primary care clinics, where “transition” may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when “transition” to autonomy might occur, we evaluated pre‐ and post‐transition outcomes among AYLH. Methods We included AYLH aged

Adolescents with perinatal HIV (PHIV) may be at higher risk of anxiety and depression than HIV negative young people. We investigated the prevalence of symptoms of anxiety and depression in PHIV and HIV-affected (siblings of PHIV and/or had an HIV positive mother) young people in England. Symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) scores. A cross-sectional analysis was conducted of data from 283 young people with PHIV aged 13-21 years and 96 HIV-affected young people aged 13-23 years in the Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort. Linear regression investigated factors associated with higher (worse) anxiety and depression scores.115 (41%) and 29 (30%) PHIV and HIV-affected young people were male, median age was 16 [interquartile range 15,18] and 16 [14,18] years and 241 (85%) and 71 (74%) young people were black African, respectively. There were no differences in raw or z-scores of anxiety and depression, or self-esteem, between PHIV and HIV-affected participants (all p values >0.1). Across both PHIV and HIV-affected groups, factors associated with higher anxiety scores were having more carers in childhood, speaking a language other than English at home, lower self-esteem, and ever thinking life was not worth living and lower social functioning. Factors associated with higher depression scores were male sex, death of one or both parents, ever excluded from school, lower self-esteem and lower social functioning. This study found anxiety and depression scores were similar among PHIV and HIV-affected young people and similar to that of population norms. Other studies have found an association between poorer mental health and worse health outcomes in young people with PHIV, highlighting the need to identify young people at increased risk and provide timely support.

BACKGROUND: Increasing numbers of children infected perinatally with human immunodeficiency virus (HIV) are surviving to adolescence and transitioning to adult care, yet there are scarce data on their clinical status at transfer. METHODS: We analyzed prospective cohort data from the UK/Ireland national Collaborative HIV Pediatric Study (CHIPS). Clinical status at last pediatric clinic visit prior to transfer was described. Factors associated with higher CD4 cell count and viral load (VL) suppression

There are few data on gynecomastia in HIV-infected children. Within the UK/Ireland’s national cohort, 56 of 1873 (3%) HIV-infected children had gynecomastia, of which 10 (0.5%) were severe. All 10 had received antiretroviral therapy for a median of 27.5 (21, 42) months; 4 of 10 had received efavirenz, 7 of 10 and 6 of 10 had received stavudine and/or didanosine respectively. Five were nonreversible, despite changing antiretroviral therapy, and required breast reduction surgery.

Background Self-harm in adolescents is of growing concern internationally but limited evidence exists on the prevalence of self-harm in those living with HIV, who may be at higher risk of poor mental health outcomes. Therefore our aim was to determine the prevalence and predictors of self-harm among young people with perinatally-acquired HIV (PHIV) and HIV negative (with sibling or mother living with HIV) young people living in England. Methods 303 PHIV and 100 HIV negative young people (aged 12–23 years) participating in the Adolescents and Adults Living with Perinatal HIV cohort study completed an anonymous self-harm questionnaire, as well as a number of standardised mental-health assessments. Logistic regression investigated predictors of self-harm. Results The median age was 16.7 years in both groups, and 40.9% of the PHIV and 31.0% of the HIV negative groups were male. In total 13.9% (56/403) reported having ever self-harmed, with no difference by HIV status (p = 0.089). Multivariable predictors of self-harm were female sex (adjusted odds ratio (AOR) 5.3, (95% confidence interval 1.9, 14.1), p = 0.001), lower self-esteem (AOR 0.9 (0.8, 0.9) per 1 point increase, p

Background: Ukraine’s perinatally HIV-infected (PHIV) young people are ageing into adolescence/young adulthood and, alongside those with horizontally-acquired HIV infections, require transitional and other support services. We aimed to map this population and policies/service provision at specialist HIV centres, to inform future service development. Methods: A national survey was conducted of 28 HIV/AIDS centres on number, characteristics (age group, HIV acquisition mode) and care setting (paediatric/adult) of 10-24 year olds in HIV care in each of 24 regions in January 2016. Information was collected on policies/service provision at each centre. Results: Of 13,286 young people aged 10-24 years registered for HIV care nationally in Ukraine in January 2016, 1,675 were aged 10-18 years. Three-quarters of ≤19 year olds were PHIV, while 72% of 20-24-year-olds had sexually-acquired infection. Five regions accounted for two-thirds of 10-18 year olds in paediatric and 85% of 19-24 year olds in adult services. In 2015, 97 young people transitioned from paediatric to adult services nationally, typically at 18 years although with flexibility in timing at 17/28 centres. At 27/28 centres, horizontally HIV-infected young people aged Only 5/28 centres offered routine HIV care during the evening or weekend, and availability of integrated sexual/reproductive health and harm reduction services was uneven. Of 16/28 centres selectively following-up patients who did not attend for care, 15 targeted patients in paediatric services. Conclusions: Heterogeneity in the population and in service availability at the main regional/municipal HIV/AIDS centres has implications for potential structural barriers to HIV care, and development of services for this group.

BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

OBJECTIVES: Combination neonatal prophylaxis (CNP) is recommended in high-risk situations for the prevention of mother-to-child HIV transmission, although data on its safety are limited. The aim of the study was to identify whether neonatal prophylaxis (NP) type is associated with the risk of severe anaemia or neutropaenia. METHODS: An individual patient data meta-analysis was conducted within six European cohorts, in infants at high risk for acquiring HIV infection. Adjusted logistic regression models were used to assess the risk of National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) grade 3-4 anaemia/neutropaenia at ages 0-6 months. Mixture models of haemoglobin (Hb) level and log(10) -transformed neutrophil count (NC) were used to explore associations with NP type at ages 0-18 months. RESULTS: Of 1836 infants, 25% were preterm, 1149 (63%) had antenatal combination antiretroviral therapy (cART) exposure and 395 (22%) received NP (125 received CNP with three drugs). Overall, 117 (6.7%) infants had grade 3-4 anaemia at age 0-6 months and 140 (9.1%) had grade 3-4 neutropaenia. The presence of grade 3-4 anaemia or neutropaenia was not associated with NP type [adjusted odds ratio (aOR) 1.04 for one-drug NP and 1.60 for three-drug NP versus two-drug NP (P = 0.879 and P = 0.277, respectively) for anaemia; aOR 1.33 for one-drug NP and 1.98 for three-drug NP versus two-drug NP (P = 0.330 and P = 0.113, respectively) for neutropaenia], but was associated with preterm delivery. Overall, 7746 Hb and NC results were available for 1836 infants up to age 18 months; no significant differences in predicted Hb level or NC were apparent by NP type. CONCLUSIONS: A small proportion of infants experienced grade 3-4 haematological adverse events; risk of anaemia or netropenia was not associated with type of NP.

Background. There is limited evidence about the cognitive performance of older adolescents with perinatally acquired human immunodeficiency virus (HIV) compared with HIV-negative (HIV−) adolescents.\ud \ud Methods. A total of 296 perinatally HIV-infected (PHIV+) and 97 HIV− adolescents (aged 12–21 and 13–23 years, respectively) completed 12 tests covering 6 cognitive domains. The HIV− participants had PHIV+ siblings and/or an HIV-infected mother. Domain-specific and overall (NPZ-6) z scores were calculated for PHIV+ participants, with or without Centers for Disease Control and Prevention (CDC) stage C disease, and HIV− participants. Linear regression was performed to explore predictors of NPZ-6.\ud \ud Results. One hundred twenty-five (42%) of the PHIV+ and 31 (32%) of the HIV− participants were male; 251 (85%) and 69 (71%), respectively, were black African; and their median ages (interquartile range) were 16 (15–18) and 16 (14–18) years, respectively. In PHIV+ participants, 247 (86%) were receiving antiretroviral therapy, and 76 (26%) had a previous CDC C diagnosis. The mean (standard deviation) NPZ-6 score was −0.81 (0.99) in PHIV+ participants with a CDC C diagnosis (PHIV+/C), −0.45 (0.80) in those without a CDC C diagnosis (PHIV+/no C), and −0.32 (0.76) in HIV− participants (P < .001). After adjustment, there was no difference in NPZ-6 scores between PHIV+/no C and HIV− participants (adjusted coefficient, −0.01; 95% confidence interval, −.22 to .20). PHIV+/C participants scored below the HIV− group (adjusted coefficient, −0.44; −.70 to −.19). Older age predicted higher NPZ-6 scores, and black African ethnicity and worse depression predicted lower NPZ-6 scores. In a sensitivity analysis including PHIV+ participants only, no HIV-related factors apart from a CDC C diagnosis were associated with NPZ-6 scores.\ud \ud Conclusions. Cognitive performance was similar between PHIV+/no C and HIV− participants and indicated relatively mild impairment compared with normative data. The true impact on day-to-day functioning needs further investigation.

We assessed HIV antibody prevalence in children with perinatally acquired HIV in England. Eighteen percent (10/55) of those starting combination antiretroviral therapy

BackgroundFollowing widespread use of stavudine, a thymidine analogue, in antiretroviral therapy (ART) over the past three decades, up to a third of children developed lipoatrophy (LA) and/or lipohypertrophy (LH). Following phasing-out of stavudine, incidence of newly-diagnosed LA and LH declined dramatically. However, the natural history of existing cases should be explored, particularly with prolonged protease inhibitor exposure.MethodsThe Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort study of most HIV-infected children in the United Kingdom and Ireland. Those on ART with a LA/LH assessment recorded in 2003-2011 were included. Assessments were completed annually by consultant physicians. Using the 0-3 grading system, LA or LH was defined as grade 2 or 3. Resolution was defined as return to grade 1 or 0 in all body regions.ResultsOf 1345 children followed for median (IQR) 5.5 (2.9, 8.2) years after ART initiation, 30 developed LA and 27 developed LH, all at least 2 years after ART initiation. Median age at LA diagnosis was 11 (10, 13) years and at LH diagnosis was 13 (11, 15) years. Children with LA were more likely white (pConclusionsPrevalence of LA and LH were low, with some resolution noted, especially for LA. More long-term data are needed.

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

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 heightfor- 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.

Purpose of review Recent WHO guidelines recommend immediate initiation of lifelong antiretroviral therapy (ART) in all children below 5 years, irrespective of immune/clinical status, to improve access to paediatric ART. Interim trial results provide strong evidence for immediate ART during infancy because of high short-term risk of mortality and disease progression, but there is wider debate regarding the potential risks and benefits of immediate ART in asymptomatic children aged above 1 year. Concerns include long-term toxicities and treatment failure, particularly in resource-constrained settings with limited paediatric treatment options. Recent findings Benefits of immediate ART among infants appear to be maintained in the mid-term to long-term, with low risk of treatment failure, and better neurodevelopmental outcomes. In contrast, a trial reported no benefits of immediate versus deferred ART in asymptomatic children aged above 1 year. However, observational studies suggest that ART initiation at older ages and lower CD4 reduces the probability of immune reconstitution, with unclear implications on risk of clinical events or treatment change. A recent trial on treatment interruption following early intensive ART suggest that this may be a safe alternative approach. Summary Although there are clear benefits of immediate ART among infants, there remains conflicting evidence on the benefits for older children.

Purpose: Fosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged ≥6years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration. Methods: Retrospective analysis of individual patient data for all children aged 6-18years 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 6-18years 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 6years (interquartile range 1-11years), and median age at start of FPV/r was 15years (12-17years). Estimated median time on an FPV-containing regimen was 52months, 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. Conclusions: Results suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported. © 2013 The Authors.

[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, [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.

BACKGROUND The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged

Background: Lopinavir/ritonavir ‘pellets’ were recently tentatively approved for licensing. We describe their acceptability for infants and children up to 48 weeks. Methods: CHAPAS-2 was a randomised, 2-period crossover trial comparing syrup and pellets in HIV-infected infants (n=19, group A, aged 3-Results: For groups A and B overall, the proportion preferring pellets increased between week 0 and week 12 and decreased at week 48 (group A 37%, 72%, 44%; group B 12%, 64% and 36% respectively), although there were marked differences between clinics. For group C, pellets were progressively less preferred to tablets over time: 41%,19%,13% at weeks 0,12,48 respectively. During follow-up unpleasant taste was similarly reported among young children taking pellets and syrups (37%/43% group A; 29%/26% group B), whereas among older children, pellets tasted worse than tablets (40%/2%). No participants reported problems with storage/transportation for pellets (0%/0%) unlike syrups (23%/13%). Conclusions: For children

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

Background Surveillance for mid- and long-term anti-retroviral 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 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 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.

Antiretroviral therapy (ART) has greatly improved the survival of HIV-infected children. However, ART is associated with immediate and long-term adverse events. Pharmacovigilance systems, although imperfect, have been developed in many high-income countries (HICs), but coverage in low- and middle-income countries (LMICs) is poor and uneven. This review covers the recent advances in the understanding of adverse events following perinatal ART exposure, including surveillance from birth cohorts; we also describe the adverse events of antiretroviral drugs among HIV-infected children, focussing particularly on those relevant to LMICs, where more than 90% of HIV-infected children live.ART is largely safe in both HIV-infected and HIV-exposed uninfected children, in whom no significant increase in birth defects has been noted. Among HIV-infected children, toxicity to some drugs may be less frequent than in adults, possibly related to immature immune systems in younger children. As per WHO guidelines, many countries are moving from stavudine-based to zidovudine-based or abacavir-based fixed-dose combination (with nevirapine/lamivudine) paediatric mini-pills. However, reassuring data are emerging about short-term stavudine use in LMICs, as this remains an important first-line regimen for young children, as well as an alternative to zidovudine for anaemic children. Zidovudine appears to be well tolerated in young children living in nonmalarious areas, and, among African children, concerns about abacavir hypersensitivity have not been substantiated.Optimization of first-line ART regimens needs to take account of the toxicities in HIV-infected children, in particular as they will take ART much longer than adults and during the period of growth and development. The benefits of ART in pregnancy are clear, but long-term follow-up of ART-exposed infants in LMICs through integrated surveillance systems would be invaluable.

Objective: To investigate the association between tenofovir disoproxil fumarate (TDF) use and renal abnormality in a large cohort of HIV-1-infected children on antiretroviral therapy (ART). Design: Nested case-control study. Methods: Patients were from the Collaborative HIV Paediatric Study, a cohort of approximately 95% of HIV-1-infected children in the UK/Ireland. Serum (but not urine) biochemistry results for 2002-2008 were obtained for 456 ART-exposed children (2-18 years) seen at seven hospitals. Cases had either confirmed hypophosphataemia DAIDS grade at least 2 or estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m 2 ; three controls per case were matched by hospital. Conditional logistic regression identified risk factors for renal abnormality. Results: Twenty of 456 (4.4%) had hypophosphataemia, and one had eGFR less than 60 ml/min per 1.73 m 2 . Ten of 20 (50%) cases versus 11 of 60 (18%) controls had taken TDF-containing ART for a median [interquartile range (IQR)] of 18 [17-20] months, as part of second-line or salvage therapy. The hypophosphataemia incidence rate was 4.3/100 person-years in the TDF group versus 0.9/100 person-years in those not exposed to TDF. In multivariable analysis, only TDF exposure in the previous 6 months was associated with hypophosphataemia [odds ratio (OR)=4.81, 95% confidence interval (CI) 1.45-16.0, P= 0.01]. In six of 10 children with hypophosphataemia and at least four subsequent phosphate measurements, phosphate values returned to normal when TDF was stopped; in four with three measures or less, values rose but remained subnormal. Conclusions: Hypophosphataemia was uncommon (4%), but was associated with prolonged TDF use, and was generally reversible following TDF withdrawal. Findings highlight the importance of continuing to monitor longer-term renal function, in particular tubular function, especially in those taking TDF. Further studies assessing urine biochemistry measures which more accurately indicate renal tubular damage are required.

BACKGROUND: Future strategies aiming to achieve HIV-1 remission are likely to target individuals with small reservoir size. SETTING: We retrospectively investigated factors associated with HIV-1 DNA levels in European, perinatally HIV-infected children starting antiretroviral therapy (ART)

Children with perinatally acquired HIV-1 infection are surviving into adolescence and increasingly transitioning toward adult services. Planning appropriate services in adult life requires an understanding of their progress through pediatric care. We describe the demographic features, disease progression, antiretroviral therapy (ART), and resistance in young people aged 10 years or more living in the United Kingdom and Ireland reported to the National Study of HIV in Pregnancy and Childhood (NSHPC) with prospective annual follow-up in the Collaborative HIV Paediatric Study (CHIPS) between 1996 and September 2007. Six hundred fifty-four perinatally infected young people were identified; 76% black African, 57% born abroad. Median age at presentation and duration of follow-up was 1 and 11 years, respectively, if born in the United Kingdom/Ireland, and 8 and 5 years if born elsewhere. One hundred sixty-nine (26%) ever had an AIDS-defining illness. Ten died during adolescence. At last follow-up, 64% were on ART, 18% off treatment having previously received ART and 18% were ART naive. Of 518 who had received highly active antiretroviral therapy (HAART), 47% were triple class experienced. At last follow-up 77 (12%) had CD4 counts less than 200 per microliter; of those on HAART, 78% had HIV-1 RNA/=400 copies per milliliter, median CD4 count 554 (interquartile range [IQR] 324-802). Among 166 with resistance assays on HAART, 52% and 12% had dual- and triple-class HIV-1-associated resistance mutations, respectively. One hundred three (16%) young people had transferred to adult services. Young adults with perinatally acquired HIV-1 infection require coordinated multidisciplinary transitional care services and careful long-term follow-up in adult life.

The objective of this study was to assess whether introducing dried blood spot testing can increase hepatitis C virus (HCV) diagnostic testing. A cluster randomized controlled trial was conducted. Sites were matched into pairs, with one site in each pair randomly allocated to receive the intervention (training and use of dried blood spot). Data were collected from all sites for 6 months before and 6 months after the start of the intervention. The participants were 22 specialist drug clinics and six prisons in England and Wales. The main outcome measure of this study was percentage point difference in individuals tested for HCV (the difference between the percentage of patients tested 6 months after and 6 months before the introduction of dried blood spot tests). Before the trial, 8% of patients at control and intervention sites had been tested for HCV, with 16 sites testing less than 5% of their caseload. The average percentage point difference between intervention and control sites was 14.5% (95% CI 1.3-28%, paired t-test, P = 0.03); with 13 of the 14 pairs contributing to the positive effect of the intervention (Wilcoxon matched-pairs signed-rank-test, P = 0.002). The size of the difference between intervention and control sites varied considerably. The study provides preliminary supporting evidence that dried blood spot testing may increase the uptake of HCV diagnostic testing, by increasing the opportunity for patients to be offered testing. Additional trials with a larger number of sites are justified, ideally in the context of drug and treatment policies that gave clearer priority (and targets) to infection control and testing.

Objectives. We examined risk factors for syphilis infection among injection drug users in 3 Russian Federation cities, focusing particular attention on the potential roles of gender and sex work. Methods. We conducted a cross-sectional survey of injection drug users in Moscow, Volgograd, and Barnaul, collecting behavioral data and testing for antibodies to Treponema pallidum. Associations between presence of antibodies to T pallidum and covariates were explored. Results. Overall, the prevalence of antibodies to T pallidum was 11% (95% confidence interval=9.7%, 13.1%). Syphilis was associated with involvement in sex work and with gender in Moscow and Barnaul but not in Volgograd. Female injection drug users not involved in sex work were more likely than men to be younger and to have recently begun to inject; female injection drug users involved in sex work were more likely than those not involved in sex work to inject daily. Conclusions. Syphilis transmission dynamics varied by region. Sex work can increase syphilis risk among injection drug users, potentially feeding the momentum of sexually transmitted HIV and syphilis among noninjectors. Targeted interventions are needed to reduce both sexual and injection risk behaviors among injection drug users.

Hepatitis C virus (HCV) prevalence and incidence among injecting drug users (IDUs) has increased in London and rest of UK. To inform public health action, mathematical modelling is used to explore the possible impact of strategies to decrease syringe sharing.A mathematical model was developed to simulate HCV transmission amongst IDUs in London. Because of parameter uncertainty, numerical search algorithms were used to obtain different model fits to HCV seroprevalence data from London for 2002-03. These simulations were used to explore the likely impact of HCV prevention activities that reduce syringe sharing amongst all IDUs, IDUs that have injected for greater than one year, or IDUs with lower or higher frequencies of syringe sharing.Key differences between model fits centred on how they simulated the high HCV incidence amongst new injectors, either through assuming increased HCV infectivity during acute infection, a large sub-group of high frequency syringe sharers, or increased sharing among new IDUs. Despite parameter uncertainty, the model projections suggest that modest reductions in syringe sharing frequency (25%) will reduce the HCV seroprevalence in newly initiated IDUs (injecting less than four years) but much larger and sustained reductions (50%) are required to reduce the HCV seroprevalence in long-term IDUs (injecting more than 8 years). Critically the model also suggested that large reductions in HCV seroprevalence will be achieved only if interventions target all IDUs and reach IDUs within 12 months of injecting.Public health interventions must reduce syringe sharing amongst all IDUs, including newly initiated IDUs, and be sustained for many years to reduce HCV infection. More accurate data on key behavioural (sharing frequency) and biological (percentage of infected IDUs that clear infection) parameters is required to improve model projections.

Summary Background Tuberculosis is the most common serious co-infection in people living with HIV worldwide, but little is known about its incidence in HIV-infected children living in high-resource settings with low tuberculosis prevalence. We aimed to assess the incidence and prevalence of tuberculosis in children with HIV living in the UK and Ireland to understand rates, risk factors, and outcomes of the disease in this group. Methods We did an analysis of children enrolled in CHIPS, an observational multicentre cohort of children receiving HIV care in the UK and Ireland. We assessed characteristics and prevalence of tuberculosis at baseline, measured incidence of disease through the follow-up period using the CHIPS database, and calculated associated risk factors in these children with multivariable logistic and Cox regression models. Findings Between Jan 1, 1996, to Sept 18, 2014, data for 1848 children with 14 761 years of follow-up were reported to CHIPS. 57 (3%) children were diagnosed with tuberculosis: 29 children had tuberculosis at presentation (prevalent tuberculosis) and 29 had the disease diagnosed during follow-up (incident tuberculosis), including one child with recurrent tuberculosis events. Median age at diagnosis was 9 years (IQR 5–12). 25 (43%) children had pulmonary tuberculosis, 24 (41%) had extrapulmonary tuberculosis with or without pulmonary involvement, and the remainder (n=9; 16%) had unspecified-site tuberculosis. The overall incidence rate for the follow-up period was 196 cases per 100 000 person-years (95% CI 137–283). In our multivariable model, tuberculosis at presentation was associated with more severe WHO immunological stage at baseline (odds ratio 0·25, 95% CI 0·08–0·74; p=0·0331; for none vs severe) and being born abroad (odds ratio 0·28, 0·10–0·73; p=0·0036; for UK and Ireland vs abroad). Incident tuberculosis was associated with time-updated more severe WHO immunological stage (hazard ratio 0·15, 95% CI 0·06–0·41; p=0·0056; for none vs severe) and older age at baseline (1·11, 0·47–2·63; p=0·0027; for age >10 years vs 5–9 years). Interpretation Tuberculosis rates in HIV-infected children in the UK and Ireland were higher than those reported in the general paediatric population. Further study is warranted of tuberculosis screening and preventive treatment for children at high-risk of this disease to avoid morbidity and mortality in this population. Funding NHS England, PENTA Foundation.

About a third of children with HIV have virological failure within 2 years of beginning antiretroviral treatment (ART). We assessed the probability of switch to second-line ART or virological re-suppression without switch in children who had virological rebound on first-line ART in the UK and Ireland.In this study, we used data reported to the Collaborative HIV Paediatric Study (CHIPS), a national multicentre observational cohort. We included children with virological rebound (confirmed viral load400 copies per mL after suppression400 copies per mL) on first-line ART. We did a competing-risk analysis to estimate the probability of switch to second-line treatment, confirmed resuppression (two consecutive viral load measurments400 copies per mL) without switch, and continued viral load above 400 copies per mL without switch. We also assessed factors that predicted a faster time to switch.Of the 900 children starting first-line ART who had a viral load below 400 copies per mL within a year of starting treatment, 170 (19%) had virological rebound by a median of 20·6 months (IQR 9·7–40·5). At rebound, median age was 10·6 years (5·6–13·4), median viral load was 3·6 log10 copies per mL (3·1–4·2), and median CD4% was 24% (17–32). 89 patients (52%) switched to second-line ART at a median of 4·9 months (1·7–13·4) after virological rebound, 53 (31%) resuppressed without switch (19 [61%] of 31 patients on a first-line regimen that included a protease inhibitor and 31 [24%] of 127 patients on a first-line regimen that included a non-nucleoside reverse transcriptase inhibitor; NNRTI), and 28 (16%) neither resuppressed nor switched. At 12 months after rebound, the estimated probability of switch was 38% (95% CI 30–45) and of resuppression was 27% (21–34). Faster time to switch was associated with a higher viral load (p0·0001), later calendar year at virological rebound (p=0·02), and being on an NNRTI-based or triple nucleoside reverse transcriptase inhibitor-based versus protease-inhibitor-based first-line regimen (p=0·001).A third of children with virological rebound resuppressed without switch. Clinicians should consider the possibility of resuppression with adherence support before switching treatment in children with HIV.NHS England (London Specialised Commissioning Group).

Evidence suggests rapid diffusion of injecting drug use and associated outbreaks of HIV among injecting drug users (IDUs) in the Russian Federation and Eastern Europe. There remains a need for research among non-treatment and community-recruited samples of IDUs to better estimate the dynamics of HIV transmission and to improve treatment and health services access. We compare two sampling methodologies "respondent-driven sampling" (RDS) and chain referral sampling using "indigenous field workers" (IFS) to investigate the relative effectiveness of RDS to reach more marginal and hard-to-reach groups and perhaps to include those with the riskiest behaviour around HIV transmission. We evaluate the relative efficiency of RDS to recruit a lower cost sample in comparison to IFS. We also provide a theoretical comparison of the two approaches. We draw upon nine community-recruited surveys of IDUs undertaken in the Russian Federation and Estonia between 2001 and 2005 that used either IFS or RDS. Sampling effects on the demographic composition and injecting risk behaviours of the samples generated are compared using multivariate analysis. Our findings suggest that RDS does not appear to recruit more marginalised sections of the IDU community nor those engaging in riskier injecting behaviours in comparison with IFS. RDS appears to have practical advantages over IFS in the implementation of fieldwork in terms of greater recruitment efficiency and safety of field workers, but at a greater cost. Further research is needed to assess how the practicalities of implementing RDS in the field compromises the requirements mandated by the theoretical guidelines of RDS for adjusting the sample estimates to obtain estimates of the wider IDU population.

We found a high prevalence of HIV among injecting drug users (IDU) 54% in Tallinn and 90% in Kohtla Jarve, Estonia. Risk factors for HIV in Tallinn included use of the drug 'china white', being registered as an IDU at a drug treatment clinic, and sharing injecting equipment with sex partners. Differences existed in risk behaviour between the cities. An urgent scale-up of HIV prevention is needed. It is also important to explore how local 'risk environments' mediate the risk of HIV transmission.

Drawing on data from recent surveys and pilot qualitative interviews among injecting drug users (IDUs) in England, we highlight the potential ‘normalisation’ of the use of the femoral vein (groin) as a site of injection. We estimate that 45% (428/952) of IDUs in English cities report groin injecting in the last 4 weeks, rising to over 50% in some areas. We also note transitions towards the injection of crack cocaine among poly drug injectors in some UK locations. We estimate that 40% (381/952) of IDUs in English cities report crack injection in the last 4 weeks, rising to over 70% in some cities. Findings from pilot qualitative interviews among homeless injectors in London are suggestive of groin injecting being situated as an ‘acceptable risk’. We emphasise the need for research to explore the potential interplay between unstable housing, groin injecting and crack injecting. We call for renewed emphasis within harm reduction interventions advising injectors how to maximise the health and longevity of arm and other peripheral veins, and for greater preparedness to advise known groin injectors how to minimise health risks associated with groin injecting. © 2006 Published by Elsevier B.V.

The objective of this study was to estimate the prevalence of hepatitis C virus (HCV) infection and co-infection with HIV among injecting drug users (IDUs) in Togliatti City, Russia. Unlinked anonymous cross-sectional survey of IDUs recruited from community settings, with oral fluid sample collection for HCV and HIV antibody (anti-HCV, anti-HIV) testing, was carried out. The anti-HCV prevalence was 87% (357/411), anti-HIV prevalence 56% (234/418), and 93% (214/230) of HIV-positive IDUs were co-infected with HCV. Only 23% (94/411) of those HCV positive self-reported as such. In an adjusted model, increased odds of HCV positivity were associated with needle and syringe, as well as injecting paraphernalia sharing in the last four weeks. IDUs injecting more than once with the same needle also had raised odds. There were no marked associations between HCV positivity and the duration of injecting or age group. Almost all IDUs were HCV positive, and almost all HIV-positive IDUs were HCV co-infected. There is an urgent need to maximize syringe distribution coverage, develop health promotion targeting HCV prevention for IDUs, and improve access among IDUs to treatments for HIV and HCV infection.

The aim of this study was to carry out a comprehensive and systematic review of the literature on drug-use prevention with vulnerable young people. A search of electronic databases was conducted to find evaluations of prevention programmes targeted at high-risk young people and including illegal drug use as an outcome measure. Sixteen relevant studies were found that used a suitable quality of research design, involving at least a comparison group. The most common setting for these evaluations was in schools, where life-skills training interventions showed positive results in reducing drug use (at least in the short term). In the community an intensive multi-component intervention (the Children at Risk program) was the most effective. Across different settings the 11–13 age range appeared to be a crucial period for intervention with vulnerable young people. All of the sixteen studies included in the review were from North America and therefore there is a need for outcome evaluations of targeted drug preve...

AIM: Recognizing the dearth of qualitative research on hepatitis C virus (HCV) infection associated with injecting drug use in the UK, this paper summarizes qualitative insights from a study exploring the social relations of HCV risk management among drug injectors in London. METHOD: Adopting an inductive approach to data collection and analysis, 59 depth tape-recorded qualitative interviews were undertaken in 2001 with drug injectors recruited via drug user networks. RESULTS: While access to injecting equipment was reportedly good, needle and syringe sharing continued in exceptional circumstances and in the context of 'trust relationships'. Analyses of drug injectors' accounts of variations of 'I never share' showed that this construction denoted less a descriptor of actual risk behaviour than presentation of perceived risk status. Paraphernalia sharing, including spoons and filters, was common. There was much confusion and uncertainty concerning HCV knowledge, including its medical and transmission risks. Injectors were aware of the provisionality and partiality of their HCV knowledge. Confusion also surrounded the meaning of HCV antibody test results, with some feeling that their positive diagnosis had been 'trivialized' by their experiences of HCV testing. Injectors tended to make sense of HCV risk in relation to HIV. With most viewing HCV prevalence as high and HCV transmission as an inevitable consequence of injecting, HCV risk was perceived as ubiquitous and unavoidable. CONCLUSIONS: There is an urgent need to renew UK policies of harm reduction in order to support perceptions that HCV is avoidable and preventable.

OBJECTIVE: To compare risk factors for injecting equipment sharing among injecting drug users (IDUs) in Togliatti City, Russia. DESIGN: Unlinked, anonymous, cross-sectional community-recruited survey with oral fluid sample collection. METHODS: Between September and October 2001, 426 IDUs completed an interviewer-administered questionnaire and oral fluid samples were tested for HIV. Univariate and multivariate analyses compared potential risk factors for injecting equipment sharing. RESULTS: More than half (56% [234/418]) of the sample were positive for antibodies to HIV. A third (36%) had injected with used needles and syringes in the last 4 weeks. IDUs who reported syringe exchanges or outreach workers as their main sources of new needles and syringes in the last 4 weeks had 0.3 times the odds of sharing compared with those obtaining them from a pharmacy or shop, whereas those whose main source was buying them from the streets or obtaining them from friends, sexual partners, or other drug users had 12 times the odds of receptive needle and syringe sharing. IDUs who reported being last arrested or detained by the police for a drug-related offense had higher odds of sharing. CONCLUSIONS: Findings highlight the delicate balance in HIV prevention between potentially competing strategies of law enforcement and syringe distribution.

Fatal overdose and drug-related mortality are key harms associated with heroin use, especially injecting drug use (IDU), and are a significant contribution to premature mortality among young adults. Routine mortality statistics tend to underreport the number of overdose deaths and do not reflect the wider causes of death associated with heroin use. Cohort studies could provide evidence for interpreting trends in routine mortality statistics and monitoring the effectiveness of strategies that aim to reduce drug-related deaths. We aimed to conduct a retrospective mortality cohort study of heroin users recruited from an anonymous reporting system from specialist drug clinics. Our focus was to test whether (1). specialist agencies would agree to participate with a mortality cohort study, (2). a sample could be recruited to achieve credible estimates of the mortality rate, and (3). ethical considerations could be met. In total, 881 heroin users were recruited from 15 specialist drug agencies. The overall mortality rate of the cohort of heroin users was 1.6 (95% confidence interval [CI], 1.1 to 2.2) per 100 person-years. Mortality was higher among males, heroin users older than 30 years, and injectors, but not significantly higher after adjustment in a Cox proportional hazard model. Among the 33 deaths, 17 (52%) were certified from a heroin/methadone or opiate overdose, 4 (12%) from drug misuse, 4 (12%) unascertained, and 8 (24%) unrelated to acute toxic effects of drug use. Overall, the overdose mortality rate was estimated to be at least 1.0 per 100 person-years. The standardized mortality ratio (SMR) was 17 times higher for female and male heroin users in the cohort compared to mortality in the non-heroin-using London population aged 15-59 years. The pilot study showed that these studies are feasible and ethical, and that specialist drug agencies could have a vital role to play in the monitoring of drug-related mortality.

Introduction : With improved survival, adolescents with perinatal HIV (PHIV) are transitioning from paediatric to adult care, but there are few published data on clinical outcomes post-transfer. Using linked data from patients in the national UK/Ireland paediatric cohort (CHIPS) and an adult UK cohort of outpatient clinics (UK CHIC), we describe mortality and changes in immunological status post-transfer. Methods : Participants in CHIPS aged ≥13 years by the end of 2013 were linked to the UK CHIC database. Mixed effects models explored changes in CD4 count before and after transfer, including interactions between time and variables where interaction p 400 copies/mL or one viral load >10,000 copies/mL, and likewise 102 (52%) in the 12 months post-transfer ( p = 0.79). Seven (3%) people died in adult care. In multivariable analysis, CD4 declined as patients approached transition with a greater decline in those with higher nadir CD4 count (mean rates of decline of 3, 13, 15, 30 cells/mm 3 per year for those with nadir CD4 < 100, 100–199, 200–299 and ≥300 cells/mm 3 , respectively). Post-transition, CD4 continued to decline in some groups (e.g. black males, −20 (−34, −5) cells/mm 3 per year post transition, p = 0.007)) while it improved in others. Overall CD4 was higher with later year of birth (14 (7, 21) cells/mm 3 per later year). There was no effect of age at transfer or changing hospital at transfer on CD4. Conclusions : Our findings suggest that CD4 in adolescents with perinatal HIV in the UK was declining in the period before transition to adult care, and there was some reversal in this trend post-transfer in some groups. Across the transition period, CD4 was higher in those with later birth years, suggesting improvements in clinical care and/or transition planning over time. Keywords adolescent; young person; perinatal; HIV; United Kingdom; transition; transfer; adult care; paediatric (Published: 16 May 2017) Judd A et al. Journal of the International AIDS Society 2017, 20(suppl 3) :21577 http://www.jiasociety.org/index.php/jias/article/view/21577 | http://dx.doi.org/10.7448/IAS.20.4.21577

To define the burden of hospitalization due to 2 vaccine-preventable infections, invasive pneumococcal disease (IPD) and varicella zoster (VZ), among HIV-infected children in the UK and Ireland.Analysis of hospitalizations of HIV-infected children18 years receiving pediatric care and reported to the Collaborative HIV Paediatric Study (CHIPS) between 1996 and 2011.Admissions for IPD and VZ combined accounted for ~5% of all hospital admissions for HIV-infected children each year. When compared with background rates for healthy children, the admission rate ratio for HIV-infected children on combination antiretroviral therapy (cART) was 16.7, 14.8 and 126.7 for IPD, varicella and herpes zoster, respectively, and 156.7, 86.1 and 470, respectively, for HIV-infected children not on cART. Those admitted with IPD or VZ were more likely to have Centers for Disease Control stage B/C at presentation with HIV than those without such admissions (36.8% for IPD, 29.7% for VZ and 22.1% for no IPD or VZ, P = 0.006), and were more likely to subsequently commence cART (94.7%, 91.3% and 80.2% respectively, P = 0.004).There is a clear increased risk of admission with IPD or VZ in HIV-infected compared with uninfected children, magnified in those who have not yet commenced cART. It is anticipated that the introduction of new guidelines will result in improved vaccine uptake and thereby reduce the burden of IPD and VZ disease. Subsequent evaluation will assess the impact of these guidelines.

OBJECTIVES: To describe the incidence of gonorrhoea diagnosed in genitourinary medicine (GUM) clinics in South Thames (West) between 1995 and 1996, and how it changed among population subgroups. SETTINGS AND SUBJECTS: Cases of uncomplicated and complicated gonorrhoea diagnosed at 13 GUM clinics in the former South Thames West (STW) Regional Health Authority that reported disaggregate data to the South Thames GUM Clinic Collaborative STD Surveillance Scheme. METHODS: Annual incidence rates (per 100,000) of gonorrhoea diagnoses by sex, age group, ethnic group, area of residence, and year were calculated. Poisson regression models were used to calculate risk ratios (RR) to describe the key differences in the variation of gonorrhoea cases by these variables. Relative differences in the incidence of diagnosed gonorrhoea between 1995 and 1996 were investigated by including an interaction between year and the other variables (age group, sex, ethnic group, region) and testing whether any were significant using a likelihood ratio test. RESULTS: Area of residence, sex, age group, and ethnic group were key predictors of the rates of diagnosed gonorrhoea. The risk ratio for gonorrhoea (after adjustment for the other variables) was: 13 times higher among blacks than the white population; twice as high in inner London compared with outer London; and three times lower in the "shire" region compared with outer London. The rate of diagnosed gonorrhoea was significantly higher in the black population in the shire region than the inner London white population. The rate of gonorrhoea diagnosed by GUM clinics from 1995 to 1996 almost doubled in the white population aged 15-44 years, from 16 cases per 100,000 to 30 cases per 100,000 (adjusted RR 2.0, 95% CI 1.6 to 2.4), whereas increased rates in the black and Asian/other ethnic groups were not statistically significant (adjusted RR 1.1, 95% CI 0.9 to 1.4; and 1.4, 95% CI 0.7 to 2.7 respectively). CONCLUSION: The observed increase in gonorrhoea between 1995 and 1996 occurred mostly among heterosexual white men and women. Overall, the rates of gonorrhoea among young people, especially in the black population and in inner London represent a significant public health problem that may merit further targeted interventions, the effectiveness of which could be monitored through further development of routine surveillance data.

Objective: To describe trends in HIV prevalence among female injecting drug users (IDU) in London between 1990 and 1996. Design: HIV prevalence and risk behaviour were measured yearly between 1990 and 1993, and in 1996, in point prevalence HIV surveys of IDU recruited from both drug-treatment and community-based settings within Greater London. Sample sizes were 173 in 1990, 111 in 1991, 128 in 1992, 146 in 1993 and 200 in 1996. Methods: Each survey used structured questionnaires and common sampling and interview strategies. Oral fluid specimens were collected for testing for antibodies to HIV (anti-HIV). Multiple logistic regression was used to assess the trend in HIV prevalence. Results: The percentage of female IDU testing positive for antibodies to HIV showed a marked decline over the study period, from 15.0% in 1990 to 1.0% in 1996 (P < 0.001). This trend was independent of all other variables examined. Each year, higher HIV prevalences were found among IDU recruited from community settings compared with treatment agencies. Conclusions: These results concur with those of IDU recruited from treatment sites, although the yearly estimates in this study are higher. London benefits from low prevalence of HIV infection among IDU, coupled with behaviour change facilitated by early intervention. Continued surveillance of injectors recruited from both community and treatment settings is necessary in order properly to assess HIV prevalence among IDU.

Background We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second- line protease inhibitor (PI). Methods The prevalence of DRV RAMs, identified from IAS 2010 and Stanford, and the Stanford susceptibility score, were estimated in PI-naive and PI-experienced children in the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database 1998–2008. Associations between type/duration of PI exposure and area under the viraemia curve on PI with the number of RAMs were investigated using multivariate Poisson regression. Results A total of 17/417 (4%) children with a resistance test when PI-naive had one IAS DRV RAM, and 1 had a Stanford mutation; none had multiple DRV RAMs. A total of 177 PI-experienced children had a test after a median 2.7 years (IQR 1.1–5.2) on PIs; 19 (11%) had one IAS DRV RAM, 7 (4%) had two RAMs, 1 (0.6%) had three RAMs and 1 (0.6%) had four RAMs. DRV RAMs were independently associated with increased years on a PI, a larger area under the viraemia curve since starting PIs, and any exposure to PIs other than lopinavir (all P≤0.05). Only 6 (3%) PI-experienced children had intermediate-level DRV/ritonavir resistance; none had high-level resistance. Conclusions DRV resistance was negligible in PI-naive children and those with lopinavir PI exposure alone. However resistance increased with increasing time, and with higher levels of viraemia, on PIs. Once-daily DRV/ritonavir would be valuable as a second PI or an alternative first PI, particularly if coformulated with a booster in an appropriate formulation for children.

Summary 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

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