ObjectivesThe 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

ObjectivesWe undertook a prospective study to estimate the prevalence of gestational diabetes mellitus (GDM) and associated risk factors in a cohort of 669 HIV-1 infected women. MethodsThe O'Sullivan and glucose tolerance tests were performed during regular visits of 609 mothers. ResultsThe median age of the cohort was 30.7 years (range 16-44), with most women having had heterosexual contact (67%). The majority were in Centers for Disease Control (CDC) category A (71%) and 53% exhibited hepatitis C co-infection. Median viral load and CD4 count at third trimester were 545 cells/mL (range 139-1690 cells/mL) and 1.9 log (range 1.7-5.4), respectively. Seventy-four per cent of the patients were treated with highly active antiretroviral therapy (HAART), of whom 41% received a protease inhibitor (PI). An above-average prevalence of 7% [95% confidence interval (CI) 5.2-9.5] for positive GDM diagnosis was found. Risk factors associated with GDM in univariate analysis included older age, hepatitis C co-infection, stavudine and PI exposure. However, only older age [adjusted odds ratio (AOR) 1.09, 95% CI 1-1.1] and PI exposure (AOR 2.4, 95% CI 1-5.3) remained as independent risk factors for GDM development in multivariate analysis. ConclusionsIn our cohort, the prevalence of GDM appears to be increased, with older age and PI exposure contributing as significant independent risk factors.Keywords: antiretroviral therapy, gestational diabetes mellitus, HIV infection, pregnancy, protease inhibitor IntroductionThe effect of highly active antiretroviral therapy (HAART) on glucose metabolism in pregnant HIV-infected women remains poorly understood. This is partly because data on the use of antiretrovirals (ARVs) in gestational diabetes mellitus (GDM) patients are limited and because previous studies have shown contradictory results. The incidence of GDM in HIV-negative Spanish pregnant women ranges from 2% to 5% [1][2][3]. Some studies have reported an increased prevalence of diabetes ranging from 2% to 7% among HIV-infected patients receiving protease inhibitors (PIs) [4][5][6][7][8][9][10][11][12][13][14]. Although PI treatment has previously been associated with diabetes mellitus (DM), other factors such as age or body mass index (BMI) may also contribute to its development [15]. Classical risk factors for the development of DM in the general population include genetic make-up and individual factors such as race, age, family history of DM and obesity, which can also contribute to changes in plasma glucose levels in HIV-infected patients.The aim of this study is to assess the prevalence of GDM in a large cohort of HIV-1 infected women and to determine possible risk factors associated with its development in these women.Correspondence: Dr Maria Isabel Gonzalez-Tomé, Department of Immunodeficiencies, Hospital 12 de Octubre, Madrid 28041, Spain. Tel: 1 34 9 1390 8569; fax: +34 9 1390 8375; e-mail: maribelgt@hotmail.com DOI: 10.1111/j.1468-1293.2008.00639.x HIV Medicine (2008 Every 3 months, additional testing was carried out. Son...

We evaluated the efficacy, safety and tolerability of etravirine in paediatric patients vertically infected with HIV-1. MethodsA multicentre retrospective study of 23 multidrug-resistant paediatric patients (five children and 18 adolescents) enrolled in the study from 1 September 2007 to 28 February 2010 was carried out. We performed a longitudinal analysis of immunological, virological and clinical data. ResultsThe median age of the patients was 14.2 years [interquartile range (IQR) 12.5-15.8 years]. At baseline, the median HIV-1 RNA was 29 000 (4.5 log 10 ) HIV-1 RNA copies/mL (range 4300-83 000 copies/mL), the median CD4 T-cell count was 445 cells/mL (range 221-655 cells/mL) and the median CD4 percentage was 19.6% (IQR 13.0-31.0). Remarkably, 16 of 23 patients (70%) harboured one or more etravirineassociated resistance mutations. The backbone regimen included at least two fully active drugs in 91% of patients. After etravirine-based therapy, 20 patients (87%) achieved HIV-1 RNAo400 copies/mL and 18 of 23 (78%) achieved HIV-1 RNAo50 copies/mL: three (13%) within the first month, seven (30%) within the first 4 months, and six (26%) between the 5th and 8th months. CD4 T-cell recovery was observed in 19 patients (83%). The median follow-up time was 48.4 weeks .4 weeks); four patients (17%) were exposed to etravirine for 4120 weeks. Three mild/short-term and two moderate skin rashes were observed in the adolescents. Laboratory abnormalities included hypercholesterolaemia (11 of 23 patients), hypertriglyceridaemia (eight of 23 patients), and reduced high-density lipoprotein cholesterol (10 of 23 patients). Adherence was complete in seven patients (30%). No patients showed complete resistance to etravirine after follow-up. However, three of 21 patients (14%) who initially showed intermediate resistance interrupted etravirine treatment because of virological failure. ConclusionsWe observed a sustained antiviral response and improved immunological parameters in multidrugresistant paediatric patients, most of whom had received etravirine as part of salvage regimens with at least two fully active drugs.

ObjectivesHighly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ-specific diseases in HIV-infected children. MethodsAn observational study of a cohort of 366 vertically HIV-infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990CP1 ( -1996: no patients on HAART), CP2 (1997)(1998)(1999): o60% on HAART) and CP3 (2000)(2001)(2002)(2003)(2004)(2005)(2006): 460% on HAART). ResultsChildren experienced a progressive increase in CD4 T cell count (Po0.05) and a decrease in HIV viral load from 1996 onwards (Po0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ-specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIVassociated encephalopathy) were lower in CP2 and CP3 than in CP1. ConclusionsThis study provides evidence of improved clinical outcomes in HIV-infected children over time and shows that mortality, AIDS, opportunistic infections and organ-specific diseases declined as HAART was progressively instituted in this population. There are some specific issues related to paediatric, as opposed to adult, HIV infection. For example, the number of available formulations is limited. There is also a scarcity of clinical trials in children, and insufficient data on the efficacy and toxicity of antiretrovirals for paediatric use, and on the long-term consequences of perinatally acquired HIV infection and drug toxicity. In the last few decades, outcomes for HIV-infected children and adolescents have improved dramatically with the widespread use of antiretrovirals, despite delayed introduction of their use in this population relative to the adult population. Data on changes in the incidence of OIs in the paediatric population with the widespread use of HAART are scarce as compared with the information available in adults [4,11]. To our knowledge, only two recent reports have estimated the incidence of OSDs during the HAART era [6,12].The aim of this study was to assess the influence of the widespread use of HAART on clinical outcomes, especially the development of OIs and OSDs, in perinatally HIVinfected children. Methods Design of the study and settingA multicentre observational study of a cohort of 366 vertically HIV-infected children was conducted from January 1990 to December 2006 at the eight main referral paediatric hospitals of Madrid. Data were retrospectively collected from clinical charts for 1990 to 2003. From January 2003 to December 2006 all data were recorded prospectively. Children were followed at least e...

Background: Protease inhibitors (PIs) have been associated with metabolic complications. There is a trend to switch to simpler therapy to improve these disturbances. We report a case-series describing the effects in metabolic abnormalities in seven HIV-infected children, previously treated with protease inhibitor (PI) after switching to nevirapine.

BACKGROUND: Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain.METHODS: Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified. The incidence and clinical presentation were compared in three periods: 1995–1999 (P1, before initiation of combined antiretroviral therapy, cART), 2000–2009 (P2, increase in immigration), and 2010–2016 (P3, decrease in immigration).RESULTS: We included 29 TB cases among 1183 children aged <18 years (2.4%, 243/100 000 person-years). The proportion was stable in P1 and P2 (1.3%), but decreased in P3 (0.8%). The median age at TB diagnosis was 6.4 years (IQR 4–10.6); most children in P3 were aged >10 years (20% vs. 23.1% vs. 83.3%, P = 0.01). TB was diagnosed at HIV presentation in 11/29 children (37.9%). Foreign-born children accounted for respectively 0%, 8% and 67% of the total number of children in each period (P ≤ 0.0001). One third had extrapulmonary TB; four children died (13.8%).CONCLUSION: In our cohort, the incidence of TB-HIV co-infection decreased with decline in immigration. In regions with adequate cART coverage and low TB transmission, paediatric TB-HIV coinfection is uncommon, but associated with significant morbidity. Strategies for TB surveillance, diagnosis and treatment in this vulnerable population should be reinforced.

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