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.
Objectives
The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART).
Methods
Data from ...paediatric HIV‐infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r‐ART) and in the long term (up to 24 months after r‐ART) following the first TI was modelled using asymptotic regression.
Results
In 779 children with at least one TI, the median age at first TI was 10.1 interquartile range (IQR) 6.4, 13.6 years and the mean CD4% was 27.3% standard deviation (SD) 11.0%; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% 95% confidence interval (CI) 18.3, 20.1% at r‐ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r‐ART and long‐term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long‐term CD4% was highest in those with a TI lasting 1 to <3 months, those with r‐ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%.
Conclusions
After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.
Objectives
We 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.
Methods
The ...O'Sullivan and glucose tolerance tests were performed during regular visits of 609 mothers.
Results
The 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/μL (range 139–1690 cells/μL) 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.
Conclusions
In our cohort, the prevalence of GDM appears to be increased, with older age and PI exposure contributing as significant independent risk factors.
Objectives
Highly 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.
Methods
An 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 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).
Results
Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). 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 HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.
Conclusions
This 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.
Background
We evaluated the efficacy, safety and tolerability of etravirine in paediatric patients vertically infected with HIV‐1.
Methods
A 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.
Results
The 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 log10) HIV‐1 RNA copies/mL (range 4300‐83 000 copies/mL), the median CD4 T‐cell count was 445 cells/μL (range 221–655 cells/μL) and the median CD4 percentage was 19.6% (IQR 13.0‐31.0). Remarkably, 16 of 23 patients (70%) harboured one or more etravirine‐associated 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 RNA<400 copies/mL and 18 of 23 (78%) achieved HIV‐1 RNA<50 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 (IQR 35.7–63.4 weeks); four patients (17%) were exposed to etravirine for >120 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.
Conclusions
We observed a sustained antiviral response and improved immunological parameters in multidrug‐resistant paediatric patients, most of whom had received etravirine as part of salvage regimens with at least two fully active drugs.
To identify predictors of faster time to virological suppression among infants starting combination antiretroviral therapy (cART) early in infancy.
Cohort study of infants from Europe and Thailand ...included in studies participating in the European Pregnancy and Paediatric HIV Cohort Collaboration.
Infants with perinatal HIV starting cART aged less than 6 months with at least 1 viral load measurement within 15 months of cART initiation were included. Multivariable interval-censored flexible parametric proportional hazards models were used to assess predictors of faster virological suppression, with timing of suppression assumed to lie in the interval between last viral load at least 400 and first viral load less than 400 copies/ml.
Of 420 infants, 59% were female and 56% from Central/Western Europe, 26% United Kingdom/Ireland, 15% Eastern Europe and 3% Thailand; 46 and 54% started a boosted protease inhibitor-based or nonnucleoside reverse transcriptase inhibitor-based regimen, respectively. At cART initiation, the median age, CD4% and viral load were 2.9 interquartile range (IQR): 1.4-4.1 months, 34 (IQR: 24-45)% and 5.5 (IQR: 4.5-6.0) log10 copies/ml, respectively. Overall, an estimated 89% (95% confidence interval: 86-92%) achieved virological suppression within 12 months of cART start. In multivariable analysis, younger age adjusted hazard ratio (aHR): 0.84 per month older; P < 0.001, higher CD4% (aHR: 1.11 per 10% higher; P = 0.010) and lower log10 viral load (aHR: 0.85 per log10 higher; P < 0.001) at cART initiation independently predicted faster virological suppression.
We observed a significant independent effect of age at cART initiation, even within a narrow 6 months window from birth. These findings support the earliest feasible cART initiation in infants and suggest that early therapy influences key virological and immunological parameters that could have important consequences for long-term health.
Background
Drug resistance mutations affect antiretroviral therapy (ART) effectiveness in HIV-1-infected children, compromising long-term therapy. HIV-1 variants and drug resistance mutations were ...identified in HIV-infected children from Madrid, Spain.
Methods
Patients from the Madrid cohort of HIV-infected children (1993-2009) with available pol sequences or infected samples stored at the Spanish HIV-1 BioBank were selected. Specimens were used to perform new pol sequences when not available. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations were identified according to the International AIDS Society-USA list (2009).
Results
In 198 patients, pol sequences were recovered from routine resistance testing (n = 98) or newly performed using stored plasma, lymphocytes or DNA (n = 100). Patients were mostly Europeans (90%), with moderate to severe AIDS symptoms (65%), on ART (85%) when the specimen was sequenced and infected by subtype B (90%). Among the 19 HIV-1 non-B variants found, 58% were recombinants (8CRF02_AG, 1CRF08_BC, 1CRF12_BF and 1CRF13_cpx) and the rest were 'pure' non-B subtypes (1A2, 2C, 2D, 1F1, 1G and 1H). Transmitted drug resistance (TDR) mutations were detected in 13% of naive children; 4%, 7% and 10% for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), respectively. Global resistance prevalence was higher (66%) among ART-exposed children; 37% for PIs, 54% for NRTIs and 35% for NNRTIs.
Conclusions
HIV-1 non-B variants infected 10% of the cohort during 1993-2009. Resistant viruses were present in 26.5% and 66% of naive and pretreated children, respectively. Our data suggest that TDR prevalence in children could be higher than that reported in adults in Spain. The provided data will help to improve clinical management of HIV-infected children in Spain.
The effect of enfuvirtide (ENF) in 11 HIV-1 heavily antiretroviral-experienced children and adolescents enrolled in the HIV-1 Paediatric Spanish cohort was further investigated. Patients who received ...ENF with novel drugs (etravirine, darunavir, and/or tipranavir) reached and maintained undetectable plasma HIV-1 RNA levels and showed immunological recovery within the first 3 months of therapy that was maintained during the follow-up. Viremia was not fully suppressed in patients who did not combine ENF with novel drugs but interestingly, immunological benefit was observed in half of these patients. Therefore, ENF showed a greater and more stable efficacy when administrated with novel drugs.
En los últimos años estamos asistiendo a un aumento de la inmigración, de los niños viajeros y de adopción internacional, lo cual ha favorecido el resurgimiento de la malaria. Dado que la mortalidad ...asociada no es despreciable, resultan esenciales tanto el diagnóstico como el tratamiento precoz. Por otra parte, se han producido cambios terapéuticos importantes (nuevos fármacos, desarrollo de resistencias…). En este artículo se realiza una puesta al día y se recogen las nuevas recomendaciones siguiendo las directrices de las principales guías disponibles (OMS, CDC).
An increase in the cases of malaria in our country has been observed due to immigration, and adopted children. Malaria management requires an integrate approach, including prompt diagnoses and treatment to avoid the associated morbidity and mortality. In the last years, new recommendations have been introduced due to the appearance of new resistant areas. In this article we aim to provide a summary of the key recommendations following the main malaria guidelines (WHO and CDC).
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