Network For Treatment Of AIDS Research Articles

Optimizing Pediatric Dosing Recommendations and Treatment Management of Antiretroviral Drugs Using Therapeutic Drug Monitoring Data in Children Living With HIV.

This review summarizes the current dosing recommendations for antiretroviral (ARV) drugs in the international pediatric guidelines of the World Health Organization (WHO), US Department of Health and Human Services (DHHS), and Pediatric European Network for Treatment of AIDS (PENTA), and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring in optimizing the dosing of ARVs in children. A PubMed search was conducted for the literature on ARV dosing published in English. In addition, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by the WHO, DHHS, and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration-time curve, trough concentration, and peak concentration. Studies with enrolled participants with a median or mean age of ≥18 years were excluded. No restriction on publishing date was applied. Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic parameters of pediatric ARVs are subject to high interpatient variation and this leads to a potential risk of underdosing or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse subpopulations. Therapeutic drug monitoring data generated in children, where available and affordable, have the potential to enhance our understanding of the appropriateness of simplified pediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues postmarketing, further facilitating the ultimate goal of optimizing pediatric ARV treatment.

Tuberculosis in HIV-infected children in Europe, Thailand and Brazil: paediatric TB-HIV EuroCoord study.

Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil. To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children. Observational study of TB diagnosed in HIV-infected children in 2011-2013. Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0-11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes. Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.

Immunisation practices in centres caring for children with perinatally acquired HIV: A call for harmonisation

BackgroundCurrent national immunisation schedules differ between countries in terms of vaccine formulation, timing of vaccinations and immunisation programme funding and co-ordination. As a result, some HIV infected paediatric population may be left susceptible to vaccine preventable infections. Vaccines used in healthy population should be subjected to high quality ethical research and be explicitly validated for use in children with special vaccination needs such as those infected with HIV. This survey was completed to assess current vaccination practices and attitudes toward vaccination among pediatricians who care for vertically HIV infected children. MethodsAn online questionnaire was completed by 46 experts in paediatric HIV-infection from the Paediatric European Network for Treatment of AIDS (PENTA). Data were collected between November 2013 and March 2014. Results46units looking after 2465 patients completed the questionnaire. The majority of units (67%) reported that common childhood immunisation were administered by the family doctor or local health services rather than in the HIV specialist centre. Vaccination histories were mostly incomplete and difficult to obtain for 40% of the studied population. Concerns were reported regarding the use of live attenuated vaccines, such as varicella and rotavirus, and these were less frequently recommended (61% and 28% of the units respectively). Monitoring of vaccine responses was employed in a minority of centres (41%). A range of different assays were used resulting in diverse units of measurement and proposed correlates of protection. ConclusionVaccination practices for perinatally HIV-infected children vary a great deal between countries. Efforts should be made to improve communication and documentation of vaccinations in healthcare settings and to harmonise recommendations relating to additional vaccines for HIV infected children and the use of laboratory assays to guide immunisation. This will ultimately improve coverage and vaccine induced immunity in this vulnerable patient group.

Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption.

Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Children previously randomized to continuous (continuous ART, n = 41) vs. planned treatment interruption (PTI, n = 47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale (≥17 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Characteristics were similar between arms with a median age of 12.6 years, CD4⁺ of 830 cells/μl and HIV RNA of 1.7 log10copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P = 0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV-1 infection 2015: optimizing health in preparation for adult life.

The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study

Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery. CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4-17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n = 914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization-recommended CD4 thresholds for starting ART in children ≥5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled. Although younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and Prevention guidelines. In contrast, to maximise CD4 reconstitution in treatment-naïve children >10 y, ART should ideally be considered even if there is a low risk of immediate disease progression. Further exploration of the immunological mechanisms for these CD4 recovery profiles should help guide management of paediatric HIV infection and optimise children's immunological development. Please see later in the article for the Editors' Summary.

The Immunological and Virological Consequences of Planned Treatment Interruptions in Children with HIV Infection

ObjectivesTo evaluate the immunological and viral consequences of planned treatment interruptions (PTI) in children with HIV.DesignThis was an immunological and virological sub-study of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial, which compared CD4-guided PTI of antiretroviral therapy (ART) with continuous therapy (CT) in children.MethodsHIV-1 RNA and lymphocyte subsets, including CD4 and CD8 cells, were quantified on fresh samples collected during the study; CD45RA, CD45RO and CD31 subpopulations were evaluated in some centres. For 36 (18 PTI, 18 CT) children, immunophenotyping was performed and cell-associated HIV-1 DNA analysed on stored samples to 48 weeks.ResultsIn the PTI group, CD4 cell count fell rapidly in the first 12 weeks off ART, with decreases in both naïve and memory cells. However, the proportion of CD4 cells expressing CD45RA and CD45RO remained constant in both groups. The increase in CD8 cells in the first 12 weeks off ART in the PTI group was predominantly due to increases in RO-expressing cells. PTI was associated with a rapid and sustained increase in CD4 cells expressing Ki67 and HLA-DR, and increased levels of HIV-1 DNA.ConclusionsPTI in children is associated with rapid changes in CD4 and CD8 cells, likely due to increased cell turnover and immune activation. However, children off treatment may be able to maintain stable levels of naïve CD4 cells, at least in proportion to the memory cell pool, which may in part explain the observed excellent CD4 cell recovery with re-introduction of ART.

When to Start, What to Start and Other Treatment Controversies in Pediatric HIV Infection

Over the last decade there have been dramatic changes in the management of pediatric HIV infection. Whilst observational studies and several randomized control trials (RCTs) have addressed some questions about when to start antiretroviral therapy (ART) in children and what antiretrovirals to start, many others remain unanswered. In infants, early initiation of ART greatly reduces mortality and disease progression. Treatment guidelines now recommend ART in all infants younger than 1 or 2 years of age depending on geographical setting. In children >1 year of age, US, European (Paediatric European Network for Treatment of AIDS; PENTA) and WHO guidelines differ and debate is ongoing. Recent data from an RCT in Thailand in children with moderate immune suppression indicate that it is safe to monitor asymptomatic children closely without initiating ART, although earlier treatment was associated with improved growth. Untreated HIV progression in children aged over 5 years is similar to that in adults, and traditionally adult treatment thresholds are applied. Recent adult observational and modeling studies showed a survival advantage and reduction of age-associated complications with early treatment. The current US guidelines have lowered CD4+ cell count thresholds for ART initiation for children aged >5 years to 500 cells/mm3. Co-infections influence the choice of drugs and the timing of starting ART. Drug interactions, overlapping toxicities and adherence problems secondary to increased pill burden are important issues. Rapid changes in the pharmacokinetics of antiretrovirals in the first years of life, limited pharmacokinetic data in children and genetic variation in metabolism of many antiretrovirals make correct dosing difficult. Adherence should always be addressed prior to starting ART or switching regimens. The initial ART regimen depends on previous exposure, including perinatal administration for prevention of mother to child transmission (PMTCT), adherence, co-infections, drug availability and licensing. A European cohort study in infants indicated that treatment with four drugs produced superior virologic suppression and immune recovery. Protease inhibitor (PI)-based ART has the advantage of a high barrier to viral resistance. A recent RCT conducted in several African countries showed PI-based ART to be advantageous in children aged <3 years compared with nevirapine-based ART irrespective of previous nevirapine exposure. Another trial in older children from resource rich settings showed both regimens were equally effective. Treatment interruption remains a controversial issue in children, but one study in Europe demonstrated no short-term detrimental effects. ART in children is a rapidly evolving area with many new antiretrovirals being developed and undergoing trials. The aim of ART has shifted from avoiding mortality and morbidity to achieving a normal life expectancy and quality of life, minimizing toxicities and preventing early cancers and age-related illnesses.

First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial

Children with HIV will be on antiretroviral therapy (ART) longer than adults, and therefore the durability of first-line ART and timing of switch to second-line are key questions. We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line ART and viral load switch criteria in children. In a randomised open-label factorial trial, we compared effectiveness of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America. Random assignment was by computer-generated sequentially numbered lists stratified by age, region, and by exposure to perinatal ART. Primary outcome was change in viral load between baseline and 4 years. Analysis was by intention to treat, which we defined as all patients that started treatment. This study is registered with ISRCTN, number ISRCTN73318385. Between Sept 25, 2002, and Sept 7, 2005, 266 children (median age 6.5 years; IQR 2.8-12.9) were randomly assigned treatment regimens: 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL (PI-low), 65 protease inhibitor and switch at 30,000 copies per mL (PI-higher), 68 NNRTI and switch at 1000 copies per mL (NNRTI-low), and 67 NNRTI and switch at 30,000 copies per mL (NNRTI-higher). Median follow-up was 5.0 years (IQR 4.2-6.0) and 188 (71%) children were on first-line ART at trial end. At 4 years, mean reductions in viral load were -3.16 log(10) copies per mL for protease inhibitors versus -3.31 log(10) copies per mL for NNRTIs (difference -0.15 log(10) copies per mL, 95% CI -0.41 to 0.11; p=0.26), and -3.26 log(10) copies per mL for switching at the low versus -3.20 log(10) copies per mL for switching at the higher threshold (difference 0.06 log(10) copies per mL, 95% CI -0.20 to 0.32; p=0.56). Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group. NNRTI resistance was selected early, and about 10% more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group. Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events; both were balanced across randomised groups. Good long-term outcomes were achieved with all treatments strategies. Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited, because the risk of selecting for NRTI and protease-inhibitor resistance is low. Paediatric European Network for Treatment of AIDS (PENTA) and Pediatric AIDS Clinical Trials Group (PACTG/IMPAACT).

Response to planned treatment interruptions in HIV infection varies across childhood

To evaluate clinical, immunological and virological consequences of CD4-guided antiretroviral therapy (ART) planned treatment interruptions (PTIs) compared with continuous therapy in children with chronic HIV infection in the Paediatric European Network for Treatment of AIDS 11 trial. This was a multicentre, 72-week, open, randomized, phase II trial. One hundred and nine children with HIV-RNA below 50 copies/ml and CD4% of at least 30% (2-6 years) or at least 25% and CD4 cell count of at least 500 cells/microl (7-15 years) were randomized to continuous therapy (53) or PTI (56). In PTI, ART was restarted if confirmed CD4% was less than 20% or more than 48 weeks had been spent off ART. The primary outcome was Centers for Disease Control and Prevention (CDC) stage C event, death or CD4% less than 15% (and CD4 cell count less than 200 cells/microl for children aged 7-15 years). At baseline, median (interquartile range) age was 9 (6-12) years, CD4% 37% (33-41), CD4 cell count 966 (793-1258) cells/microl, nadir CD4% before combination ART 18% (10-27), time on ART 6 (3-6) years and 26% were CDC stage C. After median (range) 130 (33-180) weeks of follow-up, 4 versus 48% of time was spent off ART in continuous therapy and PTI, respectively. No child died or had a new CDC stage C event; one (2%) continuous therapy versus four (7%) PTI children had a primary outcome based on CD4%/cell count (P = 0.2). Lower nadir CD4% predicted faster CD4% decline after stopping ART. Younger age and higher nadir CD4% predicted being off ART for at least 48 weeks and better CD4% recovery following PTI. In this first paediatric trial of PTI, there were no serious clinical outcomes. Younger children had better CD4% recovery after PTIs. Immunology substudies and long-term follow-up in Paediatric European Network for Treatment of AIDS 11 trial are ongoing. Further research into the role of treatment interruption in children is required, particularly, as guidelines now recommend early ART for all infected infants.

Response to planned treatment interruptions in HIV infection varies across childhood

OBJECTIVE: To evaluate clinical, immunological and virological consequences of CD4-guided antiretroviral therapy (ART) planned treatment interruptions (PTIs) compared with continuous therapy in children with chronic HIV infection in the Paediatric European Network for Treatment of AIDS 11 trial. DESIGN: This was a multicentre, 72-week, open, randomized, phase II trial. METHODS: One hundred and nine children with HIV-RNA below 50 copies/ml and CD4% of at least 30% (2-6 years) or at least 25% and CD4 cell count of at least 500 cells/microl (7-15 years) were randomized to continuous therapy (53) or PTI (56). In PTI, ART was restarted if confirmed CD4% was less than 20% or more than 48 weeks had been spent off ART. The primary outcome was Centers for Disease Control and Prevention (CDC) stage C event, death or CD4% less than 15% (and CD4 cell count less than 200 cells/microl for children aged 7-15 years). RESULTS: At baseline, median (interquartile range) age was 9 (6-12) years, CD4% 37% (33-41), CD4 cell count 966 (793-1258) cells/microl, nadir CD4% before combination ART 18% (10-27), time on ART 6 (3-6) years and 26% were CDC stage C. After median (range) 130 (33-180) weeks of follow-up, 4 versus 48% of time was spent off ART in continuous therapy and PTI, respectively. No child died or had a new CDC stage C event; one (2%) continuous therapy versus four (7%) PTI children had a primary outcome based on CD4%/cell count (P = 0.2). Lower nadir CD4% predicted faster CD4% decline after stopping ART. Younger age and higher nadir CD4% predicted being off ART for at least 48 weeks and better CD4% recovery following PTI. CONCLUSION: In this first paediatric trial of PTI, there were no serious clinical outcomes. Younger children had better CD4% recovery after PTIs. Immunology substudies and long-term follow-up in Paediatric European Network for Treatment of AIDS 11 trial are ongoing. Further research into the role of treatment interruption in children is required, particularly, as guidelines now recommend early ART for all infected infants.

O222 Treatment interruption in children with chronic HIV-infection: the results of the paediatric European network for treatment of AIDS (PENTA) 11 trial

ss Open Acce Oral presentation O222 Treatment interruption in children with chronic HIV-infection: the results of the paediatric European network for treatment of AIDS (PENTA) 11 trial DM Gibb*1, A Compagnucci2, H Green3, M Lallemant4, Y Saidi2, N NgoGiang-Huong4, C Taylor3, L Mofenson5, F Monpoux6, MIG Tome7, M Marczynska8, D Nadal9, U Wintergerst10, S Kanjavanit11, H Lyall12, C Giaquinto13 and J Moye4

Current and Future Antiretroviral Treatment Options in Paediatric HIV Infection

Because of a lack of prevention policies or problems in implementing prevention of mother-to-child transmission (P-MTCT), most of the 1500 daily new HIV infections in children aged<15 years are caused by MTCT. Fifteen percent of all HIV-infected individuals are children, but the vast majority lack access to highly active antiretroviral therapy (HAART), which can drastically reduce morbidity and mortality. There are 22 antiretroviral drugs currently approved by the US FDA for use in the treatment of HIV-infected adults and adolescents, but only 12 of these drugs are approved for use in children. Antiretroviral drugs belong to four major classes: nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors and fusion inhibitors. According to international guidelines developed by organizations including WHO, the Paediatric European Network for Treatment of AIDS (PENTA) and the US National Institutes of Health (US-NIH), the treatment of choice for HIV-infected children and adults is a combination of two NRTIs (backbone treatment) plus a third potent agent from a different class, either an NNRTI or a ritonavir-boosted protease inhibitor. There are specific challenges in treating HIV-infected children, including uncertainty about the best time to start treatment, the need for more paediatric formulations, the lack of pharmacokinetic studies for new drugs, and incomplete dosing guidelines. Furthermore, the most appropriate regimen for an individual child depends on a variety of factors, including the age of the child; the availability of appropriate drug formulations; the potency, complexity and toxicity of the drug regimen; the home situation; the child and caregiver's ability to adhere to the regimen; and the child's antiretroviral treatment history. In addition, antiretroviral drugs are not licensed for all age groups and the drugs are often not affordable. This review describes NNRTI and protease inhibitors as key components of first- and second-line antiretroviral therapy (ART), focusing on the rationale for choosing an NNRTI- versus protease inhibitor-based regimen based on the results of available phase II and III studies. Some of the new agents available for children as second-line and salvage therapy both on- and off-label are also discussed. The drug regimens described in this review are relevant to clinicians in developed and developing countries. The availability of new, potent compounds with different resistance and toxicity profiles may represent an alternative option to interclass switching and could redefine ART strategy, including the option of first-line NRTI-sparing regimens.

AIDS on the internet

Entering the terms “HIV” or “AIDS” into most search engines may produce in excess of 500 000 000 sites. Potentially bewildering for both doctor and patient, fortunately some search engines now sort the sites into categories such as diagnosis, treatment, etc, and also specify which sites are more aimed at health professionals and which at patients. Both health professionals and patients worldwide may find the World Health Organisation's web page on HIV infections (http://www.who.int/topics/hiv_infections/) of value. The web site is multilingual (click on the menu at the top of the page for translation into Arabic, Chinese, French, Russian, or Spanish), and provides a large number of links to further pages outlining the situation with regard to infection with HIV/AIDS in different parts of the world, fact sheets particularly focusing on issues that primarily affect women, and information about other issues including how the condition may be diagnosed. Much of the information is very general however, and patients wishing to find out more about the condition and how they themselves may be affected may find http://www.aidsmeds.com/ useful. This American site (available in English and Spanish) provides a wide range of easy to read information about many different aspects of HIV/AIDS, including diagnosis and current treatments available, BLOGS written by people living with HIV/AIDS, and the web site even provides the facility for patients to produce graphs to track their own blood test results. Although some of the details particularly with regard to the treatments will be more applicable to the American audience, patients everywhere may find the site helpful. The site does have some pharmaceutical sponsorship, but this is discrete and non-promotional. Patients wanting to use a UK based web site may wish to see the web site of the Terence Higgins Trust (http://www.tht.org.uk/), which provides information on services available particularly for those living in England and Wales, although much of the information on the web site is likely to be of interest to people in Scotland and Ireland also. A brief assessment of a number of the sites labelled as being more suited to health professionals shows that the general information provided is probably equally suited to patients and health professionals wishing a general overview of HIV/AIDS, and often do not provide a great wealth of medical detail, which is probably best found within a text book or by searching peer reviewed journals. What is covered is some detail however, are the various groups running clinical trials for the treatment of HIV/AIDS. Many of these again are US based, and provide general information for patients interested in participating in trials, and for those doctors and other health professionals already involved in their care. For those treating children with HIV/AIDS, the web site of PENTA (Paediatric European Network for Treatment of AIDS) http://www.ctu.mrc.ac.uk/penta/ provides guidelines for the treatment of children, details of clinical trials currently running, and lists of publications that the group has produced. To summarise, the internet provides a wealth of information on HIV/AIDS. This is only a small selection of the web sites that may be useful both to ourselves and to our patients.

PENTA guidelines for the use of antiretroviral therapy in paediatric HIV infection

To produce European Guidelines for the use of antiretroviral therapy (ART) in HIV-infected children. Systematic literature review using Medline, the major antiretroviral conference reports, and IDSA recommendations on guideline production. Pediatric European Network for Treatment of AIDS (PENTA) Steering Committee. Guidelines have been produced for the use of antiretroviral therapy in HIV-infected children in Europe. Recommendations on when to start ART and which ART to start, with dosages and a summary of the relevant literature, have been produced. These guidelines are aimed at assisting paediatricians in Europe with ART prescribing, and provide a more cautious approach to starting therapy than current paediatric USA guidelines.