1,721,037 research outputs found
Antiretroviral therapy for prevention of mother-to-child HIV transmission - Focus on single-dose nevirapine
No full textAdministration of potent antiretroviral combination therapy in the second and third trimester of pregnancy and during delivery, and for 6 weeks postpartum to the infant, may reduce HIV transmission from the mother to the child to < 2% in formula-fed infants. In resource-constrained settings where women have limited access to antenatal care, use of shorter and more practical regimens, including nucleoside reverse transcriptase inhibitors (NRTIs) and/or non-NRTIs (NNRTIs) commenced later in pregnancy, has demonstrated efficacies ranging from 18% to 70% in breast- and bottle-fed populations. Because shorter interventions include regimens such as single-dose nevirapine or zidovudine monotherapy, which do not provide maximal suppression of viral replication, emergence of resistant mutations in mother and infant occurs frequently, primarily after exposure to drugs with low genetic barriers (i.e. those requiring only one genotypic mutation to develop resistance), such as nevirapine.
Different studies have reported nevirapine resistance rates ranging from 25% to 69% in mothers receiving single-dose nevirapine alone. Because NNRTI-based combinations of antiretroviral agents are recommended as first-line therapy in countries where single-dose nevirapine is the main option for preventing mother-to-child transmission of HIV, concerns have been raised as to whether single-dose nevirapine prophylaxis can compromise the efficacy of subsequent NNRTI-based antiretroviral therapy regimens. However, although some studies have shown that nevirapine exposure may impact on short-term virological outcome, the clinical relevance of nevirapine resistance remains unclear, especially in women who start treatment > 6 months after delivery or in those who are not severely immunocompromised. Furthermore, studies have shown that adding short-course (up to 7 days) zidovudine or zidovudine/lamivudine prophylaxis after delivery may dramatically reduce the occurrence of nevirapine resistance in both mothers and infants.
Until data are available that allow a better understanding of the relevance of antiretroviral drug resistance acquired as a result of mother-to-child HIV transmission prophylaxis, women and children who have previously received single-dose nevirapine as part of a mother-to-child transmission prevention strategy should be considered eligible for NNRTI-based regimens and should not be denied access to antiretroviral therapy
Correlazione tra viremia CD4+ - CD8+ e manifestazioni orali in bambini HIV+ i era HAART,
No full textMulticenter study on 30 children Hiv+. Correlation berween viral load, plasma levels of lynphocytes CD4-CD8 and oral didease Aids-related in era highly active antiretroviral therapy (haart)
No full textLong-term decay of the HIV-1 reservoir in HIV-1-infected children treated with highly active antiretroviral therapy
No full textTo investigate the decay of the human immunodeficiency virus type 1 (HIV-1) reservoir in children receiving highly active antiretroviral therapy (HAART), we measured HIV-1 DNA in peripheral blood mononuclear cells from 14 children who achieved and maintained suppression of plasma viremia up to 48 months after the initiation of HAART. Levels of intracellular unspliced and multiply spliced HIV-1 RNA were used as markers of residual viral replication. During the first month of HAART, there were significant decays in levels of both plasma HIV-1 RNA and multiply spliced HIV-1 RNA, yet unspliced HIV-1 RNA persisted in most of the children. Greater HIV-1 DNA decay during the first month of HAART correlated with a higher concomitant increase in CD4(+) cell counts (P=.028) and a smaller subsequent HIV-1 DNA decay (P=.0012). Furthermore, HIV-1 DNA decayed faster from 1 to 9 months of HAART (median half-life, 5 months) than during the subsequent follow-up period (median half-life, 30 months). Moreover, after 9 months of HAART, HIV-1 DNA tended to decay more slowly in children with detectable levels of unspliced HIV-1 RNA. These findings suggest that clearance of the viral reservoir in HAART-treated children may be influenced by immune repopulation and residual viral replication and may help in refining long-term treatment strategies
Maternal and infant factors and lymphocyte, CD4 and CD8 cell counts in uninfected children of HIV-1-infected mothers
Full text linkObjective: To evaluate the effects of antiretroviral treatment (ART) for mother-to-child transmission of HIV and infant/maternal characteristics on total lymphocytes (TLC) and lymphocyte subsets in uninfected children of HIV-1-infected mothers.
Design: The European Collaborative Study followed 1663 uninfected children from birth until at least 8 years of age using a standard protocol.
Methods: Smoothers (running medians) illustrated patterns of immune markers over age by ART exposure and race. Associations between lymphocyte parameters and maternal/infant characteristics were quantified in linear regression analyses using z-scores obtained after modelling log(10)-transformed TLC, CD4 and CD8 cell counts using the LMS method. Cox proportional hazard models assessed time to TLC, CD4 and CD8 cell counts below the defined cut-off. Covariates included prematurity, gender, race, drug withdrawal and ART exposure.
Results: Overall, black children had lower TLC, CD4 and CD8 cell counts than white children, and an increased risk of TLC, CD4 and CD8 cell counts below the cut-off. ART exposure was associated with TLC levels (but not with TLC below the cut-off for lymphopenia), with reduced CD4 cell counts in the first year of life, and with reduced CD8 cell counts until at least 8 years of age. Duration and intensity of ART exposure was associated with TLC levels.
Conclusion: The effect of ART exposure in fetal and early life on TLC and CD8 cell counts was prolonged until at least 8 years. These results add to the growing list of adverse effects associated with ART used as prevention of mother-to-child transmission of HIV
Current and future antiretroviral treatment options in paediatric HIV infections
No full textAbstract: 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
Correlation between viral load, plasma levels of CD4-Cd8 T lymphocytes and AIDS-related oral disease: a multicentre study on 30 HIV+children in the HAART era
No full textNucleoside and nucleotide reverse transcriptase inhibitors in children
No full textAbstract: By the end of 2006, approximately 2.3 million children worldwide were living with HIV infection, representing about 15% of all HIV-infected individuals but only 5-7% of the total population of treated patients worldwide. Despite a general increase in the use of antiretroviral therapy (ART) in resource-limited settings, appropriate care and ART remain inaccessible for most of the world's HIV-infected children. ART of children is challenging because of a general lack of paediatric formulations (including tablets in paediatric strengths), limited options of drugs available for children (some have been approved only for use in adults), different viral and immunological responses, dependency on caregivers for administration of the therapy, and specific issues of toxicity in long-term therapy related to maturation and development. As in adults, nucleoside reverse transcriptase inhibitors (NRTIs) are a key component of any ART schedule in children, being the recommended 'backbone' treatment in US, European and WHO guidelines, and, indeed, NRTIs have been extensively studied in children. NRTIs are the class of antiretroviral drugs that have more drugs licensed for paediatric use and more paediatric formulations.
Generally, the dual NRTI backbone treatment of combination with a non-NRTI (NNRTI) or protease inhibitor (PI) should comprise a cytidine analogue (lamivudine, emtricitabine) and a thymidne analogue (stavudine, zidovudine), guanosine analogue (i.e. abacavir), or nucleotide RTI (NtRTI; i.e. tenofovir). European and US guidelines recommend the use of triple NRTI therapy (abacavir/ lamivudine/zidovudine) in children with anticipated poor adherence to other treatment regimens because of tablet burden.
In conclusion, while use of ART in children needs to be dramatically increased, selecting and administering the best drug combination for children is still limited by a lack of paediatric formulations and knowledge of drug metabolism, safety and efficacy in children. NRTIs are already a key component of paediatric ART, but fixed-dose combinations and specific research in children are needed to optimise their use. In this article we review the available information to facilitate selection of the best NRTI for backbone treatment in combination ART for HIV-infected children
Epidemiological study of the incidence of Oral Diseases in HIV+ children in the Era of Highly Active Antiretroviral Therapy.
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