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Background:
Genotyping tests were developed to attenuate the impact of viral resistance. Data on the use antiretroviral therapy genotype based in children is rare, and even more in low and middle-income countriesMethods:16 Children with ART failure and triple-class drug resistant viruses were included. Protease and retrotranscriptase genotypes wer...
Context in source publication
Context 1
... most common drug resistance mutations present for nucleoside reverse-transcriptase inhibitors were M184V (81%), M41L (56%), T215Y/I/F (50%), K219Q/E (37%), and K70R (31%), for non-nucleoside reverse-transcriptase inhibi- tors were K103N (31%), Y188L (25%), and G190S/A (25%), and for PIs were L54V (100%), V82A/S (75%), M46I/L (69%), and L90M (44%) ( Table 5). ...
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Methods
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Citations
... Ten studies of children and adolescents prescribed raltegravir were identified, with median follow-up duration ranging from 11 to 55 months: one RCT (REALITY) [34], one single-arm trial (IMPAACT P1066) [35] and eight observational studies [16,17,[36][37][38][39][40][41] (Table 3). Two studies reported outcome data on children and adolescents receiving raltegravir in combination with darunavir [36,41]. ...
... Ten studies of children and adolescents prescribed raltegravir were identified, with median follow-up duration ranging from 11 to 55 months: one RCT (REALITY) [34], one single-arm trial (IMPAACT P1066) [35] and eight observational studies [16,17,[36][37][38][39][40][41] (Table 3). Two studies reported outcome data on children and adolescents receiving raltegravir in combination with darunavir [36,41]. Four studies were set only in Europe [16,17,38,41], one only in sub-Saharan Africa [34], three in Central or South America [36,37,40] and two in multiple geographic regions [35,39]. ...
... Two studies reported outcome data on children and adolescents receiving raltegravir in combination with darunavir [36,41]. Four studies were set only in Europe [16,17,38,41], one only in sub-Saharan Africa [34], three in Central or South America [36,37,40] and two in multiple geographic regions [35,39]. Across the studies, 649 children received raltegravir-based therapy (Table 3). ...
Introduction:
Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0-19 years.
Methods:
Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009-March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post-treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted.
Results and discussion:
In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single-arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single-arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second- or subsequent-line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second- or subsequent-line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0-50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug.
Conclusions:
These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer-term outcomes, such as weight and metabolic changes.
... The term "pharmacogenomics" was introduced in 1959 by Friedrich Vogel [2] and the first pharmacogenomics test, namely AmpliChip CYP450, was approved by the US Food and Drug Administration in 2004 [3]. Since then, pharmacogenomics testing has been applied in personalizing drug treatment of various diseases, including cardiovascular disease [4], cancer [5], gout [6], autoimmune diseases [7], and infectious diseases [8] to personalize the therapy with the aim of achieving maximum efficacy while reducing the ADR that attributes to a high economic burden, high mortality and morbidity, and higher hospitalization costs globally [9][10][11][12]. ...
The major challenges that delay the implementation of pharmacogenomics based clinical practice in the developing countries, primarily the low- and middle-income countries need to be recognized. This review was conducted to systematically review evidence of the cost-effectiveness for the conduct of pharmacogenomics testing in the developing countries. Studies that evaluated the cost-effectiveness of pharmacogenomics testing in the developing countries as defined by the United Nations were included in this study. Twenty-seven articles met the criteria. Pharmacogenomics effectiveness were evaluated for drugs used in the treatment of cancers, cardiovascular diseases and severe cutaneous adverse reactions in gout and epilepsy. Most studies had reported pharmacogenomics testing to be cost-effective (cancers, cardiovascular diseases, and tuberculosis) and economic models were evaluated from multiple perspectives, different cost categories and time horizons. Additionally, most studies used a single gene, rather than a gene panel for the pharmacogenomics testing. Genotyping cost and frequency of risk alleles in the populations influence the cost-effectiveness outcome. Further studies are warranted to examine the clinical and economic validity of pharmacogenomics testing in the developing countries.
... Quando há falha na regularidade e no horário de tomar os medicamentos, a pressão que a droga exerce sobre o vírus é diminuída favorecendo o aparecimento de mutações de resistência. As cepas virais resistentes passam a não responder ao tratamento instituído, restringindo o arsenal terapêutico capaz de conter a infecção, agravando o problema existente 23,24 . ...
Objetivo: Descrever a adesão de crianças e adolescentes à terapia antirretroviral (TARV) para HIV atendidos em Unidade dispensadora de medicamentos de um hospital público situado na região central do Rio Grande do Sul.Materiais e Métodos: A adesão a TARV foi estratificada em três níveis: alta, regular e baixa adesão, de acordo com a frequência de retirada de medicamentos durante tratamento de 66 pacientes menores de 18 anos, que receberam a forma farmacêutica líquida ou sólida, no período de janeiro a dezembro de 2015. Foi verificada a idade, forma de infecção, cuidador responsável e nível da carga viral ao final do período. Os dados foram obtidos através dos registros do sistema de controle e logística de medicamentos e prontuários clínicos. Utilizou-se estatística descritiva e o estudo foi aprovado (CAAE 47638515.3.0000.5346).Resultados: A média de idade foi de 12 anos. Os pais (77%) são os principais cuidadores responsáveis pelo tratamento. Entre os pacientes que fizeram uso da TARV na forma sólida 36% apresentaram alta adesão, 36% foram considerados com adesão regular e 28% baixa adesão ao tratamento. Apenas 46% mantiveram a carga viral em nível indetectável. Entre os 16 pacientes recebendo a forma farmacêutica líquida 56,2% apresentaram alta adesão, 31,3% adesão regular e 12,5% baixa adesão, sendo que 87,5% apresentaram níveis da última carga viral do período estudado em valores indetectáveis.Conclusão: A adesão à TARV é melhor entre crianças que entre adolescentes, sendo necessário acompanhamento direto para cumprimento da ingestão diária dos medicamentos, com maior comprometimento e conscientização dos cuidadores.
Antiretroviral drug-resistance mutations compromise the successful treatment of children and adolescents infected with human immunodeficiency virus type 1 (HIV-1). We describe the clinical, virological, and immunological follow-up of a cohort of children and adolescents perinatally infected with HIV-1 treated at Hospital Estadual de Doenças Tropicais Dr. Anuar Auad – HDT, in Central Brazil, after therapeutic failure related to drug resistance mutations.We analyzed the results of the genotypic test (protease codons 1–99 and reverse transcriptase codons 1–325) performed from 2003 to 2015. The ARV susceptibility profile was analyzed according to Stanford HIV drug resistance database. A total of 65 patients (median age of 10 years; range, 18 m–18 y) with therapeutic failure (after a median of 55 months of follow up; range, 9 m–13 y) and plasma levels of HIV-1 RNA greater than 1,000 copies/mL which were included and demonstrated mutations in: nucleoside reverse transcriptase inhibitors (NRTIs), 98.5%; non nucleoside reverse transcriptase inhibitors (NNRTIs), 75.4%; and protease inhibitors (PI), 44.6%. The most frequent NRTI mutations were found in codon T215 (83.1%) with a predominance of T215Y (56.9%), followed by M184V (69.3%). In the NNRTI class, mutations K103N (36.9%) and 190A (23.1%) were predominant, and, in the protease, mutations 54VL (35.4%) and 82ASTL (32.3%) were found in approximately the same proportion, with a predominance of the M54V mutation. These results demonstrate the high levels of resistance to different classes of antiretrovirals in HIV-infected children and adolescents and the importance of genotypic resistance tests in this population.KEY WORDS: HIV; drug resistance; genotypes; child; adolescent.
