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

Sharland, Mike; Zub, di; Ramos, JT; Blanche, Stéphane; Gibb, Diana M

doi:10.1046/j.1468-1293.2002.00120.x

Cited by 53 publications

(27 citation statements)

References 51 publications

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“…Although the criteria of when to start HAART have changed over time, 15,16 the clinical implications of our findings on a strong association between young age and virologic failure are important. In light of our data and recent discussion on clinical practice and regimen switches, 41,42 when to start with HAART in young children remains unclear and may be reconsidered.…”

Section: Discussionmentioning

confidence: 85%

“…Current American and European treatment guidelines for HIV-1 infection in children recommend the use of 2 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with either a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor. 15,16 According to the history of antiretroviral therapy, some children in PEACH had initially been treated with azidothymidine (AZT), followed by AZT combined with dideoxyinosine (ddI) or dideoxycytidine (ddC), until the introduction of nelfinavir (NFV) as the first PI available for children. Because of the previous use of certain NRTIs, NFV was combined with stavudine (d4T) plus lamivudine (3TC).…”

Section: Patientsmentioning

confidence: 99%

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Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Scherpbier

Bekker

Leth³

et al. 2006

Pediatrics

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OBJECTIVE. We sought to provide long-term data on the clinical, immunologic, and virologic response to highly active antiretroviral therapy in infants and children who are naive to protease inhibitors.METHODS. HIV-1-infected children who were naive to protease inhibitors were treated with a combination of nelfinavir and 2 nucleoside reverse transcriptase inhibitors (stavudine and lamivudine) in an observational, prospective, singlecenter study. Virologic failure-free survival was assessed by Kaplan-Meier analyses. The increase in CD4 ϩ T cells during follow-up was estimated with a generalized linear model incorporating repeated measurements.RESULTS. Thirty-nine HIV-1-infected children were included and followed for a median period of 227 weeks (interquartile range: 108 -275 weeks). The virologic failure-free survival rate was 74%, 66%, 58%, and 54% after 48, 96, 144, and 240 weeks, respectively. Children who experienced virologic failure in 48 weeks (or 96 weeks) were younger at baseline compared with the responders (0.8 vs 5.3 years). Eighteen children remained on the regimen for Ͼ5 years. All children, including the nonresponders, showed a sustained immunologic response. Grades 3 to 4 toxicity was observed in 2 patients only. Eleven developed clinically evident lipodystrophy.CONCLUSION. Combination therapy can be used safely in infants and children over a long period. Young age is strongly associated with virologic failure. Although the virologic response declined, immunologic parameters and clinical improvement were sustained up to 7 years, at the expense of lipodystrophy. [1][2][3] Mortality, disease progression, and hospital admissions in HIV-infected children have declined substantially since the introduction of highly active antiretroviral therapy (HAART), just as has been seen in adults. [4][5][6] In adults, it was shown that most patients had changed their first regimen after 4 years of HAART because of virologic failure and the availability of alternative drug regimens. In adults, a continued increase in CD4 ϩ T cell count was seen in patients who experienced sustained virologic suppression. 7,8 However, one cannot extrapolate results in adults to children because of differences in immunity (eg, the immaturity of the immune system and larger thymic output); in pharmacokinetics and pharmacodynamics of antiretroviral drugs in infants and children; and, most important, in formulation, availability of drugs, and strict adherence to therapy. Studies have shown that the age-adjusted CD4 ϩ T-cell numbers increase in infants and children, especially in the more immunocompromised ones, even when failing in viral suppression. 9 Despite reasonably good virologic response rates at 48 and 96 weeks of HAART, data from several pediatric studies have shown that the virologic response in children is less prominent compared with adults. 1,3,[9][10][11][12][13][14] Infants and children often start antiretroviral therapy at very young ages and have to use their medication lifelong. Hence, there is an urgent need ...

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Section: Discussionmentioning

confidence: 85%

Section: Patientsmentioning

confidence: 99%

Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Scherpbier

Bekker

Leth³

et al. 2006

Pediatrics

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“…Apesar de o Consenso Brasileiro de Terapia Anti-retroviral em Crianças Infectadas pelo HIV 23 recomendar a terapia dupla em crianças com doença leve ou moderada, outros grupos já recomendavam a terapia tríplice ou HA-ART 24,26 . Na população estudada, a escolha do regime antiretroviral ficou a cargo do médico assistente, não havendo interferência da equipe de pesquisadores.…”

Section: Métodosunclassified

Effectiveness of dual and triple antiretroviral therapy in the treatment of HIV-infected children

Romanelli¹,

Pinto²,

Melo³

et al. 2006

J Pediatr (Rio J)

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Objective: The use of antiretroviral therapy in HIV-infected children has been a widely discussed issue. The aim of this study was to compare the effectiveness of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) regimens and three-drug regimens [2NRTI+ nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI)] in a cohort of HIV-infected children. Methods:The study was carried out in a referral center for the management of infected children, which is affiliated with the School of Medicine of Universidade Federal de Minas Gerais (UFMG). Those children whose antiretroviral therapy was implemented between January 1998 and December 2000 and who were followed until December 2001 were included in the study. Therapeutic failure or death was regarded as the endpoint in our analysis.Results: A total of 101 patients were assessed, 58 (57.4%) on dual therapy and 43 (42.6%) on triple therapy. No statistically significant difference was observed between the groups in terms of gender, age, CD4+ count and baseline viral load. The average duration of dual therapy was 26.3 months (95%CI 21.3-31.3) and that of triple therapy was 34.3 months (95%CI 29.2-39.5%). There was therapeutic failure in 33 (56.9%) patients on dual therapy and in 11 (25.6%) patients on triple therapy (log rank = 5.03; p = 0.025). The relative risk of therapeutic failure of the dual therapy was 2.2 times higher (95%CI 1.3-3.9). The percentage of initial CD4+ T cells was a predictor of risk for therapeutic failure (p = 0.001). Patients on triple therapy showed a more remarkable reduction in their viral load (p = 0.001).Conclusion: Triple therapy was efficient for a longer time period and showed better virologic response than dual therapy in this cohort of HIV-infected children. Therefore, triple therapy should be the treatment of choice. ResumoObjetivos: Como iniciar a terapia anti-retroviral é uma questão amplamente discutida no manejo de crianças infectadas pelo HIV. O objetivo deste estudo foi comparar a efetividade da terapia dupla e tríplice em uma coorte de crianças infectadas pelo HIV.Método: Este estudo foi realizado em um serviço de referência para assistência à criança infectada da Faculdade de Medicina da UFMG. Foram incluídas crianças que iniciaram o primeiro regime anti-retroviral entre janeiro de 1998 e dezembro de 2000, com seguimento até dezembro de 2001. O evento final para análise foi a primeira falha terapêutica ou óbito.Resultados: Foram analisados 101 pacientes, sendo 58 (57,4%) e 43 (42,6%) com terapia dupla e tríplice, respectivamente. Não houve diferença entre os grupos quanto ao sexo, idade, contagem de linfócitos CD4+ e carga viral basal. A média de duração da terapia dupla foi de 26,3 meses (IC95% 21,3-31,3) e da terapia tríplice, de 34,3 meses (IC95% 29,2-39,5%). Falha terapêutica ocorreu em 33 (56,9%) pacientes em terapia dupla e 11 (25,6%) em terapia tríplice (log rank 5,03; p = 0,025). O risco relativo de falha para terapia dupla foi 2,2 vezes maior (IC = 1,3-3,9). O percentual de li...

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“…22 Switches in clinical classification and ART along the study were made according to clinical, immunological, and virological evolution and following the Centers for Disease Control (CDC) and European guidelines in pediatric treatments [22][23][24] and upon obtaining written informed consent from parents or legal guardians. Reduction of drug doses and temporal or permanent treatment discontinuation followed protocol guidelines.…”

Section: Study Populationmentioning

confidence: 99%

Immunological Changes after Highly Active Antiretroviral Therapy with Lopinavir–Ritonavir in Heavily Pretreated HIV-Infected Children

Resino

Galán²,

Pulido‐Pérez³

et al. 2005

AIDS Research and Human Retroviruses

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We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+ T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL < or = 400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Interestingly, we observed a significant decrease of memory (CD4+ CD45RO+) and a moderate decrease of activated (CD4+ HLA-DR+, CD4+ HLA-DR+CD38, CD4+, CD45RO+HLA-DR+) CD4+ T cells during the follow-up. On the other hand, memory (CD8+ CD45RO+ and CD8+ CD45RO+CD38+), activated (CD8+ HLA-DR+CD38+, CD8+ HLA-DR+, CD8+ CD38+), and effector (CD8+ CD57+, CD8+ CD28(-)CD57+) CD8+ T cells had a very significant decrease during follow-up. Our data indicate an immune system reconstitution in heavily pretreated HIV-infected children in response to salvage therapy with LPV/r as a consequence of a decrease in immune system activation and an increase in thymic function.

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

Abstract: 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.

Cited by 53 publications

References 51 publications

Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Long-term Experience With Combination Antiretroviral Therapy That Contains Nelfinavir for up to 7 Years in a Pediatric Cohort

Effectiveness of dual and triple antiretroviral therapy in the treatment of HIV-infected children

Immunological Changes after Highly Active Antiretroviral Therapy with Lopinavir–Ritonavir in Heavily Pretreated HIV-Infected Children

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