Factors associated with clinical, immunological and virological responses in protease-inhibitor-experienced brazilian children receiving highly active antiretroviral therapy containing Lopinavir-Ritonavir

Machado, Daisy Maria; Gouvêa, Aída de Fátima Thomé Barbosa; Cardoso, Maria Regina Alves; Beltrão, Suênia Vasconcelos; Cunegundes, Kelly Simone Almeida; Bononi, Fabiana; Almeida, Fernanda R.; Cavalheiro, Kaline; Angelis, Daniela Souza Araújo de; Succi, Regina Célia de Menezes

doi:10.1590/s1413-86702007000100006

Cited by 3 publications

(8 citation statements)

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“…Younger children and those with higher CD4, lower HIV-RNA, and better weight at the commencement of second-line bPI-based HAART recorded better treatment outcomes, similar to published reports (13, 32-34). Castro et al, reported older age at HAART initiation was associated with increased risk of triple-class failure in a retrospective cohort study of HIV-infected children in Europe (35).…”

Section: Discussionsupporting

confidence: 88%

Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected Children

et al. 2013

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Background The WHO recommends boosted protease inhibitor (bPI)-based highly active antiretroviral therapy (HAART) after failing non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment. We examined outcomes of this regimen in Asian HIV-infected children. Methods Children from five Asian countries in the TREAT Asia Pediatric HIV Observational Database (TApHOD) with ≥24 weeks of NNRTI-based HAART followed by ≥24 weeks of bPI-based HAART were eligible. Primary outcomes were the proportions with virologic suppression (HIV-RNA <400 copies/ml) and immune recovery (CD4% ≥25% if age <5 years and CD4 count ≥500 cells/mm3 if age ≥5 years) at 48 and 96 weeks. Results Of 3422 children, 153 were eligible; 52% were female. At switch, median age was 10 years, 26% were in WHO stage 4. Median weight-for-age z-score (WAZ) was −1.9 (n=121), CD4% was 12.5% (n=106), CD4 count was 237 (n=112) cells/mm3, and HIV-RNA was 4.6 log10copies/ml (n=61). The most common PI was lopinavir/ritonavir (83%). At 48 weeks, 61% (79/129) had immune recovery, 60% (26/43) had undetectable HIV-RNA and 73% (58/79) had fasting triglycerides ≥130mg/dl. By 96 weeks, 70% (57/82) achieved immune recovery, 65% (17/26) virologic suppression, and hypertriglyceridemia occurred in 66% (33/50). Predictors for virologic suppression at week 48 were longer duration of NNRTI-based HAART (p=0.006), younger age (p=0.007), higher WAZ (p=0.020), and HIV-RNA at switch <10,000 copies/ml (p=0.049). Conclusion In this regional cohort of Asian children on bPI-based second-line HAART, 60% of children tested had immune recovery by one year, and two-thirds had hyperlipidemia, highlighting difficulties in optimizing second-line HAART with limited drug options.

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Section: Discussionsupporting

confidence: 88%

Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected Children

et al. 2013

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“…Some studies found improved early CD4 response in younger children [3], [10], [11], while others found no difference [18]. A similar discrepancy exists for baseline CD4% as a predictor of CD4 response [10].…”

Section: Introductionmentioning

confidence: 95%

“…Children's immune and weight response to ART differs based on age at ART initiation and degree of viral suppression [3], [9], [10], [11]. As shown in recent adult studies [12], there are likely other baseline factors contributing to differential immunologic responses.…”

Section: Introductionmentioning

confidence: 98%

“…Antiretroviral therapy (ART) has been shown to dramatically improve clinical outcomes, immune status, and growth parameters among children infected with HIV [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] . Children's immune and weight response to ART differs based on age at ART initiation and degree of viral suppression [3] , [9] , [10] , [11] . As shown in recent adult studies [12] , there are likely other baseline factors contributing to differential immunologic responses.…”

Section: Introductionmentioning

confidence: 99%

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Predictors of Poor CD4 and Weight Recovery in HIV-Infected Children Initiating ART in South Africa

et al. 2012

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ObjectiveTo identify baseline demographic and clinical risk factors associated with poor CD4 and weight response after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency virus (HIV)-infected children in KwaZulu-Natal, South Africa.MethodsWe performed a retrospective cohort study of 674 children initiating antiretroviral therapy at McCord and St. Mary's hospitals in KwaZulu-Natal, South Africa, from August 2003 to December 2008.We extracted data from paper charts and electronic medical records to assess risk factors associated with CD4 and weight response using logistic regression.ResultsFrom the initial cohort of 901 children <10 years old initiating ART between August 2003 and December 2008, we analyzed 674 children with complete baseline data. Viral suppression rates (<400 copies/ml) were 84% after six months of therapy and 88% after 12 months of therapy. Seventy-three percent of children achieved CD4 recovery after six months and 89% after 12 months. Weight-for-age Z-score (WAZ) improvements were seen in 58% of children after six months of ART and 64% after 12 months. After six months of ART, lower baseline hemoglobin (p = 0.037), presence of chronic diarrhea (p = 0.007), and virologic failure (p = 0.046) were all associated with poor CD4 recovery by multivariate logistic regression. After 12 months of ART, poor CD4 recovery was associated with higher baseline CD4% (p = 0.005), chronic diarrhea (p = 0.02), and virologic failure (p<0.001). Age less than 3 years at ART initiation (p = 0.0003), higher baseline CD4% (p<0.001), and higher baseline WAZ (p<0.001) were all associated with poor WAZ improvements after 6 months by multivariate logistic regression.ConclusionThe presence of chronic diarrhea at baseline, independent of nutritional status and viral response, predicts poor CD4 recovery. Age at initiation of ART is an important factor in early WAZ response to ART, while viral suppression strongly predicts CD4 recovery but not WAZ improvement.

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“…PI‐based treatment yields acceptable efficacy when used as salvage treatment for children failing NRTI and NNRTI drug classes. Many studies have reported the improvement of CD4 cell counts, and suppression of viraemia after the use of PIs . However, limited data exist on the long‐term safety and effectiveness of PI‐based regimens in children.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatment

2012

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ObjectivesVirological failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens has become a problem in HIV-infected children on long-term antiretroviral therapy (ART). Protease inhibitor (PI)-based regimens are therefore often given to children failing NNRTI-based regimens. The aim of the study was to assess the 48-week effectiveness, safety and predictive factors for viral suppression of PI-based regimens in HIV-infected Thai children who had failed NNRTI-based regimens. MethodsThis study assessed 41 HIV-infected children who had failed first-line NNRTI-based regimens and were switched to PI-based regimens for at least 48 weeks. We assessed their CD4 cell counts, plasma HIV RNA levels, weight-for-age and height-for-age z-scores, and adverse events. ResultsThe children's median age was 9.5 years (range 1.5-15.8 years). At baseline, their median CD4 cell count was 276 cells/mL [interquartile range (IQR) 160-749 cells/mL], and their median plasma HIV RNA level was 4.5 log10 HIV-1 RNA copies/mL (IQR 3.9-4.8 log10 copies/mL). After 48 weeks of PI-based therapy, their CD4 cell counts increased to a median of 572 cells/mL (IQR 343-845 cells/mL) and in 73.2% plasma HIV RNA levels decreased to < 50 copies/mL. Their median weight-for-age and height-for-age z-scores were stable over the period of the study. Diarrhoea occurred in 29.3% of patients. Triglyceride levels were significantly higher at weeks 24 and 48 in comparison to baseline measurements. ConclusionsPI-based regimens are safe and effective for HIV-infected Thai children who have failed first-line NNRTI-based regimens. However, long-term follow-up is warranted in order to ascertain the feasibility and sustainability of these new regimens. Keywords: HIV-infected children, effectiveness, PI-based regimens Accepted 18 September 2012 IntroductionAccording to global estimates, in 2009 about 2.5 (1.7-3.4) million children under the age of 15 years were living with HIV infection [1], and at the end of 2009, about 356 400 of these children were receiving antiretroviral therapy (ART) [2]. The use of ART for the treatment of HIV infection in children has greatly changed the course of the disease, increasing survival rates and improving quality of life [3][4][5]. Children living with HIV are now surviving through adolescence into adult life, which creates new challenges in terms of adherence to treatment regimens, drug resistance and pill burdens. With expanding access to ART, many are experiencing treatment failures requiring second-line regimens [6][7][8] DOI: 10.1111/j.1468-1293.01061.x © 2012 British HIV Association HIV Medicine (2013 ORIGINAL RESEARCH 226In 2008, 10% of Asian and 3.3% of African HIV-infected children were on second-line ART [9]. The recommended second-line regimen for children who fail first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART is boosted protease inhibitors (PIs) with nucleoside reverse transcriptase inhibitors (NRTIs). World Health Organization (WHO) treatment guidelines...

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Factors associated with clinical, immunological and virological responses in protease-inhibitor-experienced brazilian children receiving highly active antiretroviral therapy containing Lopinavir-Ritonavir

Cited by 3 publications

References 18 publications

Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected Children

Second-Line Protease Inhibitor-Based Haart after Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in Asian HIV-Infected Children

Predictors of Poor CD4 and Weight Recovery in HIV-Infected Children Initiating ART in South Africa

Effectiveness and safety of protease inhibitor‐based regimens in HIV‐infected Thai children failing first‐line treatment

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