Effectiveness of highly active antiretroviral therapy in HIV-positive children: Evaluation at 12 months in a routine program in Cambodia

Médecins Sans Frontières, Phnom Penh, Cambodia.
PEDIATRICS (Impact Factor: 5.47). 11/2007; 120(5):e1134-40. DOI: 10.1542/peds.2006-3503
Source: PubMed


Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia.
Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load.
Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure.
This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.

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    • "Recently, access to highly active antiretroviral therapy (HAART) has increased in South Africa. HAART helps improve growth parameters, reduce the incidence of opportunistic infections and hospital admissions, and reduce mortality (Bracher et al., 2007; Buonora et al., 2008; Chiappini et al., 2007; Guillén, Ramos, Resino, Bellón, & Muñoz, 2007; Janssens et al., 2007; Nesheim et al., 2007; Resino et al., 2006; Song et al., 2007; Violari et al., 2008). Several studies have shown HAART to be effective in decreasing the incidence of HIV encephalopathy in children (Chiriboga, Fleishman, Champion, Gaye-Robinson, & Abrams, 2005; McCoig et al., 2002; Patel et al., 2009; Sánchez-Ramón et al., 2003). "
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    ABSTRACT: The aim of this study was to compare the neurodevelopment of HIV-infected (HI) infants in combination with antiretroviral therapy also known as HAART (highly active antiretroviral therapy) to HIV-exposed uninfected (HEU) infants. Twenty-seven HIV infected and 29 HEU infants under the age of one year attending the Empilweni Clinic at Rahima Moosa Mother and Child Hospital were studied. HI infants were assessed prior to initiating HAART and then for six months whilst on HAART. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, 3rd ed (Bayley III). The HI infants scored significantly lower when compared to HEU infants for motor and language development at baseline, three months and six months follow up. No significant improvement in language (p = 0.46) and motor function (p = 0.91) occurred over time; however, developmental scores did not decrease. Cognitive development in the HI group was significantly lower when compared to the HEU group at visit one (p = 0.003). By six months follow-up, there were no significant differences between the two groups for cognitive development (p = 0.18). This study suggests that HIV-positive infants are delayed when compared to HEU infants. HAART may help to prevent further delay; however, it does not reverse the neurological damage already present. There is a need for therapists to be involved in pediatric HIV clinical services in order to provide early developmental screening as well as rehabilitative services to those children in need.
    Full-text · Article · Oct 2013 · AIDS Care
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    • "One possible reason for the lack of timely detection of ART failure in the current study is the poor recording of growth parameters (through plotting) which was not regularly done in all the ART centers included in the study. The rate of development of OIs in the current study is less than that reported in Jimma [22]; but higher than the Cambodian [26] and the United States perinatal AIDS collaborative transmission studies [8]. "
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    ABSTRACT: Background The emergence of resistance to first line antiretroviral therapy (ART) regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. Methods A retrospective cohort study was conducted from 2005 to 2011. All HIV infected children under the age of 15 who took first line ART for at least six months at the four major hospitals of Addis Ababa, Ethiopia were included. Data were collected, entered and analyzed using Epi info/ENA version 3.5.1 and SPSS version 16. The Cox proportional-hazard model was used to assess the predictors of first line ART failure. Results Data of 1186 children were analyzed. Five hundred seventy seven (48.8%) were males with a mean age of 6.22 (SD = 3.10) years. Of the 167(14.1%) children who had treatment failure, 70 (5.9%) had only clinical failure, 79 (6.7%) had only immunologic failure, and 18 (1.5%) had both clinical and immunologic failure. Patients who had height for age in the third percentile or less at initiation of ART were found to have higher probability of ART treatment failure [Adjusted Hazard Ratio (AHR), 3.25 95% CI, 1.00-10.58]. Patients who were less than three years old [AHR, 1.85 95% CI, 1.24-2.76], chronic diarrhea after initiation of antiretroviral treatment [AHR, 3.44 95% CI, 1.37-8.62], ART drug substitution [AHR, 1.70 95% CI, 1.05-2.73] and base line CD4 count below 50 cells/mm3 [AHR, 2.30 95% CI, 1.28-4.14] were also found to be at higher risk of treatment failure. Of all the 167 first line ART failure cases, only 24 (14.4%) were switched to second line ART with a mean delay of 24 (SD = 11.67) months. The remaining 143 (85.6%) cases were diagnosed to have treatment failure retrospectively by the authors based on their records. Hence, they were not detected and these patients were not offered second line ARTs. Conclusions Having chronic malnutrition, low CD4 at base line, chronic diarrhea after initiation of first line ART, substitution of ART drugs and age less than 3 years old were found to be independent predictors of first line ART failure in children. Most of the first line ART failure cases were not detected early and those that were detected were not switched to second line drugs in a timely fashion. Children with the above risk factors should be closely monitored for a timely switch to second line highly active anti-retroviral therapy.
    Full-text · Article · Aug 2012 · BMC Infectious Diseases
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    • "The most commonly used first-line antiretroviral therapy (ART) in HIV-infected children in resource-limited settings (RLS) is a non nucleoside reverse transcriptase inhibitor (NNRTI)-based treatment [1,2]. Data from individual cohorts in Thailand [3], Uganda [4] Cambodia[5] and those from a meta-analysis of 1457 children [1] showed that 70–81% had viral suppression after 1 year of first-line treatment. Several pediatric programs in RLS have begun to provide second-line therapy; 5.8% and 20% among cohorts of HIV-infected children in South Africa [6] and the TREAT Asia regional network [7], but treatment outcomes data are limited. "
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    ABSTRACT: Background Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. Methods A retrospective chart review was conducted at 8 Thai sites of children who switched to PI –based regimens due to failure of NNRTI –based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks. Results Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002). Conclusion Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed.
    Full-text · Article · Jun 2012 · AIDS Research and Therapy
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