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

Abstract

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...

Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor–Based Antiretroviral Therapy

“…Younger age of HIV-infected children at start of second-line PI-based ART was found to be a significant correlate of virologic suppression [20,22], but these studies did not assess the effect of adherence. One study evaluating adherence in children on PIbased second-line ART did find that adherence was the only independent predictive factor of virologic success [19]. In our study, older age and lack of adherence measured by drug levels were strong and independent predictors of failure.…”

“…Those rates are higher than most of those reported in resource-limited settings. In Thailand, previous studies reported a 24-month virologic failure between 22% and 28% in children on PI-based second-line ART (median age, 8.9-9.4 years) [19][20][21].…”

Outcomes of second‐line antiretroviral therapy among children living with HIV: a global cohort analysis

“…At two years of follow‐up, we observed improvements in CD4 counts similar to what have been reported in previous studies conducted primarily in Asia [14,16,18‐21]. While it is reassuring to observe immune recovery after switch to second‐line ART, we noted a large proportion of children with severe immune deficiency and AIDS progression at the time of switch to second‐line ART in some settings.…”

“…Responses to first‐line ART among children have been evaluated in large randomized trials and observational studies [4‐12]. Studies evaluating outcomes on second‐line ART in children; however, have been limited by small sample sizes in both resource‐rich and resource‐limited settings [6,13‐21]. Of the four published studies on second‐line ART with larger sample sizes, ranging from 111 to 277 children, three were conducted in Thailand or the Asia‐Pacific region [18‐20], and one followed Ugandan children who were switched to a lopinavir/ritonavir (LPV/r)‐based second‐line regimen [21].…”