Research Article: High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting

Date Published: June 18, 2012

Publisher: BioMed Central

Author(s): Thanyawee Puthanakit, Gonzague Jourdain, Piyarat Suntarattiwong, Kulkanya Chokephaibulkit, Umaporn Siangphoe, Tulathip Suwanlerk, Wasana Prasitsuebsai, Virat Sirisanthana, Pope Kosalaraksa, Witaya Petdachai, Rawiwan Hansudewechakul, Naris Waranawat, Jintanat Ananworanich.


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.

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. 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). 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.

Partial Text

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. The second-line regimen for children failing NNRTI-based treatment in all treatment guidelines is a low-dose ritonavir boosting protease inhibitors (boosted PI) in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs) [8,9] which was reasonably effective [10].

Our study provides information on outcomes of second-line ART in NNRTI-failing children as part of a large multicenter observational study in a RLS. This study showed good virologic efficacy of second-line boosted PI regimens with 81% achieving HIV RNA < 400 copies/ml at 48 weeks of treatment. Children with more advanced HIV disease were preferentially treated with double-boosted PI versus single-boosted PI regimens. Both regimen types performed equally well in suppressing HIV below 400 copies/ml but further suppression to less than 50 copies/ml was significantly less with double-boosted PI. All authors declare no conflict of interest and that member of their immediate families do not have a financial interest in or arrangement with any commercial organization that may have a direct interest in the subject matter of this article. TP, GJ, KC, and JA designed the study, collected data, wrote the first draft, reviewed manuscript before submission. PS, TS,WP,VS, PK,WP,RH, NW collected data, reviewed and commented of manuscript before submission. US analyzed, reviewed and commented draft of manuscript before submission. All authors have read and approved the final manuscript.   Source: