Antiretroviral treatment outcome following genotyping in Thai children who failed dual nucleoside reverse transcriptase inhibitors

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• 作者：Torsak Bunupuradah ; Piyarat Suntarattiwong ; Andrea Li ; Sunee Sirivichayakul ; Chitsanu Pancharoen ; Pitch Boonrak ; Thanyawee Puthanakit ; Stephen J. Kerr ; Kiat Ruxrungtham ; Tawee Chotpitayasunondh ; Berna
• 关键词：HIV children ; Dual NRTIs ; Genotypic resistance ; HAART
• 刊名：International Journal of Infectious Diseases
• 出版年：2010
• 出版时间：April 2010
• 年：2010
• 卷：14
• 期：4
• 页码：e311-e316
• 全文大小：211 K

文摘

Objective

To evaluate outcomes in dual nucleoside reverse transcriptase inhibitor (NRTI) pretreated children after genotyping (GT).

Methods

We assessed CD4 and viral load (VL) in children three years after baseline GT at the time of dual NRTI failure. Baseline high grade resistance (HR) was defined as ≥4 nucleoside analogue mutations (NAMs) ± Q151 M or 69 insertion complex, and low grade resistance (LR) was defined as <4 NAMs. Genotypic susceptibility scores (GSS) were determined. The current selection of antiretrovirals (ARV) was based on physician judgment and ARV availability.

Results

Seventy-two children were enrolled, with a mean age of 9.3 years; 61 % were female. Baseline median CD4 was 18 % , VL was 1.7 log₁₀ with HR 37.5 % , LR 56.9 % and no mutation (NR, no resistance) 5.6 % . Sixty-five (90.3 % ) switched ARV: 46.2 % non-nucleoside reverse transcriptase inhibitor (NNRTI), 30.8 % protease inhibitor (PI), and 23.1 % PI + NNRTI based highly active antiretroviral therapy (HAART). The choice of regimen did not differ based on baseline HR, LR, and NR. The median duration from dual NRTI therapy to HAART was 5.4 years (interquartile range (IQR) 4.0–6.9 years) and the mean (SD) duration of current HAART regimen was 1.51 (1.78) years; both were similar between ARV groups. Five children continued dual NRTI, two interrupted therapy. The GSS score was significantly higher in the PI group (3.1) vs. PI + NNRTI (2.5) vs. NNRTI (2.6) groups. Sixty-three percent of the HR group used PI or PI + NNRTI-based HAART compared to 41 % of the LR group, p = not significant. At follow-up, median CD4 changes from baseline were +5 % and VL −2.2 log₁₀ (p < 0.001). VL <1.7 log₁₀ was seen in 59.3 % of HR, 58.5 % of LR, and 50.0 % of NR groups (no significant difference). More children on PI (75 % ) and PI + NNRTI (80 % ) based HAART had VL <50 compared to NNRTI-based HAART (50 % ), p = 0.003.

Conclusion

PI-based regimens showed a higher rate of undetectable VL compared with NNRTI-based regimens. Having GT may not affect second-line treatment choices in developing countries, most likely due to late VL failure and limited availability of PIs.