Effectiveness of Protease Inhibitor - Based Regimens as Switching Regimen for HIV - Infected Children Failing Reverse Transcriptase Inhibitors in Bamrasnaradura Infectious Diseases Institute

Abstract

A number of HIV infected children treated with 2 Nucleoside reverse transcriptase inhibitors ( NRTI) and 1 Non Nucleoside reverse transcriptase inhibitor ( NNRTI) in Thailand have currently been facing with treatment failure and the effectiveness of the Protease Inhibitors (PI) based regimens as the switching regimen have been questioned. This retrospective study was aimed to study the effectiveness of the PI based regimens for the cohort of PI- naive HIV- infected children, treated at the pediatric unit in Bamrasnaradura Infectious Diseases Institute , who failed NNRTI - based regimens. There were 55 cases with male to female ratio around 1:1, the mean age at initiation of antiretroviral drugs was 3.88 years. The mean age at starting PI was 9.18 years. The mean duration for NRTI and NNRTI treatments prior to initiation of PI were 5.23 and 2.53 years respectively. The mean CD4 , CD4 percentage and plasma HIV RNA before initiation of PI were 363.8 cells/mm3 ,12.2 % and 4.8 log10 copies/mL respectively. The prevalence of M184V/I mutations and NNRTI mutations were 92 % and 83%. Thymidine Analogue - associated mutations ( TAMs) were found in 86 % of cases with 54% of > 4 TAMs. Twenty one cases received single boosted PI, which Indinavir /ritonavir was most frequently used (71%). Thirty four cases received double boosted PI, which Indinavir/ Lopinavir/ ritonavir was most frequently used ( 67%). Comparing single boosted PI vs double boosted PI, within 1 year of treatment, the mean increase of CD4 was 183 vs 260 cells/mm3 ( p = 0.5), the mean increase of CD4 percentage was 3.9 vs 5.5% ( p= 0.8) , the earliest time to achieve an increase of CD4 was 5.2 vs 4.7 months ( p = 0.5), the percentage of the children who achieved plasma HIV viral load < 50 copies/ml (1.69 log10) was 50 vs 45% ( p = 0.6) , the earliest time to achieve plasma HIV viral load < 50 copies/ml was 4.5 vs 5.9 months ( p = 0.17) , and the percentage of the children with viral load > 400 copies/ml ( 2.6log10) was 16 vs 3% ( p= 0.12). Comparing single boosted PI vs double bossted PI , after 1 year of treatment, the mean increase of CD4 was 265 vs 722 cells/mm3 ( p = 0.004), the mean increase of CD4 percentage was 15.2 vs 15.3 % ( p= 0.97) , the longest time to sustain a CD4 increase was 21.1 vs 26.6 months ( p = 0.14), the percentage of the children who achieved plasma HIV viral load < 50 copies/ml was 71 vs 93 % ( p = 0.1), the longest time to sustain plasma HIV viral load < 50 copies/ml was 26.4 vs 31.4 months ( p = 0.14) , and the percentage of the children with viral load > 400 copies/ml was 28 vs 0% ( p= 0.1). In conclusion, the PI based regimens revealed good effectiveness for children failing NRTIs and NNRTI regimens. However, double boosted PI seemed to be more potent and offered long term effectiveness than single boosted PI.