Their median age (interquartile range) was 9.1 (6.8–11.0) years, the median duration of their NNRTI regimens was 23.7 (15.7–32.6) months, their median CD4 percentage was 12% (4–20%), and their median plasma HIV RNA at the time of genotype testing was 4.8 (4.3–5.2) log10 HIV-1 RNA copies/mL. The nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations found were as follows: 85% of the
children had M184V/I, 23% had at least four thymidine analogue mutations, 12% had the selleck inhibitor Q151M complex, 5% had K65R, and 1% had the 69 insertion. Ninety-eight per cent of the children had at least one NNRTI resistance mutation, and 48% had etravirine mutation-weighted scores ≥4. CD4 percentage <15% prior to switching regimens [odds ratio (OR) 5.49; 95% confidence interval (CI) 2.02–14.93] and plasma HIV RNA>5 log10 copies/mL (OR 2.46; 95% CI 1.04–5.82) were independent predictors of at least four thymidine analogue mutations, the Q151M complex or the 69 insertion. In settings without routine viral load monitoring, second-line antiretroviral therapy regimens should be designed assuming that clinical or immunological failure is associated with high rates of multi-NRTI resistance and NNRTI resistance,
including resistance to etravirine. The widespread LY2109761 use of antiretroviral therapy (ART) for the treatment of HIV-infected children has dramatically changed the course of HIV infection, leading to reductions in morbidity and mortality [1–3]. A triple drug combination including two nucleoside reverse transcriptase inhibitors (NRTIs) plus one nonnucleoside reverse transcriptase inhibitor
(NNRTI) or one Smoothened protease inhibitor (PI) [4] is widely recommended as first-line therapy. For resource-limited settings, the World Health Organization (WHO) recommends an NNRTI-based regimen, which is preferred because it is effective, well tolerated and inexpensive. Plasma HIV RNA monitoring after initiation of ART is usually not available through treatment programmes in resource-limited settings [5]. For example, the Thai national AIDS programme provides antiretroviral drugs for HIV-infected patients and CD4 monitoring every 6 months. Annual plasma HIV viral load monitoring was only recently incorporated into the national programme in 2008. Thus, in the past, the majority of Thai children were diagnosed with treatment failure when they had clinical or immunological failure, that is a long time after virological replication had resumed while they were still on treatment. Consequently, resistance-associated mutations may have occurred in these children as a result of persistent viral replication under drug pressure. The goal of second-line treatment is to fully suppress HIV replication; therefore, the new regimen should comprise at least two, but preferably three, fully active drugs.