HIV-1 drug resistance mutations in children after failure of first-line nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess the prevalence, predictors and patterns of genotypic resistance mutations in children after failure of World Health Organization-recommended initial nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens. METHODS: We carried out a multicentre retrospective study of genotyping tests performed for all HIV-infected children at eight paediatric centres in Thailand who experienced failure of NNRTI therapy at a time when virological monitoring was not routinely available. RESULTS: One hundred and twenty children were included in the study. 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) log(10) 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 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 log(10) 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. CONCLUSIONS: 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.

Epidemiology of invasive meningococcal disease in 13 government hospitals in Thailand, 1994-1999.

This study was conducted to elucidate the magnitude of problem and the clinical course of invasive meningococcal infection from 13 government hospitals in Thailand between 1994 and 1999. Thirty-six strains of Neisseria meningitidis were isolated from 16 blood and 24 cerebrospinal fluid specimens; 4 patients had positive culture in both blood and CSF. Of the 16 strains, 9 (56.3%) were serogroup B. Seventy-one and eighty-four percent of the isolates were susceptible to penicillin and cefotaxime/ceftriaxone respectively. Five out of six penicillin-nonsusceptible strains were found to be relatively resistant to penicillin with the MIC of 0.125 microg/ml. Of 33 patients whose medical records were available, 21 were males and 12 were females, with a mean age of 11.2 years. Fifteen patients (45.5%) presented with meningococcemia and 18 patients (54.5%) presented with meningococcal meningitis. Hypotension and purpura were found in 24.2% and 33.3% of patients respectively. The overall mortality rate was 9.1%. In conclusion, meningococcal disease is not common in Thailand, meningococcemia is a life-threatening condition whereas meningococcal meningitis is much less severe. The prevalence of meningococci relatively resistant to penicillin seems to be increasing.