Publications by authors named "Tawan Mengthaisong"

4 Publications

  • Page 1 of 1

Immunologic and virologic failure after first-line NNRTI-based antiretroviral therapy in Thai HIV-infected children.

AIDS Res Ther 2011 Oct 26;8:40. Epub 2011 Oct 26.

Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand.

Background: There are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART.

Methods: Antiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count ≥30% from baseline. VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF.

Results: 107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5) log10copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%≥25%) and 75% of children had HIV-RNA <1.7log10copies/ml.Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively.Only 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and specificity was 100 (93.9-100)%.

Conclusion: Immunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure.

Trial Registration: identification number NCT00476606.
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October 2011

Monoboosted lopinavir/ritonavir as simplified second-line maintenance therapy in virologically suppressed children.

AIDS 2011 Jan;25(3):315-23

The HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand.

Background: Monoboosted protease inhibitor is being evaluated as a strategy to simplify therapy in virologically suppressed patients who are on complex regimens.

Methods: Children with two consecutive HIV-RNA below 50 copies/ml at least 3 months apart while on double boosted protease inhibitor (dPI) were switched to monoboosted lopinavir/r (mLPV/r). The previous dPI regimen was resumed within 4 weeks in children who experienced virological failure defined as two HIV-RNA at least 500 or three HIV-RNA at least 50 copies/ml. Primary endpoint was the proportion of children still on mLPV/r and having HIV-RNA less than 50 copies/ml at week 48.

Results: Forty children on LPV/r + saquinavir (90%) or LPV/r + indinavir (10%) were enrolled, 50% were female, median [interquartile range (IQR)] age was 11.7 (10.2-13.5) years, and body weight was 29.4 (24.1-40.2 kg). The median (IQR) CD4% was 27 (23.5-29.5%). At 48 weeks, none had died or had HIV disease progression. Thirty-one children were on mLPV/r and 29 (72.5%) had HIV-RNA less than 50 copies/ml. Nine resumed dPI due to mLPV/r failure with four achieving undetectable HIV-RNA. Overall, 31 children (82.5%) had HIV-RNA suppression. Predicting factor for failing mLPV/r was baseline HIV-RNA at least 50 copies/ml. No major protease mutations were found.

Conclusion: By simplifying second-line treatment from dPI to mLPV/r, the majority of children had sustained viral suppression at 48 weeks. Randomized study of simplified mono protease inhibitor therapy in children is warranted.
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January 2011

Characteristics of lymphocyte subsets in HIV-infected, long-term nonprogressor, and healthy Asian children through 12 years of age.

J Allergy Clin Immunol 2010 Dec;126(6):1294-301.e10

HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Center, Bangkok, Thailand.

Background: There are limited data on the immune profiles of HIV-positive children compared with healthy controls, and no such data for Asian children.

Objectives: To immunophenotype HIV-positive Asian children, including long-term nonprogressors (LTNPs), compared with age-matched healthy controls.

Methods: We used flow cytometry to analyze 13 lymphocyte and monocyte subsets from 222 untreated, HIV-positive children with 15% to 24% CD4(+) T cells and no AIDS-related illnesses and 142 healthy children (controls). Data were compared among age categories. Profiles from LTNPs (n = 50), defined as children ≥8 years old with CD4(+) T-cell counts ≥350 cells/mm(3), were compared with data from age-matched non-LTNPs (n = 17) and controls (n = 53).

Results: Compared with controls, HIV-positive children had lower values (cell count per mm(3) and percent distribution) for T(H) cells and higher values for cytotoxic T cells, with reductions in populations of naive T(H) and cytotoxic T cells, B cells, and natural killer (NK) cells. HIV-positive children had high values for activated T(H) and cytotoxic T cells. Compared with non-LTNPs, LTNPs had higher values of T(H) and cytotoxic T cells, naive and memory T-cell subsets, and B and NK cells. Surprisingly, counts of activated T(H) and cytotoxic T cells were also higher among LTNPs. LNTPs were more frequently male.

Conclusion: Untreated, HIV-infected Asian children have immune profiles that differ from those of controls, characterized by low values for T(H) cells, naive T cells, B cells, and NK cells but high values for cytotoxic, activated T(H), and cytotoxic T cells. The higher values for activated T cells observed in LTNPs require confirmation in longitudinal studies.
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December 2010

Safety and efficacy of a double-boosted protease inhibitor combination, saquinavir and lopinavir/ritonavir, in pretreated children at 96 weeks.

Antivir Ther 2009 ;14(2):241-8

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand.

Background: This study aimed to assess the long-term efficacy, safety and use of therapeutic drug monitoring (TDM) of a double-boosted protease inhibitor (PI) combination, saquinavir (SQV) and lopinavir/ritonavir (LPV/r), in Thai HIV type-1 (HIV-1)-infected children who had failed on reverse transcriptase inhibitors.

Methods: In total, 50 children from two sites in Thailand were treated with standard dosing of SQV and LPV/r. CD4(+) T-cell count and percentage, viral load (VL; HIV-1 RNA), minimum plasma drug concentrations (C(min)) and drug safety laboratory evaluations were monitored. Virological failure was defined as having two consecutive VL measures >400 copies/ml after week 12. An intention-to-treat analysis was performed.

Results: Baseline data were a median age of 9.3 years (interquartile range [IQR] 7.1-11.2), VL 4.8 log(10) copies/ml (IQR 4.5-5.1) and CD4(+) T-cell percentage 7% (IQR 3.0-9.5). CDC classifications were N=4%, A=14%, B=68% and C=14% of participants. Median CD4(+) T-cell percentage and CD4(+) T-cell count increase were 14% (IQR 7-19) and 558 cells/mm(3) (IQR 308-782), respectively (both P<0.001). Overall, 37 (74%) children achieved VL<50 copies/ml with significant differences between sites (90% versus 63%). Over 96 weeks, 10 patients had virological failure. Total cholesterol and high-density lipoprotein increased significantly over time, whereas the triglycerides and low-density lipoprotein did not. Approximately 50% of participants reported no change in body shape, and 33%, 43% and 39% reported fatter arms, face and abdomen, respectively. LPV and SQV C(min) were high and stable over time.

Conclusions: Double-boosted SQV+LPV/r was an effective and safe alternative for a second-line regimen in children. Hypercholesterolaemia needs close follow-up. On the basis of the TDM results, PI dose reduction in this population should be considered.
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June 2009