In Thailand, more than 150,000 patients are currently treated with antiretroviral drugs under the support of the National AIDS Program (NAP). The appointed Adults and Adolescents Committee consisted of 28 members who are experts in HIV research, patient care or health care policy. Relevant published literature, guidelines, and the most recent relevant clinical trials presented internationally were reviewed. Several peer review and clinical studies conducted in Thailand were included in the review process. Special considerations for patients with co-infection of tuberculosis or hepatitis B were incorporated. Appropriate cut-off of CD4+ T-cell counts when to commence ART among Thai patients have been considered. It is now recommended to start ART at CD4+ T-cell count <350 cells/mm3. For treatment-naive patients, the preferred initial therapy is a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen containing lamivudine plus zidovudine or tenofovir. Stavudine will be phased out in a two-year plan at the national program level. Viral load and CD4+ T-cell counts should be monitored at least once and twice a year. To achieve long-term treatment success, enhancing adherence together with the proper management of antiretroviral-related toxicity is critical. In summary, the major changes from the Thai 2008 guidelines include commencing ART earlier. ART is recommended regardless of CD4+ T cell count if patients have an indication to treat their HBV co-infection. Preferred first regimen uses AZT or TDF, not d4T as the NRTI-backbone. Furthermore, efavirenz is now considered a preferred NNRTI, along with nevirapine.

New evidence has emerged regarding when to commence antiretroviral therapy (ART), optimal treatment regimens, management of HIV co-infection with opportunistic infections, and management of ART failure. The 2014 guidelines were developed by the collaborations of the Department of Disease Control, Ministry of Public Health (MOPH) and the Thai AIDS Society (TAS). One of the major changes in the guidelines included recommending to initiating ART irrespective of CD4 cell count. However, it is with an emphasis that commencing HAART at CD4 cell count above 500 cell/mm3 is for public health, in term of preventing HIV transmission and personal benefit. In tuberculosis co-infected patients with CD4 cell counts ≤50 cells/mm3 or with CD4 cell counts >50 cells/mm3 who have severe clinical disease, ART should be initiated within 2 weeks of starting tuberculosis treatment. The preferred initial ART regimen in treatment naïve patients is efavirenz combined with tenofovir and emtricitabine or lamivudine. Plasma HIV viral load assessment should be done twice a year until achieving undetectable results; and will then be monitored once a year. CD4 cell count should be monitored every 6 months until CD4 cell count ≥350 cells/mm3 and with plasma HIV viral load <50 copies/mL; then it should be monitored once a year afterward. HIV drug resistance genotypic test is indicated when plasma HIV viral load >1,000 copies/mL while on ART. Ritonavir-boosted lopinavir or atazanavir in combination with optimized two nucleoside-analogue reverse transcriptase inhibitors is recommended after initial ART regimen failure. Long-term ART-related safety monitoring has also been included in the guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12981-015-0053-z) contains supplementary material, which is available to authorized users.

BackgroundSusceptibility testing of pyrazinamide (PZA) against Mycobacterium tuberculosis is difficult to perform because the acidity of culture medium that is required for drug activity also inhibits the growth of bacteria. In Thailand, very limited information has been generated on PZA resistance, particularly among multidrug-resistant tuberculosis (MDR-TB) isolated from Thailand. Only two studies on PZA susceptibility among Thai M. tuberculosis strains have been reported; one used a pyrazinamidase assay, and the other used the BACTEC 460 TB for PZA susceptibility testing. In this study, we determined the percentage of strains possessing pyrazinamide resistance among pan-susceptible M. tuberculosis and MDR-TB isolates by using the pyrazinamidase assay, BACTEC MGIT 960 PZA method and pncA sequencing, and assessed the correlation in the data generated using these methods. The type and frequency of mutations in pncA were also determined.ResultsOverall, 150 M. tuberculosis isolates, consisting of 50 susceptible and 100 MDR-TB isolates, were tested for PZA susceptibility by BACTEC MGIT 960 PZA, the pyrazinamidase assay and pncA sequencing. The study indicated PZA resistance in 6% and 49% of susceptible and MDR-TB isolates, respectively. In comparison to the BACTEC MGIT 960 PZA, the PZase assay showed 65.4% sensitivity and 100% specificity, whereas pncA sequencing showed 75% sensitivity and 89.8% specificity. Twenty-four mutation types were found in this study, with the most frequent mutation (16%) being His71Asp. Of these mutations, eight have not been previously described. The Ile31Ser and Ile31Thr mutations were found both in PZA susceptible and resistant isolates, suggesting that mutation of this codon might not play a role on PZA resistance.ConclusionsOur findings suggest that phenotypic susceptibility testing is still essential for the detection of PZA resistance, especially for MDR-TB isolates. Some mutations were not associated with resistance and could lead to misinterpretation of the genotypic methods. This information could be helpful for clinicians in managing tuberculosis patients and frequencies, and the types of pncA mutations should offer baseline information on PZA resistance.

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