Genotypic resistance profiles in antiretroviral-naive HIV-1 infections before and after initiation of first-line HAART: impact of polymorphism on resistance to therapy.

Genotypic testing using TRUGENE was performed for treatment-naive, human immunodeficiency virus type 1 (HIV-1)-infected patients at baseline and after initiation of protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens. The genetic diversity of HIV-1 pol sequences from 92 CRF01_AE and 21 B strains was compared. Subsequently, the impact of polymorphism on resistance to therapy was studied in CRF01_AE-infected (n=29) and subtype B-infected (n=14) patients. At baseline, the differences between CRF01_AE and B strain were mainly observed in the minor mutations L10I/V, M36I and L63P/I/H (P<0.001, chi(2)). In the reverse transcriptase sequence, M41L and T215Y/S were more common in patients infected with subtype B virus (P<0.05, chi(2)). Although all patients treated with PI-based HAART had pre-existing minor mutations, a low prevalence of resistance to PIs was observed (5/43; 11.6%). Moreover, major mutations (D30N and N88D) conferring resistance to PIs were found in patients infected with subtype B strain. In conclusion, polymorphisms at the protease region may not reduce PI susceptibility during treatment. However, this study also revealed the difference in natural mutations among subtypes, which may affect the manifestation of drug resistance.

Genotypic resistance mutations in treatment-naïve and treatment-experienced patients under widespread use of antiretroviral drugs in Thailand: implications for further epidemiologic surveillance.

The aims of this study were to illustrate the prevalence and determinants of mutations associated with antiretroviral drug resistance in a group of antiretroviral-naive and treatment-experienced patients in Thailand, where antiretroviral drugs are widely used. One hundred and thirteen treatment-naive (92 CRF01_AE and 21 subtype B patients) and 1,709 treatment-experienced patients were recruited. Genotypic resistance to antiretroviral drugs was studied by sequencing the isolated viruses. Mutation frequencies in treatment-naive patients were reported along with those for treatment-experienced patients. The results showed that all of the patients with treatment-experienced patients showed the same pattern of genotypic resistance. The results also showed that only 14 drug-naive patients (12.4%) carried HIV-1, with at least one drug-resistant mutation. Moreover, four drug-naive patients were found to carry the marker mutations for transmission of drug resistance. The most commonly found marker in drug-naive patients was M36I/V/L (n=90, 81.1%), which is a common natural polymorphism among HIV-1 subtype CRF01_AE individuals. In order to prevent the rapid emergence of resistant virus strains, a national program to monitor antiretroviral drug resistance should be established. We also recommend routine genotypic testing in treatment-naive patients before starting antiretroviral therapy to prevent subtherapeutic response and viral failure.

Therapeutic vaccine trails in Thailand.

An effective therapeutic HIV vaccine will not only benefit the HIV-infected person but will also provide invaluable information on effective immune response in designing or selecting a preventive vaccine. A phase II double-blind controlled clinical trial using HIV-1 immunogen (Remune) was undertaken in Thailand in 1995 in conjunction with phase III approval in the USA. In most instances, immune response to the virus was induced. The results from this study led to the extension of further trials over the following 4 years. At present, the Thai Food and Drug Administration (FDA) is in the process of reviewing the files on all information to assess the effectiveness of this therapeutic vaccine as well as reviewing the proposal to conduct a phase III trial to further confirm previous efficacy results from the phase II trials.