Prevalence of antiretroviral drug resistance in treated HIV-1 infected patients: under the initiative of access to the NNRTI-based regimen in Thailand.

To determine the prevalence of antiretroviral resistance in treatment-failure HIV-1 infected individuals, under the initiative of the non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in Thailand, plasma samples were collected from 1,376 HIV-1 infected patients, who were failing in their current HAART therapy during 2000-2004. They were stratified into 2 intervals: group one (1), 558 HIV-1 infected patients (2000-2002; before the initiative of access to HAART), and group two (2), 818 HIV-1 infected patients (2003-2004; after the initiative of access to HAART). Genotypic resistance testing was performed. The frequency of antiretroviral drug resistance in treatment-failure HIV-1 infected patients has significantly increased over time from 68.5% (382/558) during 2000-2002 to 74.9% (613/818) during 2003-2004 (P<0.01). Resistance to NNRTI during 2003-2004 (59.2%) was much higher than that during 2000-2002 (36.9%; P<0.001). However, the frequency of nucleoside reverse transcriptase inhibitor (NRTI) drug resistance was not significantly higher (P=0.153). We showed that this correlated with an increase in the NNRTI-based regimen prescribed during 2003-2004, especially the Thai-produced combination pill, GPO-VIR. Our finding also showed that a high level of genotypic drug resistance is associated with GPO-VIR (40.8% lamivudine, 40.6% stavudine, 43.8% nevirapine). In order to avoid the rapid emergence of resistant viruses in a resource-poor setting, a close surveillance of antiretroviral drug resistance is feasible and should be considered.

Surveillance of genotypic resistance mutations in chronic HIV-1 treated individuals after completion of the National Access to Antiretroviral Program in Thailand.

BACKGROUND: Due to the establishment of the National Access to Antiretroviral Program for People who have AIDS (NAPHA), approximately 80,000 Thai HIV-1 infected patients received antiretroviral drugs through the NAPHA program, which was completed at the end of 2005. The development of drug resistance is required for access to ARV drugs. The objective of this study was to determine the prevalence of antiretroviral drug resistance in Thai HIV-1 treated individuals after completing the NAPHA program. PATIENTS AND METHODS: Viral genotypic resistance testing was carried out for 1,880 HIV-infected patients experiencing treatment failure, who enrolled during 2000-2005. All patients were in a follow-up treatment with ARV drugs available in clinical practice. The genotype was performed with the TRUGENE HIV-1 kit to assess resistant mutations to reverse transcriptase inhibitors and to protease inhibitors. RESULTS: The frequency of ARV drug resistance has significantly increased after the National Access To Antiretroviral Program was implemented. The reverse transcriptase genes M184V/I (919/1,880; 48.9%) and K103S/H (416/1,880; 22.1%) were the most frequent in nucleoside reverse transcriptase and non-nucleoside reverse transcriptase, respectively. In the protease genes, minor mutations or polymorphisms were found in the majority. Thymidine analogue mutations were presented and increased over time. This study showed a sharp increase in the prevalence of mutations associated with the GPO-VIR combination; nevirapine (948/1,880; 50.4%), lamivudine (889/1,880; 47.3%), and stavudine (703/1,880; 37.4%) after the program was completed. CONCLUSION: With the increased availability of antiretroviral therapy in a resource-constrained country, antiretroviral drug resistance should be closely monitored. HIV-1 drug resistance testing to enable the salvage therapy will remain a priority in Thailand. Furthermore, resistance testing should also become routine before prescribing treatment, and the consequences of continuing to provide a failing regimen must be considered.