Prevalence And Evolution Of HIV-1 Drug Resistance In Patients Receiving Free Antiretroviral Therapy In China

The introduction of highly active antiretroviral therapy (HAART) has markedly decreased mortality and morbidity in patients infected with HIV/AIDS. However, HAART cannot completely eradicate HIV from the body, results in long-term toxicity and eventually leads to the emergence of drug-resistant HIV strains under the drug pressure in vivo, which was the main obstacle to the effectiveness of antiretroviral therapy (ART). Free HAART therapy was introduced in China since 2003 and has been spread on a large-scale throughout the country. It becomes more and more important to implement drug resistance surveillance in patients undergoing ART ensuring the optimal curative effect of treatment. It showed in our cross-section survey in Queshan, Henan that the prevalence of primary drug-resistance in antiretroviral treatment-na(?)ve patients was extremely low. There had been optimal viral suppression in patients undergoing treatment for less than 6 months. Drug-resistant HIV-1 strains emerged quickly after therapy begun, and the prevalence of drug-resistance increased significantly in patients treated for more than 6 months than that treated for less than 6 months, reached as high as 70% in patients with detectable plasma viral load, causing a considerable rate of virological failure in patients treated for more than 6 months. The identification of virological failure raises complex management issues: when to switch to a different regimen and which element of the regimen to change. So, we did retrospective trial in patients remaining on a virologically failing combination antiretroviral regimen of AZT/DDI/NVP from our cohort samples in Queshan, Henan. The results showed that CD4 and viral load (VL) level remained stable in patients maintaining the same virologically failing regimen for no more than 12 months, however, CD4 counts decreased significantly in patients maintaining the virologically failing regimen for 18 months. Maintaining the virologically failing regimen led to the acquisition of new drug resistance mutations (DRM), the rate of acquisition of new DRM increased significantly with the continuation of the virologically failing regimen and was 34.6%, 56.5% and 68% in patients maintaining the virologically failing regimen for 6 months, 12 months and 18 months, respectively. The prevalence of non-nucleoside reverse transcriptease inhibitor (NNRTI) related drug resistance mutations was higher than that of nucleoside reverse transcriptease inhibitor (NRTI) related drug resistance mutations at the time of virological failing. A small rise in the prevalence of NNRTI related drug resistance mutations was observed with the continuation of the virologically failing regimen; however, the prevalence of NRTI related drug resistance mutations increased significantly after maintaining the virologically failing regimen for more than 12 months and trended to reach the level of the rate of NNRTI related drug resistance mutations. The loss of future drug options (FDO) was 0.7, 1.2 and 2.1 in patients maintaining the virologically failing regimen for 6 months, 12 months and 18 months, respectively, which revealed an average loss of 0.7 drugs per 6 months of maintaining the virologically failing regimen.