Rapid development of rategravir resistance in a CRF01_AE-infected patient

Abstract

BACKGROUND: Raltegravir primary resistance mutations located near to the catalytic site of HIV-1 integrase, which based on three distinct positions (N155H, Q148K/R/H and Y143R/C/H). Studies with subtype B cohort showed that these resistance mutations were usually appeared after 24 – 48 weeks of raltegravir treatment. The duration of resistance development is unknown for CRF01_AE, which is the pre-dominant HIV-1 genotype in Southeast Asia. MATERIALS & METHODS: Multiple plasma samples of a 49-year-old CRF01_AE infected German heterosexual male were collected at different time point between 2002 and 2009. Genotyping resistance test on protease, reverse transcriptase and integrase were conducted by the Viroseq HIV-1 Genotyping System before and after the initiation of the HAART and raltegravir-containing salvage therapy. RESULTS: This patient first received zidovudine/lamivudine/indinavir in 2002 and responded with fully suppressed viral load. His viral load was raised to 4.9 log10 copies/mL in 2009 after 5 years of zidovudine/lamivudine/lopinavir/ritonavir treatment. At this stage, no primary raltegravir resistance mutation was detected. In September 2009, zidovudine/tenofovir/emtricitabine/raltegravir substituted his previous regimen. The patient responded well clinically for 11 weeks and 3-months post-treatment genotyping and viral load test, we observed HAART resistance mutations and the primary raltegravir resistance mutation N155HN emerged, which caused clinical failure with viral load suddenly raised to 4.7 log10 copies/mL. CONCLUSIONS: Our study observed a CRF01_AE case which rapidly developed raltegravir resistance in 11 weeks. It has been proved that in other antiretroviral classes, non-B subtypes often have a different pattern of resistance mutations, drug susceptibility and viral fitness. The low genetic barrier of raltegravir was particularly concerned for the rapid development of resistance in HIV-1 CRF01_AE as demonstrated in our study. A closer monitoring of genotyping test in every 6-10 months is highly recommended for routine practice. Furthermore, clinical response of raltegravir treatment on CRF01_AE patients will be necessarily needed in the future.