In-depth analysis of HIV-1 drug resistance mutations in HIV-infected individuals failing first-line regimens in West and Central Africa.

摘要: OBJECTIVE: In resource-limited countries, antiretroviral therapy (ART) has been scaled up, but individual monitoring is still suboptimal. Here, we studied whether or not ART had an impact on the frequency and selection of drug resistance mutations (DRMs) under these settings. We also examined differences exist between HIV-1 genetic variants. DESIGN: A total 3736 sequences from individuals failing standard first-line (n = 1599, zidovudine/stavudine + lamivudine + neviparine/efavirenz) were analyzed compared with reverse transcriptase inhibitor (RTI)-naive (n = 2137) 10 West Central African countries. METHODS: Fisher exact tests corrections for multiple comparisons used to assess significance associations. RESULTS: All RTI-DRM 2015 International Antiviral Society list, except F227C, nine other expert lists observed confer extensive cross-resistance. Five additional independently selected (I94L, L109I, V111L, T139R T165L) statistically associated treatment. The proportion all thymidine analog mutations, M184V, certain NNRTIS, I94L L109I showed substantial increase time ART. Only one nucleoside two nonnucleoside RTI-DRMs differed by subtype/circulating recombinant form. CONCLUSION: This study validates global robustness actual DRM repertoire, in particular circulating form 02 predominating Africa, despite our finding five mutations. However, long-term without virological clearly leads accumulation emergence variations, which limit options treatment can be transmitted. Improved optimization are necessary effectiveness