Transmitted drug resistance to NRTIs and risk of virological failure in naïve patients treated with integrase inhibitors.

OBJECTIVES: Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. METHODS: Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load ≥ 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. RESULTS: From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. CONCLUSIONS: NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

The evidence for using tenofovir disoproxil fumarate plus lamivudine as a nucleoside analogue backbone for the treatment of HIV.

This article evaluates the evidence supporting use of the tenofovir disoproxil fumarate (TDF) plus lamivudine (3 â€‹TC) combination as a dual nucleoside backbone within a triple drug antiretroviral regimen. Key trials that assess the relative efficacy, safety and resistance profile of 3 â€‹TC and emtricitabine (FTC) are discussed. Clinical use of 3 â€‹TC and FTC with two tenofovir prodrugs -TDF and tenofovir alafenamide (TAF) - is presented. Recommendations from various international guidelines for the construction of triple and emerging dual regimens are summarised. In conclusion, data suggest the therapeutic equivalence of 3 â€‹TC and FTC, especially when 3 â€‹TC is combined with TDF.