Pre-existent NRTI and NNRTI resistance impacts on maintenance of virological suppression in HIV-1-infected patients who switch to a tenofovir/emtricitabine/rilpivirine single-tablet regimen.

Objectives: To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes). Methods: pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated. Results: Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P < 0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P < 0.001); and (iii) patients with pre-therapy viraemia >500 000 copies/mL compared with those with lower viraemia levels (>500 000: 16.0%; 100 000-500 000: 9.3%; <100 000 copies/mL: 4.8%, P = 0.009). pRes and pre-therapy viraemia >500 000 copies/mL were independent predictors of VR by multivariable Cox regression. Conclusions: TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia >500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification.

Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000-14.

Background: Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. Methods: In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Results: Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P < 0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P = 0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P = 0.047]. Conclusions: The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.