Virological failure to raltegravir in Spain: incidence, prevalence and clinical consequences

Autores de IIS La Fe

• Miguel Masia Massoni

  Autor

• Miguel Salavert Lletí

  Autor

Participantes ajenos a IIS La Fe

• Santos JR
• Blanco JL
• Gutiérrez F
• Pérez-Elías MJ
• Iribarren JA
• Force L
• Antela A
• Knobel H
• López Bernaldo De Quirós JC
• Pino M
• Paredes R
• Clotet B
• Integrase Resistance Study Group in Spain (INI-VAIN Study Group)
• Integrase Resistance Study Group in Spain INI-VAIN Study Group

Grupos

• Infección Grave

Abstract

Objectives: The objective of this study was to evaluate the incidence, prevalence and clinical consequences of virological failure (VF) to raltegravir-based regimens in Spain. Methods: A multicentre, retrospective, observational study was performed in 10 tertiary hospitals (January 2006 to June 2013). The study included HIV-1-infected patients with loss of virological suppression (LVS; two consecutive HIV-1 RNA >= 50 copies/mL) while receiving raltegravir. VF and low-level viraemia (LLV) were defined as two consecutive HIV-1 RNA = 200 copies/mL and 50 to <200 copies/mL, respectively. Integrase strand-transfer inhibitor resistance was investigated at LVS. During the 48 weeks following LVS, recorded data included clinical characteristics, treatment discontinuations, AIDS-associated events and deaths. Effectiveness of therapy following LVS was evaluated by ITT and PP. Multivariate regression was used to assess predictors of efficacy. Results: Of the 15009 HIV-infected patients in participating centres, 2782 (18.5%) had received raltegravir-based regimens. Of those, 192 (6.9%), 125 (4.5%) and 67 (2.4%) experienced LVS, VF and LLV, respectively. The incidence of VF was 1.8 (95% CI, 1.5-2.1) per 100 patients/year. The prevalence of VF was 4.5% (95% CI, 3.8%-5.3%). Integrase-associated mutations were found in 78.8% of patients with integrase genotyping results available. High-level resistance to dolutegravir was not observed. Salvage therapy failed in 34.1% of patients; progression to AIDS/death occurred in 8.3% during the first year following LVS. The latter was associated with intravenous drug use, time on raltegravir and lower CD4+ count nadir in patients who started raltegravir-based treatments as salvage regimens. Conclusions: VF with raltegravir is infrequent, but often associated with major clinical complications in treatment-experienced patients.