Virological failure to raltegravir in Spain: incidence, prevalence and clinical consequences.
OBJECTIVE
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 15 009 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.
Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain jrsantos@flsida.org.
José Ramón
JR
Santos
Hospital Clinic de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain.
José Luis
JL
Blanco
Infectious Diseases Unit, Elche University General Hospital, Elche, Spain Miguel Hernández University, Elche, Spain.
Mar
M
Masiá
Infectious Diseases Unit, Elche University General Hospital, Elche, Spain Miguel Hernández University, Elche, Spain.
Félix
F
Gutiérrez
Infectious Diseases Unit, Ramón y Cajal Hospital, IRYCIS, Madrid, Spain.
María Jesús
MJ
Pérez-Elías
Infectious Diseases Unit, Donostia University Hospital, San Sebastián, Spain.
José Antonio
JA
Iribarren
Infectious Diseases Unit, Mataró Hospital, Mataró, Spain.
Lluis
L
Force
Infectious Diseases Unit, University Hospital, Santiago de Compostela, Spain.
Antonio
A
Antela
Service of Infectious Diseases, Hospital del Mar, IMIM (Hospital del Mar Research Institute), Barcelona, Spain.
Hernando
H
Knobel
Infectious Diseases Unit, La Fe University and Polytechnic Hospital, Valencia, Spain.
Miguel
M
Salavert
Infectious Diseases Unit, Gregorio Marañón University Hospital, Madrid, Spain.
Juan Carlos
JC
López Bernaldo De Quirós
IrsiCaixa AIDS Research Institute, Barcelona, Spain.
María
M
Pino
Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain IrsiCaixa AIDS Research Institute, Barcelona, Spain Universitat de Vic-Universitat Central de Catalunya, Vic, Spain.
Roger
R
Paredes
Lluita contra la SIDA Foundation, Germans Trias i Pujol University Hospital, Barcelona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain IrsiCaixa AIDS Research Institute, Barcelona, Spain Universitat de Vic-Universitat Central de Catalunya, Vic, Spain.
Bonaventura
B
Clotet
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D015995:Prevalence; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D012189:Retrospective Studies; D013030:Spain; D062606:Tertiary Care Centers; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D000068898:Raltegravir Potassium