Clinical and virological efficacy of etravirine plus two active Nucleos(t)ide analogs in an heterogeneous HIV-infected population.
Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity.


BACKGROUND
ClinicalTrials.gov NCT01437241.
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Luis F
LF
López-Cortés
Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Pompeyo
P
Viciana
Hospital Universitario Puerta del Mar, Cádiz, Spain.
José A
JA
Girón-González
Hospital Universitario de Puerto Real, Cádiz, Spain.
Alberto
A
Romero-Palacios
Hospital Universitario Virgen de la Victoria, Málaga, Spain.
Manuel
M
Márquez-Solero
Hospital Universitario San Cecilio, Granada, Spain.
Maria A
MA
Martinez-Perez
Hospital Universitario Virgen de las Nieves, Granada, Spain.
Miguel A
MA
López-Ruz
Hospital Costa del Sol, Málaga, Spain.
Javier
J
de la Torre-Lima
Hospital La Línea, Cádiz, Spain.
Francisco
F
Téllez-Pérez
Hospital Universitario Carlos Haya, Málaga, Spain.
Marcial
M
Delgado-Fernández
Hospital Universitario Reina Sofía, Córdoba, Spain.
Milagros
M
Garcia-Lázaro
Hospital Universitario de Valme, Sevilla, Spain.
Fernando
F
Lozano
Complejo Hospitalario de Jaén, Jaén, Spain.
Mohamed O
MO
Mohamed-Balghata
D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D009570:Nitriles; D011724:Pyridazines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines; D012367:RNA, Viral / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016879:Salvage Therapy / Q000379:methods*; D013030:Spain; D016896:Treatment Outcome
D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine