Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study.
BACKGROUND
In a previous interim 24-week virological safety analysis of the PROTEST study (1), initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study.


METHODS
PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naïve HIV-1-positive adults with HIV-1 RNA (VL) <50 c/mL on stable ART during the previous 6 months, requiring an ART change due to toxicity, with no antiretroviral resistance to the ART started, and R5 HIV by proviral DNA genotypic tropism testing (defined as a G2P FPR >10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100.


RESULTS
Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm(3) at screening, and median nadir CD4+ counts were 143 cells/mm(3). Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL<50 c/mL through week 48, whereas 12 (16%) discontinued treatment: two (3%) withdrew informed consent, one (1%) had a R5→X4 shift in HIV tropism between the screening and baseline visits, one (1%) was lost to follow-up, one (1%) developed an ART-related adverse event (rash), two (3%) died due to non-study-related causes (1 myocardial infarction at week 0 and 1 lung cancer at week 36), and five (7%) developed protocol-defined virological failure, although two of them regained VL<50 c/mL with the same MVC regimen (Table 1).


CONCLUSIONS
Initiation of MVC plus 2 NRTIs in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure up to one year.
Hospital Universitario San Cecilio, Granada, Spain.
Federico
F
Garcia
INIBIC-Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain.
Eva
E
Poveda
Hospital Ramón y Cajal, Madrid, Spain.
Maria Jesús
MJ
Pérez-Elías
Hospital Universitario San Cecilio, Granada, Spain.
José Hernández
JH
Quero
Hospital Son Espases, Palma de Mallorca, Spain.
Maria Angels
MA
Ribas
Hospital General Universitario Santa Lucía, Cartagena, Spain.
Onofre J
OJ
Martínez-Madrid
Hospital Arnau de Vilanova, Valencia, Spain.
Juan
J
Flores
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Manel
M
Crespo
Hospital Universitario de Elche, Elche, Spain.
Félix
F
Gutiérrez
Hospital General Universitario de Valencia, Valencia, Spain.
Miguel
M
García-Deltoro
Hospital de Bellvitge, Barcelona, Spain.
Arkaitz
A
Imaz
Hospital Xeral de Vigo, Vigo, Spain.
Antonio
A
Ocampo
Hospital Universitario Dr. Peset, Valencia, Spain.
Arturo
A
Artero
Hospital Carlos III, Madrid, Spain.
Francisco
F
Blanco
Hospital Reina Sofía, Murcia, Spain.
Enrique
E
Bernal
Hospital Virgen de la Nieves, Granada, Spain.
Juan
J
Pasquau
Hospital General de Castelló, Castelló, Spain.
Carlos
C
Mínguez-Gallego
Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
Núria
N
Pérez
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Aintzane
A
Aiestarán
irsiCaixa AIDS Research Institute, Badalona, Spain.
Roger
R
Paredes