Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial.
BACKGROUND
Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs.


METHODS
We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+<200/µL and/or CD4+ recovery ≤ 25% and HIV-RNA<50 cp/mL. Patients were randomized 1:1 to HAART+maraviroc or continued HAART. CD4+ and CD8+ CD45+RA/RO, Ki67 expression and plasma IL-7 were quantified at W0, W12 and W48.


RESULTS
By W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/µL and CD4>200/µL + CD4 gain ≥ 25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=.01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48.


CONCLUSIONS
Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations.


BACKGROUND
ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858.
Divisione Clinicizzata di Malattie Infettive, DIBIC "Luigi Sacco", Università degli Studi, Milano, Italy.
Stefano
S
Rusconi
Paola
P
Vitiello
Fulvio
F
Adorni
Elisa
E
Colella
Emanuele
E
Focà
Amedeo
A
Capetti
Paola
P
Meraviglia
Clara
C
Abeli
Stefano
S
Bonora
Marco
M
D'Annunzio
Antonio
A
Di Biagio
Massimo
M
Di Pietro
Luca
L
Butini
Giancarlo
G
Orofino
Manuela
M
Colafigli
Gabriella
G
d'Ettorre
Daniela
D
Francisci
Giustino
G
Parruti
Alessandro
A
Soria
Anna Rita
AR
Buonomini
Chiara
C
Tommasi
Silvia
S
Mosti
Francesca
F
Bai
Silvia
S
Di Nardo Stuppino
Manuela
M
Morosi
Marco
M
Montano
Pamela
P
Tau
Esther
E
Merlini
Giulia
G
Marchetti
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D003510:Cyclohexanes / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016867:Immunocompromised Host; D015851:Interleukin-7 / Q000097:blood; D019394:Ki-67 Antigen / Q000097:blood; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D012367:RNA, Viral / Q000037:antagonists & inhibitors* / Q000097:blood; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D015415:Biomarkers; D003510:Cyclohexanes; C508605:IL7 protein, human; D015851:Interleukin-7; D019394:Ki-67 Antigen; D012367:RNA, Viral; D014230:Triazoles; D000077592:Maraviroc