Maraviroc 150 mg QD plus lopinavir/ritonavir, a NRTI‐sparing regimen for HIV‐infected naïve patients: 48‐weeks final results
Authors: Nozza S , Galli L , Chiappetta S , Antinori A , Tommasi C , Di Pietro M , Malnati M , De Battista D , Tambussi G , Lazzarin A 
Published: November 2012

Novel strategies with NRTIs‐sparing regimen in antiretroviral naïve HIV‐infected patients are currently used in clinical trials [1]. We previously presented preliminary results of this study [2] and here we present the 48‐weeks final results. Prospective, open‐label, randomised (1:1), multicenter, proof‐of‐concept trial. HIV‐infected naïve patients were assigned to once daily maraviroc (MVC) plus lopinavir/ritonavir (LPV/r) or to tenofovir/emtricitabine (TDF/FTC) plus LPV/r. Objectives of the study were the 48‐weeks virological and immunological efficacy. Data were collected at baseline (BL) and at 4, 12, 24, 36 and 48 weeks. T cell subsets from frozen peripheral blood mononuclear cells collected at BL, 4 and 48 weeks were also evaluated. ANOVA for repeated measures performed and Greenhouse‐Geisser probabilities calculated. Results reported as median (Q1–Q3) or frequency (%). Fifty patients (26 in MVC group and 24 in TDF/FTC group) were enrolled and reached week 48. Similar BL characteristics were observed in the two study groups; age: 39.1 (34.2–44) years, 2/50 (4%) females, infected since 2.9 (0.8–5.3) years, CD4+ nadir 266 (242–315) cells/µL, BL CD4+ 295 (260–369) cells/µL; CD4% 18.6 (14.6–23), HIV‐RNA 4.4 (3.9–4.8) log10 copies/mL. At W48, all patients in MVC group and 22/24 (96%) in TDF/FTC group had HIV‐RNA<50 copies/ml (p=0.225). CD4+ trend during follow‐up was different between the two groups (p=0.046) with a higher CD4 gain of 286 (183–343) vs 199 (125–285) cells/mL in MVC and TDF/FTC, respectively (p=0.033). In MVC vs TDF/FTC group, we observed a higher expression of CCR5+CD4+ T cells [W48 change: +7.5% (−4.5/11) vs −5.4 (−15.1/−0.5), p=0.016] and a higher increase of CD4+ effector memory [W48 change: +1.6% (0.7/4.8) vs ‐4.4 (−13.5/−0.2), p=0.007]. No significant variations in naïve and central memory CD4+ T cells. Treatment was well tolerated, without grade 3 or 4 adverse events. No significant difference between the two groups as for the 48‐weeks trend of bone marrow function, AST, ALT and CPK values, creatinine value, glicyde profile (fasting glucose, fasting insuline) and lipid profile (total cholesterol, LDL and HDL cholesterol, tryglicerides). Results are shown in Table 1. In naïve‐patients, virological efficacy and tolerability of a NRTIs‐sparing regimen with maraviroc and lopinavir/ritonavir was similar to conventional treatment in addition to a better immunological recovery, in particular of the Effector Memory CD4+ cells subset.

Baseline
Week 12
Week 24
Week 36
Week 48
p‐valuea

CD4+ cells/mm3
MVC+LPV/r
292 (261–359)
438 (381–500)
517 (432–620)
533 (457–682)
614 (455–709)
0.046

TDF/FTC+LPV/r
297 (257–373)
450 (354–511)
496 (367–568)
470 (402–568)
505 (419–705)

CD4%
MVC+LPV/r
19.5 (16.3–24.3)
24 (18–29.5)
26.2 (22.2–29)
28.2 (21.3–32.2)
27.7 (21.6–33)
0.718

TDF/FTC+LPV/r
18.8 (14.3–22.3)
24.7 (18.4–26.2)
25.2 (21.3–30.1)
24.9 (21.5–31.6)
25.7 (22.1–30.2)

CD4/CD8 ratio
MVC+LPV/r
0.35 (0.25–0.48)
0.45 (0.3–0.62)
0.54 (0.4–0.67)
0.66 (0.4–0.82)
0.72 (0.47–0.93)
0.316

TDF/FTC+LPV/r
0.33 (0.26–0.4)
0.44 (0.33–0.55)
0.51 (0.39–0.66)
0.52 (0.48–0.7)
0.54 (0.49–0.72)

HIV‐RNA log10 copies/ml
MVC+LPV/r
4.42 (4.07–4.84)
1.56 (1.56–1.56)
1.56 (1.56–1.56)
1.56 (1.56–1.56)
1.56 (1.56–1.56)
0.188

TDF/FTC+LPV/r
4.41 (3.84–4.76)
1.56 (1.56–1.56)
1.56 (1.56–1.56)
1.56 (1.56–1.56)
1.56 (1.56–1.56)

Haemoglobin (g/dL)
MVC+LPV/r
14.7 (13.7–15.1)
14 (13.5–14.6)
14.3 (13.7–14.9)
14.1 (13.3–15.1)
14.5 (13.6–15.2)
0.357

TDF/FTC+LPV/r
14.1 (13.8–14.9)
14.4 (13.5–15.1)
14.8 (13.5–15.3)
14.7 (13.7–15.3)
14.7 (13.6–15.2)

White blood cell (109/mm3)
MVC+LPV/r
5 (4.6–5.6)
5.6 (5.2–6.9)
5.8 (4.8–7.2)
5.9 (5–7.7)
5.9 (5–7.5)
0.806

TDF/FTC+LPV/r
4.5 (3.9–5.2)
4.3 (4.3–6.5)
5.1 (4.5–7.1)
5.1 (4.3–6.8)
5.5 (4.4–6.7)

Cholesterol (mg/dl)
MVC+LPV/r
178 (149–204)
–
202 (177–233)
–
218 (167–260)
0.794

TDF/FTC+LPV/r
160 (144–194)
–
189 (157–239)
–
199 (164–239)

Tryglicerides (mg/dl)
MVC+LPV/r
91 (64–126)
–
193 (113–254)
–
170 (105–270)
0.825

TDF/FTC+LPV/r
91 (66–148)
–
159 (106–203)
–
147 (110‐187)

Glucose (mg/dl)
MVC+LPV/r
84 (78–91)
–
86 (75–89)
–
84 (76–93)
0.200

TDF/FTC+LPV/r
81 (75–89)
–
85 (79–92)
–
82 (77–88)

Insulin (U/L)
MVC+LPV/r
5.7 (4–10.2)
–
7 (5.1–8.4)
–
6.8 (5.8–10.8)
0.554

TDF/FTC+LPV/r
7.2 (5.7–14.6)
–
6.8 (5.7–10)
–
5.8 (5.3–9.3)

Creatinine (mg/dl)
MVC+LPV/r
0.83 (0.77–0.95)
0.79 (0.72–0.85)
0.78 (0.69–0.87)
0.78 (0.71–0.86)
0.81 (0.75–0.87)
0.149

TDF/FTC+LPV/r
0.83 (0.78–0.98)
0.88 (0.79–1)
0.85 (0.75–0.93)
0.85 (0.77–0.92)
0.85 (0.74–0.95)