Maraviroc Group Research Articles

Role of maraviroc and/or rapamycin in the liver of IL10 KO mice with frailty syndrome.

Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.

Implications of maraviroc and/or rapamycin in a mouse model of fragility.

Background: As age increases, the risk of developing fragility also increases. Improving the knowledge of frailty could contribute to maintaining the functional ability of elderly people. Interleukin (IL)-10 homozygous knockout mice (IL-10tm/tm [IL10KO]) constitute an excellent tool for the study of frailty. Because patients with frailty demonstrate an overexpression of CCR5, rapamycin (RAPA) and/or maraviroc (MVC), two molecules able to decrease CCR5 expression, were evaluated.Results: Muscle myostatin was reduced in all the therapeutic groups but the MVC group (p <0.001 for RAPA and MVC-RAPA) and in serum samples (p <0.01 for all the groups). Serum CK levels were also significantly lower in MVC and RAPA groups (p <0.01 in both cases). Lower AST levels were observed in all the therapeutic groups (p <0.05 for all of them). The apoptotic effector caspase-3 was significantly lower in MVC and RAPA groups (p<0.05 in both cases). Combined treatment with MVC-RAPA showed a synergistic increase in p-AKT, p-mTOR and SIRT1 levels.Conclusions: MVC and RAPA show a protective role in some factors involved in frailty. More studies are needed to prove their clinical applications.Material and methods: Eighty male homozygous IL10KOs were randomly assigned to one of 4 groups (n= 20): i) IL10KO group (IL10KO); ii) IL10KO receiving MVC in drinking water (MVC group), iii) IL10KO receiving RAPA in drinking water (RAPA group), and finally, iv) MVC-RAPA group that received MVC and RAPA in drinking water. Blood and muscle samples were analysed. Survival analysis, frailty index calculation, and functional assessment were also performed.

Impact of prolonged maraviroc treatment on non-AIDS-related comorbidities in HIV-positive patients: a retrospective cohort study.

This retrospective study evaluates the effect of maraviroc, the first CCR5 receptor antagonist, on non-AIDS-related comorbidity incidence and its impact on inflammatory and lipid parameters. Seventy-four HIV patients on maraviroc treatment were compared with 312 patients never exposed to maraviroc (matched for sex, age and CD4 nadir). At baseline (T0), maraviroc patients presented a longer duration of HIV infection, a higher prevalence of comorbidities and a greater frequency of polypharmacy. Non-AIDS-defining disease incidence was lower in the maraviroc group than in the non-maraviroc group (without achieving statistical significance). Except triglycerides (TGL), which dropped only in the maraviroc group, inflammatory and immunological parameters did not significantly change in either group by the end of the study period (T3). At T3, high-sensitivity C-reactive protein (hsCRP) and high-density lipoprotein were inversely correlated in both groups (Spearman's rho: maraviroc -0.30, P = 0.05; non-maraviroc -0.23, P = 0.0003). Only in the non-maraviroc group was the positive correlation between hsCRP and lipids observed both at T0 (hsCRP/low-density lipoprotein (LDL) +0.17, P = 0.004; hsCRP/total cholesterol +0.20, P = 0.0007; hsCRP/TGL +0.12, P = 0.04) and T3 (hsCRP/LDL +0.26, P < 0.0001; hsCRP/total cholesterol +0.24, P = 0.0001; hsCRP/TGL +0.15, P = 0.02). These correlations were not found in the maraviroc group. A significant positive correlation was found at T0 and at T3 between hsCRP and D-dimer in both groups (maraviroc: T0 +0.46, P = 0.0007; T3 +0.41, P = 0.006; non-maraviroc: T0 +0.17, P = 0.02; T3: +0.17, P = 0.017). These data suggest a possible protective role of maraviroc in the incidence of non-AIDS-related comorbidities in a population with longer-lasting infection and allow us to hypothesize its role in the modulation of lipid-dependent inflammation.

Role of spinal CCR5 in remifentanil-induced hyperalgesia in rats with incisional pain

Objective To evaluate the role of spinal C-C motif chemokine receptor 5 (CCR5) in remifentanil-induced hyperalgesia in rats with incisional pain. Methods Thirty-two male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, in which intrathecal and caudal catheters were successfully implanted, were divided into 4 groups (n=8 each) using a random number table: control group (group C), CCR5 antagonist maraviroc group (group M), remifentanil plus incisional pain group (group R+ I) and maraviroc plus remifentanil plus incisional pain group (group M+ R+ I). Phosphate buffer solution (PBS) 10 μl was intrathecally injected and normal saline was infused for 60 min at 1 μg·kg-1·min-1 via the caudal vein in group C. Maraviroc 100 pmol (in 10 μl of PBS) was intrathecally injected and normal saline was infused for 60 min at 1 μg·kg-1·min-1 via the caudal vein in group M. PBS 10 μl was intrathecally injected, then the model of incisional pain was established, and remifentanil 1 μg·kg-1·min-1 was infused for 60 min via the caudal vein in group R+ I.Maraviroc 100 pmol (in 10 μl of PBS) was intrathecally injected, then the model of incisional pain was established, and remifentanil 1 μg·kg-1·min-1 was infused for 60 min via the caudal vein in group M+ R+ I.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusion of remifentanil or normal saline (T0) and 2, 6, 24 and 48 h after stopping infusion (T1-4). The rats were sacrificed after the last measurement of pain threshold, and L4-6 segments of the spinal cord were removed for determination of the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule-1 (Iba-1) by Western blot. Results Compared with group C, the MWT was significantly decreased and TWL was shortened at T1-4, and the expression of GFAP and Iba-1 in the spinal cord was up-regulated in R+ I and M+ R+ I groups (P 0.05). Compared with group R+ I, the MWT was significantly increased and TWL was prolonged at T1-4, and the expression of GFAP and Iba-1 in the spinal cord was down-regulated in group M+ R+ I (P<0.05). Conclusion Spinal CCR5 is involved in remifentanil-induced hyperalgesia in the rats with incisional pain, and the mechanism may be related to activating astrocytes and microglias. Key words: Piperidines; Hyperalgesia; Pain, postoperative; Receptors, CCR5; Spinal cord

Hepatic Safety of Maraviroc in Patients with HIV-1 and Hepatitis C and/or B Virus: 144-Week Results from a Randomized, Placebo-Controlled Trial

In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 coinfected with HBV and/or HCV, maraviroc-containing treatment regimens were not associated with increased hepatotoxicity. In this randomized, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (Clinicaltrials.gov identifier, NCT01327547). The primary end point was the proportion of patients with protocol-defined Grade 3/4 alanine aminotransferase (ALT) abnormalities through week 48. Key secondary end points included 144-week analysis of Grade 3/4 ALT abnormalities and liver fibrosis by enhanced liver fibrosis (ELF) testing, hepatic elastography and an optional biopsy substudy. Through 144 weeks of treatment, two (maraviroc) and three (placebo) patients met the protocol-defined Grade 3/4 ALT end point. Similar to the 48-week results, there were no statistically significant differences between groups in change from baseline in ELF or hepatic elastography. However, decreased elastography scores were noted in the maraviroc group. Blinded pathologist review suggested that 2 of 11 paired biopsies (both on maraviroc) showed signs of decreased fibrosis. One (maraviroc) and two (placebo) patients experienced treatment-related hepatobiliary adverse events (AEs). Five patients in the maraviroc group discontinued because of treatment-related AEs versus three in the placebo group. One death in the maraviroc group and two deaths in the placebo group were reported. Use of maraviroc did not increase hepatotoxicity in this population through 144 weeks. Further investigation regarding possible beneficial effects of maraviroc on liver fibrosis may be warranted.

Potential anti-inflammatory effects of maraviroc in HIV-positive patients: a pilot study of inflammation, endothelial dysfunction, and coagulation markers.

Persistent immune activation and chronic inflammation significantly contribute to non-AIDS morbidity in HIV-infected patients. The HIV inhibitor maraviroc (MVC) targets the cellular chemokine CCR5 HIV co-receptor, which is involved in important inflammatory pathways. MVC could have significant anti-inflammatory and anti-atherosclerotic effects, also reducing immune activation. We designed a pilot study to determine which plasma biomarkers of inflammation, endothelial dysfunction, and hypercoagulability were modified by MVC in 2 groups of 10 patients starting MVC-free or MVC-containing regimens. Ten age- and gender-matched healthy controls were also included. We found higher levels of all inflammatory biomarkers in HIV-infected patients compared to healthy controls. Both groups showed decreasing levels of interleukin (IL)-17, IL-10, and macrophage inflammatory protein (MIP)-1a following the achievement of viral suppression. Vascular cell adhesion molecule (VCAM)-1 levels were decreased in the MVC group and increased in the MVC-free group. In conclusion, some inflammatory biomarkers tend to decrease with the salvage regimen; MVC was not associated with a better impact on these measured markers.

Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model. A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed. Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group. Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD.

Maraviroc Once-Daily Nucleoside Analog-Sparing Regimen in Treatment-Naive Patients

This study was performed to evaluate a once-daily dual-therapy regimen, maraviroc (MVC) + atazanavir/ritonavir (ATV/r), in treatment-naive patients. A phase 2b, randomized, open-label pilot study. In Study A4001078 (NCT00827112), treatment-naive patients with CCR5-tropic HIV-1 (HIV-1 RNA ≥1000 copies/mL; CD4 cell count ≥100 cells/mm) were randomized to receive either MVC 150 mg once daily (n = 60) or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily (n = 61) + ATV/r 300/100 mg once daily. Primary endpoint was proportion of patients with HIV-1 RNA <50 copies per milliliter at week 48. At week 48, 44 (74.6%) and 51 (83.6%) patients in the MVC and TDF/FTC treatment groups, respectively, had plasma HIV-1 RNA <50 copies per milliliter. Median change from baseline in CD4 cell count at week 48 was +173 and +187 cells per cubic millimeter with MVC and TDF/FTC, respectively. Seven patients discontinued from each arm; there were no deaths. The incidence of serious adverse events (AEs) was similar in each group; however, there were more grade 3/4 AEs in the MVC group (18 vs 11), mostly due to hyperbilirubinemia. Three patients in each arm were evaluable for virological analysis at discontinuation or failure (HIV-1 RNA >500 copies/mL); no genotypic resistance, change in tropism, or loss of susceptibility relevant to treatment was observed. The virological activity and immunological benefit of once-daily MVC + ATV/r were confirmed. Indirect hyperbilirubinemia and associated signs were the most commonly reported AEs in both study treatment groups and were not associated with significant transaminase increases. No drug resistance occurred.

Maraviroc 150 mg QD plus lopinavir/ritonavir, a NRTI‐sparing regimen for HIV‐infected naïve patients: 48‐weeks final results

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&lt;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)

Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial

IntroductionThe purpose of this study was to determine whether maraviroc, a human CC chemokine receptor 5 (CCR5) antagonist, is safe and effective in the treatment of active rheumatoid arthritis (RA) in patients on background methotrexate (MTX).MethodsThis phase IIa study comprised two distinct components: an open-label safety study of the pharmacokinetics (PK) of MTX in the presence of maraviroc, and a randomized, double-blind, placebo-controlled, proof-of-concept (POC) component. In the PK component, patients were randomized 1:1 to receive maraviroc 150 or 300 mg twice daily (BID) for four weeks. In the POC component, patients were randomized 2:1 to receive maraviroc 300 mg BID or placebo for 12 weeks. Patients were not eligible for inclusion in both components.ResultsSixteen patients were treated in the safety/PK component. Maraviroc was well tolerated and there was no evidence of drug-drug interaction with MTX. One hundred ten patients were treated in the POC component. The study was terminated after the planned interim futility analysis due to lack of efficacy, at which time 59 patients (38 maraviroc; 21 placebo) had completed their week 12 visit. There was no significant difference in the number of ACR20 responders between the maraviroc (23.7%) and placebo (23.8%) groups (treatment difference -0.13%; 90% CI -20.45, 17.70; P = 0.504). The most common all-causality treatment-emergent adverse events in the maraviroc group were constipation (7.8%), nausea (5.2%), and fatigue (3.9%).ConclusionsMaraviroc was generally well tolerated over 12 weeks; however, selective antagonism of CCR5 with maraviroc 300 mg BID failed to improve signs and symptoms in patients with active RA on background MTX.Trial RegistrationClinicalTrials.gov: NCT00427934

Concurrent use of statins does not influence efficacy of maraviroc in Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients 1 and 2 trials

Chemokine receptors 5 (CCR5), the target of maraviroc (MVC), are located on cholesterol-rich domains called ‘lipid rafts’ within cell membranes [1]. In-vitro data suggest that 3-hydroxy-3-methyl-glutaryl co-reductase inhibitors (statins) may reduce lipid raft numbers, which in turn may alter CCR5 availability for HIV attachment [2]. In-vivo data indicate limited or no independent antiretroviral activity for statins [3]. We hypothesized that statins could alter the activity of MVC by reducing the number of target receptors. We performed a post-hoc analysis using data from the Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) studies, which demonstrated the superior antiretroviral efficacy of MVC [daily (q.d.) and twice daily (b.i.d.)] relative to placebo when combined with an optimized background regimen in triple class-resistant and/or experienced patients [4,5]. In this analysis, we evaluated changes in HIV-1 RNA and CD4 cell count in MVC and placebo groups based on statin coadministration. Patients were considered to be on statins if these were started prior to or at baseline, and patients remained on the medication throughout the study or stopped at least 300 days after baseline. Among 1049 patients in the combined MOTIVATE trials, 103 met the above criteria, so were considered as receiving a statin. Data from the MVC groups (q.d. and b.i.d.) were combined (n = 840). Nineteen (10%) patients in the placebo group and 84 (10%) in the MVC group were on a statin. At baseline, both the ‘no statin’ and ‘statin’ groups had similar HIV RNA concentrations across the two treatment arms: 4.9 versus 4.9 log10 copies/ml for MVC versus placebo in the ‘no statin’ group, and 4.6 versus 4.5 log10 copies/ml in the ‘statin’ group. Mean drop in HIV RNA at week 48 was comparable across the two statin groups: −1.7 versus −0.8 log10 copies/ml (MVC versus placebo) in the ‘no statin’ and −1.9 versus −0.6 log10 copies/ml in the ‘statin’ group. The proportions of patients with HIV RNA below 50 copies/ml at week 48 for MVC versus placebo were 47% versus 20%, and 57% versus 11% in the ‘no statin’ and ‘statin’ groups, respectively. No interaction between the use of MVC and use of statin on the odds of achieving a viral load of less than 50 copies/ml was observed. CD4 cell counts at baseline were 161 versus 166 cells/μl within ‘no statin’ and 238 versus 209 cells/μl within ‘statin’ group (MVC versus placebo). At week 48, the median increases in CD4 cell counts were: 103 versus 29 cells/μl, and 75 versus 11 cells/μl for MVC versus placebo within ‘no statin’ and ‘statin’ groups, respectively. These data indicate that the antiviral and immunological efficacy of MVC in persons with CCR5-using HIV appears not to be significantly influenced by coadministration with statins. Acknowledgement This study was sponsored by Pfizer Inc., New York, USA.

Eficacia de maraviroc en los ensayos clínicos de desarrollo de la molécula

Maraviroc is the first co-receptor antagonist to be approved for use in HIV infected patient. In a phase II trial, in which the drug was administered as a single therapy, the most suitable maintenance dose was 300 mg, once or twice per day. The MOTIVATE double blind, placebo-compared studies, were carried out on patients infected by HIV-1 with R5 tropism and resistant to drugs from three families of retrovirals. Maraviroc two times per day achieved < 50 copies/mL in 45.5% of the patients compared to 16.7% in the placebo group (p < 0.001). The CD4+ lymphocyte count had a mean of 63 cells/mm(3) higher with Maraviroc. The drug was shown to be superior in all patient groups regardless of the baseline viral load, the baseline CD4+ lymphocyte count or the number of accompanying active drugs. In the study on patients infected by HIV with X4/dual/mixed tropism, Maraviroc, was not virologically effective, but did produce a CD4 increase higher than the placebo. Maraviroc was compared with Efavirenz in the study on patients with no previous treatment and with R5-tropic virus. At 48 weeks, the percentage of patients with a viral load of <50 copies/mL was 69.3% in the group that received Efavirenz and 65.3% in the Maraviroc group. In conclusion, Maraviroc has demonstrated its increased efficacy in patients with CCR5-tropic virus and a long history of antiretroviral use and failure, and in patients with no previous treatment.