Effects of Maraviroc (MVC) on HIV-related Kaposi's Sarcoma (KS)

• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 1 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 1 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 2 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 2 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 4 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 4 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 8 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 8 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 16 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 16 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 36 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 36 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 56 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 56 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 76 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 76 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.
• Change in Kaposi's Sarcoma Lesion Burden between Baseline and Week 96 [ Time Frame: Evaluations of the lesions will occur at baseline (week 0) and at week 96 ] [ Designated as safety issue: No ]
  The subjects' Kaposi's sarcoma related lesions will be evaluated during each visit for an increase or decrease in the number of lesions and whether the quality of the lesions show improvement or worsening of the condition.

• Effects of Maraviroc on CCR5 and KSHV levels in lesional skin. [ Time Frame: Week 0 (baseline), and week 96 or at the end of the therapy if it is discontinued early. ] [ Designated as safety issue: No ]
  A biopsy will be taken from the subjects' lesions at baseline and at the end of the study to determine whether there has been a change in CCR5 receptor levels or KSHV levels.
• Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 4 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 4. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
• Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 16 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 16. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
• Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 36 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 36. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
• Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 56 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 56. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
• Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 76 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 76. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
• Change in CD4 count, and HIV viral load with Maraviroc from Baseline to Week 96 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 96. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in CD4 count or HIV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 1 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 1. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 2 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 2. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 4 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 4. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 16 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 16. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 36 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 36. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 56 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 56. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 76 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 76. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects on KSHV Viral Load with Maraviroc treatment from Baseline to Week 96 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline) and 96. ] [ Designated as safety issue: No ]
  Blood and saliva samples will be obtained from the subjects throughout the study at different points to assess if there are any changes in KSHV viral load.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 1 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 1. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 2 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 2. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 4 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 4. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 16 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 16. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 36 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 36. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 56 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 56. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 76 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 76. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Effects of Maraviroc on CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells from Baseline to Week 96 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 96. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in CCR5 receptor expression in T and B lymphocytes, monocytes, and natural killer cells.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 1 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 1. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 2 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 2. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 4 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 4. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 16 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 16. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 36 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 36. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 56 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 56. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 76 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 76. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.
• Changes in T Cell activation and exhaustion with Maraviroc treatment between Baseline and Week 96 [ Time Frame: Data will be collected on this measure during the subjects' visits on Weeks 0 (baseline), and 96. ] [ Designated as safety issue: No ]
  Blood samples will be obtained from the subjects throughout the study and cryopreserved to assess if there are any changes in T cell activation and exhaustion.

The purpose of this study is to determine whether Maraviroc is effective in the treatment of Kaposi's Sarcoma (KS), when it does not remit with standard antiretroviral drug therapy.

Although the advent of antiretroviral therapy (ART) may have greatly decreased the incidence of Kaposi's Sarcoma (KS) in resource rich settings, KS continues to be the most prevalent AIDS-defining malignancy in the world and carries with it significant morbidity and mortality[1]. Indeed, in a recent epidemiological study examining cancers in Kampala, Uganda, KS was found to be second only to prostate cancer in terms of incidence rates[2].

There is growing evidence that CCR5 may be involved in the pathogenesis of KS. Kaposi's Sarcoma-associated Herpes Virus (KSHV), an agent found as necessary for KS pathogenesis [10, 11], encodes viral macrophage inflammatory proteins or vMIP [7-9]. vMIP-I and vMIP-II have been found to be ligands for chemokine receptors, and in particular the CCR5 receptor [5, 6], suggesting a potential role in the inflammatory process needed for KS pathogenesis. Further, vMIP-I induces Ca(2+) mobilization in monocytes expressing CCR5, suggesting an agonistic relationship between vMIP-I and the CCR5 receptor [4]. In addition, vMIP has been found to be proangiogenic when expressed in endothelial cells, a key feature of KS tumor survival [12]. As well, CCR5 has been found to be significantly increased in T cells populations of KS patients (from a preliminary study), and in 2 double-blind, placebo-controlled phase 3 studies in which a total of 1049 patients received the randomly assigned drug MVC, there was a trend revealing a lower incidence of KS in MVC arms vs placebo (0.36% vs 1.43%) [3]. This agonistic binding relationship between protein vMIP and CCR5, the proangiogenic activity associated with vMIP, the increased expression of CCR5 in KS, and trend towards lower incidence of KS when patients are taking MVC, suggest CCR5 may play an important role in KS pathogenesis. This involvement of CCR5 in KS pathogenesis implies that MVC may function as a potential therapeutic for KS. To date, there have been no studies examining the effect of MVC on KS.

There is a need for therapeutic development for KS. Standard of care for KS involves initiation or optimization of antiretroviral therapy. A significant proportion of KS cases do not respond to ART alone, with non-response rates ranging from 25-55%, with response times averaging 9 or more months depending on which patient series is identified [13, 14]. In severe or in cases of KS unresponsive to ART, standard of care involves systemic chemotherapy with liposomal doxorubicin [15], which is not without adverse reactions. Adverse reactions to liposomal doxorubicin include cardiac toxicity, nausea, vomiting, diarrhea, abdominal pain, fatigue, and patients may require pre-regime tests of varying costs, along with resources and time needed for intravenous infusion [16]. Nonresponse rates for liposomal doxorubicin hover around 20% [15, 17]. Focal cases may be more amenable to radiation therapy or intralesional velban [18, 19]. However, radiation and intralesional therapies are limited to focal sites, require monitored visits and specialized care, can be given only in limited amounts, and carry various adverse effects [18, 19]. With these nonresponse rates, potential adverse reactions, and resources and time needed for therapeutic delivery, there are clear benefits proferred by an effective oral therapy requiring minimal monitoring, as is the case with MVC.

Maraviroc (MVC) is a member of a new class of antiretroviral compounds known as small molecule CCR5 antagonists that block R5 HIV entry into CD4 cells. Maraviroc has demonstrated selective and reversible binding to CCR5, as well as potent antiviral activity in vitro against a wide range of laboratory adapted strains of R5 HIV from Clades A, B, C, D, E, F, G, J and O. Maraviroc also retains in vitro antiviral activity against clinical isolates resistant to the existing drug classes, but has no activity against viruses that enter CD4+ cells using CXCR4. In vitro studies with approved antiretroviral medications indicate that there is no evidence of antagonism with any members of the other four classes of antiretroviral medications; nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non- nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) or fusion inhibitors.

Although there is growing evidence that CCR5, a potential therapeutic target, is involved in KS pathogenesis [3-9], to date there are no studies examining the effects of a CCR5 inhibitor such as Maraviroc (MVC) on KS. As such, the aim of this study is to examine the effect of Maraviroc, a CCR5 inhibitor, on KS.

• Engels EA, Pfeiffer RM, Goedert JJ, Virgo P, McNeel TS, Scoppa SM, Biggar RJ; for the HIV/AIDS Cancer Match Study. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS. 2006 Aug 1;20(12):1645-54.
• Parkin DM, Nambooze S, Wabwire-Mangen F, Wabinga HR. Changing cancer incidence in Kampala, Uganda, 1991-2006. Int J Cancer. 2010 Mar 1;126(5):1187-95.
• Gulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, Montana JB, McHale M, Sullivan J, Ridgway C, Felstead S, Dunne MW, van der Ryst E, Mayer H; MOTIVATE Study Teams. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008 Oct 2;359(14):1429-41.
• Nakano K, Isegawa Y, Zou P, Tadagaki K, Inagi R, Yamanishi K. Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded vMIP-I and vMIP-II induce signal transduction and chemotaxis in monocytic cells. Arch Virol. 2003 May;148(5):871-90.
• Navenot JM, Wang ZX, Trent JO, Murray JL, Hu QX, DeLeeuw L, Moore PS, Chang Y, Peiper SC. Molecular anatomy of CCR5 engagement by physiologic and viral chemokines and HIV-1 envelope glycoproteins: differences in primary structural requirements for RANTES, MIP-1 alpha, and vMIP-II Binding. J Mol Biol. 2001 Nov 9;313(5):1181-93.
• Shao W, Fernandez E, Sachpatzidis A, Wilken J, Thompson DA, Schweitzer BI, Lolis E. CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure. Eur J Biochem. 2001 May;268(10):2948-59.
• Nicholas J, Ruvolo VR, Burns WH, Sandford G, Wan X, Ciufo D, Hendrickson SB, Guo HG, Hayward GS, Reitz MS. Kaposi's sarcoma-associated human herpesvirus-8 encodes homologues of macrophage inflammatory protein-1 and interleukin-6. Nat Med. 1997 Mar;3(3):287-92.
• Boshoff C, Endo Y, Collins PD, Takeuchi Y, Reeves JD, Schweickart VL, Siani MA, Sasaki T, Williams TJ, Gray PW, Moore PS, Chang Y, Weiss RA. Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines. Science. 1997 Oct 10;278(5336):290-4.
• Kledal TN, Rosenkilde MM, Coulin F, Simmons G, Johnsen AH, Alouani S, Power CA, Lüttichau HR, Gerstoft J, Clapham PR, Clark-Lewis I, Wells TN, Schwartz TW. A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science. 1997 Sep 12;277(5332):1656-9.
• Moore PS, Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med. 1995 May 4;332(18):1181-5.
• Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9.
• Cherqui S, Kingdon KM, Thorpe C, Kurian SM, Salomon DR. Lentiviral gene delivery of vMIP-II to transplanted endothelial cells and endothelial progenitors is proangiogenic in vivo. Mol Ther. 2007 Jul;15(7):1264-72. Epub 2007 May 1.
• Dupont C, Vasseur E, Beauchet A, Aegerter P, Berthé H, de Truchis P, Zucman D, Rouveix E, Saiag P. Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodéficience humaine. AIDS. 2000 May 26;14(8):987-93.
• Nguyen HQ, Magaret AS, Kitahata MM, Van Rompaey SE, Wald A, Casper C. Persistent Kaposi sarcoma in the era of highly active antiretroviral therapy: characterizing the predictors of clinical response. AIDS. 2008 May 11;22(8):937-45.
• Cooley T, Henry D, Tonda M, Sun S, O'Connell M, Rackoff W. A randomized, double-blind study of pegylated liposomal doxorubicin for the treatment of AIDS-related Kaposi's sarcoma. Oncologist. 2007 Jan;12(1):114-23.
• Cainelli F, Vallone A. Safety and efficacy of pegylated liposomal doxorubicin in HIV-associated Kaposi's sarcoma. Biologics. 2009;3:385-90. Epub 2009 Sep 15.
• Lichterfeld M, Qurishi N, Hoffmann C, Hochdorfer B, Brockmeyer NH, Arasteh K, Mauss S, Rockstroh JK; German Clinical AIDS Working Group (KAAD). Treatment of HIV-1-associated Kaposi's sarcoma with pegylated liposomal doxorubicin and HAART simultaneously induces effective tumor remission and CD4+ T cell recovery. Infection. 2005 Jun;33(3):140-7.
• Saran FH, Adamietz IA, Thilmann C, Mose S, Böttcher HD. HIV-associated cutaneous Kaposi's sarcoma--palliative local treatment by radiotherapy. Acta Oncol. 1997;36(1):55-8.
• McCormick SU. Intralesional vinblastine injections for the treatment of oral Kaposi's sarcoma: report of 10 patients with 2-year follow-up. J Oral Maxillofac Surg. 1996 May;54(5):583-7; discussion 588-9.
• Maurer T, Ponte M, Leslie K. HIV-associated Kaposi's sarcoma with a high CD4 count and a low viral load. N Engl J Med. 2007 Sep 27;357(13):1352-3. No abstract available.

Inclusion Criteria:

• HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• Active biopsy confirmed KS
• Screening plasma HIV RNA < 75 copies/mL
• Patients have unremitting KS. Unremitting is defined as having active biopsy confirmed KS in spite of having had sustained HIV RNA < 75 copies/mL for 24 prior months. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable.
• >90% adherence to therapy within the preceding 30 days, as determined by self-report.
• Both male and female subjects are eligible. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
• Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

• Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
• Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
• Concurrent treatment with immunomodulatory drugs or therapies, or exposure to any immunomodulatory drug or therapy in past 16 weeks.
• Prior exposure to CCR5 inhibitors
• Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.
• Elevated transaminases greater than 2.5 times the upper limit of normal.
• Evidence of cirrhosis
• Pregnant or breastfeeding women
• Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.
• Local therapy for any KS index lesion in preceding 60 days, unless lesion has clearly progressed with enlargement since the local therapy

• Pfizer
• ViiV Healthcare