Lebbe, C. et al. Clinical and biological impact of antiretroviral therapy with protease inhibitors on HIV-related Kaposi's sarcoma. AIDS 12, F45−F49

Centre Hospitalier René Dubos, 95001 CEDEX, Ile-de-France, France
AIDS (Impact Factor: 5.55). 06/1998; 12(7):F45-9. DOI: 10.1097/00002030-199807000-00002
Source: PubMed


To evaluate the clinical and biological impact of protease inhibitors on HIV-associated Kaposi's sarcoma.
A cohort of 10 patients included prospectively from April 1996 to June 1997 were studied in one institutional centre after initiation of protease inhibitors.
All patients but one (stable disease) had progressive Kaposi's sarcoma. Three out of 10 patients had stopped specific chemotherapy for Kaposi's sarcoma for more than 4 weeks, three were still under chemotherapy, and four had never received specific treatment of Kaposi's sarcoma. Plasma HIV viral load, human herpesvirus (HHV)-8 viraemia in peripheral blood mononuclear cells (PBMC), and CD4 cell count were sequentially assessed from the beginning of therapy. For six patients, a semiquantitative evaluation of HHV-8 viral load in the Kaposi's sarcoma lesions was performed during treatment using polymerase chain reaction.
After initiation of HIV triple therapy with protease inhibitors, we observed six complete responses, two partial responses, and two patients with progressive disease. All patients had undetectable plasma HIV viral load within 2 months of treatment. Undetectable HHV-8 viraemia in PBMC occurred in seven out of eight patients with partial or complete response and in none of the progressive patients. A decrease or negation of HHV-8 viral load in Kaposi's sarcoma lesions was observed in two complete responders.
Our results suggest that antiviral therapy with protease inhibitors are clinically efficient in HIV-associated Kaposi's sarcoma and that there exists a correlation between clinical response and negation of HHV-8 viraemia.

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    • ". Treatment with a regimen that includes a protease inhibitor was associated with the clearance of KSHV DNA in KS lesions and PBMCs, and with the regression of KS lesions in AIDS patients [Blum et al., 1997; Lebbé et al., 1998]. Furthermore, a number of reports have linked tumor regression after the initiation of HAART to the restoration of immune function [Dupont et al., 2000; Marcelin et al., 2004], and it has been reported that KSHV DNA amount in PBMCs rebounded in patients with KS after a short interruption of efficient antiretroviral therapy [Parisi et al., 2002b]. "
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    ABSTRACT: To evaluate the relevance and the virological and immunological markers of Kaposi sarcoma herpesvirus 8 (KSHV) viremia in Italian male patients at the time of diagnosis of infection with HIV-1, 481 men infected with HIV were recruited consecutively. The presence of KSHV DNA was evaluated in peripheral blood mononuclear cells (PBMCs) and in plasma and correlated with demographic and viro-immunological parameters. Seventy-four patients had KSHV DNA detected in PBMCs. By univariate analysis, the presence of KSHV DNA was associated significantly with unprotected homosexual relationships (P=0.003) and it was significantly higher in patients with CD4+ cell <350 (P=0.025). By multivariate analysis, homosexual relationships were associated independently with KSHV DNA in PBMCs (OR: 3.25; 95% CI: 1.1-9.7; P=0.035). Among the 74 patients with KSHV DNA detected in PBMCs, plasma samples from 60 were analyzed and 33 were positive for KSHV DNA. The CD4+ cell counts and percentages were significantly lower in patients with KSHV DNA in both PBMCs and plasma as compared to patients with only KSHV DNA in PBMCs (P=0.006 and P=0.019, respectively). Among the patients with KSHV DNA detected in PBMCs, all 13 patients with CD4+ cells count <200 had detectable levels of KSHV in their plasma. By multivariate analysis adjusted for the epidemiologic and virological parameters, low CD4+ cell count was the only independent variable associated with the presence of KSHV DNA in plasma (OR, 0.001; 95% CI: <0.001-0.001; P=0.03). In HIV-positive antiretroviral therapy-naïve males, KSHV active replication as detected by KSHV DNA in plasma was associated significantly with low CD4+ cell count.
    No preview · Article · Mar 2011 · Journal of Medical Virology
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    • "The use of highly active antiretroviral therapy (HAART) has resulted in a dramatic reduction in the morbidity and mortality in HIV-seropositive subjects [33-36]. HAART, although not directly affecting HHV-8 replication, indirectly brings about a decrease in HHV-8 viral load [37], a substantial reduction in the prevalence and incidence of HIV-KS [38-42], and improvement in the clinical manifestation of KS [43-52]. "
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    ABSTRACT: A decrease in the incidence of human immune deficiency virus-associated Kaposi sarcoma (HIV-KS) and regression of some established HIV-KS lesions is evident after the introduction of highly active anti-retroviral treatment (HAART), and is attributed to generalized immune restoration, to the reconstitution of human herpesvirus (HHV)-8 specific cellular immune responses, and to the decrease in HIV Tat protein and HHV-8 loads following HAART. However, a small subset of HIV-seropositive subjects with a low CD4+ T cell count at the time of introduction of HAART, may develop HIV-KS as immune reconstitution inflammatory syndrome (IRIS) within 8 weeks thereafter.
    Full-text · Article · Feb 2008 · Infectious Agents and Cancer
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    • "For AIDS-associated and iatrogenic KS, immune reconstitution is sometimes suffi cient to trigger tumor remission . HAART alone caused KS remission in 48%–86% of HIV positive KS patients (Lebbe et al 1998; Dupin et al 1999; Dupont et al 2000; Cattelan et al 2001; Murdaca et al 2002; Paparizos et al 2002; Wilkinson et al 2002). Similarly, iatrogenic KS can be controlled by limiting the dosage, or switching the type of immunosuppressive therapy employed. "
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    ABSTRACT: Anthracycline compounds including daunorubicin are the foundation of many modem chemotherapeutic regimens. However, the side-effects of these compounds can be severe, leading to alopecia, nausea, immune deficiency, and cardiotoxicity. For immunocompromised patients with aggressive Kaposi's sarcoma (KS), these complications often preclude the completion of appropriate chemotherapeutic regimens. This review focuses on the development and efficacy of liposomal daunorubicin (DaunoXome; DNX) carriers for the treatment of KS. Encouragingly, DNX demonstrated increased in vivo stability and specificity. As a result, KS patients benefit from higher cumulative chemotherapeutic doses without significant cardiotoxicity. Tumor response to DNX treatment surpasses that of non-encapsulated daunorubicin and is similar to that observed with conventional multi-drug therapies such as ABV (doxorubicin, bleomycin, vincristine). Moreover, some reports indicate the patient quality of life during therapy may improve with DNX treatment. Although the development of DNX represents a significant advance in KS therapy, recent data suggest that additional modification of the liposomal carrier to include pegylation or target specific antibodies may further increase daunorubicin efficacy in the future.
    Full-text · Article · Feb 2007 · International Journal of Nanomedicine
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