This large single-institution cohort included 254 patients with histologically confirmed Kaposi's sarcoma who have been treated in a uniform fashion and followed up for a median of over 4 years and a maximum of 12 years. Many studies [7,26–29] have reported the declining incidence of Kaposi's sarcoma in the era of HAART amongst cohorts of patients with access to these medicines. In this study, 81% of patients were not receiving HAART at the time Kaposi's sarcoma was diagnosed and nearly two-thirds (30/48) of the patients who were on HAART at the time of Kaposi's sarcoma diagnosis had detectable HIV viral load, suggesting failure of HAART due to drug resistance or adherence problems. In all, only 18 patients (7% of the cohort) were diagnosed with Kaposi's sarcoma while on a fully suppressive HAART regimen. These 18 patients were generally older (mean age 43 years, range 25–66 years) and had a higher CD4 cell count at Kaposi's sarcoma diagnosis (median 277 cells/μl, range 49–732 cells). These patients had been HIV positive for a mean of 7.7 years and on HAART for a mean of 31 months when the Kaposi's sarcoma was diagnosed. Similar patients on HAART with undetectable HIV viraemia and high CD4 cell counts who developed Kaposi's sarcoma have been described [30–32], and indeed one group of authors has suggested that these patients represent a new disease process, although this is highly controversial .
The histological classification of these biopsy-confirmed Kaposi's sarcoma lesions fell into the three most commonly recognized groups, reflecting the progression from patch to plaque and finally nodular grades [34,35]. Nodular grade Kaposi's sarcoma represented 28% of the Kaposi's sarcoma diagnosed and this grade of histology was significantly associated with black African ethnicity and ACTG T1 stage disease. In particular, nodular histology was significantly associated with extensive oral and gastrointestinal involvement. These findings would support the hypothesis that nodular grade histology represents a more aggressive disorder. In contrast, nodular grade Kaposi's sarcoma was not associated with more advanced immunodeficiency as there were no significant differences in CD4 cell counts or plasma HIV viral load, nor in the proportion of patients on HAART at the time of their Kaposi's sarcoma diagnosis. The OS from Kaposi's sarcoma diagnosis was inferior (log rank P = 0.026) for patients with nodular grade histology (5-year survival rate 79%, 95% CI 68–90) compared with patch grade (5-year survival rate 91%, 95% CI 84–98) or plaque grade (5-year survival rate 92%, 95% CI 86–98). However, the majority of this difference is attributable to the greater proportion of patients with T1 stage disease amongst those with nodular grade histology. The treatment-free survival for patients with T0 disease treated with HAART alone in contrast reveals no significant difference in outcomes by histological grading (log rank P = 0.73). These findings suggest that the histological grading of the Kaposi's sarcoma has far less influence on outcome than the staging of the disease and that histological grading should not influence treatment strategies.
The protease inhibitor class of antiretrovirals have been shown to possess antiangiogenic and antiproliferative properties in-vitro and in experimental animal models , leading many clinicians to advocate their use in HIV-associated Kaposi's sarcoma. However, the incidence of Kaposi's sarcoma was significantly lower in HIV-seropositive patients receiving an NNRTI-based regimen than those receiving a protease inhibitor-based regimen in a cohort of 8640 . Moreover, NNRTI-based HAART is as effective as protease inhibitor-based HAART in prolonging time to treatment failure in Kaposi's sarcoma , and in a small cohort of naive patients, protease inhibitor-based regimens were as likely to induce remission of Kaposi's sarcoma as protease inhibitor-sparing regimens . This study again confirms the efficacy of protease inhibitor-sparing regimens and also supports the view that the effects of HAART are mediated by immune restoration rather than a direct antiangiogenic or antitumour effect of the antiretrovirals.
This large cohort confirms the previous reports of an improved survival following a diagnosis of Kaposi's sarcoma in the era of HAART [12,13,36,44]. The actuarial 5-year OS in this cohort of 254 patients is 89% and it is striking that the deaths of only 12 patients were attributed to Kaposi's sarcoma, whereas nine patients died of other malignancies. Amongst the 163 patients who were treated with HAART alone for their Kaposi's sarcoma, the 5-year OS is 91% (95% CI 87–95) and in this group only a single death was attributed to Kaposi's sarcoma. The high success rate of HAART in a large cohort of antiretroviral-naive patients over a prolonged period of follow-up will reassure patients and clinicians that this is a well tolerated and effective approach to stage T0 Kaposi's sarcoma and supports published guidelines.
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