AIDS-associated Kaposi's Sarcoma Research Articles

Treatment Outcomes of AIDS-Associated Kaposi's Sarcoma under a Routine Antiretroviral Therapy Program in Lilongwe, Malawi: Bleomycin/Vincristine Compared to Vincristine Monotherapy

PurposeDespite Kaposi's sarcoma (KS) being the most prevalent AIDS-associated cancer in resource limited settings, optimal treatment options remain unknown. We assessed whether bleomycin/vincristine compared to vincristine monotherapy was associated with improved treatment outcomes for AIDS-associated KS among patients initiating combination antiretroviral therapy (cART) in Malawi.MethodsAll patients initiating cART and chemotherapy for AIDS-related KS were identified from an electronic data system from the HIV Lighthouse Clinic from 2002 to 2011. Treatment responses were compared between patients receiving vincristine monotherapy and vincristine/bleomycin. Binomial regression models were implemented to assess probability of tumor improvement for patients receiving vincristine/bleomycin compared to vincristine monotherapy after a complete cycle of chemotherapy (9–10 months). A chi-squared test was used to compare changes in CD4 count after six months of chemotherapy.ResultsOf 449 patients with AIDS-associated KS on chemotherapy, 94% received vincristine monotherapy and 6% received bleomycin/vincristine. Distribution of treatment outcomes was different: 29% of patients on vincristine experienced tumor improvement compared to 53% of patients on bleomycin/vincristine. Patients receiving bleomycin/vincristine were 2.25 (95% CI: 1.47, 3.44) times as likely to experience tumor improvement as to those on vincristine monotherapy. This value changed little after adjustment for age and baseline CD4 count: 2.46 (95% CI: 1.57, 3.86). Change in CD4 count was similar for patients receiving vincristine monotherapy and bleomycin/vincristine (p = 0.6).ConclusionBleomycin/vincristine for the treatment of AIDS-associated KS was associated with better tumor response compared to vincristine monotherapy without impairing CD4 count recovery. Replication in larger datasets and randomized controlled trials is necessary.

IFNL4 ss469415590 variant is a better predictor than rs12979860 of pegylated interferon-alpha/ribavirin therapy failure in hepatitis C virus/HIV-1 coinfected patients

A new transiently induced region (interferon-λ 4 protein; IFNL4) harbouring a dinucleotide variant ss469415590 (TT or ΔG), upstream of IFNL3 (IL28B), was recently found to be associated with hepatitis C virus (HCV) clearance. To determine the effect of IFLN4 ss469415590 variation on the HCV response to IFN-based therapy in HCV/HIV-1 coinfected patients, ss469415590 was genotyped in a cohort of 207 patients from our clinic. Treatment failure occurred in 77% of minor ΔG-allele carriers versus 48% of noncarriers, indicating that the ΔG allele was strongly associated with treatment failure. Importantly, multivariate logistic analysis revealed that ss469415590 genotype was a better predictor of treatment failure than rs12979860.

Treatment Outcomes of AIDS-Associated Kaposi's Sarcoma under a Routine Antiretroviral Therapy Program in Lilongwe, Malawi: Bleomycin/Vincristine Compared to Vincristine Monotherapy

Treatment Outcomes of AIDS-Associated Kaposi's Sarcoma under a Routine Antiretroviral Therapy Program in Lilongwe, Malawi: Bleomycin/Vincristine Compared to Vincristine Monotherapy

Risk of Kaposi Sarcoma Among Immigrants to Sweden

Kaposi sarcoma (KS) is a locally aggressive endothelial tumour that is classified into 4 clinico-epidemiological forms: classic KS affecting lower limbs in elderly Mediterranean or East European men; endemic KS occurring in extremities among Equatorial African middle-aged men and children; iatrogenic KS involving lower limbs in immunosuppressive patients; and AIDS-associated (epidemic) KS observed among homo- and bisexual HIV-1-infected young men (1, 2). The world-wide epidemiology of KS has changed by spreading of HIV infection (1). For example, KS represented 7% of all cancers in Sub-Saharan African men in the 1960s, whereas in the 1980s the rate increased to 50%. Furthermore, the age distribution of KS has changed from elderly (in classic form) to the late thirties (in epidemic form). KS is a rare tumour in Nordic countries; the incidence is 0.1-0.2/100,000 according to the Cancer Incidence in Five Continents (CI5) report (3). According to this source, the rate in many Asian countries is <0.5/100,000, whereas African American men have a rate of 6.2/100,000. The highest rate is in men from Zimbabwe (52.2/100,000) (3). Human herpesvirus 8 (HHV-8) is the recognised cause of all forms of KS (2). There is discrepancy between the prevalence of HHV-8 and KS incidence in some populations suggesting underreporting of KS or the existance of some unknown protective factors for KS (1). Migrant studies provide data on international differences in cancer rates (4). Furthermore, studies on immigrants may provide supplementary and confirmatory data on the incidence of cancer in countries without local cancer registries. A few available studies on immigrants have focused only on classic KS (5, 6). In the present study, we report mean age at diagnosis and KS rates by site in first-generation immigrants to Sweden. (Less)

Disseminated Kaposi's Sarcoma Without Cutaneous Involvement

Kaposi's sarcoma (KS) is a low-grade vascular tumor caused by infection with human herpesvirus 8. Prior to the AIDS epidemic, KS was rare in the United States. With the advent of highly active antiretroviral therapy, KS has become far less common, now occurring at a rate of about 6 cases per million people each year. It is still seen most commonly in those infected with HIV, and cutaneous manifestations represent the most common presentation. In this case, we describe a patient with disseminated AIDS-associated KS lacking cutaneous manifestations.

Phase II Trial of Imatinib in AIDS-Associated Kaposi's Sarcoma: AIDS Malignancy Consortium Protocol 042

Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients. This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable. Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines. Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS.

One hundred and five Kaposi sarcoma patients: a clinical study in Xinjiang, Northwest of China

Kaposi's sarcoma (KS) is an unusual illness that may be associated with human herpes virus 8 (HHV-8) infections, and appears mainly in Jews, Italians and Greeks. There is a lack of patient data in Xinjiang regarding the clinical characteristics of KS. To review the clinical characteristics of a series of patients with KS in Xinjiang, Northwest China, over 16-year period. A retrospective analysis of patients referred to a Xinjiang hospital in Northwest China with classic KS (CKS) and AIDS-associated KS (AIDS-KS) between January 1997 and April 2013 was performed. Reviewed information included demographics, clinical features, histopathological traits, treatment and presence of HHV-8 infection. During the study period, 105 patients with a diagnosis of KS, including 77 CKS and 28 AIDS-KS, were referred to our hospital. Mean age at diagnosis was 55.8±16.8years (range: 25-85years). There were 70 (90.9%) males and 7 (9.1%) females (male-to-female ratio: 10:1) having CKS and 21 (75.0%) males and 7 (25.0%) females (male-to-female ratio: 3:1) with AIDS-KS. Most of the patients were Uyghur, including 67 CKS and 24 AIDS-KS. The rate of multifocal lesions at diagnosis was 98.1% (103/105). The most common area of lesions was between 1% and 5% of CKS and AIDS-KS. The main types of lesions were nodules, patches and plaques. The lower extremity and foot were the most common locations for CKS and AIDS-KS. In addition to skin damage, the penis, mouth, lymph nodes and interstitial lung tissues were involved in some cases. No second primary malignancy was diagnosed. Systemic chemotherapy and radiotherapy were effective treatments for CKS. The HHV-8 positivity rate was 98.98% in 98 KS cases. In Xinjiang, most CKS and AIDS-KS patients were older Uyghur men. AIDS-KS was found predominantly among 30-year-old Uyghur patients, compared with 60years for those having CKS. The latter exhibited certain characteristics such as disseminated skin disease; in some patients, the condition was accompanied by lymphedema, visceral or lymph node involvement, but no secondary malignancies. In addition, the HHV-8 positivity rate associated with KS was very high.

Peginterferon Alfa-2a for AIDS-Associated Kaposi Sarcoma: Experience With 10 Patients

In this observational cohort study, 10 patients with extensive or treatment-refractory AIDS-associated Kaposi sarcoma were treated with peginterferon alfa-2a. Tumor responses were observed in 9 patients with a median progression-free survival of 645 days. Peginterferon alfa-2a could be an effective therapy for extensive or treatment-resistant Kaposi sarcoma.

AIDS-associated Kaposi sarcoma: outcomes after initiation of antiretroviral therapy at a university-affiliated hospital in urban Zimbabwe

To retrospectively investigate the outcomes of patients with AIDS-associated Kaposi sarcoma (AIDS-KS) after initiation of antiretroviral therapy (ART), under routine practice conditions, at a university-affiliated hospital in urban Zimbabwe. While studies from developed nations have demonstrated excellent outcomes for AIDS-KS patients treated with ART, few studies have examined the outcomes of African AIDS-KS patients after starting therapy. A retrospective cohort of 124 AIDS patients initiating ART under routine practice conditions was studied. Thirty-one patients with AIDS-KS were matched 1:3 to 93 AIDS patients without KS (non-KS). The primary outcome was loss-to-care after initiation of therapy. Multivariate analysis was performed to identify significant predictors of loss-to-care. The percent change in weight at 6 months after starting ART was a secondary outcome. A sub-group analysis evaluated differences in pre-treatment variables between AIDS-KS patients retained-in-care compared to those lost-to-care. AIDS-KS patients had significantly greater 2-year proportional loss-to-care than matched non-KS AIDS patients (26.4% vs. 9.5%; p = 0.01) after initiation of ART. In multivariate analysis, the presence of KS (p = 0.02) was the only significant predictor of loss-to-care. AIDS-KS patients had significantly less weight gain after starting ART than non-KS AIDS patients (+3.4% vs. +6.4%; p = 0.03). AIDS-KS patients retained-in-care had significantly higher pre-treatment CD4+ lymphocyte counts than AIDS-KS patients lost-to-care (223 vs. 110 cells/mm(3); p = 0.04). In this retrospective study, AIDS-KS patients experienced significantly worse outcomes than matched non-KS AIDS patients after initiation of ART. AIDS-KS patients with higher pre-treatment CD4+ lymphocyte counts were more likely to be retained in care.

Lymphangiectatic Kaposi's sarcoma in a patient with AIDS

Kaposi's sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi's sarcoma. In non-HIV-associated Kaposi's sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi's sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis's sarcoma.

Do we still need chemotherapy for AIDS-associated Kaposi’s sarcoma?

The widespread introduction of effective combination antiretroviral therapy (cART) has had a major influence on the epidemiology and natural history of AIDS-associated Kaposi’s sarcoma (AIDS-KS). cART has reduced the incidence of AIDS-KS, and it has been shown to be an effective treatment for early-stage KS. So with the widespread availability of cART, is systemic chemotherapy still required for AIDS-KS? Two indications appear to remain: advanced-stage AIDS-KS and patients who have progressive KS despite effective cART including immune reconstitution inflammatory syndrome KS.

Bioprocessing of Plant In Vitro Systems for the Mass Production of Pharmaceutically Important Metabolites: Paclitaxel and its Derivatives

Taxol (paclitaxel) and its derivatives are microtubule-stabilizing drugs widely used in the treatment of several types of cancer, including mammary, prostate, ovarian and non-small-cell lung carcinoma, as well as AIDS-associated Kaposi's sarcoma and other types of tumor. Taxanes stabilize microtubules by enhancing their polymerization and inhibiting depolymerization. Microtubule dynamics are crucial to mitotic spindle formation and function; therefore, cells exposed to taxanes are unable to undergo chromosomal separation during mitosis, become arrested in the G2/M phases of the cell cycle, and are subsequently targeted for apoptosis. Plant cell cultures are used for industrial-scale biotechnological production of important bioactive plant secondary metabolites, including the anticancer agent paclitaxel. In the last two decades, there have been numerous empirical approaches to improve the biotechnological production of taxanes, leading to the conclusion that treatment of Taxus sp. cells with methyl jasmonate or other elicitors is the most effective strategy. However, little insight has been gained into how the elicitors increase taxane biosynthesis or how this process is regulated. In recent years, with the help of "omics" tools, a rational approach has provided new information about taxane metabolism and its control. Once pathway bottlenecks have been identified, it will be possible to engineer Taxus sp. cell lines with overexpression of genes that control the flux-limiting steps, thus boosting taxane productivity. This review describes the chemical and biological characterization of paclitaxel and its derivatives and discusses future prospects for their biotechnological production.

Kaposi Sarcoma

Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection. Kaposi sarcoma lesions predominantly present at mucocutaneous sites, but may involve all organs and anatomic locations. Recognized epidemiologic-clinical forms of KS include classic, African (endemic), AIDS-associated (epidemic), and iatrogenic KS. New clinical manifestations have been described, such as antiretroviral therapy-related KS regression or flares. Kaposi sarcoma lesions evolve from early (patch stage) macules into plaques (plaque stage) that grow into larger nodules (tumor stage). Newer histologic variants include anaplastic, hyperkeratotic, lymphangioma-like, bullous, telangiectatic, ecchymotic, keloidal, pyogenic granuloma-like, micronodular, intravascular, glomeruloid and pigmented KS, as well as KS with sarcoidlike granulomas and KS with myoid nodules. Latency-associated nuclear antigen (HHV8) is the most specific immunohistochemical marker available to help distinguish KS from its mimics. Since KS remains one of the most common AIDS-defining malignancies, it is important that pathologists be able to recognize KS and its contemporary manifestations.

A case of AIDS-associated oral Kaposi's sarcoma of the tongue

Kaposi's sarcoma (KS) is one of the most common diseases seen in patients presenting with acquired immunodeficiency syndrome (AIDS); however, it is rare in Japan. We herein report a case of AIDS-associated KS of the tongue, which was initially misdiagnosed as recurrent hemangioma according to the initial histopathological diagnosis. The patient is a 42-year-old male who had been suffering from a painful vascular neoplasm-like mass on the dorsum of the tongue. The patient did not complain of any other distinct symptoms and a debulking operation was planned based on the clinical diagnosis of hemangioma. However, preoperative blood tests revealed the presence of syphilis and the human immunodeficiency virus and the patient was therefore diagnosed to have full-blown AIDS. Therefore, the patient's oral lesion was then instead suspected to be oral KS (OKS). A histopathological examination of the tongue biopsy specimen showed the typical findings of KS. Combination active antiretroviral therapy (cART) combined with liposomal doxorubicin was administered and the patient achieved a complete remission (CR). In conclusion, clinicians including oral surgeons, should take OKS into account in the diagnosis of vascular neoplasm-like masses of the tongue in adults since this complication may occur as a result of AIDS.

Epidemiological and clinical features of AIDS-Associated Kaposi′s sarcoma in Northern Nigeria

Introduction : The incidence of AIDS-associated Kaposi's sarcoma (AAKS) is increasing in the West African sub-region. The objective of this study was to describe the epidemiologic and clinical features of AAKS. Materials and Methods : This study was carried out in a tertiary health center with a federal government supported AIDS treatment program in Zaria, Nigeria. The subjects comprised 137 consecutive patients evaluated for AAKS from 2006 to 2011. Following evaluation appropriate specimens were taken for histologic, virologic, and immunologic assessment. Result : There were 137 patients representing 1.4% of HIV infected patients seen during the study period. The male to female ratio was 1.3:1. Their ages ranged from 2 to 58 years, mean of 32 ± 6 and females were younger than males. Mean duration of symptoms was 4.2 ± 1.5 months. Kaposi's sarcoma was the AIDS-defining disease in 95 (69.3%) patients while in 42 (30.7%) it was diagnosed between 1 and 15 months after the diagnosis of HIV infection. The lower limbs were the most frequent sites of lesions. Females had more disseminated lesions involving an increased number of lesions at multiple anatomical sites compared with more localized lesions in the males (OR 2.7, 95% CI 1.5-7.0). The CD4 count ranged from 19 to 798 cells/mm 3 , median 132; interquatile range 102-317 cells/mm 3 while the median HIV RNA copies/ml of plasma was 51,723 (ranged 250-917, 254).Conclusion : The prevalence of AAKS is increasing in our institution. Female patients were younger and had more disseminated disease that progressed faster than in males. Timely identification of HIV-infected patients is essential to avoid the consequences of immunological deterioration associated with delayed anti-retroviral therapy.

AIDS and HIV Infection after Thirty Years.

AIDS and HIV Infection after Thirty Years.

Pulmonary Kaposi Sarcoma in AIDS

A 34-year-old man presented to the hospital with a productive cough, dyspnea, subjective fever, chills, and myalgias. Fever, tachycardia, tachypnea, and severe hypoxemia were noted on arrival. Examination revealed a frail, diaphoretic man in considerable respiratory distress, with diffuse bilateral rales and rhonchi; a violaceous, raised rash over the limbs and trunk was also noted. Findings on chest radiography were suggestive of multilobar pneumonia. A rapid oral antibody test for human immunodeficiency virus (HIV) returned a positive result. Computed tomography of the chest showed striking flame-shaped opacities and spicular thickening of the bronchovascular bundles in all lobes (panels A, B, and C, arrows). These findings are characteristic of pulmonary Kaposi sarcoma (KS).1 In our patient, the diagnosis was confirmed by bronchoscopy and skin biopsy. Computed tomographic features of KS are extremely helpful in guiding the initial management of HIV-infected patients presenting with symptoms of pneumonia. Kaposi sarcoma in HIV-infected patients is diagnostic of AIDS. The goals of therapy in AIDS-associated pulmonary KS are prevention of progression and reduction of tumor burden. Initial management consists of highly active antiretroviral therapy, as this is associated with lesion regression and prolonged survival.2 After optimizing highly active antiretroviral therapy, systemic chemotherapy can be initiated for pulmonary KS. Single-agent chemotherapy can include liposomal doxorubicin, liposomal daunorubicin, paclitaxel, or etoposide. Various combination chemotherapy regimens have been studied and may provide higher response rates compared with single agents.3 Immunosuppression remains a major concern with the use of these agents in patients with AIDS-associated KS. Antiviral therapy directed against human herpesvirus 8 have shown variable success.4 Agents such as interleukin 12 and a variety of angiogenesis inhibitors are under investigation as potential therapies. Our patient initially received noninvasive positive pressure ventilation. He subsequently had worsening respiratory failure and required endotracheal intubation. Until the diagnosis of KS was confirmed, the patient was treated with broad-spectrum antibiotics for severe community-acquired pneumonia as well as coverage for Pneumocystis jirovecii pneumonia. Highly active antiretroviral therapy, in the form of emtricitabine, tenofovir, and efavirenz was administered after stabilization. The patient's respiratory status improved over the following days, and he was successfully extubated and transferred to the medical floor. He experienced a prolonged hospital course that was complicated by suspected immune reconstitution inflammatory syndrome and hospital-acquired pneumonia. Eventually, he was given valganciclovir, doxorubicin, and vinblastine for treatment of KS, but he died after developing overwhelming sepsis.

Corticosteroid induced, HHV-8 positive Kaposi’s sarcoma in a non-HIV elderly patient

Kaposi’s sarcoma (KS) was first described in 1872 by Moritz Kaposi. In 1994, Chang et al. first identified DNA sequences corresponding to human herpesvirus-8 (HHV-8) in AIDS-associated Kaposi sarcoma biopsies. It is now believed that presence of HHV-8 is necessary but not sufficient to cause KS. Other factors like immunosuppressive therapy also play a role. We describe an HIV-negative elderly patient who developed KS of skin and mucous membrane after prolonged use of corticosteroids for knee pain. The patient was positive for HHV-8.

Management of AIDS-Associated Kaposi’s Sarcoma in Nigerian Children: A Case Series and Review of Literature

There is a paucity of published studies on the management and outcome of AIDS-associated Kaposi's sarcoma (AAKS) in African children. In this study, we reviewed the management and literature of AAKS in Nigerian children. A prospective review of children aged 1 to 14 years and adolescents aged 15 to 18 years who presented with AAKS. Following clinical evaluation and resuscitation, patients were treated with highly active antiretroviral therapy (HAART). Stable patients were further treated with chemotherapy consisting of vincristine, doxorubicin, and bleomycin. Patients were monitored until death or loss to follow-up. There were 9 patients: 6 children and 3 adolescents. Three children had vertical transmission of HIV infection. Kaposi's sarcoma was the AIDS-defining disease in 5 patients. One patient was on HAART at the time of diagnosis. There were multiple skin lesions in all patients, and cervical lymph nodes and oropharynx were frequently affected. The CD4 counts at the time of AAKS diagnosis ranged 78 to 601 cells/ uL, mean of 317. Five patients had best palliative care. Three had anticancer chemotherapy, of which 2 were alive 4 years after diagnosis. Three patients died at the initial hospitalization 2 to 6 weeks after diagnosis. Children and adolescents with AAKS presented with generalized skin lesions and lymphadenopathy, which facilitated the diagnosis. The majority of the patients presented with advanced disease that was rapidly fatal. However, patients with good immunity may have a prolonged control of symptoms if treated with HAART and appropriate anticancer chemotherapy.

Oral HIV‐associated Kaposi sarcoma

Kaposi sarcoma (KS), an AIDS defining condition, remains one of the most commonly HIV-associated neoplasms. While the use of highly active antiretroviral therapy (HAART) has brought about a dramatic decrease in the prevalence and incidence of AIDS-KS worldwide, this has not been the case in resource-poor sub-Saharan African countries, where HIV has reached epidemic proportions and human herpesvirus-8 infection is endemic. Oral involvement is a common manifestation of AIDS-associated KS and may be an early presenting finding of HIV infection. The clinical manifestation of oral KS can vary and may have an unpredictable course ranging from mild to fulminant. Rapidly progressive facial lymphoedema associated with extensive advanced oral KS portends a poor prognosis. Oral KS may regress with antiretroviral therapy or may flare up as part of the immune reconstitution inflammatory syndrome. The oral lesions of AIDS-KS are best managed with HAART together with systemic chemotherapy. This article provides a review of contemporary knowledge of the biology, pathology, clinical features and management of oral AIDS-KS.