HIV-associated Kaposi's Sarcoma Research Articles

British HIV Association guidelines for HIV‐associated malignancies 2008

British HIV Association guidelines for HIV‐associated malignancies 2008

Characteristics of HIV-1-associated Kaposi's sarcoma among women and men in South Africa

Despite the increase of HIV-1-associated Kaposi's sarcoma (KS), little is known about HIV-associated KS in the African setting, particularly among women. A descriptive study of the demographic, clinical, immunological and virological features of AIDS-associated KS from KwaZulu-Natal, South Africa was undertaken. Consecutively, recruited patients were clinically staged; CD4/CD8 cell counts, HIV-1 viral loads and clinical parameters were evaluated. Of the 152 patients (77 male and 75 female) 99% were black. Females were significantly younger (P = 0.02) and had poorer disease prognosis (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.4-5.4, P = 0.003) and were more likely to have extensive cutaneous KS when compared with males (OR = 3.1, 95% CI = 1.4-6.7, P = 0.003). One-third of patients had coexisting HIV-related disease, most commonly tuberculosis, and these were more frequent in females (56.7 vs. 43.3%). In conclusion, HIV-associated KS in South Africans has an equal female-to-male ratio. Females are younger and have more severe disease than males.

AIDS-associated Kaposi's sarcoma associated with a low viral load and a high CD4 cell count

It is well known that HIV-associated Kaposi's sarcoma (HIV-KS) has a higher incidence at lower CD4 cell counts. A recent letter by Maurer et al.[1] described a cluster of nine individuals presenting with HIV-KS with CD4 cell counts greater than 300 cells/μl and suppression of HIV viraemia. The a

Human Immunodeficiency Virus–Associated Kaposi Sarcoma as an Immune Reconstitution Inflammatory Syndrome: A Literature Review and Case Report

Kaposi sarcoma (KS) is the most common human immunodeficiency virus (HIV)-associated neoplasm (HIV-KS). Highly active antiretroviral therapy (HAART) results in a decrease in the incidence and prevalence of HIV-KS as well as in clinical improvement. However, in a subset of subjects who are HIV seropositive, KS may recrudesce early following the introduction of HAART as an immune reconstitution inflammatory syndrome (IRIS). The management of a patient who is HIV seropositive with rapid clinical worsening of oral KS lesions shortly after the initiation of HAART was documented. Repeated serologic testing for CD4(+) T-cell count and microscopic examination of two biopsy specimens of the oral lesion, one taken before and the other taken after cytotoxic chemotherapy, followed by surgical excision was the treatment modality used. Microscopic examination of the incisional biopsy specimen taken from the oral lesion at the time of the initial consultation confirmed the clinical diagnosis of KS. The sequential serological tests showed a progressive increase in CD4(+) T-cell counts that paralleled the rapid clinical worsening of the KS disease. This was consistent with the diagnosis of IRIS-associated HIV-KS. Subsequent cytotoxic chemotherapy brought about resolution of the IRIS and regression of the HIV-KS lesions. Microscopic examination of a biopsy specimen obtained after cytotoxic chemotherapy did not show any of the original KS. The residual palatal exophytic mass was excised. IRIS-associated HIV-KS is not a disease, but rather a temporary paradoxical immunoinflammatory reaction brought about by improvement in immune status following HAART. IRIS-associated HIV-KS can be controlled effectively by limited systemic cytotoxic chemotherapy in the setting of HAART.

More on HIV-Associated Kaposi's Sarcoma

More on HIV-Associated Kaposi's Sarcoma

HIV-Associated Kaposi's Sarcoma

A 25-year-old man was diagnosed with HIV infection and a CD4 count of 21/μl. He presented with chills, fever up to 39.5°C and dry cough since 1 week. Antibiotic treatment for suspected pneumonia resulted in some clinical improvement. He had a blackish spot on his right forearm, which slowly evolved into a firm nodule (panel A), and a small purple spot on the hard palate. Both were interpreted as Kaposi's sarcoma (KS). Endoscopy revealed no gastrointestinal or pulmonary lesions. Human herpes virus 8 (HHV8) IgG EIA was negative both initially and after starting highly active antiretroviral therapy (HAART). Despite an increase of CD4 to 207/μl, the oral nodule evolved into a prominent tumor of 2.5x2.5 cm (panel B). Biopsy confirmed KS, showing irregular vascular spaces, prominent endothelium, extravasated erythrocytes, and atypical spindle cells positive for CD31, CD34 and HHV8 (panel C). Several weeks later, the patient developed increasing dyspnea; a CT scan revealed perihilar, radially configured pulmonary infiltrates predominantly of the left lower lobe (panel D), consistent with pulmonary KS. HIV-associated KS affects the skin and/or mucous membranes and is strictly associated with HHV8 coinfection. However, HHV8 serology may be unreliable especially in the setting of severe immunodeficiency. Usually, immune reconstitution with HAART leads to resolution of KS, but in some cases chemotherapy may be necessary. Treatment with liposomal doxorubicin led to rapid improvement of his dyspnea, weight gain of 3 kg within 6 weeks, and complete flattening of the lesion on the palate within 9 weeks.

Phase 1/2 trial of BMS‐275291 in patients with human immunodeficiency virus‐related Kaposi sarcoma

Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS-275291, was evaluated in patients with human immunodeficiency virus-associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored. Cohorts of 6 patients were to be treated with BMS-275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose-limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response. Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3-54 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation/de-escalation decisions utilizing the apoptosis assay was not feasible. BMS-275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better-tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus-associated KS. The apoptosis assay was not helpful in predicting response.

Insights into pathogenic events of HIV-associated Kaposi sarcoma and immune reconstitution syndrome related Kaposi sarcoma

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.

The prognostic significance of facial lymphoedema in HIV-seropositive subjects with Kaposi sarcoma

BackgroundKaposi Sarcoma (KS) is a multifocal angioproliferative neoplasm characterized by inflammation, oedema, neoangiogenesis and spindle cell proliferation. The pathogenesis of human immunodeficiency virus (HIV)-associated KS (HIV-KS) is multifactorial. HHV-8 is an essential factor but not in itself sufficient to cause HIV-KS, the development of which is influenced by HIV, by increased production of cytokines and by growth factors. Whether HIV-KS is a true malignancy or a reactive hyperplastic inflammatory condition is debatable.Results and ConclusionOedema of the face, legs and hands is a prominent feature of HIV-KS and is probably caused by lymphoedema related to the HIV-KS lesions. The cases of two HIV-seropositive subjects with KS-associated facial lymphoedema are reported. Extensive oral HIV-KS in association with facial oedema in the absence of anti-retroviral treatment appears to be an indication of a poor prognosis.

The malignant potential of HIV-associated Kaposi sarcoma

Human herpesvirus (HHV)-8 associated oncogenesis, a state of immune impairment, a local inflammatory environment, angiogenesis and HIV infection occurring concurrently are important factors for the development of HIV-associated Kaposi sarcoma (KS).Activation of the interleukin (IL)-6 receptor signalling pathway and constitutive signalling of viral G protein-coupled receptor (vGPCR) play an important role in the activation, proliferation and transformation of HHV-8 infected endothelial cells thus contributing to the initiation and progression of KS. HIV-tat protein, HIV-induced immune suppression and a hyperinflammatory state facilitate the oncogenic activity of HHV-8.In this article we reviewed some aspects of HIV-KS pathogenesis and tried to establish, according to the available information in the literature, whether HIV-KS is a monoclonal neoplasm or a benign angioproliferative disorder.From the data of this review it is evident that most of the HIV-KS lesions are oligoclonal in origin. It remains to be demonstrated whether these multiple monoclonal populations of cells are neoplastic, harbouring specific cytogenetic alterations such as mutations, rearrangements and amplifications, or are, as the current evidence shows, the result of HHV-8 induced intracellular signalling pathways that modulate the expression of cellular genes associated with cell cycle regulation, apoptosis, inflammatory response and angiogenesis, and represent a reactive angioproliferative disorder.

An Unusual Cluster of HIV-Associated Kaposi Sarcoma?

HIV-associated Kaposi sarcoma (KS) typically occurs in patients who have low CD4 counts ( 10,000 copies/mL). In

HIV-Associated Kaposi's Sarcoma with a High CD4 Count and a Low Viral Load

To the Editor: Kaposi's sarcoma associated with HIV infection has been decreasing in incidence and severity since the introduction of antiretroviral therapy.1 These reductions have been attributed ...

Phase III study of paclitaxel (Pac) versus pegylated liposomal doxorubicin (PLD) for the treatment of advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS): An Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium

20503 Background: PLD (doxorubicin HCL liposome injection, Doxil®, Tibotec Therapeutics, Raritan, NJ) and paclitaxel (Taxol®, Bristol Myers, Inc, New York, NY) are active in the treatment of HIV-associated KS; however, optimal therapy is undefined. Methods: A randomized phase III, multicenter trial was initiated to compare the efficacy of Pac (100 mg/m2) every 2 weeks to PLD (20 mg/m2) every 3 weeks for chemotherapy-naïve AIDS-related KS. Treatment continued until disease progression or unacceptable toxicity; concurrent antiretrovirals were permitted. 216 pts were required to detect at least a 3-month improvement in median progression free survival (PFS) for Pac compared with PLD (80% power, 2-sided alpha 0.05). Response was assessed using KS response and clinical benefit criteria, and global assessment of quality of life (QOL) using the Functional Assessment of Health Index (FAHI; version 3) plus 3 supplemental questions concerning pain, swelling, and satisfaction with physical appearance (measured at baseline and during/after treatment). Results: The trial was terminated early due to poor accrual; 46 pts were randomized to PLD, 43 to Pac. 11 pts were ineligible, 4 never started therapy and 6 lacked disease assessment or progression data, resulting in 68 pts for the efficacy analysis (34 in each arm) and 82 in the toxicity analysis. After a median follow-up of 35.8 months (mo.), there was no significant difference in PFS, response rate, or overall survival. Due to early termination, the study was not adequately powered to detect the hypothesized difference in PFS. There was no significant difference in QOL between the two arms. Grade 3–4 toxicity was comparable, including grade 4 neutropenia (34% vs. 27%) and infection (13% vs. 11%). Conclusions: Paclitaxel and PLD have comparable efficacy and toxicity in patients with HIV-associated KS. [Table: see text] [Table: see text]

Prolonged Diarrhea, Protein Losing Enteropathy, and Intestinal Perforation: An Illustrative Case of HIV-Associated Kaposi Sarcoma

A 24 year-old male with AIDS, chronic non-bloody diarrhea, abdominal pain, and anasarca, developed a jejunal perforation. This case highlights a constellation of rare findings associated with Kaposi's sarcoma – GI lesions in the absence of cutaneous lesions, protein losing enteropathy with anasarca, and intestinal perforation.

HIV-associated Kaposi sarcoma: pathogenic mechanisms

Kaposi sarcoma (KS) is a multicentric angioproliferative disorder characterized by spindle cell proliferation, neo-angiogenesis, inflammation, and edema. Human herpesvirus (HHV)-8, a gamma-herpesvirus, is a critical factor, but is not alone sufficient for the initiation of KS. Other cofactors such as human immunodeficiency virus (HIV), host-derived cytokines, chemokines, and growth factors are required for the development of KS. Whether HIV-associated KS is a reactive hyperplastic inflammatory lesion or a true neoplasm is still controversial. It is likely that HIV-associated KS begins as a reactive disorder that in some cases progresses to a monoclonal, an oligoclonal, and a polyclonal neoplasm.

Differential Impact of Combination Antiretroviral Therapy in Preventing Kaposi's Sarcoma With and Without Visceral Involvement

To study the impact of different potent combined antiretroviral treatment (cART) on the incidence of HIV-associated Kaposi's sarcoma (KS) with and without visceral involvement. Patients were selected from the French Hospital Database on HIV, a large hospital cohort. The risk of KS was estimated by using Cox proportional hazards models adjusting for age, the CD4 cell nadir, the HIV exposure category, prior AIDS, cART, and the type of cART regimen. cART regimens were distinguished according to whether they contained protease inhibitor (PI), non-nucleoside analog (NNRTI), both, or only nucleoside analog (NRTI). Separate analyzes were conducted according to the initial visceral involvement of KS. Among the 54,999 patients included in this study (182,756 person-years of follow-up), 1,634 patients were diagnosed with KS during follow-up, of whom 421 had visceral involvement at diagnosis. The KS incidence rate fell from 32 per 1,000 person-years in 1993 to 1994 to 3 per 1,000 person-years after 1999. PI-containing and NNRTI-containing cART regimens were associated with similar reductions in the risk of KS (hazard ratio, 0.68; 95%CI, 0.61 to 0.75; HR, 0.62; 95% CI, 0.54 to 0.71, respectively). The risk of visceral KS fell more strongly than the risk of cutaneous KS (> 50% and < 30%, respectively). The incidence of KS, and especially visceral KS, has fallen sharply since the advent of cART. This effect is likely due to immune restoration rather than to a specific effect on the tumoral process, as PI-containing and NNRTI-containing regimens had similar preventive efficacy.

Lymphedematous HIV‐associated Kaposi's sarcoma

Advanced Kaposi's sarcoma is frequently associated with chronic lymphedema (cLO). The histopathological features of lymphedematous HIV-associated KS (KS) are poorly documented and the co-existence of fibroma-like nodules in lymphedematous KS is under-recognized. The aims of this study were to assess the clinicopathological spectrum and diagnostic difficulties associated with lymphedematous KS and to highlight the clinicopathological profile of fibroma-like nodules. In addition, the pathogenesis of fibroma-like nodules and cLO is revisited. Prospective 17-month clinicopathological study of all biopsies from patients with lymphedematous KS. Seventy-four biopsies, the majority from the lower limbs, from 41 patients were evaluated. Nineteen, 14, five and three patients had one, two, three or four biopsies each, respectively. In 14 biopsies, there was poor clinicopathological correlation of KS stage. Exclusive lesional KS (patch, plaque, nodule or lymphangioma-like) was identified in 29 biopsies; 23 and eight biopsies demonstrated KS or fibroma-like morphology and the adjacent dermis demonstrated cLO. There was variable intratumoral and peritumoral venous compression and lymphatic dilatation. Fourteen biopsies demonstrated cLO exclusively. Smaller fibroma-like nodules lacked KS spindle cells, whereas >5 mm nodules demonstrated focal KS spindle cell proliferation and aggregation on extensive sectioning. The subcutis of 42 biopsies demonstrated variable fibrosis, hemosiderin deposits, lymphocytes, plasma cells, KS, interstitial granular material and pools of lymph fluid. Subcutaneous abscesses were identified in six biopsies. All biopsies had variable epidermal features of cLO. cLO influences clinicopathological correlation of KS stage and may also mask the presence of KS and the co-existence of subcutaneous abscesses. Smaller fibroma-like nodules are hypothesized to be a manifestation of cLO that have the potential to acquire the characteristics of KS. Lymphatic and venous obstruction, protein-rich interstitial fluid, tissue hemosiderin and subcutaneous infection are hypothesized to play a combined role in the evolution and perpetuation of cLO.

Generic antiretroviral efficacy in AIDS-associated Kaposi's sarcoma in sub-Saharan Africa

Generic antiretroviral drugs are pivotal in the implementation of WHO's '3 by 5' programme. However, clinical experience with generics in sub-Saharan Africa is insufficiently documented. We report on 50 patients with HIV-associated Kaposi's sarcoma treated with generic fixed-dose highly active antiretroviral therapy. At 52 weeks, 74% achieved an undetectable viral load of < 50 copies/ml, 86% achieved < 400 copies/ml, and a 3.1 log10 decline from baseline. Side-effects were minimal. The outcomes support the use of generic antiretroviral therapy.

HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma

Polymorphisms of genes in the human leukocyte antigen (HLA) complex, particularly those encoding HLA-DR, have been suggested as markers of susceptibility to Kaposi's sarcoma (KS). We conducted a case-control study comparing 147 homosexual men who developed KS after infection by human immunodeficiency virus-1 (HIV-1) and human herpes virus 8 (HHV8) with 147 matched dually infected men without HIV-associated KS (HIV-KS) from the Multicenter AIDS Cohort Study. HLA-B, DRB1, DRB3, DRB4, DRB5, and DQB1 polymorphisms were examined by high-resolution DNA-based methods. Differences in distributions of genetic variants were tested by conditional logistic regression. Previously reported relationships with HLA-DRB1 alleles could not be confirmed. Instead, other associations were observed. In univariate analysis, KS was weakly associated with B*2702/5 (odds ratio (OR)=0.40, 95% confidence interval (CI)=0.18-0.91). Similar or stronger associations, positive or negative, were seen for haplotypes containing class II alleles: DRB1*1302-DQB1*0604 (OR=3.67, 95% CI=1.02-13.1), DRB4 (DR53) haplotype family members [OR=0.52, 95% CI=0.32-0.85], and DRB3 (DR52) haplotype family members (OR=1.69, 95% CI=1.07-2.67). The B*1402-DRB1*0102 haplotype, which invariably contains the V281L mutation in the 21-hydroxylase gene governing adrenal steroid biosynthesis, occurred in five cases and one control (OR=5.0, 95% CI=0.58-42.8). In a final multivariable analysis, only DRB1*1302-DQB1*0604 (OR=6.43, 95% CI=1.28-32.3, P=0.02) remained significantly associated with KS. Associations of HLA-DRB families with HIV-KS could reflect underlying immune dysregulation. The HLA B*1402-DRB1*0102 haplotype associated with increased risk of KS might represent an antigen-presenting pathway unfavorable for immune response to HHV8. Alternatively, the relationship might hold a clue to the predilection of KS for men because that haplotype harbors the mutant form of the 21-hydroxylase gene.

Physiotherapy management of patients with HIV‐associated Kaposi's sarcoma

Kaposi's sarcoma is the most common form of cancer in patients with human immunodeficiency virus (HIV) infection. Although Kaposi sarcoma lesions may contribute to significant physical impairments, there is a lack of scientific literature detailing the role of physiotherapy in the treatment of HIV-associated Kaposi's sarcoma. The present Case Report includes two males, aged 36 and 39 years, seropositive for HIV with invasive Kaposi's sarcoma. Patient A was evaluated for bilateral foot pain caused by plantar surface Kaposi s sarcoma lesions that rendered him unable to walk. He progressed to walking 400feet after a treatment regimen of gait training with the use of custom plastazote sandals. Patient B was evaluated for right lower extremity lymphoedema secondary to invasive Kaposi's sarcoma. He experienced an 18% reduction in limb volume, a 38% reduction in pain and a 20 degrees increase in terminal knee flexion after therapeutic exercise and the use of compressive bandaging and garments. This Case Report suggests that physiotherapy interventions may be valuable in the conservative management of patients with HIV-associated Kaposi s sarcoma.