Publications by authors named "Susan E Krown"

Background: AIDS-related Kaposi sarcoma (AIDS-KS) remains a leading cause of morbidity and mortality among people living with HIV in Africa. Mortality among people with AIDS-KS on antiretroviral therapy remains high compared with people on antiretroviral therapy who do not have AIDS-KS.

Setting: People living with HIV with Kaposi sarcoma (KS) who participated in 2 randomized trials (A5263/AMC066 [advanced stage] and A5264/AMC067 [mild-to-moderate stage]) conducted by AIDS Clinical Trials Group/AIDS Malignancy Consortium in low- and middle-income countries.

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In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed.

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Article Synopsis
  • The study investigates the role of serum biomarkers related to inflammation, immune activation, and angiogenesis in identifying limited-stage AIDS-related Kaposi sarcoma patients who may need additional chemotherapy alongside antiretroviral therapy (ART).
  • It analyzes serum samples from a trial that tested the efficacy of adding oral etoposide chemotherapy to ART in treatment-naïve patients with limited-stage AIDS-KS, focusing on baseline biomarker levels and how they correlate with disease progression and treatment response.
  • Results indicated that higher levels of certain biomarkers like C-reactive protein (CRP) and interleukin-10 (IL-10) were linked to worse outcomes, suggesting that monitoring these biomarkers could help tailor treatment plans for better management of AIDS-K
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Purpose: Given the increasing availability of radiation therapy in sub-Saharan Africa, clinical trials that include radiation therapy are likely to grow. Ensuring appropriate delivery of radiation therapy through rigorous quality assurance is an important component of clinical trial execution. We reviewed the process for credentialing radiation therapy sites and radiation therapy quality assurance through the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center for AIDS Malignancy Consortium (AMC)-081, a multicenter study of cisplatin and radiation therapy for women with locally advanced cervical cancer living with HIV, conducted by the AIDS Malignancy Consortium at 2 sites in South Africa and Zimbabwe.

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Purpose: The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research.

Methods: All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status.

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The purpose of this article is to describe lessons from the first lymphoma clinical trial conducted by the AIDS Malignancy Consortium (AMC) in sub-Saharan Africa (SSA). AMC-068 was a randomized phase II comparison of intravenous versus oral chemotherapy for HIV-positive diffuse large B-cell lymphoma. Opening in 2016, AMC-068 planned to enroll 90 patients (45 per arm) in Kenya, Malawi, Uganda, and Zimbabwe over 24 months and follow patients for 24 months to assess overall survival.

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Background: Early progression of AIDS-associated Kaposi sarcoma (KS-PD) and immune reconstitution inflammatory syndrome (KS-IRIS) sometimes occur after the initiation of antiretroviral therapy (ART).

Methods: Early KS-PD and KS-IRIS were assessed in the A5264/AMC-067 trial in which participants with mild-to-moderate AIDS-KS were randomized to initiate ART with either immediate or as-needed oral etoposide. Early KS-PD was defined as tumor progression within 12 weeks of ART initiation.

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Background: Optimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources.

Methods: In this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe.

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Purpose: To determine the feasibility, safety, and tolerability of concomitant chemoradiotherapy administered at standard doses in HIV-infected women with locally-advanced cervical cancer (LACC) receiving antiretroviral therapy (ART).

Patients And Methods: Eligible participants had HIV infection and untreated, histologically-confirmed, invasive carcinoma of the uterine cervix, FIGO stages IB2, IIA (if tumor >4 cm), IIB, IIIA, IIIB, or IVA and met standard eligibility criteria. Subjects were prescribed 41.

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Kaposi sarcoma (KS) gained public attention as an AIDS-defining malignancy; its appearance on the skin was a highly stigmatizing sign of HIV infection during the height of the AIDS epidemic. The widespread introduction of effective antiretrovirals to control HIV by restoring immunocompetence reduced the prevalence of AIDS-related KS, although KS does occur in individuals with well-controlled HIV infection. KS also presents in individuals without HIV infection in older men (classic KS), in sub-Saharan Africa (endemic KS) and in transplant recipients (iatrogenic KS).

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Background: Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART.

Methods: Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy "as-needed" arm) vs ART plus up to 8 cycles of oral ET (immediate arm).

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Objective: Geographic and racial disparities may contribute to variation in the incidence and outcomes of HIV-associated cancers in the United States.

Method: Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed Kaposi sarcoma (KS) incidence and survival by race and geographic region during the combined antiretroviral therapy era. Reported cases of KS in men from 2000 to 2013 were obtained from 17 SEER cancer registries.

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The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (<30, 30-39, 40-49, 50-59, and >60 years) was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER) program.

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Vascular endothelial growth factor (VEGF) plays an important role in Kaposi's sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received 3 different doses of PTC299.

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Cancers associated with immunosuppression and infections have long been recognized as a major complication of HIV/AIDS. More recently, persons living with HIV are increasingly diagnosed with a wider spectrum of HIV-associated malignancies (HIVAM) as they live longer on combination antiretroviral therapy. This has spurred research to characterize the epidemiology and determine the optimal management of HIVAM with a focus on low-and middle-income countries (LMICs).

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Purpose: 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.

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We studied the presence of Kaposi sarcoma herpesvirus sequences in cell-free DNA (cfDNA) isolated from the blood of patients with AIDS-related Kaposi sarcoma (KS) and primary effusion lymphoma (PEL). The use of paramagnetic beads linked to methyl-CpG binding domain protein allowed separation of virion and cell-derived DNA. Only virion DNA was detected in the blood of KS patients, whereas cell-derived DNA was detected in a patient with AIDS-related PEL.

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Purpose: The mammalian target of rapamycin is activated in Kaposi sarcoma (KS) and its inhibitor, rapamycin, has induced KS regression in transplant-associated KS. This study aimed to evaluate rapamycin's safety and toxicity in HIV-infected individuals with KS receiving antiretroviral therapy (ART), investigate rapamycin interactions with both protease inhibitor (PI)-containing and nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing ART regimens, and assess clinical and biological endpoints including KS response and mammalian target of rapamycin-dependent signaling.

Methods: Seven participants, 4 on PI-based and 3 on NNRTI-based ART, had rapamycin titrated to achieve trough concentrations of 5-10 ng/mL.

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Purpose Of Review: The purpose of this review is to summarize recent published literature on treatment of AIDS-associated Kaposi sarcoma, the most common HIV-associated malignancy and a leading cancer diagnosis in sub-Saharan Africa (SSA), and to highlight the challenges faced in treating Kaposi sarcoma in this resource-limited environment.

Recent Findings: There are few prospective clinical trials for Kaposi sarcoma treatment in SSA, along with a relatively poor cancer treatment infrastructure, leading to late diagnosis and poor access to therapy. The only prospectively randomized trial of chemotherapy compared antiretroviral therapy (HAART) alone to HAART with combination chemotherapy with doxorubicin, bleomycin and vincristine (ABV), and documented a significantly higher rate of tumor regression for the combination along with improvement in quality of life and no adverse effects on HIV control.

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We conducted a clinical trial of oral valganciclovir, a drug with in vitro activity against Kaposi sarcoma (KS)-associated herpesvirus (KSHV), in classic KS. Five human immunodeficiency virus-seronegative participants received valganciclovir for up to six 4-week cycles at doses used for cytomegalovirus infection. None of the study subjects showed an objective response; KS progressed in 4 subjects after 1-4 cycles and remained stable in 1 subject after 6 cycles.

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Purpose: Paclitaxel, a cytotoxic agent metabolized by cytochrome P450 hepatic enzymes, is active for the treatment of human immunodeficiency (HIV) associated Kaposi's sarcoma. Protease inhibitors are commonly used to treat HIV infection and are known to inhibit cytochrome P450. We sought to determine whether protease inhibitors alter the pharmacokinetics of paclitaxel.

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