Breast Health Awareness: Understanding Health-Seeking Behavior in Western Kenya.

INTRODUCTION: In Kenya, patients with breast cancer predominantly present with late-stage disease and experience poor outcomes. To promote early-stage diagnosis, we implemented the Academic Model Providing Access to Healthcare (AMPATH) Breast and Cervical Cancer Control Program (ABCCCP) in Western Kenya. OBJECTIVE: The aim of this study was to assess differences between patients presenting to health facilities and health fairs. METHODS: This was an institutional Review and Ethics Commitee-approved retrospective cohort study of all individuals who underwent clinical breast examination (CBE) via local healthcare workers in Western Kenya. From 2017 to 2021, the program hosted health fairs, and trained healthcare providers at health facilities to complete CBEs. Results were analyzed using the Chi-square and Kruskal-Wallis tests, with an α < 0.05. RESULTS: Over a 5-year period, the ABCCCP completed 61,812 CBEs with 75.9% (n = 46,902) performed at a health facility. Patients presenting to health fairs were older (44 vs. 38 years; p < 0.0001) and had higher risk factor rates including early menarche, family history of breast and ovarian cancer, and use of alcohol or smoking. Only 27.6% of patients with an abnormal CBE underwent core needle biopsy, and only 5.2% underwent repeat CBE over the 5-year period, of whom 90.3% presented to health facilities. CONCLUSIONS: Successful uptake of CBE through the ABCCCP is the first step to introduce breast health awareness (BHA). Benefits of broad advertisements for health fairs in promoting BHA may be limited to a single event. Poor rates of repeat examinations and diagnostic testing of abnormal CBEs indicate additional resources should be allocated to educating patients, including about possible treatment trajectories for breast cancer.

Risk of Bleeding Associated With Outpatient Use of Rivaroxaban in VTE Management at a National Referral Hospital in Western Kenya.

There is limited data on the bleeding safety profile of direct oral anticoagulants, such as rivaroxaban, in low- and middle-income country settings like Kenya. In this prospective observational study, patients newly started on rivaroxaban or switching to rivaroxaban from warfarin for the management of venous thromboembolism (VTE) within the national referral hospital in western Kenya were assessed to determine the frequency of bleeding during treatment. Bleeding events were assessed at the 1- and 3-month visits, as well as at the end of follow-up. The International Society of Thrombosis and Hemostasis (ISTH) and the Bleeding Academic Research Consortium (BARC) criteria were used to categorize the bleeding events, and descriptive statistics were used to summarize categorical variables. Univariate and multivariate logistic regression model was used to calculate unadjusted and adjusted associations between patient characteristics and bleeding. The frequency of any type of bleeding was 14.4% (95% CI: 9.3%-20.8%) for an incidence rate of 30.9 bleeding events (95% CI: 20.1-45.6) per 100 patient-years of follow-up. The frequency of major bleeding was 1.9% while that of clinically relevant non-major bleeding was 13.8%. In the multivariate logistic regression model, being a beneficiary of the national insurance plan was associated with a lower risk of bleeding, while being unemployed was associated with a higher bleeding risk. The use of rivaroxaban in the management of VTE was associated with a higher frequency of bleeding. These findings warrant confirmation in larger and more targeted investigations in a similar population.

Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings.

BACKGROUND: Guidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking. SETTING: We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART. METHODS: Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART. RESULTS: Pretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment. CONCLUSIONS: Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.

Telehospice for Cancer Patients Discharged from a Tertiary Care Hospital in Western Kenya.

CONTEXT: Worldwide, most patients lack access to hospice services. OBJECTIVES: Assess the feasibility of telephone monitoring (Telehospice) in providing symptom management for patients discharged from a tertiary care hospital in Western Kenya. METHODS: Inclusion criteria included adults with cancer no longer eligible for chemo-radiation and receiving opioid therapy. Thirty patients were enrolled in a weekly monitoring program assessing physical symptoms and patient and caregiver distress. The participants also had access to a 24-hour hotline. Symptom assessment included 18 questions with 8 from the African Palliative Outcome Scale. Participants were followed for eight weeks or until death or admission to an inpatient hospital or hospice. RESULTS: The primary objective was participation in weekly calls, and we obtained 100% participation. A secondary objective was the use of "comfort kits" which contained 30 doses of six medications. Most patients utilized one or more of the provided medications, with high usage of bisacodyl, paracetamol, and omeprazole. While 12% of weekly calls and 24% of hotline calls led to medication changes, participants continued to express worry and there was only a modest decrease in pain scores despite having morphine available throughout the follow-up period. Family confidence in providing care and access to information remained high. At the end of the eight-weeks of observation, eight participants were alive, 10 died at home, and 12 were admitted to an in-patient facility. CONCLUSION: Patient and family participation in Telehospice is feasible and may provide an interim solution to managing end-of-life patients who lack access to home hospice.

Barriers and facilitators to chemotherapy initiation and adherence for patients with HIV-associated Kaposi's sarcoma in Kenya: a qualitative study.

BACKGROUND: Kaposi sarcoma is one of the most prevalent HIV-associated malignancies in sub-Saharan Africa and is often diagnosed at advanced stage of disease. Only 50% of KS patients who qualify for chemotherapy receive it and adherence is sub-optimal. METHODS: 57 patients > 18 years with newly diagnosed KS within the AMPATH clinic network in Western Kenya were purposively selected to participate in semi-structured interviews stratified by whether they had completed, partially completed, or not completed chemotherapy for advanced stage KS. We based the interview guide and coding framework on the situated Information, Motivation, Behavioral Skills (sIMB) framework, in which the core patient centered IMB constructs are situated into the socioecological context of receiving care. RESULTS: Of the 57 participants, the median age was 37 (IQR 32-41) and the majority were male (68%). Notable barriers to chemotherapy initiation and adherence included lack of financial means, difficulty with convenience of appointments such as distance to facility, appointment times, long lines, limited appointments, intrapersonal barriers such as fear or hopelessness, and lack of proper or sufficient information about chemotherapy. Factors that facilitated chemotherapy initiation and adherence included health literacy, motivation to treat symptoms, improvement on chemotherapy, prioritization of self-care, resilience while experiencing side effects, ability to carry out behavioral skills, obtaining national health insurance, and free chemotherapy. CONCLUSION: Our findings about the barriers and facilitators to chemotherapy initiation and adherence for KS in Western Kenya support further work that promotes public health campaigns with reliable cancer and chemotherapy information, improves education about the chemotherapy process and side effects, increases oncology service ability, supports enrollment in national health insurance, and increases incorporation of chronic disease care into existing HIV treatment networks.

Evaluation of four chemotherapy regimens for treatment of advanced AIDS-associated Kaposi sarcoma in Kenya: a cost-effectiveness analysis.

BACKGROUND: The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan Africa due to limited availability and high cost. We examined the clinical impact, costs, and cost-effectiveness of paclitaxel or PLD in Kenya, compared with etoposide or bleomycin-vincristine. METHODS: In this study, we use the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International Model to project clinical outcomes and costs among people living with HIV and advanced Kaposi sarcoma on antiretroviral therapy. We compared four different treatment strategies: etoposide, bleomycin-vincristine, paclitaxel, or PLD. We derived cohort characteristics and costs from the Kenyan Academic Model for Providing Access to Healthcare network, and adverse events, efficacy, and mortality from clinical trials. We projected model outcomes over a lifetime and included life expectancy, per-person lifetime costs, and incremental cost-effectiveness ratios (ICERs). We conducted budget impact analysis for 5-year total costs and did deterministic and probabilistic sensitivity analyses to evaluate the effect of uncertainty in input parameters. FINDINGS: We found that paclitaxel would be more effective than bleomycin-vincristine and would increase life expectancy by 4·2 years per person. PLD would further increase life expectancy by 0·6 years per person. Paclitaxel would be the most cost-effective strategy (ICER US$380 per year-of-life-saved compared with bleomycin-vincristine) and would remain cost-effective across a range of scenarios. PLD would be cost-effective compared with paclitaxel if its price were reduced to $100 per cycle (base case $180 per cycle). Implementing paclitaxel instead of bleomycin-vincristine would save approximately 6400 life-years and would increase the overall 5-year Kenyan health-care costs by $3·7 million; increased costs would be primarily related to ongoing HIV care given improved survival. INTERPRETATION: Paclitaxel would substantially increase life expectancy and be cost-effective compared with bleomycin-vincristine for advanced AIDS-associated Kaposi sarcoma in Kenya and should be the standard of care. PLD would further improve survival and be cost-effective with a 44% price reduction. FUNDING: US National Institutes of Health and Massachusetts General Hospital. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.

Telling the story of intersectional stigma in HIV-associated Kaposi's sarcoma in western Kenya: a convergent mixed-methods approach.

INTRODUCTION: The experience of stigma can be multifaceted for people with HIV and cancer. Kaposi's sarcoma (KS), one of the most common HIV-associated cancers in sub-Saharan Africa, often presents with visible skin lesions that may put people at risk for stigmatization. In this way, HIV-associated KS is unique, as people with KS can experience stigma associated with HIV, cancer, and skin disease simultaneously. The aim of this study is to characterize the intersectionality of HIV-related, cancer-related and skin disease-related stigma in people living with HIV and KS. METHODS: We used a convergent mixed-methods approach nested within a longitudinal study of people with HIV-associated KS in western Kenya. Between February 2019 and December 2020, we collected quantitative surveys among all participants and conducted semi-structured interviews among a purposive sample of participants. Quantitative surveys were adapted from the abridged Berger HIV Stigma Scale to assess overall stigma, HIV-related stigma, cancer-related stigma, and skin disease-related stigma. Qualitative data were coded using stigma constructs from the Health Stigma and Discrimination Framework. RESULTS: In 88 semi-structured interviews, stigma was a major barrier to KS diagnosis and treatment among people with HIV-associated KS. Participant's stories of stigma were dominated by HIV-related stigma, more than cancer-related or skin disease-related stigma. However, quantitative stigma scores among the 117 participants were similar for HIV-related (Median: 28.00; IQR: 28.0, 34.0), cancer-related (Median: 28.0; IQR: 28.0, 34.8), and skin disease-related stigma (Median: 28.0; IQR: 27.0, 34.0). In semi-structured interviews, cancer-related and skin disease-related stigma were more subtle contributors; cancer-related stigma was linked to fatalism and skin-related stigma was linked to visible disease. Participants reported resolution of skin lesions contributed to lessening stigma over time; there was a significant decline in quantitative scores of overall stigma in time since KS diagnosis (adjusted ß = -0.15, p <0.001). CONCLUSIONS: This study highlights the role mixed-method approaches can play in better understanding stigma in people living with both HIV and cancer. While HIV-related stigma may dominate perceptions of stigma among people with KS in Kenya, intersectional experiences of stigma may be subtle, and quantitative evaluation alone may be insufficient to understand intersectional stigma in certain contexts.

Understanding Diagnostic Delays for Kaposi Sarcoma in Kenya: A Qualitative Study.

BACKGROUND: Although HIV-associated Kaposi sarcoma (KS) is frequently diagnosed at an advanced stage in sub-Saharan Africa, reasons for diagnostic delays have not been well described. METHODS: We enrolled patients >18 years with newly diagnosed KS between 2016 and 2019 into the parent study, based in western Kenya. We then purposively selected 30 participants with diversity of disease severity and geographic locations to participate in semistructured interviews. We used 2 behavioral models in developing the codebook for this analysis: situated Information, Motivation, and Behavior framework and Andersen model of total patient delay. We then analyzed the interviews using framework analysis. RESULTS: The most common patient factors that delayed diagnosis were lack of KS awareness, seeking traditional treatments, lack of personal efficacy, lack of social support, and fear of cancer, skin biopsy, amputation, and HIV diagnosis. Health system factors that delayed diagnosis included previous negative health care interactions, incorrect diagnoses, lack of physical examination, delayed referral, and lack of tissue biopsy availability. Financial constraints were prominent barriers for patients to access and receive care. Facilitators for diagnosis included being part of an HIV care network, living near health facilities, trust in the health care system, desire to treat painful or disfiguring lesions, and social support. CONCLUSIONS: Lack of KS awareness among patients and providers, stigma surrounding diagnoses, and health system referral delays were barriers in reaching KS diagnosis. Improved public health campaigns, increased availability of biopsy and pathology facilities, and health provider training about KS are needed to improve early diagnosis of KS.

Compression Therapy for HIV-Associated Kaposi Sarcoma Leg Lymphedema: Results of the Kenyan Improvised Compression for Kaposi Sarcoma Randomized Controlled Trial.

PURPOSE: Evaluate the effectiveness of compression while receiving chemotherapy compared with chemotherapy alone in the treatment of HIV-associated Kaposi sarcoma (KS) lymphedema. METHODS: A randomized controlled trial was conducted in a single oncology clinic in western Kenya (NCT03404297). A computer-generated randomization schedule was used to allocate treatment arms. Randomized block design was used for stratification by lymphedema stage. Participants were HIV positive adults age ≥ 18 years on antiretroviral therapy with biopsy-proven KS associated with leg lymphedema and being initiated on chemotherapy. The intervention was 10 weeks of weekly clinic-based application of two-component paste compression bandages. The primary outcome was change in the Lower Extremity Lymphedema Index (LELI) score from week 0 to week 14. The secondary outcomes were change in the Lymphedema Quality of Life measure (LYMQOL) and change in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 score from week 0 to week 14. Blinded outcome assessments were conducted. RESULTS: Of 30 participants randomly assigned, 25 eligible patients (chemotherapy [control], n = 13; compression plus chemotherapy [intervention], n = 12) returned at week 14. Change in LELI, LYMQOL, and EORTC QLQ-C30 scores between week 14 and week 0 did not significantly differ by arm. The mean (standard deviation) change in LELI score was -25.9 (34.6) for the control arm compared with -13.3 (29.5) for the intervention arm, P = .340. The difference (95% CI) in the change in LELI score was -12.6 (-39.3 to 14.1). CONCLUSION: Future studies evaluating a 14-week change in LELI for KS lymphedema should assume a standard deviation of approximately 30. Lessons learned from this pilot trial should inform the development of a larger, multicenter trial to evaluate the effectiveness of compression for KS lymphedema.

Feasibility of Rapid Case Ascertainment for Cancer in East Africa: An Investigation of Community-Representative Kaposi Sarcoma in the Era of Antiretroviral Therapy.

BACKGROUND: Rapid case ascertainment (RCA) refers to the expeditious and detailed examination of patients with a potentially rapidly fatal disease shortly after diagnosis. RCA is frequently performed in resource-rich settings to facilitate cancer research. Despite its utility, RCA is rarely implemented in resource-limited settings and has not been performed for malignancies. One cancer and context that would benefit from RCA in a resource-limited setting is HIV-related Kaposi sarcoma (KS) in sub-Saharan Africa. METHODS: To determine the feasibility of RCA for KS, we searched for all potential newly diagnosed KS among HIV-infected adults attending three community-based facilities in Uganda and Kenya. Searching involved querying of electronic medical records, pathology record review, and notification by clinicians. Upon identification, a team verified eligibility and attempted to locate patients to perform RCA, which included epidemiologic, clinical and laboratory measurements. RESULTS: We identified 593 patients with suspected new KS. Of the 593, 171 were ineligible, mainly because biopsy failed to confirm KS (65%) or KS was not new (30%). Among the 422 remaining, RCA was performed within 1 month for 56% of patients and within 3 months for 65% (95% confidence interval: 59 to 70%). Reasons for not performing RCA included intervening death (47%), inability to contact (44%), refusal/unsuitable to consent (8.3%), and patient re-location (0.7%). CONCLUSIONS: We found that RCA - an important tool for cancer research in resource-rich settings - is feasible for the investigation of community-representative KS in East Africa. Feasibility of RCA for KS suggests feasibility for other cancers in Africa.

Beyond T Staging in the "Treat-All" Era: Severity and Heterogeneity of Kaposi Sarcoma in East Africa.

BACKGROUND: Although many patients with Kaposi sarcoma (KS) in sub-Saharan Africa are diagnosed with AIDS Clinical Trials Group (ACTG) T1 disease, T1 staging insufficiently captures clinical heterogeneity of advanced KS. Using a representative community-based sample, we detailed disease severity at diagnosis to inform KS staging and treatment in sub-Saharan Africa. METHODS: We performed rapid case ascertainment on people living with HIV, aged 18 years or older, newly diagnosed with KS from 2016 to 2019 at 3 clinic sites in Kenya and Uganda to ascertain disease stage as close as possible to diagnosis. We reported KS severity using ACTG and WHO staging criteria and detailed measurements that are not captured in the current staging systems. RESULTS: We performed rapid case ascertainment within 1 month for 241 adults newly diagnosed with KS out of 389 adult patients with suspected KS. The study was 68% men with median age 35 years and median CD4 count 239. Most of the patients had advanced disease, with 82% qualifying as ACTG T1 and 64% as WHO severe/symptomatic KS. The most common ACTG T1 qualifiers were edema (79%), tumor-associated ulceration (24%), extensive oral KS (9%), pulmonary KS (7%), and gastrointestinal KS (4%). There was marked heterogeneity within T1 KS, with 25% of patients having 2 T1 qualifying symptoms and 3% having 3 or more. CONCLUSION: Most of the patients newly diagnosed with KS had advanced stage disease, even in the current antiretroviral therapy "treat-all" era. We observed great clinical heterogeneity among advanced stage patients, leading to questions about whether all patients with advanced KS require the same treatment strategy.

Challenges of HIV Lymphoma Clinical Trials in Africa: Lessons From the AIDS Malignancy Consortium 068 Study.

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. In 2018, the study closed after screening 42 patients but enrolling only 7. Challenges occurred during protocol development, pre-activation, and postactivation. During protocol development (2011-2012), major obstacles were limited baseline data to inform study design; lack of consensus among investigators and approving bodies regarding appropriateness of the oral regimen and need for randomized comparison with cyclophosphamide, doxorubicin, vincristine, and prednisone; and heterogeneity across sites in local standards for diagnosis, staging, and treatment. During pre-activation (2012-2016), challenges included unexpected length and layers of regulatory approval across multiple countries, need to upgrade pathology capacity at sites, need to augment existing chemotherapy infusion capacity at sites, and procurement issues for drugs and supplies. Finally, during postactivation (2016-2018), challenges included long delays between symptom onset and screening entry for many patients, leading to compromised performance status and organ function; other patient characteristics that frequently led to exclusion, including high tumor proliferative index or other pathologic features that were disallowed; and costs of routine diagnostic procedures often being borne by patients, which also contributed to pre-enrollment delays. Lessons from AMC-068 are being applied to the design and conduct of new AMC lymphoma trials in SSA, and the study has contributed to a strong operational foundation that will support innovative clinical trials in the future.

Clinical Trials for Treatment and Prevention of HIV-Associated Malignancies in Sub-Saharan Africa: Building Capacity and Overcoming Barriers.

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. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives. RESULTS: Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region. CONCLUSION: As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA.

Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial.

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. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018. FINDINGS: 334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were -30% (95% CI -52 to -8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and -20% (-33% to -7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms. INTERPRETATION: Non-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings. FUNDING: US National Institute of Allergy and Infectious Diseases and National Cancer Institute, National Institutes of Health.

Real-world use of chemotherapy for Kaposi's sarcoma in a large community-based HIV primary care system in Kenya.

BACKGROUND: Kaposi's sarcoma (KS) is one of the most common HIV-associated malignancies in sub-Saharan Africa. Worldwide, the availability of antiretroviral therapy (ART) has improved KS survival. In resource-rich settings, survival has also benefited from chemotherapy, which is widely available. Little is known, however, about the epidemiology of chemotherapy use for HIV-associated KS in resource-limited regions such as sub-Saharan Africa. METHODS: We identified all patients newly diagnosed with HIV-related KS from 2009 to 2012 in the 26-clinic AMPATH network, a large community-based care network in Kenya. We ascertained disease severity at diagnosis, frequency of initiation of chemotherapy, and distribution of chemotherapeutic regimens used. Indications for chemotherapy included AIDS Clinical Trial Group T1 stage and/or "severe" disease defined by WHO KS treatment guidelines. RESULTS: Of 674 patients diagnosed with KS, charts were available for 588; 61% were men, median age was 35 years, and median CD4 at KS diagnosis was 185 cells/µl. At time of diagnosis, 58% had at least one chemotherapy indication, and 22% had more than one indication. For patients with a chemotherapy indication, cumulative incidence of chemotherapy initiation (with death as a competing event) was 37% by 1 month and 56% by 1 year. Median time from diagnosis to chemotherapy initiation was 25 days (IQR 1-50 days). In multivariable regression, patients with > 3 chemotherapy indications at time of diagnosis had a 2.30 (95% CI 1.46-3.60) increased risk of rapid chemotherapy initiation (within 30 days of diagnosis) compared to those with only one chemotherapy indication (p < 0.001). Initial regimens were bleomycin-vincristine (78%), adriamycin-bleomycin-vincristine (11%), etoposide (7%), and gemcitabine (4%). CONCLUSIONS: A substantial fraction of patients with KS in East Africa are diagnosed at advanced disease stage. For patients with chemotherapy indications, nearly half did not receive chemotherapy by one year. Liposomal anthracyclines, often used in resource-rich settings, were not first line. These findings emphasize challenges in East Africa cancer care, and highlight the need for further advocacy for improved access to higher quality chemotherapy in this setting.

Developing medical oncology in Africa.

BACKGROUND: Kenya, like most other developing countries, is undergoing an epidemiologic shift of disease patterns characterized by an increasing prevalence of cancer and other non-communicable diseases straining health care resources which were mainly intended for communicable diseases. We describe the development of sustainable cancer prevention and control programs at Moi University and Moi Teaching and Referral Hospital in Western Kenya. METHODS: The cancer prevention and control program at Moi Teaching and Referral Hospital was started by volunteer nurses and clinicians in 2005 in response to a high prevalence of AIDS-related Kaposi sarcoma. Chemotherapy was donated by a local drug store until 2007 when Eli Lilly pharmaceuticals from Indianapolis in the USA started helping the program through the Academic Model Providing Access to Healthcare (AMPATH). Due to good response rates of patients with AIDS-related Kaposi sarcoma, and lobbying by volunteers, the service became a formal department of Moi Teaching and Referral hospital in 2008. RESULTS: The department has now grown to become the second largest public cancer centre in the country registering about 9000 patient visits per year. In addition, staff have now specialized in various areas such as medical oncology, palliative care, surgical oncology, nursing and gynaecology oncology. CONCLUSIONS: The development of a medical oncology program requires a multi-disciplinary team focused on integration within existing programs and expansion of collaborative networks in order to provide the best care to patients.

Three year survival among patients with aids-related Kaposi sarcoma treated with chemotherapy and combination antiretroviral therapy at Moi teaching and referral hospital, Kenya.

BACKGROUND: AIDS-related Kaposi sarcoma (AIDS-KS), a common malignancy in Kenya is associated with high morbidity and mortality. AIDS-KS is treated using bleomycin and vincristine (BV) plus or minus doxorubicin in most low resource settings, with response rates ranging from 24.8 to 87%. Survival in low resource settings has not been well documented. We report the three-year survival in a cohort of seventy patients referred to Moi Teaching and Referral Hospital (MTRH). METHODS: Study participants are part of a randomized phase IIA trial on the use of gemcitabine compared to bleomycin plus vincristine for the treatment of Kaposi sarcoma after combination antiretroviral therapy (cART) in Western Kenya. All patients were followed for three years in MTRH. Survival was determined by three monthly physical examination and analysed using Kaplan-Meier method, while possible determinants of survival such as baseline characteristics, type of chemotherapy, initial CD4 counts, age at enrolment, gender and early response to chemotherapy were analysed using univariate and multivariate Cox regression. RESULTS: Participants were aged between 19 and 70 years with 56% being male. The median CD4 count was 224 cells/µl, median duration of HIV diagnosis was 12.0 months and median duration of KS lesions after histology diagnosis before initiating chemotherapy was 4.8 weeks. At three years, 60 (85.7%) patients were alive. Six of those who died were under treatment with BV while four with gemcitabine. There was no difference in the probability of survival between the patients on either treatment arm (HR = 0.573 [95% C. I 0.143, 2.292; p = 0.4311]). Additionally, the hazard ratio (HR) for response after six weeks, age at enrolment and gender indicated that they were not significant determinants of survival. Patients with normal CD4 cell counts (> = 500/µl), had a HR of 0.401(0.05,3.23; p = 0.391), suggesting better survival. CONCLUSIONS: Patients with AIDS-KS treated with combined antiretroviral drugs had excellent three-year survival regardless of whether they were treated with BV or gemcitabine as first line therapy. An initial CD4 cell count of > = 500/µl appeared to improve survival while gender, age and early response to chemotherapy were not predictors of survival after three years. TRIAL REGISTRATION: Number PACTR201510001.