SARS-CoV-2 cross-sectional serosurvey across three HIV-1 therapeutic clinical trials in Africa.

Objective: Data on the impact of COVID-19 in people living with HIV (PWH) are lacking in resource-constrained settings. We utilised existingrandomised clinical trials (RCTs) on antiretroviral therapies (ART) in HIV-1 infection to conduct a SARS-CoV-2 serosurvey, between January and March 2021, while characterising participants' features.

Design: Cross-sectional serosurvey.

Mortality and Associated Risk Factors Among People Living With HIV With Kaposi Sarcoma: A5263/AMC066 and A5264/AMC067.

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.

Associations between antiretroviral regimen and changes in blood pressure: results from the D2EFT study.

In this randomised, controlled study in 14 low- and middle-income countries, individuals taking dolutegravir with darunavir/ritonavir for 48 weeks had a greater increase in systolic and diastolic blood pressure than individuals taking two nucleoside reverse transcriptase with darunavir/ritonavir. The difference remained significant after controlling for confounding factors including weight gain.

Differential effects of antiretroviral treatment on immunity and gut microbiome composition in people living with HIV in rural versus urban Zimbabwe.

Background: The widespread availability of antiretroviral therapy (ART) has dramatically reduced mortality and improved life expectancy for people living with HIV (PLWH). However, even with HIV-1 suppression, chronic immune activation and elevated inflammation persist and have been linked to a pro-inflammatory gut microbiome composition and compromised intestinal barrier integrity. PLWH in urban versus rural areas of sub-Saharan Africa experience differences in environmental factors that may impact the gut microbiome and immune system, in response to ART, yet this has not previously been investigated in these groups.

Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.

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.

Metabolic and cardiovascular disease risk for Zimbabwean men with prostate cancer receiving long-term androgen deprivation therapy.

Introduction: Prostate cancer is a leading cause of cancer-related mortality in the majority of sub-Saharan Africa region countries. Androgen deprivation therapy (ADT) is effective treatment, however ADT is associated with complications including metabolic syndrome and cardiovascular disease. Although cardiovascular disease is a leading cause of mortality among prostate cancer patients, there is limited information on ADT impact on metabolic syndrome and cardiovascular disease risk among Africans.

Characterizing HIV status documentation among cancer patients at regional cancer centers in Malawi, Zimbabwe, and South Africa.

Introduction: In East and Southern Africa, people with HIV (PWH) experience worse cancer-related outcomes and are at higher risk of developing certain cancers. Siloed care delivery pathways pose a substantial barrier to co-management of HIV and cancer care delivery.

Methods: We conducted cross-sectional studies of adult cancer patients at public radiotherapy and oncology units in Malawi (Kamuzu Central Hospital), Zimbabwe (Parirenyatwa Group of Hospitals), and South Africa (Charlotte Maxeke Hospital) between 2018-2019.

Antiretroviral treatment is less effective at reducing gut microbiome-associated inflammation and T cell activation in people living with HIV in rural versus urban Zimbabwe.

The widespread availability of antiretroviral therapy (ART) for people living with HIV (PLWH) has dramatically reduced mortality and improved life expectancy. However, even with suppression of HIV-1 replication, chronic immune activation and elevated inflammation persist. Chronic immune activation has been linked to a pro-inflammatory gut microbiome composition, exacerbated by compromised intestinal barrier integrity that occurs after HIV infection.

Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study.

Background: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region.

Methods: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA.

Unfractionated Bulk Culture of Mouse Skeletal Muscle to Recapitulate Niche and Stem Cell Quiescence.

Skeletal muscle is the largest tissue of the body and performs multiple functions, from locomotion to body temperature control. Its functionality and recovery from injuries depend on a multitude of cell types and on molecular signals between the core muscle cells (myofibers, muscle stem cells) and their niche. Most experimental settings do not preserve this complex physiological microenvironment, and neither do they allow the ex vivo study of muscle stem cells in quiescence, a cell state that is crucial for them.

Overlapping functions of SIX homeoproteins during embryonic myogenesis.

Four SIX homeoproteins display a combinatorial expression throughout embryonic developmental myogenesis and they modulate the expression of the myogenic regulatory factors. Here, we provide a deep characterization of their role in distinct mouse developmental territories. We showed, at the hypaxial level, that the Six1:Six4 double knockout (dKO) somitic precursor cells adopt a smooth muscle fate and lose their myogenic identity.

Pharmacogenetics and Adverse Events in the Use of Fluoropyrimidine in a Cohort of Cancer Patients on Standard of Care Treatment in Zimbabwe.

Fluoropyrimidines are commonly used in the treatment of colorectal cancer. They are, however, associated with adverse events (AEs), of which gastrointestinal, myelosuppression and palmar-plantar erythrodysesthesia are the most common. Clinical guidelines are used for fluoropyrimidine dosing based on dihydropyrimidine dehydrogenase () genetic polymorphism and have been shown to reduce these AEs in patients of European ancestry.

Cardiotoxicity and pharmacogenetics of doxorubicin in black Zimbabwean breast cancer patients.

Aims: Doxorubicin-induced cardiotoxicity (DIC) is a significant cause of mortality in cancer care. This study was conducted to establish the frequency of DIC in Zimbabwean breast cancer patients on doxorubicin and to test the DIC predictive power of genetic biomarkers.

Methods: A cohort of 50 Zimbabwean breast cancer patients treated with doxorubicin were followed up for 12 months with serial echocardiography and genotyped for UGTA1A6*4, SLC28A3 and RARG.

Stakeholder perspectives on current determinants of ultrasound-guided thoracentesis in resource limited settings: a qualitative study.

Objective: Preprocedure pleural fluid localization using bedside ultrasound has been shown to reduce complications related to thoracentesis and is now considered the standard of care. However, ultrasound-guided thoracentesis (USGT) has not been broadly adopted in many low-resource settings. With increasing affordability and portability of ultrasound equipment, barriers to USGT are changing.

Evaluation of a training intervention to improve cancer care in Zimbabwe: Strategies to Improve Kaposi Sarcoma Outcomes (SIKO), a prospective community-based stepped-wedge cluster randomized trial.

Introduction: Most Zimbabweans access medical care through tiered health systems. In 2013, HIV care was decentralized to primary care clinics; while oncology care remained centralized. Most persons in Zimbabwe with Kaposi sarcoma (KS) are diagnosed late in their disease, and the prognosis is poor.

Obesity impairs skeletal muscle repair through NID-1 mediated extracellular matrix remodeling by mesenchymal progenitors.

Obesity triggers skeletal muscle physio-pathological alterations. However, the crosstalk between adipose tissue and myogenic cells remains poorly understood during obesity. We identified NID-1 among the adipose tissue secreted factors impairing myogenic potential of human myoblasts and murine muscle stem cells in vitro.

Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial.

Background: WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.

Methods: In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe.

Breast Cancer Diagnostics, Therapy, and Outcomes in Sub-Saharan Africa: A Population-Based Registry Study.

Background: Breast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival.

Compartmentalized T cell profile in the lungs of patients with HIV-1-associated pulmonary Kaposi sarcoma.

Pulmonary Kaposi sarcoma (pKS) caused by Human herpesvirus 8 (HHV-8) is a devastating form of KS in patients with advanced acquired immunodeficiency syndrome (AIDS) and is associated with increased morbidity and mortality. Blood T cells play a central role in the response of HIV-1 and HHV-8. However, little information is available on T cells in the alveolar space of HIV-1-associated pKS patients.

Cancer incidence among people living with HIV in Zimbabwe: A record linkage study.

Background: People living with HIV (PLWH) are at increased risk of developing cancer. Cancer diagnoses are often incompletely captured at antiretroviral therapy (ART) clinics.

Aim: To estimate the incidence and explore risk factors of cancer in a cohort of PLWH in Harare using probabilistic record linkage (PRL).

Castleman disease.

Castleman disease (CD), a heterogeneous group of disorders that share morphological features, is divided into unicentric CD and multicentric CD (MCD) according to the clinical presentation and disease course. Unicentric CD involves a solitary enlarged lymph node and mild symptoms and excision surgery is often curative. MCD includes a form associated with Kaposi sarcoma herpesvirus (KSHV) (also known as human herpesvirus 8) and a KSHV-negative idiopathic form (iMCD).