71 results match your criteria: "Joint Clinical Research Center[Affiliation]"

Enhanced Prophylaxis plus Antiretroviral Therapy for Advanced HIV Infection in Africa.

N Engl J Med

July 2017

From the University of Zimbabwe Clinical Research Center, Harare, Zimbabwe (J.H., M.B.-D., G.M., K.N.); Joint Clinical Research Center, Kampala (V.M., C.K., P.M.), Mbarara (A.L.), and Fort Portal (S. Kabahenda) - all in Uganda; Medical Research Council Clinical Trials Unit at University College London (A.J.S., S.L.P., A.G., M.J.T., A.S.W., D.M.G.), Wellcome Trust Centre for Clinical Tropical Medicine and Department of Paediatrics, Imperial College (K.M.), and Queen Mary University of London (A.J.P.), London, and the Centre for Health Economics, University of York, York (S.W.) - all in the United Kingdom; the Department of Medicine and Malawi-Liverpool-Wellcome Trust Clinical Research Program, Blantyre, Malawi (J.M., S. Kaunda); and Moi University School of Medicine, Eldoret (A.S., M.K.), and the Kenya Medical Research Institute (KEMRI) Wellcome Trust Research Program, Kilifi (C.A., K.M.) - both in Kenya.

Article Synopsis
  • In sub-Saharan Africa, about 10% of patients with advanced HIV infection die soon after starting antiretroviral therapy (ART), often due to infections like tuberculosis and cryptococcus.
  • A clinical trial in Uganda, Zimbabwe, Malawi, and Kenya involved HIV-infected adults and children starting ART, randomizing participants to receive either enhanced or standard prophylaxis, alongside other treatments, to see how it affected mortality rates after 24 and 48 weeks.
  • The results showed that enhanced prophylaxis significantly reduced the mortality rate at 24 weeks (8.9% vs. 12.2%) and continued to show a lower death rate at 48 weeks, indicating better patient outcomes with the enhanced treatment regimen.
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Background: CD4 T-cells expressing Foxp3 are expanded systemically during active tuberculosis (TB) regardless of HIV-1 co-infection. Foxp3 CD4 T cells are targets of HIV-1 infection. However, expansion of HIV-1 infected Foxp3 CD4 T cells at sites of HIV/TB co-infection, and whether they contribute to promotion of HIV-1 viral activity is not known.

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Background: Couple HIV Counseling and Testing (CHCT) is one of the key preventive strategies used to reduce the spread of HIV. In Uganda, HIV prevalence among married/living together is 7.2% among women and 7.

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Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and is accentuated in HIV/TB co-infected patients. The contribution of immune activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count, and productive HIV-1 infection remain unclear. In this study, we measured markers of immune activation both in pleural fluid and plasma, and in T cells in pleural fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in HIV/TB co-infected subjects.

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Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

Clin Infect Dis

December 2016

Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles.

Background:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.

Methods:  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer.

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Psychological distress is common among adolescents living with HIV (ALHIV) worldwide, and has been associated with non-adherence to anti-retroviral therapy (ART), leading to poor virologic suppression, drug resistance, and increased risk for AIDS morbidity and mortality. However, only a few studies have explored the relationship between psychological distress and ART adherence among adolescents in sub-Saharan Africa. The paper examines the relationship between psychological distress and ART adherence, and effect of psychosocial resources on ART adherence.

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Background: Over the last 20 years, countries in sub Saharan Africa have made significant strides in the implementation of programs for HIV prevention, care and treatment. Despite, the significant progress made, many targets set by the United Nations have not been met. There remains a large gap between the ideal and what has been achieved.

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Background: WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low-cost, qualitative viral-failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda.

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A higher human immunodeficiency virus 1 (HIV-1) viral load at pleural sites infected with Mycobacterium tuberculosis (MTB) than in peripheral blood has been documented. However, the cellular source of productive HIV infection in HIV-1/MTB-coinfected pleural fluid mononuclear cells (PFMCs) remains unclear. In this study, we observed significant quantities of HIV-1 p24(+) lymphocytes in PFMCs, but not in peripheral blood mononuclear cells (PBMCs).

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Bovine tuberculosis (BTB), a zoonotic infection of cattle caused by Mycobacterium bovis, results in losses of $3 billion to the global agricultural industry and represents the fourth most important livestock disease worldwide. M. bovis as a source of human infection is likely underreported due to the culture medium conditions used to isolate the organism from sputum or other sample sources.

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Brief Report: Prevalence of Latent Rheumatic Heart Disease Among HIV-Infected Children in Kampala, Uganda.

J Acquir Immune Defic Syndr

February 2016

*Case Western Reserve University School of Medicine, Cleveland, OH; †University Hospitals Case Medical Center, Cleveland, OH; ‡Joint Clinical Research Center, Kampala, Uganda; §Makerere University School of Medicine, Kampala, Uganda; and ‖Uganda Heart Institute, Kampala, Uganda.

Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained settings around the world, including countries with high rates of HIV/AIDS. Although both are immune-mediated diseases, it is unknown whether HIV modifies the risk or progression of RHD. We performed screening echocardiography to determine the prevalence of latent RHD in 488 HIV-infected children aged 5-18 in Kampala, Uganda.

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Sites of HIV/TB coinfection are characterized by increased HIV-1 replication and a TH1 profile. However, expression of HIV-1 restriction factors, such as APOBEC3G (A3G) in situ, is unknown. Using an RT-profiler focused on genes related to HIV-1 expansion, we examined pleural fluid mononuclear cells (PFMCs) from patients with HIV/TB coinfection in comparison to HIV-uninfected patients with TB disease.

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Mental health and support among young key populations: an ecological approach to understanding and intervention.

J Int AIDS Soc

April 2016

Center for Sexuality and Health Disparities, Department of Health Behavior and Health Education, University of Michigan, Ann Arbor, MI, USA.

Introduction: The patterning of the HIV epidemic within young key populations (YKPs) highlights disproportionate burden by mental disorders in these populations. The mental wellbeing of YKPs is closely associated with biological predispositions and psychosocial factors related to YKPs' sexual and gender identities and socio-economic status. The purpose of this paper is to highlight sources of risk and resilience, as well as identify treatment and supports for mental health disorders (MHDs) among YKPs.

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In STRIDE, slow metabolizer CYP2B6 and NAT2 genotypes were each associated with increased plasma efavirenz concentrations during antituberculosis therapy. Concentrations were greater on therapy than off therapy in 58% with CYP2B6 and 93% with NAT2 slow metabolizer genotypes. Individuals with slow metabolizer genotypes in both genes had markedly elevated concentrations.

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Aims: The World Heart Federation (WHF) guidelines for rheumatic heart disease (RHD) are designed for a standard portable echocardiography (STAND) machine. A recent study in a tertiary care centre demonstrated that they also had good sensitivity and specificity when modified for use with handheld echocardiography (HAND). Our study aimed to evaluate the performance of HAND for early RHD diagnosis in the setting of a large-scale field screening.

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Article Synopsis
  • - This study investigated the impacts of T-cell activation, viral load, and virus subtype on HIV disease progression in Ugandan patients, finding that while activated T cells were more frequent in HIV-infected individuals, their levels did not significantly differ by virus subtype.
  • - Results showed that a higher viral load, older age, and subtype D were linked to faster progression to AIDS or death, with viral load being the strongest predictor of disease progression in the cohort studied.
  • - The findings imply that factors influencing disease progression in Europe and North America may not apply to East Africa, where HIV-1 load is the key factor determining health outcomes.
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Mortality and immunological recovery among older adults on antiretroviral therapy at a large urban HIV clinic in Kampala, Uganda.

J Acquir Immune Defic Syndr

December 2014

*Infectious Disease Institute, Makerere University, Kampala, Uganda; †Joint Clinical Research Center, Kampala, Uganda; ‡University of Michigan, Ann Arbor, MI; §College of Health Sciences, Makerere University, Kampala, Uganda; and ‖University of Sydney, Sydney, Australia.

Background: We describe older (>50 years) HIV-infected adults after antiretroviral therapy (ART) initiation, evaluating immunological recovery by age category, considering individual trajectories based on the pretreatment CD4. We also describe mortality on ART and its risk factors by age category including the contribution of poor immunological recovery at a large urban clinic in Kampala, Uganda.

Methods: We performed a cohort analysis of adult (>18 years) HIV-infected patients who initiated ART between January 1, 2004 and January 3, 2012.

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A randomized trial of prolonged co-trimoxazole in HIV-infected children in Africa.

N Engl J Med

January 2014

University of Zimbabwe, College of Health Sciences, Harare (M.B.-D., K.N., T.M.); the Medical Research Council Clinical Trials Unit at University College London (L.K., M.J.S., D.M.G., A.S.W., A.J.P.) and Centre for Paediatrics, Blizard Institute, Queen Mary, University of London (A.J.P.), London; and the Paediatric Infectious Diseases Clinic of Baylor Uganda, Mulago Hospital (S.B.-K., A.K., P.K.), and Joint Clinical Research Center (R.K., V.M.), Kampala, and the Medical Research Council and Uganda Virus Research Institute, Uganda Research Unit on AIDS, Entebbe (P.N.-N., J.L., P.M.) - all in Uganda.

Background: Co-trimoxazole (fixed-dose trimethoprim-sulfamethoxazole) prophylaxis administered before antiretroviral therapy (ART) reduces morbidity in children infected with the human immunodeficiency virus (HIV). We investigated whether children and adolescents receiving long-term ART in sub-Saharan Africa could discontinue co-trimoxazole.

Methods: We conducted a randomized, noninferiority trial of stopping versus continuing daily open-label co-trimoxazole in children and adolescents in Uganda and Zimbabwe.

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Immunogenicity of ALVAC-HIV vCP1521 in infants of HIV-1-infected women in Uganda (HPTN 027): the first pediatric HIV vaccine trial in Africa.

J Acquir Immune Defic Syndr

March 2014

*Medical Research Council/Uganda Virus Research Institute, Entebbe, Uganda; †SCHARP, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA; ‡Viral and Rickettsial Disease Laboratory, Richmond, CA; §Joint Clinical Research Center, Kampala, Uganda; ‖Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; ¶Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda; #Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda; **George Washington University School of Public Health and Health Services, Washington, DC; ††FHI 360, Durham, NC; and ‡‡Sanofi Pasteur, Discovery Drive, Swiftwater, PA.

Objective: Maternal-to-child-transmission of HIV-1 infection remains a significant cause of HIV-1 infection despite successful prevention strategies. Testing protective HIV-1 vaccines remains a critical priority. The immunogenicity of ALVAC-HIV vCP1521 (ALVAC) in infants born to HIV-1-infected women in Uganda was evaluated in the first pediatric HIV-1 vaccine study in Africa.

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Background: Bacteremia is common in HIV-infected children in Africa, including after start of antiretroviral therapy (ART), but there are limited data on causative pathogens and their antimicrobial sensitivity patterns in this population.

Methods: We analyzed data on blood cultures taken from HIV-infected children developing acute febrile illness after enrollment to the Antiretroviral Research for Watoto (ARROW) clinical trial in Uganda and Zimbabwe. Patterns of bacterial pathogens and their antimicrobial susceptibilities were determined and bacteremia rates calculated over time from ART initiation.

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Convenient, non-food-dependent dosing, low tablet volume, and relatively low cost have made nonnucleoside reverse transcriptase inhibitors a first choice for both clinicians and patients in Uganda. Concerns exist as to their efficacy in patients with viral loads (VL) above 100,000 copies/ml, a feature common to about 75% of HIV-1-infected patients presenting at the Joint Clinical Research Center (JCRC) in Uganda. Furthermore, there are few data on the response to such therapy of non-B subtypes, A and D, predominant in Uganda.

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