@article{Okello2019,

title = {Biomass fuel as a risk factor for esophageal squamous cell carcinoma: a systematic review and meta-analysis},

author = {Samson Okello and Suzan Joan Akello and Emmanuel Dwomoh and Emmanuel Byaruhanga and Christopher Kenneth Opio and Ruyang Zhang and Kathleen E. Corey and Winnie R. Muyindike and Ponsiano Ocama and David D. Christiani },

url = {https://ehjournal.biomedcentral.com/articles/10.1186/s12940-019-0496-0},

doi = {https://doi.org/10.1186/s12940-019-0496-0},

year  = {2019},

date = {2019-07-01},

journal = {Environmental Health },

volume = {18},

number = {1},

pages = {60},

abstract = {Abstract



Background

The link between use of solid biomass fuel (wood, charcoal, coal, dung, and crop residues) for cooking and/or heating and esophageal squamous cell carcinoma (ESCC) is inconclusive.



Objective

We systematically reviewed the literature and performed a meta-analysis to determine whether cooking fuel type influences esophageal squamous cell carcinoma.



Methods

We searched MEDLINE, EMBASE, Web of Knowledge and Cochrane Database of Systematic Reviews for studies investigating cooking fuel and ESCC from 2000 until March 2019. We performed random effects meta-analysis stratified by the continent, World Bank’s country income classifications and fuel type and calculated pooled odds ratios and 95% CIs for the risk of esophageal squamous cell carcinoma in biomass fuel users compared with non-users.



Results

Our analysis included 16 studies (all case-control) with 16,189 participants (5233 cases and 10,956 controls) that compared risk of ESCC among those using nonsolid fuels and biomass fuels. We found use of biomass fuel was associated with Esophageal squamous cell carcinoma with a pooled odds ratio (OR) 3.02 (95% CI 2.22, 4.11, heterogeneity (I2) = 79%). In sub-group analyses by continent, Africa (OR 3.35, 95%CI 2.34, 4.80, I2 = 73.4%) and Asia (OR 3.08, 95%CI 1.27, 7.43, I2 = 81.7%) had the highest odds of ESCC. Use of wood as fuel had the highest odds of 3.90, 95% CI 2.25, 6.77, I2 = 63.5%). No significant publication bias was detected.



Conclusions

Biomass fuel is associated with increased risk of Esophageal squamous cell carcinoma. Biomass fuel status should be considered in the risk assessment for Esophageal squamous cell carcinoma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{MR2019,

title = {Cerebrospinal Fluid and Brain Tissue Penetration of Tenofovir, Lamivudine, and Efavirenz in Postmortem Tissues with Cryptococcal Meningitis},

author = {Nicol MR and Pastick KA and Taylor J and Namuju OC and Rhein J and Williams DA and Meya DB and Boulware DR and Lukande R. },

url = {https://ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.12661},

doi = { https://doi.org/10.1111/cts.12661},

year  = {2019},

date = {2019-06-17},

journal = {Clinical and Translational Science},

abstract = {

Abstract



The central nervous system (CNS) is a known HIV reservoir, yet little is known about drug exposure in the brain. Our primary objective was to quantify exposure of three common antiretrovirals in brain tissue and compare exposures to plasma and cerebrospinal fluid (CSF). We also sought to identify pockets of brain most vulnerable to inadequate drug exposures and examine the role of meningitis in drug penetration into the CNS. Tenofovir, lamivudine, and efavirenz concentrations were measured using liquid chromatography and tandem mass spectrometry in plasma and CSF from 14 individuals with HIV, 7 with cryptococcal meningitis. In four individuals (three with meningitis) drug concentrations were also measured in 13 distinct brain tissue regions. In subjects with meningitis, geometric mean ratio (95% confidence interval) of tenofovir CSF to plasma was 66% (7–598%) and 14% (6–31%) in subjects without meningitis. Lamivudine CSF penetration was 100% (25–409%) in subjects with meningitis and 30% (24–37%) in subjects without meningitis. Tenofovir brain tissue concentrations were 36% (14–124%) of plasma and 49% (1–572%) of CSF. Lamivudine brain concentrations were 37% (23–64%) of plasma and 27% (1–104%) of CSF. Efavirenz brain tissue concentrations were 128% (108–179%) of plasma. Tissues collected postmortem provide a unique opportunity to assess drug distribution in tissues difficult to sample in living subjects. CSF is a poor surrogate for drug exposure throughout the CNS. Antiretrovirals differentially penetrate into the CNS and penetration may be enhanced by meningitis.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{S2019k,

title = {Lessons learned from a mobile technology-based intervenavioral economics to improve ART adherence among youth in Uganda},

author = {MacCarthy S and Mendoza-Graf A and Saya U and Samba C and Birungi J and Okoboi S and Linnemayr S. },

url = {https://www.tandfonline.com/doi/abs/10.1080/09540121.2019.1622630},

doi = {doi: 10.1080/09540121.2019.1622630. },

year  = {2019},

date = {2019-05-28},

journal = {AIDS Care, Psychological and Socio-medical Aspects of AIDS/HIV },

pages = {616-622},

abstract = {ABSTRACT



Evidence suggests that simple text messaging interventions may not suffice to improve ART adherence among youth in low-resource settings. To address this shortcoming, we developed an intervention that shared weekly real-time adherence feedback to youth in Uganda using short message services (SMS), based on information tracked by an electronic device (Wisepill). We present results from 7 formative and 6 exit focus groups (FGs) in Mulago and Entebbe, Uganda with youth ages 15–24, providers, and Community Advisory Board members. Participants consistently conveyed positive impressions of Wisepill, noting that it helped store their medications, facilitated travel, served as a reminder, and motivated adherence. Participants raised phone-related issues before the study; most were addressed but some remained (e.g., limited network access, electricity for powering phones). Further, they highlighted the importance of carefully crafting text messages (e.g., use slang rather than potentially stigmatizing words) and viewed personalizing messages favorably but were divided on the desirability of including their name in study-related texts. Exit FGs confirmed that sharing group adherence levels with participants tapped into the competitive spirit common among youth. Our results suggest future mobile technology-based interventions can be improved by providing messages that go beyond simple reminders to provide individual and group-level adherence feedback.



KEYWORDS: Mobile technology, text message, HIV, behavioral economics},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{S2019l,

title = {Reply to Banda et al., “Interpretation of Drug Interactionsbetween Dolutegravir and Artemether-Lumefantrine orArtesunate-Amodiaquine”},

author = {Walimbwa S and Lamorde M and Waitt C and Amara A and Khoo S.},

url = {https://sci-hub.mksa.top/10.1128/AAC.00593-19},

doi = {doi: 10.1128/AAC.00593-19. },

year  = {2019},

date = {2019-05-24},

journal = {Antimicrobial Agents and Chemotherapy},

volume = {63},

number = {6},

abstract = {We thank Banda et al. for their interest in our study and for suggesting aprocedure for handling biologically implausible concentrations. In the study group that investigated the drug-drug interaction between dolutegravir (DTG) andthe artemisinin-containing therapy (ACTs) artemether-lumefantrine (AL), we re-ported higher DTG concentrations at 24 h postdosing (C24) in the period when DTGwas administered alone.We agree with Banda et al. in their observation that participants do not perfectlyadhere to study protocol instructions. We dispensed exact numbers of pills, monitoredadherence by pill count, and directly observed the final dose. We investigated thepossibility of a dosing error and found nothing to suggest that this had occurred. Werecognize that others have reported unexplained peaks in concentration measure-ments of antiretroviral therapies. For example, Kakuda et al. reported a higherC24in ahealthy-volunteer study of a fixed-dose combination of darunavir plus cobicistat thanthat with darunavir and ritonavir as single agents (1). Unexpected peaks may occur dueto enterohepatic circulation and by other mechanisms, including drug formulation andintersubject physiological variability (2). Castellino et al. report that 33% to 48% of thefraction of DTG absorbed in the gastrointestinal tract undergoes enterohepatic recir-culation (3).For these reasons, we felt that the most appropriate approach was to retain all datapoints in our analyses. However, we have stated (and Banda et al. acknowledge) thatthe statistical difference that we reported is not clinically significant},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{I2019,

title = {Joint and unique multiblock analysis of biological data - multiomics malaria study},

author = {Surowiec I and Skotare T and Sjögren R and Gouveia-Figueira S and Orikiiriza J and Bergström S and Normark J and Trygg J},

url = {https://pubs.rsc.org/en/content/articlepdf/2019/fd/c8fd00243f},

doi = {10.1177/1744987118824625},

year  = {2019},

date = {2019-05-23},

journal = {Faraday Discussions},

volume = {218},

abstract = {Modern profiling technologies enable us to obtain large amounts of data which can be used later for a comprehensive understanding of the studied system. Proper evaluation of such data is challenging, and cannot be carried out by bare analysis of separate data sets. Integrated approaches are necessary, because only data integration allows us to find correlation trends common for all studied data sets and reveal hidden structures not known a priori. This improves the understanding and interpretation of complex systems. Joint and Unique MultiBlock Analysis (JUMBA) is an analysis method based on the OnPLS-algorithm that decomposes a set of matrices into joint parts containing variations shared with other connected matrices and variations that are unique for each single matrix. Mapping unique variations is important from a data integration perspective, since it certainly cannot be expected that all variation co-varies. In this work we used JUMBA for the integrated analysis of lipidomic, metabolomic and oxylipins data sets obtained from profiling of plasma samples from children infected with P. falciparum malaria. P. falciparum is one of the primary contributors to childhood mortality and obstetric complications in the developing world, which makes the development of new diagnostic and prognostic tools, as well as a better understanding of the disease, of utmost importance. In the presented work, JUMBA made it possible to detect already known trends related to the disease progression, but also to discover new structures in the data connected to food intake and personal differences in metabolism. By separating the variation in each data set into joint and unique, JUMBA reduced the complexity of the analysis and facilitated the detection of samples and variables corresponding to specific structures across multiple data sets, and by doing this enabled fast interpretation of the studied system. All of this makes JUMBA a perfect choice for multiblock analysis of systems biology data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DB2019,

title = {HIV-Associated Cryptococcal Immune Reconstitution Inflammatory Syndrome Is Associated with Aberrant T Cell Function and Increased Cytokine Responses},

author = {Meya DB and Okurut S and Zziwa G and Cose S and Boulware DR and Janoff EN. },

url = {https://pubmed.ncbi.nlm.nih.gov/31126019/},

doi = {doi: 10.3390/jof5020042. },

year  = {2019},

date = {2019-05-23},

journal = {Journal of Fungi (Basel)},

volume = {5},

number = {2},

abstract = {

Abstract



Cryptococcal meningitis remains a significant opportunistic infection among HIV-infected patients, contributing 15-20% of HIV-related mortality. A complication of initiating antiretroviral therapy (ART) following opportunistic infection is immune reconstitution inflammatory syndrome (IRIS). IRIS afflicts 10-30% of HIV-infected patients with cryptococcal meningitis (CM), but its immunopathogenesis is poorly understood. We compared circulating T cell memory subsets and cytokine responses among 17 HIV-infected Ugandans with CM: 11 with and 6 without CM-IRIS. At meningitis diagnosis, stimulation with cryptococcal capsule component, glucuronoxylomannan (GXM) elicited consistently lower frequencies of CD4+ and CD8+ T cell memory subsets expressing intracellular cytokines (IL-2, IFN-γ, and IL-17) among subjects who subsequently developed CM-IRIS. After ART initiation, T cells evolved to show a decreased CD8+ central memory phenotype. At the onset of CM-IRIS, stimulation more frequently generated polyfunctional IL-2+/IL-17+ CD4+ T cells in patients with CM-IRIS. Moreover, CD8+ central and effector memory T cells from CM-IRIS subjects also demonstrated more robust IL-2 responses to antigenic stimulation vs. controls. Thus, ART during CM elicits distinct differences in T cell cytokine production in response to cryptococcal antigens both prior to and during the development of IRIS, suggesting an immunologic foundation for the development of this morbid complication of CM infection.



Keywords: CD4 T cells; CD8 T cells; Cryptococcus; HIV; IRIS; adaptive immune response; cryptococcal meningitis.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{MF2019,

title = {Change in plasma CrAg titer is not associated with survival among HIV-infected persons receiving preemptive therapy for asymptomatic cryptococcal antigenemia.},

author = {Pullen MF and Kakooza F and Nalintya E and Kiragga AN and Morawski BM and Rajasingham R and Mubiru A and Manabe YC and Kaplan JE and Meya DB and Boulware DR and ORCAS study team. },

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938973/},

doi = {DOI: 10.1093/cid/ciz418 },

year  = {2019},

date = {2019-05-22},

journal = {https://pubmed.ncbi.nlm.nih.gov/31119280/},

volume = {7},

number = {2},

pages = {353-355},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ramachandran2019,

title = {Detection of Cryptococcs DNA by Metagenomic Next-generation Sequencing in Symptomatic Cryptococcal Antigenemia u},

author = {Prashanth S Ramachandran and Fiona V Cresswell and David B Meya and Charles Langelier and Emily D Crawford and Joseph L DeRisi and David R Boulware and Michael R Wilson },

url = {https://academic.oup.com/cid/article/68/11/1978/5235631?login=true},

doi = {doi: 10.1093/cid/ciy1024},

year  = {2019},

date = {2019-05-17},

journal = {Clinical Infectious Diseases},

volume = {68},

number = {11},

pages = {1978-1979},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{R2019,

title = {Burden of fungal asthma in Africa: A systematic review and meta-analysis},

author = {Kwizera R and Musaazi J and Meya DB and Worodria W and Bwanga F and Kajumbula H and Fowler SJ and Kirenga BJ and Gore R and Denning DW},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521988/},

doi = {doi: 10.1371/journal.pone.0216568},

year  = {2019},

date = {2019-05-16},

journal = {PloS One},

volume = {14},

number = {5},

abstract = {BACKGROUND:



Asthma is one of the neglected diseases in Africa with a high prevalence. Allergic fungal diseases have been reported to complicate asthma progression and treatment outcomes. However, data about fungal asthma and its associated complications are limited in Africa. We aimed to estimate the burden of fungal asthma among adults and children in Africa using a systematic review.

METHODS:



We first engaged the Institute for Health Metrics and Evaluation (IHME) to highlight the trend in morbidity and mortality attributed to asthma in Africa. We then searched PubMed, HINARI and Google Scholar for all studies of any design focusing on fungal asthma in any African country. Languages were restricted to English and French, but not year of publication. We estimated the weighted prevalence of allergic fungal infections among asthmatics with a 95% CI and pooled the results using a random effects model. This study is registered with PROSPERO, number CRD42019117319.

RESULTS:



The IHME data showed that there has been a gradual increase in morbidity and mortality due to asthma in African adults with a prevalence of 4%. Our search retrieved 5233 citations. We retained 20 studies that met our selection criteria. These were from 13 African countries published between 1967 and 2018. There were eight cross-sectional studies and twelve review articles. The average asthma prevalence in Africa was 6% from these studies. The prevalence of fungal sensitisation was relatively high (3-52%) in the asthmatic population with an average of 28% and a pooled estimate of 23.3%, mostly due to Aspergillus species. Prevalence of Allergic bronchopulmonary apsergillosis was estimated at 1.6-21.2%. Diagnosis of fungal allergy was mostly made by skin prick tests. There was no data on the use of medication to manage fungal asthma. None of the studies evaluated the association between fungal allergy and asthma severity. Data were lacking in children.

CONCLUSION:



There is a high prevalence of fungal sensitization among Africans with asthma. Fungal asthma is a significant problem in Africa but there remains a paucity of data on the epidemiology and associated complications. There is urgent need for national epidemiological studies to estimate the actual burden of fungal asthma in Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{A2019d,

title = {Research Capacity Strengthening in Sub-Saharan Africa: Recognizing the Importance of Local Partnerships in Designing and Disseminating HIV Implementation Science to Reach the 90–90–90 Goals},

author = {Kalbarczyk A and Davis W and Kalibala S and Geibel S and Yansaneh A and Martin NA and Weiss E and Kerrigan D and Manabe YC.},

url = {https://link.springer.com/article/10.1007/s10461-019-02538-0},

doi = {doi: 10.1007/s10461-019-02538-0},

year  = {2019},

date = {2019-05-16},

journal = {AIDS and Behavior },

pages = {206-213},

abstract = {Abstract



Capacity building in implementation science is integral to PEPFAR’s mission and to meeting the 90–90–90 goals. The USAID funded Project SOAR sponsored a 4 day workshop for investigators and governmental and non-governmental partners from 12 African countries. The workshop was designed to address both findings from a pre-workshop online needs assessment as well as capacity challenges across the capacity building pyramid, from individual skills to institutional systems and resources. Activities were output-oriented and skill based. An online survey evaluated sessions and changes in perceptions of needs; a majority of respondents strongly agreed that after the workshop, they better understood their personal and institutional capacity strengthening needs. Participants ‘strongly agreed’ that workshop content was relevant to their jobs (90%) and that they left the workshop with a specific plan for conducting future research (65%). Workshop results suggest that skill-building should be done in conjunction with systems capacity building within the cultural context.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang2019,

title = {HIV infection is associated with elevated biomarkers of immune activation in Ugandan adults with pneumonia},

author = {Richard J Wang and Julia Moore and Daniela Moisi and Emily G Chang and Patrick Byanyima and Sylvia Kaswabuli and Emmanuel Musisi and Ingvar Sanyu and Abdulwahab Sessolo and Rejani Lalitha and William Worodria and J Lucian Davis and Kristina Crothers Jue Lin Michael M Lederman and Peter W Hunt, Laurence Huang.},

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216680},

doi = {DOI: 10.1371/journal.pone.0216680 },

year  = {2019},

date = {2019-05-15},

journal = {PLOS ONE},

volume = {14},

number = {5},

abstract = {Abstract

Introduction



Pneumonia is an important cause of morbidity and mortality in persons living with human immunodeficiency virus (HIV) infection. How immune activation differs among HIV-infected and HIV-uninfected adults with pneumonia is unknown.

Methods



The Inflammation, Aging, Microbes, and Obstructive Lung Disease (I AM OLD) Cohort is a prospective cohort of adults with pneumonia in Uganda. In this cross-sectional analysis, plasma was collected at pneumonia presentation to measure the following 12 biomarkers: interleukin 6 (IL-6), soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2), high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer, soluble CD27 (sCD27), interferon gamma-inducible protein 10 (IP-10), soluble CD14 (sCD14), soluble CD163 (sCD163), hyaluronan, and intestinal fatty acid binding protein. We asked whether biomarker levels differed between HIV-infected and HIV-uninfected participants, and whether higher levels of these biomarkers were associated with mortality.

Results



One hundred seventy-three participants were enrolled. Fifty-three percent were HIV-infected. Eight plasma biomarkers—sTNFR-1, sTNFR-2, hsCRP, D-dimer, sCD27, IP-10, sCD14, and hyaluronan—were higher among participants with HIV infection, after adjustment for pneumonia severity. Higher levels of 8 biomarkers—IL-6, sTNFR-1, sTNFR-2, hsCRP, IP-10, sCD14, sCD163, and hyaluronan—were associated with increased 2-month mortality.

Conclusions



As in other clinical contexts, HIV infection is associated with a greater degree of immune activation among Ugandan adults with pneumonia. Some of these are also associated with short-term mortality. Further study is needed to explore whether these biomarkers might predict poor long-term outcomes—such as the development of obstructive lung disease—in patients with HIV who have recovered from pneumonia.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Goovaerts2019,

title = {Increased KLRG1 and PD-1 expression on CD8 T lymphocytes in TB-IRIS},

author = {Odin Goovaerts and Marguerite Massinga-Loembé and Pascale Ondoa and Ann Ceulemans and William Worodria and Harriet Mayanja-Kizza and Robert Colebunders and Luc Kestens },

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215991},

doi = { https://doi.org/10.1371/journal.pone.0215991},

year  = {2019},

date = {2019-04-25},

journal = {PLOS ONE},

abstract = {Abstract

Background



Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The exact contribution of T cells, natural killer (NK) cells, and monocytes to TB-IRIS development remains unclear. Here, we studied the expression of exhaustion markers on lymphocytes at different intervals during ART.

Methods



We compared 13 HIV-TB patients who developed TB-IRIS with 13 patients who did not (HIV+TB+), 13 HIV-patients without TB (HIV+TB-) and 9 HIV/TB-negative controls (HIV-TB-). Patients did not differ in age, gender, or CD4-count prior to ART. Frozen peripheral blood mononuclear cells, collected before ART and during 3 months and 9 months of ART, were analysed using flow cytometry. We examined expression of KLRG1, PD-1 and IL-27R on CD4+ and CD8hi T cells, as well as CD3-negative CD8lo lymphocytes as an approximate subset of NK cells. In addition, expression of TLR2, TLR4, IL1RL1, and TRAILR on CD14+ monocytes were investigated.

Results



Prior to ART, TB-IRIS patients had higher percentages of CD8hi T cells that are KLRG1+PD-1+ compared to each control group (p≤0.034). Though PD-1 expression decreased during ART in all groups (p≤0.026), the percentage KLRG1+PD-1+CD8hi T cells remained higher in TB-IRIS patients after 3 months of ART (p≤0.013). Though these patterns were less pronounced in CD3-CD8lo lymphocytes, the percentage of KLRG1+ cells was higher in TB-IRIS patients prior to ART (p≤0.043). In contrast, no clear differences could be observed for CD4+ T cells or monocytes.

Conclusion



TB-IRIS is preceded by a high level of exhausted (KLRG1+PD-1+) CD8hi T cells, which persists during 3 months of ART. This trait is potentially mirrored in a subpopulation of NK cells, but not CD4+ T cells. Since a dysfunctional CD8+ lymphocyte compartment could predispose patients to TB-IRIS, the functional role of these cells prior to TB-IRIS development should be further explored.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Y2019,

title = {Hepatitis B vaccination status and associated factors among undergraduate students of Makerere University College of Health Sciences.},

author = {Wibabara Y and Banura C and Kalyango J and Karamagi C and Kityamuwesi A and Amia WC and Ocama P},

doi = {10.1371/journal.pone.0214732},

year  = {2019},

date = {2019-04-05},

journal = {Plose One},

volume = {14},

number = {4},

abstract = {BACKGROUND:



Hepatitis B is a global health problem. Trainees in the health-related fields are exposed to occupational risk of Hepatitis B Virus. In Uganda, there is scarcity of information on vaccination among students in health-care. The objective of this study was to assess hepatitis B vaccination status of the students and factors associated.

METHODS AND FINDINGS:



This was a cross sectional study, conducted at Makerere University College of Health Sciences among undergraduate students who were eligible. A self-report on Hepatitis B vaccination status and various characteristics were collected on each participant, using a standardized structured self-administered questionnaire. Descriptive statistics were computed, bivariate and multivariate analysis were done using Stata 14.

RESULTS:



Out of 760 participants, 44.3% (95% CI 35.2-52.8) reported full vaccination. Vaccination was associated with gender, course, year of study and student's sponsorship. Males were less likely to be vaccinated, Prevalence Ratio (PR) 0.79; P-value <0.001, while self-sponsored students were also most likely to be vaccinated, PR 2.08; P-value <0.001. About 37% reported an accidental needle injury during their training.

CONCLUSION:



Full vaccination was low and given the high prevalence of needle injuries, it raises a safety concern. Vaccination should be mandatory for all students prior to clinical exposure. There is need for targeted interventions to increase uptake.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{A2019,

title = {Virological outcome of patients with HIV drug resistance attending an urban out-patient clinic in Uganda: a need  for structured adherence counselling and third line treatment options.},

author = {Baumann A and Musaazi J and Kambugu A and Kälin M and Weissberg D and Ssemwanga D and Fehr J and Castelnuovo B and Sekaggya-Wiltshire C and Von Braun A},

url = {https://journals.lww.com/jaids/Abstract/2019/04010/Virological_Outcome_of_Patients_With_HIV_Drug.15.aspx},

doi = {10.1097/QAI.0000000000001943},

year  = {2019},

date = {2019-04-01},

journal = {Journal of Acquired Immune Defficiency Syndrome },

volume = {80},

number = {4},

pages = {481-487},

abstract = {



Background: HIV drug resistance and suboptimal adherence are the main reasons for treatment failure among HIV-infected individuals. As genotypic resistance testing is not routinely available in resource-limited settings such as Uganda, data on transmitted and acquired resistance are sparse.



Methods: This observational follow-up study assessed the virological outcomes of patients diagnosed with virological failure or transmitted HIV drug resistance in 2015 at the adults' outpatient clinic of the Infectious Diseases Institute in Kampala, Uganda. Initially, 2430 patients on antiretroviral therapy (ART) underwent virological monitoring, of which 190 had virological failure and were subsequently eligible for this follow-up study. Nine patients diagnosed with transmitted drug resistance were eligible. In patients with a viral load > 1000 copies/mL, genotypic resistance testing was performed.



Results: Of 190 eligible patients, 30 (15.8%) had either died or were lost to follow-up. A total of 148 (77.9%) were included, of which 98 had had a change of ART regimen, and 50 had received adherence counseling only. The majority was now on second-line ART (N = 130, 87.8%). The median age was 39 years (interquartile range: 32–46), and 109 (73.6%) were women. Virological failure was diagnosed in 29 (19.6%) patients, of which 24 (82.8%) were on second-line ART. Relevant drug resistance was found in 25 (86.2%) cases, of which 12 (41.3%) carried dual and 7 (24.1%) triple drug resistance.



Conclusion: Two years after initial virological failure, most patients followed up by this study had a successful virological outcome. However, a significant proportion either continued to fail or died or was lost to follow-up.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{R2019f,

title = {Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort},

author = {Nabatanzi R and Bayigga L and Cose S and Rowland-Jones S and Canderan G and Joloba M and Nakanjako D.},

url = {https://www.sciencedirect.com/science/article/pii/S1521661619300221 },

doi = {https://doi.org/10.1016/j.clim.2019.02.010},

year  = {2019},

date = {2019-04-01},

journal = {Clinical Immunology},

volume = {201},

pages = {55-60},

abstract = {Abstract

Background



We examined NK cell phenotypes and functions after seven years of ART and undetectable viral loads (<50 copies/ml) with restored CD4 T-cell counts (≥500 cells/μl) and age-matched healthy-HIV-uninfected individuals from the same community.

Methods



Using flow-cytometry, NK cell phenotypes were described using lineage markers (CD56+/-CD16+/−). NK cell activation was determined by expression of activation receptors (NKG2D, NKp44 and NKp46) and activation marker CD69. NK cell function was determined by CD107a, granzyme-b, and IFN-gamma production.

Results



CD56 dim and CD56 bright NK cells were lower among ART-treated-HIV-infected than among age-matched-HIV-negative individuals; p = 0.0016 and p = 0.05 respectively. Production of CD107a (P = 0.004) and Granzyme-B (P = 0.005) was lower among ART-treated-HIV-infected relative to the healthy-HIV-uninfected individuals. NKG2D and NKp46 were lower, while CD69 expression was higher among ART-treated-HIV-infected than healthy-HIV-uninfected individuals.

Conclusion



NK cell activation and dysfunction persisted despite seven years of suppressive ART with “normalization” of peripheral CD4 counts.



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Keywords

Natural killer cells

NK cell activation

NK degranulation

NK Cytolytic function

NK cell dysfunction

Antiretroviral therapy

107a

Granzyme-B

Interferon gamma

NKG2D

NKp46

Sub-Saharan Africa},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{PM2019,

title = {Delayed Antiretroviral Therapy (ART) Initiation among Hospitalized Adults in a Resource-Limited Settings: A Challenge to the Global Target of ART for 90 of HIV-Infected Individuals},

author = {Ingabire PM and Semitala F and Kamya MR and Nakanjako D. },

url = {https://www.hindawi.com/journals/art/2019/1832152/},

doi = {. doi: 10.1155/2019/1832152.},

year  = {2019},

date = {2019-04-01},

journal = {AIDS Research and Treatment},

abstract = {Abstract



Background. Combination antiretroviral therapy (cART) initiation in hospital settings, where individuals often present with undiagnosed, untreated, advanced HIV disease, is not well understood. Methods. A cross-sectional study was conducted to determine a period prevalence of cART initiation within two weeks of eligibility, as determined at hospitalization. Using a pretested and precoded data extraction tool, data on cART initiation status and reason for not initiating cART was collected. Phone calls were made to patients that had left the hospital by the end of the two-week period. Delayed cART initiation was defined as failure to initiate cART within two weeks. Sociodemographic characteristics, WHO clinical stage, CD4 count, cART initiation status, and reasons for delayed cART initiation were extracted and analyzed. Results. Overall, 386 HIV-infected adults were enrolled, of whom 289/386 (74.9%) had delayed cART initiation, 77/386 (19.9%) initiated cART, and 20/386 (5.2%) were lost-to-follow-up, within two weeks of cART eligibility. Of 289 with delayed ART initiation, 94 (32.5%) died within two weeks of cART eligibility. Patients with a CD4 cell count≥ 50 cells/μl and who resided in ≥8 kilometers from the hospital were more likely to have delayed cART initiation [adjusted odds ratio (AOR) 2.34, 95% CI: 1.33-4.10, p value 0.003; and AOR 1.92, 95% CI: 1.09-3.40, p value 0.025; respectively]. Conclusion. Up to 75% of hospitalized HIV-infected, cART-naïve, cART-eligible patients did not initiate cART and had a 33% pre-ART mortality rate within two weeks of eligibility for cART. Hospital based strategies to hasten cART initiation during hospitalization and electronic patient tracking systems could promote active linkage to HIV treatment programs, to prevent HIV/AIDS-associated mortality in resource-limited settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Musaazi2019,

title = {Sustained positive impact on tuberculosis treatment outcomes of TB-HIV integrated care in Uganda},

author = {Musaazi, J. and Sekaggya-Wiltshire, C. and Kiragga, A. N. and Kalule, I. and Reynolds, S. J. and Manabe, Y. C. and Castelnuovo, B.},

doi = {https://doi.org/10.5588/ijtld.18.0306. },

year  = {2019},

date = {2019-04-01},

journal = {The International Journal of Tuberculosis and Lung Disease},

volume = {23},

number = {4},

pages = {514-521},

abstract = {OBJECTIVE:To  examine  tuberculosis  (TB)  treatmentoutcomes from a long-term TB-HIV (human immuno-deficiency  virus)  integrated  model  of  care  at  theInfectious Diseases Institute Clinic, Kampala, Uganda.METHODS:We included HIV-positive adults who werenew  TB  cases  initiated  on  anti-tuberculosis  treatmentbetween  2009  and  2015  during  TB-HIV  integration.Trends  in  TB  treatment  outcomes  and  TB-associateddeaths were analyzed using respectively thev2trend testand Kaplan-Meier methods.RESULTS:The  analysis  involved  1318  cases:  mostpatients were female  (.50%); the  median age  rangedfrom  34  to 36  years,  and.60%  were  late  presenters(CD4  count,200  cells/ll),  with  a  median  CD4  cellcount of 100–146 cells/ll at TB diagnosis. TB treatmentsuccess  (cured  or  treatment  completed)  was  67–76%.Loss to follow-up (LTFU) declined systematically from7% in 2010 to 3.4% in 2015 (P,0.01). Antiretroviraltherapy  (ART)  initiation  during  the  intensive  phaseimproved from 47% in 2009 to 97% in 2015 (P,0.01).The  mortality  rate  was.15%  over  time,  and  theprobability  of  death  at  month  2  of  anti-tuberculosistreatment was 52% higher among late presenters than inearly presenters (13% vs. 6%,P,0.01).CONCLUSION:Significant  LTFU  improvement  andprompt ART initiation could be due to well-implement-ed  TB-HIV  integration  care;  however,  static  TB-associated deaths may be due to late presentation.KEY WORDS:late  presentation;  long-term;  resource-limited setting; urban},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ndyetukira2019,

title = {The conundrum of clinical trials and standard of care in sub-Saharan Africa – the research nurse perspective},

author = {Jane Frances Ndyetukira and Richard Kwizera and Florence Kugonza and Cynthia Ahimbisibwe and Carol Namujju and Alisat Sadiq and Alice Namudde. },

url = {https://journals.sagepub.com/doi/abs/10.1177/1744987118824625},

doi = {https://doi.org/10.1177/1744987118824625},

year  = {2019},

date = {2019-03-26},

journal = { Journal of Research in Nursing},

volume = {24},

number = {8},

pages = {649-660},

abstract = {Abstract

Background



Nurses form a very important part of the health workforce in sub-Saharan Africa. Research nurses are critical to the implementation of clinical trials. The duties and responsibilities of a research nurse are complex and continue to evolve as new practices and guidelines are formulated.

Aims



In this paper, we have highlighted the major contributions of research nurses in HIV clinical trials in sub-Saharan Africa from the unique perspective of Ugandan nurses.

Methods



The requirements and challenges of two multi-site, randomised cryptococcal meningitis clinical trials in Uganda were assessed from the perspective of research nurses conducting complex research in resource-limited settings.

Results



Over the course of 8 years, approximately 1739 participants were screened and 934 people were enrolled into the two trials. The nurses found that patient education and engagement were among the most important predictors of success in minimising loss to follow-up.

Conclusions



Research nurses played a key role in communicating clinical research goals to patients, obtaining informed consent, minimising loss to follow-up, and ensuring that research practices are translated and implemented into standard of care. However, there remains a need to integrate the same level of care provided in clinical research studies to non-study patients.

Keywords clinical research, cryptococcal infection, research nurse, standard-of-care, sub-Saharan Africa},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{C2019b,

title = {Low anti-tuberculosis drug concentrations in HIV-Tuberculosis co-infected adults with low body weight; is it time to update dosing guidelines?},

author = {Sekaggya-Wiltshire C and Chirehwa M and Musaazi J and von Braun A and Buzibye A and Muller D and Gutteck U and Motta I and Calcagno A and Fehr JS and Kambugu A and Castelnuovo B and Lamorde M and Denti P},

url = {https://aac.asm.org/content/63/6/e02174-18},

doi = {10.1128/AAC.02174-18},

year  = {2019},

date = {2019-03-25},

journal = {American society for Microbiology },

abstract = {ntituberculosis drugs display large pharmacokinetic variability, which may be influenced by several factors, including body size, genetic differences, and drug-drug interactions. We set out to determine these factors, quantify their effect, and determine the dose adjustments necessary for optimal drug concentrations. HIV-infected Ugandan adults with pulmonary tuberculosis treated according to international weight-based dosing guidelines underwent pharmacokinetic sampling (1, 2, and 4 h after drug intake) 2, 8, and 24 weeks after treatment initiation. Between May 2013 and November 2015, we enrolled 268 patients (148 males) with a median weight of 53.5 (interquartile range [IQR], 47.5 to 59.0) kg and a median age of 35 (IQR, 29 to 40) years. Population pharmacokinetic modeling was used to interpret the data and revealed that patients weighing <55 kg achieved lower concentrations than those in higher weight bands for all drugs in the regimen. The models predicted that this imbalance could be solved with a dose increment of one fixed-dose combination (FDC) tablet for the weight bands of 30 to 37 and 38 to 54 kg. Additionally, the concomitant use of efavirenz increased isoniazid clearance by 24.1%, while bioavailability and absorption of rifampin and isoniazid varied up to 30% in patients on different formulations. Current dosing guidelines lead to lower drug exposure in patients in the lower weight bands. Simply adding one FDC tablet to current weight band-based dosing would address these differences in exposure and possibly improve outcomes. Lower isoniazid exposures due to efavirenz deserve further attention, as does the quality of currently used drug formulations of anti-TB drugs. (This study has been registered at ClinicalTrials.gov under identifier NCT01782950.)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{EAO2019,

title = { An observational study in an urban Ugandan clinic comparing virological outcomes of patients switched from first-line antiretroviral regimens to second-line regimens containing ritonavir-boosted atazanavir or ritonavir-boosted lopinavir},

author = {Laker EAO and Nabaggala MS and Kaimal A and Nalwanga D and Castelnuovo B and Musubire A and Kiragga A and Lamorde M and Ratanshi RP},

url = {https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-3907-5},

doi = {10.1186/s12879-019-3907-5},

year  = {2019},

date = {2019-03-25},

journal = {BMC Infectious Diseases},

volume = {19},

number = {1},

pages = {p.280},

abstract = {Background



The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir.

Methods



This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome.

Results



Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60).

Conclusions



Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nasuuna2019,

title = {Where are the HIV Positive Children? A Comparison of Facility and Community Testing Approaches in 14 Public Health Facilities in Five Ugandan Districts.},

author = {Esther Nasuuna and Lillian Babirye and Florence Namimbi and Alex Muganzi and Joanita Kigozi},

url = {https://www.idi-makerere.com/wp-content/uploads/2019/08/OJPNC-ID25-1.pdf},

year  = {2019},

date = {2019-03-25},

journal = {Open Journal of Pediatrics and Neonatal care },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{MK2019,

title = {Gut microbiota in HIV-pneumonia patients is related to peripheral CD4 counts, lung microbiota, and in vitro macrophage dysfunction},

author = {Shenoy MK and Fadrosh DW and Lin DL and Worodria W and Byanyima P and Musisi E and Kaswabuli S and Zawedde J and Sanyu I and Chang E and Fong S and McCauley K and Davis JL and Huang L and Lynch SV},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413461/},

doi = {10.1186/s40168-019-0651-4},

year  = {2019},

date = {2019-03-11},

journal = {Microbiome},

volume = {7},

number = {1},

abstract = {Pneumonia is common and frequently fatal in HIV-infected patients, due to rampant, systemic inflammation and failure to control microbial infection. While airway microbiota composition is related to local inflammatory response, gut microbiota has been shown to correlate with the degree of peripheral immune activation (IL6 and IP10 expression) in HIV-infected patients. We thus hypothesized that both airway and gut microbiota are perturbed in HIV-infected pneumonia patients, that the gut microbiota is related to peripheral CD4+ cell counts, and that its associated products differentially program immune cell populations necessary for controlling microbial infection in CD4-high and CD4-low patients. To assess these relationships, paired bronchoalveolar lavage and stool microbiota (bacterial and fungal) from a large cohort of Ugandan, HIV-infected patients with pneumonia were examined, and in vitro tests of the effect of gut microbiome products on macrophage effector phenotypes performed. While lower airway microbiota stratified into three compositionally distinct microbiota as previously described, these were not related to peripheral CD4 cell count. In contrast, variation in gut microbiota composition significantly related to CD4 cell count, lung microbiota composition, and patient mortality. Compared with patients with high CD4+ cell counts, those with low counts possessed more compositionally similar airway and gut microbiota, evidence of microbial translocation, and their associated gut microbiome products reduced macrophage activation and IL-10 expression and increased IL-1β expression in vitro. These findings suggest that the gut microbiome is related to CD4 status and plays a key role in modulating macrophage function, critical to microbial control in HIV-infected patients with pneumonia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{E2019e,

title = {Challenges faced by caregivers of virally non-suppressed children on the intensive adherence counselling program in Uganda: a qualitative study},

author = {Nasuuna E and Kigozi J and Muwanguzi PA and Babirye J and Kiwala L and Muganzi A and Sewankambo N and Nakanjako D},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407183/pdf/12913_2019_Article_3963.pdf},

doi = {10.1186/s12913-019-3963-y},

year  = {2019},

date = {2019-03-07},

journal = {BMC Health Services Research },

volume = {19},

number = {1},

abstract = {Background



Of the estimated 130,000 children living with HIV in Uganda, 47% are receiving ART. Only 39.3% have suppressed HIV-1 viral load to levels below 50 copies per ml. Caregivers are key drivers of adherence to achieve viral suppression in children. We investigated the challenges and potential support required by caregivers of ART-treated children.

Methods



A qualitative study was conducted within the Infectious Diseases Institute paediatric ART program in Kampala and Hoima districts. Caregivers of children with viral loads above 1000 copies were purposively sampled and engaged in five focus group discussions (FGD). The FGD guide highlighted questions on challenges that caregivers face and the kind of support they required to improve children’s ART adherence. Thematic analysis using the inductive approach was used. All the transcripts were read, coded and emergent themes determined.

Results



Overall, 37 caregivers participated in five FGD, of whom 29 (78%) were female, 28 (76%) were HIV-infected and 25 (68%) were biological parents of the children. The elicited challenges were either in failure to attend the counselling sessions or in supporting adherence to medication. Individual and health system challenges such as competing priorities, logistics, poor quality of counselling and lack of reminders prevented attendance at counselling sessions. Five themes emerged as challenges to supporting adherence: i) environmental (school activities, working away from home), ii) personal (non-disclosure, stigma), iii) psychological (guilt), iv) financial (lack of food and transport) and v) child-related (fatigue and peer influence). Three major themes emerged for the support that caregivers needed namely: a) health system reforms (clinic appointments outside school hours, minimize ART drug stock outs and improve quality of counselling), b) psychosocial support (support with disclosure of HIV status to children and their families, more frequent peer support groups and parenting classes) and c) economic empowerment (training in vocational skills, school fees support and opportunities to initiate income generating activities).

Discussion and conclusion



To achieve viral suppression, ART programs require targeted efforts to provide specific health facility requirements, psychological and economic needs of ART-treated children and their caregivers. Integration of HIV treatment with programs for orphans and vulnerable children may improve viral suppression rates.

Keywords: Caregivers, Adherence counselling, Paediatric HIV, Adolescent, Viral suppression},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{D2019,

title = {Availability and affordability of medicines and diagnostic tests recommended for management of asthma and chronic obstructive pulmonary disease in sub-Saharan Africa: a systematic review},

author = {Kibirige D and Sanya RE and Nantanda R and Worodria W and Kirenga B},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407228/},

doi = {10.1186/s13223-019-0329-2},

year  = {2019},

date = {2019-03-07},

journal = {Allergy, Arthma and Clinical Immunology },

volume = {15},

number = {1},

abstract = {Background:



Early accurate diagnosis and sustainable availability of affordable medicines and diagnostic tests is fundamental in optimal management of asthma and chronic obstructive pulmonary disease (COPD). We systematically reviewed original research articles about availability and affordability of medicines and diagnostic tests recommended for management of asthma and COPD in sub-Saharan Africa (SSA).

Methods:



We searched PubMed, Scopus and African Journal Online for original research articles conducted in SSA between 2000 and March 2018 containing information about availability and affordability of any recommended medicine and diagnostic test for asthma and COPD.

Results:



The search yielded 9 eligible research articles. Availability of short-acting beta agonists (SABA), inhaled corticosteroids (ICS) and short acting anti-muscarinic agents (SAMA) ranged between 19.9-100%, 0-45.5% and 0-14.3% respectively. Combination of ICS-long acting beta agonists (LABA) were available in 0-14.3% of facilities surveyed. There was absence of inhaled long acting anti-muscarinic agents (LAMA) and LAMA/LABA combinations. Spirometry and peak expiratory flow devices were available in 24.4-29.4% and 6.7-53.6% respectively. Affordability of SABA and ICS varied greatly, ranging from < 2 to 107 days' wages while ICS-LABA combinations, SAMA and oral theophylline plus leukotriene receptor antagonists cost 6.4-17.1, 13.7 and 6.9 days' wages respectively.

Conclusion:



Availability and affordability of medicines and diagnostics recommended for the management of asthma and COPD is a big challenge in SSA. Research about this subject in this region is still limited. More robustly performed studies are required to further understand the magnitude of inequity in access to these medicines and diagnostic tests in SSA and also to formulate simple pragmatic solutions to address this challenge.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Anguzu2019,

title = {Relationship between socioeconomic status and risk of sexually transmitted infections in Uganda: Multilevel analysis of a nationally representative survey },

author = {Godwin Anguzu, Andrew Flynn, Joseph Musaazi, Ronnie Kasirye, Leonard K Atuhaire, Agnes N Kiragga, Allen Kabagenyi, Andrew Mujugira},

doi = {https://doi.org/10.1177/0956462418804115},

year  = {2019},

date = {2019-03-01},

journal = {International Journal of STDs & AIDS},

volume = {30},

number = {3},

pages = {284-291},

abstract = {Socioeconomic status (SES) appears to have positive and negative associations with sexually transmitted infection (STI) risk in resource-limited settings, but few studies have evaluated nationally representative data. We assessed multiple SES measures and their effect on STI risk. We conducted a secondary analysis of data from the Uganda Demographic and Health Survey (UDHS 2011). The primary outcome (STI risk) was self-reported STIs and/or symptoms in the prior 12 months. We examined associations between multiple SES measures and STI risk using a mixed-effects Poisson regression model. The results showed that of the 9256 sexually active individuals, 7428 women and 1828 men were included in the analysis. At an individual level, middle wealth quintile and disposable income were associated with STI risk, whereas being in the richest wealth quintile was protective. Residence in wealthier regions (adjusted incidence rate ratio [aIRR] 3.92, 3.62, and 2.75, for Central, Western, and Eastern regions; p < 0.01) was associated with increased STI risk. Regional level analysis revealed stochastic variability of STI risk across geographical region (variance 0.03; p = 0.01). The bilateral association between SES and STI risk underscores the need for multi-sectoral interventions to address the upstream effects of poverty on STI risk and downstream effects of STIs on health and economic productivity.



Keywords

Uganda Demographic and Health Survey, socioeconomic status, sexually transmitted infections, mixed-effects regression models},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{RR2019,

title = {Xpert MTB/RIF Ultra for Tuberculosis Testing in Children: A Mini-Review and Commentary.},

author = {Atherton RR and Cresswell FV and Ellis J and Kitaka SB and Boulware DR. },

url = {https://www.frontiersin.org/articles/10.3389/fped.2019.00034/full#h1},

doi = {doi.org/10.3389/fped.2019.00034},

year  = {2019},

date = {2019-02-28},

journal = {Frontiers in Pediatrics},

abstract = {Tuberculosis (TB) remains a significant, yet under-recognized cause of death in the pediatric population, with a WHO estimate of 1 million new cases of childhood TB in 2016 resulting in 250,000 deaths. Diagnosis is notoriously difficult; manifestations are protean due to the high proportion of cases of extra-pulmonary TB in children, and logistical problems exist in obtaining suitable specimens. These issues are compounded by the paucibacillary nature of disease with the result that an estimated 96% of pediatric TB-associated mortality occurs prior to commencing anti-tuberculous treatment. Further development of sensitive, rapid diagnostic tests and their incorporation into diagnostic algorithms is vital in this population, and central to the WHO End-TB strategy. Initial gains were made with the expansion of nucleic acid amplification technology, particularly the introduction of the GeneXpert fully-automated PCR Xpert MTB/Rif assay in 2010, and more recently, the Xpert MTB/Rif Ultra (Ultra) assay in 2017. Ultra provides increased analytical sensitivity when compared with the initial Xpert assay in vitro; a finding now also supported by six clinical studies to date, two of which included pediatric samples. Here, we review the published evidence for the performance of Ultra in TB diagnosis in children, as well as studies in adults with paucibacillary disease providing results relevant to the pediatric population. Following on from this, we speculate upon future directions for Ultra, with focus on its potential use with alternative diagnostic specimens, which may be of particular utility in children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{A2019b,

title = {The Influence of Pharmacogenetic Variants in HIV/Tuberculosis Coinfected Patients in Uganda in the SOUTH Study. },

author = {Calcagno A and Cusato J and Sekaggya-Wiltshire C and von Braun A and Motta I and Turyasingura G and Castelnuovo B and Fehr J and Di Perri G and Lamorde M},

url = {https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.1403},

doi = {doi.org/10.1002/cpt.1403},

year  = {2019},

date = {2019-02-19},

journal = {Clinical Pharmacology & Therapeutics },

volume = {106},

number = {2},

pages = {450-457},

abstract = {Unsatisfactory treatment outcomes have been reported in patients coinfected with HIV/tuberculosis (TB). The aim of this study was to assess the influence of single‐nucleotide polymorphisms (SNPs) in genes encoding for proteins involved in antitubercular drug disposition or effect. A pharmacogenetic study was conducted in Kampala, Uganda, where all analysis was performed. The impact of SNPs on antitubercular drug exposure, adverse events, and treatment outcomes was evaluated in patients coinfected with HIV/TB receiving treatments for both conditions. In 221 participants, N‐acetyltransferase 2 (NAT2; rs1799930), solute carrier organic anion transporter family member 1B1 (SLCO1B1; rs4149032), and pregnane X receptor (PXR; rs2472677) variants affected isoniazid exposure in multivariate analysis. Most patients were deemed cured (163; 73.8%), yet PXR 63396TT carriers had a higher probability of death (P = 0.007) and of worsening peripheral neuropathy (P = 0.018). In this exploratory study in Ugandan patients coinfected with HIV/TB, genetic variants in PXR, SLCO1B1, and NAT2 were moderately associated with isoniazid exposure, whereas PXR 63396TT carriers showed worse outcomes.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{K2019b,

title = {Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda},

author = {Ssebambulidde K and Segawa I and Laker E and Lamorde M and Castelnouvo B and Nakasujja N and Calcagno A},

url = {https://academic.oup.com/omcr/article/2019/2/omy132/5321215},

doi = {10.1093/omcr/omy132},

year  = {2019},

date = {2019-02-16},

journal = {Oxford Medical case Reports },

volume = {2019},

number = {2},

abstract = {Two HIV-infected individuals on second-line atazanavir-based antiretroviral therapy presented with neuropsychiatric symptoms. Cerebrospinal fluid HIV RNA was higher than plasma HIV RNA and antiretroviral regimens’ optimization led to prompt resolution of symptoms in one. Patients on second-line atazanavir-based antiretroviral therapy with documented previous treatment failure may be at risk of symptomatic cerebrospinal fluid escape.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{MO2019,

title = {Acceptability and Predictors of Uptake of Anti-retroviral Pre-exposure Prophylaxis (PrEP) Among Fishing Communities in Uganda: A Cross-Sectional Discrete Choice Experiment Survey},

author = {Kuteesa MO and Quaife M and Biraro S and Katumba KR and Seeley J and Kamali A and Nakanjako D. },

url = {https://link.springer.com/article/10.1007%2Fs10461-019-02418-7},

doi = {10.1007/s10461-019-02418-7},

year  = {2019},

date = {2019-02-08},

journal = {AIDS and Behavior },

abstract = {We used a discrete choice experiment to assess the acceptability and potential uptake of HIV pre-exposure prophylaxis (PrEP) among 713 HIV-negative members of fishing communities in Uganda. Participants were asked to choose between oral pill, injection, implant, condoms, vaginal ring (women), and men circumcision. Product attributes were HIV prevention effectiveness, sexually transmitted infection (STI) prevention, contraception, waiting time, and secrecy of use. Data were analysed using mixed multinomial logit and latent class models. HIV prevention effectiveness was viewed as the most important attribute. Both genders preferred oral PrEP. Women least preferred the vaginal ring and men the implant. Condom use was predicted to decrease by one third among men, and not to change amongst women. Oral PrEP and other new prevention technologies are acceptable among fishing communities and may have substantial demand. Future work should explore utility of multiple product technologies that combine contraception with HIV and other STI prevention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{E2019d,

title = {Perspectives on male partner notification and treatment for syphilis among antenatal women and their partners in Kampala and Wakiso districts, Uganda},

author = {Nakku-Joloba E and Kiguli and J Kayemba CN and Twimukye A and Mbazira JK and Parkes-Ratanshi R and Birungi M and Kyenkya J and Byamugisha J and Gaydos C and Manabe YC},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366113/},

doi = {10.1186/s12879-019-3695-y.},

year  = {2019},

date = {2019-02-06},

journal = {BMC Infectious Diseases},

volume = {19},

number = {1},

pages = {124},

abstract = {BACKGROUND:



Syphilis screening can be successfully integrated into antenatal clinics, and potentially avert significant morbidity and mortality to unborn infants. A minority of male partners report for testing and treatment, increasing the likelihood of reinfection. We conducted a qualitative study to understand factors influencing male partners to seek treatment after syphilis notification by their pregnant partners.

METHODS:



A purposeful sample of 54 adults who participated in the STOP (Syphilis Treatment of Partners) study was stratified by gender (24 women, 30 male partners) and enrolled for in-depth interviews which were audio recorded, transcribed, and analyzed using the thematic approach.

RESULTS:



The participants' median age (IQR) was 32 years (25-44), 87% were married, and 57.4% (31/74) had attained secondary education. Fourteen of 22 (63%) female participants reported that they sometimes experienced domestic violence. Male participant's knowledge of syphilis and their perception of their valued role as responsible fathers of an unborn baby facilitated return. Female's fear of partner's violence and poor communication between partners, were barriers against delivery of the notification forms to partners and subsequent treatment of partners. For men, fear of injection pain, perceptions of syphilis as a genetic disease and as a woman's problem, busy work schedules, poor access to good STD services, shared facilities with women in clinics, as well as HIV-related stigma were important barrier factors.

CONCLUSIONS:



The return to the clinic for treatment of male partners after partner notification by infected pregnant women, was low due to limited knowledge about syphilis, fear of painful injection, fears of domestic violence, lack of communication skills (individual characteristics) and syphilis disease characteristics such as signs and symptoms. This, combined with health services characteristics such as structural barriers that hinder male partner treatment, low access, low capacity, work/time challenges, inadequate laboratory services and low clinic personnel capacity; threatens efforts to eliminate mother-to-child infection of syphilis. Improved public messaging about syphilis, better services, legal and policy frameworks supporting STD notification and treatment in resource-constrained settings are needed for effective STD control.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{WDF2019,

title = {Efficacy and Safety of Tenofovir Disoproxil Fumarate Versus Low-Dose Stavudine Over 96 Weeks: A Multicountry Randomized, Noninferiority Trial},

author = {Venter WDF and Kambugu A and Chersich MF and Becker S and Hill A and Arulappan N and Moorhouse M and Majam M and Akpomiemie G and Sokhela S and Poongulali S and Feldman C and Duncombe C and Ripin DHB and Vos A and Kumarasamy N},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358196/},

doi = {10.1097/QAI.0000000000001908},

year  = {2019},

date = {2019-02-01},

journal = {Journal of Acquired Immune Defficiency Syndrome (1999)},

volume = {80},

number = {2},

pages = {224–233.},

abstract = {Background:



Reducing doses of antiretroviral drugs, including stavudine (d4T), may lower toxicity, while preserving efficacy. There are substantial concerns about renal and bone toxicities of tenofovir disoproxil fumarate (TDF).

Setting:



HIV-1–infected treatment-naive adults in India, South Africa, and Uganda.

Methods:



A phase-4, 96-week, randomized, double-blind, noninferiority trial compared d4T 20 mg twice daily and TDF, taken in combination with lamivudine (3TC) and efavirenz (EFV). The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies per milliliter at 48 weeks. Adverse events assessments included measures of bone density and body fat. The trial is registered on Clinicaltrials.gov (NCT02670772).

Results:



Between 2012 and 2014, 536 participants were recruited per arm. At week 96, trial completion rates were 75.7% with d4T/3TC/EFV (n = 406) and 82.1% with TDF/3TC/EFV (n = 440, P = 0.011). Noncompletion was largely due to virological failure [6.2% (33) with d4T/3TC/EFV versus 5.4% (29) with TDF/3TC/EFV; P = 0.60]. For the primary endpoint, d4T/3TC/EFV was noninferior to TDF/3TC/EFV (79.3%, 425/536 versus 80.8% 433/536; difference = −1.49%, 95% CI: −6.3 to 3.3; P < 0.001). Drug-related adverse event discontinuations were higher with d4T (6.7%, 36), than TDF (1.1%, 6; P < 0.001). Lipodystrophy was more common with d4T (5.6%, 30) than TDF (0.2%, 1; P < 0.001). Creatinine clearance increased in both arms, by 18.1 mL/min in the d4T arm and 14.2 mL/min with TDF (P = 0.03). Hip bone density measures, however, showed greater loss with TDF.

Conclusions:



Low-dose d4T combined with 3TC/EFV demonstrated noninferior virological efficacy compared with TDF/3TC/EFV, but mitochondrial toxicity remained high. Little renal toxicity occurred in either arm. Implications of bone mineral density changes with TDF warrant investigation.

Key Words: tenofovir, stavudine DEXA, HIV, India, renal, South Africa, toxicity, trial, Uganda, dose reduction, resource allocation, public health},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{GS2019,

title = {Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission},

author = {Cooke GS and Andrieux-Meyer I and Applegate TL and Atun R and Burry JR and Cheinquer H and Dusheiko G and Feld JJ and Gore C and Griswold MG and Hamid S and Hellard ME and Hou J and Howell J and Jia J and Kravchenko N and Lazarus JV and Lemoine M and Lesi OA and Maistat L and McMahon BJ and Razavi H and Roberts T and Simmons B and Sonderup MW and Spearman CW and Taylor BE and Thomas DL and Waked I and Ward JW and Wiktor SZ.},

url = {https://www.sciencedirect.com/science/article/abs/pii/S246812531830270X},

doi = {doi: 10.1016/S2468-1253(18)30270-X.},

year  = {2019},

date = {2019-02-01},

journal = {The Lancet, Gastroenterology & Hepatology Commissioners.},

volume = {4},

number = {2},

pages = {135-184},

abstract = {

Abstract



Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.



Copyright © 2019 Elsevier Ltd. All rights reserved. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{R2019b,

title = {Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis.},

author = {Rajasingham R and Meya DB and Greene GS and Jordan A and Nakawuka M and Chiller TM and Boulware DR and Larson BA},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328136/},

doi = {10.1371/journal.pone.0210105},

year  = {2019},

date = {2019-01-29},

journal = {PloS One},

volume = {14},

number = {1},

abstract = {BACKGROUND:



Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda.

METHODS:



We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/μL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization.

RESULTS:



In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/μL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted.

CONCLUSION:



CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{K2019,

title = {The HIV care continuum among resident and non‐resident populations found in venues in East Africa cross‐border areas},

author = {Jessie K and Edwards Peter and Arimi Freddie and Ssengooba Grace and Mulholland Milissa and Markiewicz Elizabeth A and Bukusi Judy T and Orikiiriza Arti and Virkud Sharon Weir. },

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344908/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344908/},

doi = {10.1002/jia2.25226},

year  = {2019},

date = {2019-01-24},

journal = {Journal of International AIDS society },

volume = {22},

number = {1},

abstract = {INTRODUCTION:



HIV care and treatment in cross-border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross-border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed.

METHODS:



Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non-residents found in those areas.

RESULTS:



Overall, 43% of participants with HIV found in cross-border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non-resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93).

CONCLUSIONS:



People living in or travelling through cross-border areas may face barriers in learning their HIV status. Moreover, while non-residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{AN2019,

title = {A decade ofantiretroviral therapy in Uganda: what are the emerging causes of death? },

author = {Kiragga AN and Mubiru F and Kambugu AD and Kamya MR and Castelnuovo B},

url = {https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-019-3724-x},

doi = {10.1186/s12879-019-3724-x. },

year  = {2019},

date = {2019-01-21},

journal = {BMC Infectious Diseases},

volume = {19},

number = {77},

abstract = {Background



The roll out of antiretroviral therapy (ART) in Sub-Saharan Africa led to a decrease in mortality. Few studies have documented the causes of deaths among patients on long term antiretroviral therapy in Sub-Saharan Africa. Our objective was to describe the causes of death among patients on long term ART in Sub-Saharan Africa.

Methods



We used data from a prospective cohort of ART naïve patients receiving care and treatment at the Infectious Diseases Institute in Kampala, Uganda. Patients were followed up for 10 years. All deaths were recorded and possible causes established using verbal autopsy. Deaths were grouped as HIV-related (ART toxicities, any opportunistic infections (OIs) and HIV-related malignancies) and non-HIV related deaths while some remained unknown. We used Kaplan Meier survival methods to estimate cumulative incidence and rates of mortality for all causes of death.

Results



Of the 559, (386, 69%) were female, median age 36 years (IQR: 21–44), 89% had WHO clinical stages 3 and 4, and median CD4 count at ART initiation was 98 cells/μL (IQR: 21–163). A total of 127 (22.7%) deaths occurred in 10 years. The HIV related causes of death (n = 70) included the following; Tuberculosis 17 (24.3%), Cryptococcal meningitis 10 (15.7%), Kaposi’s Sarcoma 7(10%), HIV related toxicity 6 (8.6%), HIV related anemia 5(7.1%), Pneumocystis carinii Pneumonia (PCP) 5 (7.1%), HIV related chronic diarrhea 4 (5.7%), Non-Hodgkin Lymphoma 3 (4.3%), Herpes Zoster 2 (2.8%), other 10 (14.3%). The non-HIV related causes of death (n = 20) included non-communicable diseases (diabetes, hypertension, stroke) 6 (30%), malaria 3 (15%), pregnancy-related death 2 (10%), cervical cancer 2 (10%), trauma 1(5%) and others 6 (30%).

Conclusion



Despite the higher rates of deaths from OIs in the early years of ART initiation, we observed an emergence of non-HIV related causes of morbidity and mortality. It is recommended that HIV programs in resource-limited settings start planning for screening and treatment of non-communicable diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{S2019d,

title = {Incidence rate of sexually transmitted infections among HIV infected patients on long-term ART in an urban and a rural clinic in Uganda. BMC Public Health},

author = {Okoboi S and Castelnuovo B and Moore DM and Musaazi J and Kambugu A and Birungi J and Nanfuka M and Van Rie A},

url = {https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-6417-x},

doi = {10.1186/s12889-019-6417-x},

year  = {2019},

date = {2019-01-18},

journal = {BMC Public Health},

volume = {19},

number = {87},

abstract = {HIV immunosuppression increases susceptibility to other STIs and STIs can enhance HIV transmission, reduce CD4 cell count and increase viral load. Co-infections of HIV and STIs may thus reduce the preventive benefits of ART. Little is known about the incidence rate of STIs among long-term patients on ART.

Method



We conducted a secondary data analysis of all patients enrolled in a rural and an urban longitudinal cohort studies who initiated ART between April 2003 and July 2007 followed up to 2016. Patients were screened for STI every three months using “a syndromic and case management approaches”. STI incidence rate, was defined as the number of new cases per population at risk over the follow-up review period. We performed a time-to-event and Kaplan Meier analysis. We used a multivariable Cox proportional hazards regression model to assess for factors associated with STI incidence.

Result



Of 1012 participants, 402 (39.8%) were urban and 610 (60.2%) rural residents. Mean age was 42.8 years (SD 8.5). The total number of follow up time was 44,304 person years. We observed STI incidence rate of 2.1 per 1000 person-years after follow-up. Rural residence (adjusted hazard ratio [aHR] 3.53, 95% CI: 1.95–6.39), younger age (aHR 2.05, 95% CI: 1.02–4.12 for 18–34 years and aHR 1.65, 95% CI: 1.00–2.72 for 35–44 years) were factors associated with higher incidence of STIs. Being male (aHR 0.51, 95% CI: 0.27–0.93) was associated with a lower incidence of STIs.

Conclusion



We found STIs incidence rate of approximately 3 per 1000 person-years among patients on long-term (≥ 4 years) ART followed up-to 3.5 years. Rural and younger persons on ART should be routinely screened for STIs because high incidence of STIs may undo the preventative effects of ART for all.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{E2019f,

title = {Beyond HIV prevention: everyday life priorities and demand for PrEP among Ugandan HIV serodiscordant couples. },

author = {Nakku-Joloba E and Pisarski EE and Wyatt MA and Muwonge TR and Asiimwe S and Celum CL and Baeten JM and Katabira ET and Ware NC. },

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25225},

doi = { https://doi.org/10.1002/jia2.25225},

year  = {2019},

date = {2019-01-18},

journal = {Journal of the International AIDS Society},

abstract = {

Abstract

Introduction



Pre‐exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means – beyond HIV prevention – for the lives of users.

Methods



The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time‐limited PrEP served as a “bridge” to long‐term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open‐ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow‐up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio‐recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories.

Results



Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re‐establishment of intimacy and closeness. By increasing couples’ sense of protection against HIV infection and raising the prospect of a return to “live sex” (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships.

Conclusions



The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention.

Clinical Trial Number



NCT02775929

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yotebieng2019,

title = {Research priorities to inform “Treat All” policy implementation for people living with HIV in sub-Saharan Africa: a consensus statement from the International epidemiology Databases to Evaluate AIDS (IeDEA)},

author = {Marcel Yotebieng, Ellen Brazier, Diane Addison, April D Kimmel, Morna Cornell, Olivia Keiser, Angela M Parcesepe, Amobi Onovo, Kathryn E Lancaster, Barbara Castelnuovo, Pamela M Murnane, Craig R Cohen, Rachel C Vreeman, Mary-Ann Davies, Stephany N Duda, Constantin T Yiannoutsos, Rose S Bono, Robert Agler, Charlotte Bernard, Jennifer L Syvertsen, Jean d'Amour Sinayobye, Radhika Wikramanayake, Annette H Sohn, Per M von Groote, Gilles Wandeler, Valeriane Leroy, Carolyn F Williams, Kara Wools-Kaloustian, Denis Nash, for the IeDEA Treat All in sub-Saharan Africa Consensus Statement Working Groupg},

doi = {https://doi.org/10.1002/jia2.25218},

year  = {2019},

date = {2019-01-18},

journal = {Journal of the International AIDS Society},

volume = {22},

number = {1},

pages = {e25218},

abstract = {Abstract

Introduction

“Treat All” – the treatment of all people with HIV, irrespective of disease stage or CD4 cell count – represents a paradigm shift in HIV care that has the potential to end AIDS as a public health threat. With accelerating implementation of Treat All in sub-Saharan Africa (SSA), there is a need for a focused agenda and research to identify and inform strategies for promoting timely uptake of HIV treatment, retention in care, and sustained viral suppression and addressing bottlenecks impeding implementation.



Methods

The Delphi approach was used to develop consensus around research priorities for Treat All implementation in SSA. Through an iterative process (June 2017 to March 2018), a set of research priorities was collectively formulated and refined by a technical working group and shared for review, deliberation and prioritization by more than 200 researchers, implementation experts, policy/decision-makers, and HIV community representatives in East, Central, Southern and West Africa.



Results and discussion

The process resulted in a list of nine research priorities for generating evidence to guide Treat All policies, implementation strategies and monitoring efforts. These priorities highlight the need for increased focus on adolescents, men, and those with mental health and substance use disorders – groups that remain underserved in SSA and for whom more effective testing, linkage and care strategies need to be identified. The priorities also reflect consensus on the need to: (1) generate accurate national and sub-national estimates of the size of key populations and describe those who remain underserved along the HIV-care continuum; (2) characterize the timeliness of HIV care and short- and long-term HIV care continuum outcomes, as well as factors influencing timely achievement of these outcomes; (3) estimate the incidence and prevalence of HIV-drug resistance and regimen switching; and (4) identify cost-effective and affordable service delivery models and strategies to optimize uptake and minimize gaps, disparities, and losses along the HIV-care continuum, particularly among underserved populations.



Conclusions

Reflecting consensus among a broad group of experts, researchers, policy- and decision-makers, PLWH, and other stakeholders, the resulting research priorities highlight important evidence gaps that are relevant for ministries of health, funders, normative bodies and research networks.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{JP2019,

title = {A Lower Dose of Efavirenz Can Be Coadministered With Rifampicin and Isoniazid in Tuberculosis Patients},

author = {Kaboggoza JP and Wang X and Neary M and Ayuso P and Sekaggya-Wiltshire C and Nakalema S and Owen A and McClure M and Lamorde M and Boffito M},

url = {https://watermark.silverchair.com/ofz035.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlswggJXBgkqhkiG9w0BBwagggJIMIICRAIBADCCAj0GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM171Jo1MZdLPK4-CiAgEQgIICDnyb9uh2Ai8sXCED4DmtumguYfSbH3lGLmWfhenE4LFrjRAUAElNllazUkTGuNSWlPyMP9PIJUHrJRSsfmjRO6W-zjpSwTw6-A86XEYHXacYWG-DGYhAPK6hDKgr4ejiPzuv6YYTyHW3JZHfkkWTCxBKg6RIxcXdwi0OjyZxtBX_Guz8bxdGvvrZW9AbVU3uS8EhIDNjlCDL1WxITvNPsY9HFS9WOLTzC6k8uPyo0ccz9yCenTxK0cXLsFlCjpCPxtWLb7NPwaglrk37EoA9JtiBYRKkhNbDqOU0VF2ZIxZSbAliUsm1HYQFhLksy2G81GUgqXOvAgheLOqJ8r_63bPsRggw2KmPTH1cO1GsS6wBHfXpd2PNgXyAV-3gPIS1DABxdc-ahCw9fdhv-Wu6v7DIW0kQ0GaM7ERCAY6W9a-pL_UY-l4QkoHYdanKm9ggyS_pB5m3a1VOjKRzxceyhtd2kv6UyAp1a7HegcNs_7_BHSomtR81kJP4LczkF6CIykhsMAg_CDUEg8rQXlq4SnOEncZDivM8GoOPF6YZsylmJcN78c2hg_aVJE8hz1jIPOvFTkmQszEOg2PIopqKPXf2onYDVBl3-w07HzuKcrLslEMtmkmLhMhmMtCUZoext_bmMbrM9vnjr-vOJWJWldzKKZMOJhME94eCG4OkG-6C25gFGX3moLC3m8cnJjA},

doi = {10.1093/ofid/ofz035},

year  = {2019},

date = {2019-01-16},

journal = {Open Forum Diseases },

volume = {6},

number = {2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{AK2019,

title = {Epidemiology of non-traumatic spinal cord injury in Uganda: a single center, prospective study with MRI evaluation},

author = {Musubire AK and Meya DB and Katabira ET and Meyer ACL and Bohjanen PR and Boulware DR and Minja F},

doi = {10.1186/s12883-019-1236-3},

year  = {2019},

date = {2019-01-15},

journal = {BMC Neaurology },

volume = {19},

number = {1},

abstract = {Background



A few reliable national data concerning the etiology of non-traumatic spinal cord injury (SCI) in sub-Sahara Africa exists, mainly because of the limitations of diagnostic imaging. These are both expensive and mostly unavailable in several resource-limited settings. Only a few studies have employed the magnetic resonance imaging (MRI) in documenting non-traumatic SCI and most of these studies are from South Africa. We sought to describe the clinical presentation, MRI radiological patterns, and one-year survival among subjects with non-traumatic SCI in Uganda.

Methods



We enrolled a prospective cohort of 103 participants with non-traumatic SCI at Mulago National Referral Hospital Kampala, Uganda in 2013–2015. Participants received standard of care management, with surgical intervention as needed, with one-year follow up. Data were analyzed using Descriptive statistics.

Results



In 103 participants with non-traumatic SCI, the median (IQR) age was 37 (18, 85) years and 25% of the participants were HIV-infected. Paraplegia/paraparesis was the most common clinical presentation in 70% (n = 72). Severe disease was present in 82% (n = 85) as per American Spinal Injury Association (ASIA) scale A-C. On MRI, 50% had extradural lesions. However, bone lesions accounted for only 75% of all the extradural lesions. More than 60% of the patients had lesions that could only be diagnosed on MRI. Deaths occurred in 42% (n = 44) of participants, with the highest mortality among those with extradural lesions (60%).

Conclusion



The mortality following non-traumatic spinal cord injuries in Uganda is high. We demonstrated an equal distribution between extradural and intradural lesions, which differs from the historical predominance of extradural lesions. Increased utilization of MRI particularly among young age groups is needed to make a diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DS2019,

title = {Correction to: AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial. },

author = {Lawrence DS and Youssouf N and Molloy SF and Alanio A and Alufandika M and Boulware DR and Boyer-Chammard T and Chen T and Dromer F and Hlupeni A and Hope W and Hosseinipour MC and Kanyama C and Lortholary O and Loyse A and Meya DB and Mosepele M and Muzoora C and Mwandumba HC and Ndhlovu CE and Niessen L and Schutz C and Stott KE and Wang D and Lalloo DG and Meintjes G and Jaffar S and Harrison TS and Jarvis JN},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332521/},

doi = {10.1186/s13063-018-3155-9},

year  = {2019},

date = {2019-01-14},

journal = {Trails},

volume = {20},

number = {1},

abstract = {Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{R2019h,

title = {Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis},

author = {Rajasingham R and Meya DB and Greene GS and Jordan A and Nakawuka M and Chiller TM and Boulware DR and Larson BA. },

url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210105},

doi = { https://doi.org/10.1371/journal.pone.0210105},

year  = {2019},

date = {2019-01-10},

journal = {PLOS ONE},

pages = {e0210105},

abstract = {Abstract

Background



Cryptococcal meningitis accounts for 15% of AIDS-related mortality. Cryptococcal antigen (CrAg) is detected in blood weeks before onset of meningitis, and CrAg positivity is an independent predictor of meningitis and death. CrAg screening for patients with advanced HIV and preemptive treatment is recommended by the World Health Organization, though implementation remains limited. Our objective was to evaluate costs and mortality reduction (lives saved) from a national CrAg screening program across Uganda.

Methods



We created a decision analytic model to evaluate CrAg screening. CrAg screening was considered for those with a CD4<100 cells/μL per national and international guidelines, and in the context of a national HIV test-and-treat program where CD4 testing was not available. Costs (2016 USD) were estimated for screening, preemptive therapy, hospitalization, and maintenance therapy. Parameter assumptions were based on large prospective CrAg screening studies in Uganda, and clinical trials from sub Saharan Africa. CrAg positive (CrAg+) persons could be: (a) asymptomatic and thus eligible for preemptive treatment with fluconazole; or (b) symptomatic with meningitis with hospitalization.

Results



In the base case model for 1 million persons with a CD4 test annually, 128,000 with a CD4<100 cells/μL were screened, and 8,233 were asymptomatic CrAg+ and received preemptive therapy. Compared to no screening and treatment, CrAg screening and treatment in the base case cost $3,356,724 compared to doing nothing, and saved 7,320 lives, for a cost of $459 per life saved, with the $3.3 million in cost savings derived from fewer patients developing fulminant meningitis. In the scenario of a national HIV test-and-treat program, of 1 million HIV-infected persons, 800,000 persons were screened, of whom 640,000 returned to clinic, and 8,233 were incident CrAg positive (CrAg prevalence 1.4%). The total cost of a CrAg screening and treatment program was $4.16 million dollars, with 2,180 known deaths. Conversely, without CrAg screening, the cost of treating meningitis was $3.09 million dollars with 3,806 deaths. Thus, despite the very low CrAg prevalence of 1.4% in the general HIV-infected population, and inadequate retention-in-care, CrAg screening averted 43% of deaths from cryptococcal meningitis at a cost of $662 per death averted.

Conclusion



CrAg screening and treatment programs are cost-saving and lifesaving, assuming preemptive treatment is 77% effective in preventing death, and could be adopted and implemented by ministries of health to reduce mortality in those with advanced HIV disease. Even within HIV test-and-treat programs where CD4 testing is not performed, and CrAg prevalence is only 1.4%, CrAg screening is cost-effective.

    



Citation: Rajasingham R, Meya DB, Greene GS, Jordan A, Nakawuka M, Chiller TM, et al. (2019) Evaluation of a national cryptococcal antigen screening program for HIV-infected patients in Uganda: A cost-effectiveness modeling analysis. PLoS ONE 14(1): e0210105. https://doi.org/10.1371/journal.pone.0210105



Editor: Eileen Stillwaggon, Gettysburg College, UNITED STATES



Received: November 27, 2018; Accepted: December 16, 2018; Published: January 10, 2019



This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.



Data Availability: All relevant data are within the paper and its Supporting Information files.



Funding: RR is supported by the National Institute of Allergy and Infectious diseases (K23AI138851). BL is supported by the CDC foundation. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the funding agencies. The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.



Competing interests: BL was paid by the CDC foundation for this work. GG, AJ, and TC are employed by the CDC, which is a separate, independent entity from the CDC foundation The source of this information is the Global Cryptococcal Antigen Screening Initiative, a project of the CDC Foundation funded by a grant from Pfizer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{R2019c,

title = {Point-of-care diagnostics: needs of African health care workers and their role combating global antimicrobial resistance},

author = {Parkes-Ratanshi R and Kikonyogo R and Hsieh YH and Nakku-Joloba E and Manabe YC and Gaydos CA and Rompalo A},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693631/},

doi = {10.1177/0956462418807112},

year  = {2019},

date = {2019-01-09},

journal = {International Journal of STD & AIDS},

volume = {30},

number = {4},

pages = {404-410},

abstract = {Point-of-care tests (POCTs) offer the opportunity for increased diagnostic capacity in resource-limited settings, where there is lack of electricity, technical capacity, reagents, and infrastructure. Understanding how POCTs are currently used and determining what health care workers (HCWs) need is key to development of appropriate tests. In 2016, we undertook an email survey of 7584 HCWs who had received training at the Infectious Diseases Institute, Uganda, in a wide variety of courses. HCWs were contacted up to three times and asked to complete the survey using Qualtrics software. Of 555 participants answering the survey (7.3% response rate), 62% completed. Ninety-one percent were from Uganda and 50.3% were male. The most commonly-used POCTs were pregnancy tests (74%), urine dipstick (71%), syphilis rapid test (66%), and Gram stain (41%). The majority (74%) practiced syndromic diagnosis for sexually transmitted infections/HIV. Lack of availability of POCTs, increased patient wait time, and lack of training were the leading barriers for POCT use. Increasing POCT availability and training could improve uptake of POCTs for sexually transmitted infections in Africa and decrease syndromic management. This could reduce overtreatment and slow the emergence of antibiotic resistance. This is the first published email survey of HCWs in Uganda; mechanisms to increase the response rate should be evaluated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RR2019b,

title = {Ophthalmic signs in Ugandan adults with HIV-associated cryptococcal meningitis: A nested analysis of the ASTRO-CM cohort},

author = {Atherton RR and Ellis J and Cresswell FV and Rhein J and Boulware DR. },

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178913/},

doi = {doi: 10.12688/wellcomeopenres.14666.2},

year  = {2019},

date = {2019-01-01},

journal = {Wellcome Open Research},

volume = {3},

number = {20},

pages = {eCollection 2018. },

abstract = {Abstract



Cryptococcal meningitis is a leading cause of morbidity and mortality among HIV-infected persons, accounting for 15% of AIDS-related deaths. Visual disturbance is commonly reported, and a wide range of ophthalmic signs may be present on examination. There is limited published literature to date describing the range and incidence of ophthalmic signs in HIV-associated cryptococcal meningitis. Nested within the Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis (ASTRO-CM) trial (ClinicalTrials.gov number: NCT01802385), we conducted an observational study of 696 Ugandan adults with HIV-associated cryptococcal meningitis.



Patients were screened for visual disturbance and external ophthalmic signs at initial presentation and at follow-up appointments over 18 weeks. Assessment comprised simple clinical history and basic examination and required no specialist equipment.



More than a quarter of our cohort demonstrated ocular signs or symptoms, which were observed throughout the study period.  A broad range of ocular signs were demonstrated: these included neurological signs (10.9%), localized ocular pathology (4.5%), and evidence of concurrent systemic disease (12.9%).



The range of signs observed demonstrates the complexities of case management in patients with advanced HIV and cryptococcosis and also the importance of basic ocular examination in low resource settings.



There remains an urgent need for studies conducting comprehensive ocular examination in patients with HIV-associated cryptococcal meningitis; these studies should include formal assessment of visual acuity, slit lamp examination and dilated indirect ophthalmoscopy. Prospective studies should investigate whether there is a correlation between reported visual disturbance and objective signs, in order to further clarify the underlying mechanisms and to guide effective diagnosis, follow-up and management.

Keywords: Cryptococcus, cryptococcal meningitis, HIV, visual, ocular, ophthalmic},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Musubire2018,

title = {Blood neutrophil counts in HIV-infected patients with cryptococcal meningitis: Association with mortality},

author = {Abdu Kisekka Musubire , David B. Meya, Joshua Rhein, Graeme Meintjes, Paul R. Bohjanen, Edwin Nuwagira, Conrad Muzoora, David R. Boulware, Kathy Huppler Hullsiek, the COAT and ASTRO trial teams},

doi = {https://doi.org/10.1371/journal.pone.0209337},

year  = {2018},

date = {2018-12-31},

journal = {PLOS ONE},

volume = {13},

number = {12},

pages = {e0209337},

abstract = {Background



The mortality from cryptococcal meningitis remains high, despite the availability of antiretroviral therapy (ART) and amphotericin-based fungal regimens. The role of neutrophils in cryptococcosis is controversial. Our objective was to examine the association between blood neutrophil counts and outcomes in terms of mortality, the incidence of bacterial infections (including Mycobacterium tuberculosis) and hospitalization among HIV-infected patients presenting with cryptococcal meningitis.



Methods



We used data from participants from the Cryptococcal Optimal ART Timing (COAT) trial (2010–2012; Uganda and South Africa) and the Adjunctive Sertraline for Treatment of Cryptococcal Meningitis (ASTRO-CM) trial (2013–2017; Uganda). We estimated 30-day mortality risk with Cox proportional hazards models by baseline neutrophil counts (a) on a continuous scale and (b) with indicators for both relatively high (> 3,500 cells/mm3) and low (≤ 1,000 cells/mm3) counts. Follow-up neutrophil counts from the COAT trial were used to examine the time-dependent association of neutrophil counts with 12-month mortality and rehospitalization.



Results



801 participants had an absolute neutrophil value at meningitis diagnosis. The median baseline absolute neutrophil count was 2100 cells/mm3 (IQR, 1400 to 3300 cells/mm3). Baseline neutrophil count was positively associated with 30-day mortality (adjusted hazard ratio = 1.09, 95%CI, 1.04–1.13, per 1000 cells/mm3 increase; p<0.001). Baseline absolute neutrophil counts ≤ 1000 cells/mm3 did not have increased risk of 30-day mortality compared to those with baseline neutrophils of 1001–3500 cells/mm3; however, baseline >3500 cells/mm3 had significantly increased risk, with an adjusted hazard ratio of 1.85(95%CI, 1.40–2.44; p<0.001). Among the COAT participants with follow-up neutrophil data, there was a strong association between time-updated neutrophil count and 12-month mortality (adjusted hazard ratio = 1.16, 95% CI 1.09–1.24; p<0.001.



Conclusion



Higher blood neutrophil counts in HIV-infected patients with cryptococcal meningitis were associated with mortality. Neutrophils role requires further investigation as to whether this may be a mediator directly contributing to mortality or merely a marker of underlying pathologies that increase mortality risk.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Muhumuza2018,

title = {Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study},

author = {Simon Muhumuza and Evelyn Akello and Charity Kyomugisha-Nuwagaba and Rose Baryamutuma and Isaac Sebuliba and Ibrahim M. Lutalo and Edgar Kansiime and Linda N. Kisaakye and Agnes N. Kiragga and Rachel King and William Bazeyo and Christina Lindan

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Retention-in-care-among-HIV-infected-pregnant-and-breastfeeding-women-on-lifelong-antiretroviral-therapy-in-Uganda-A-retrospective-cohort-study.pdf},

doi = { 10.1371/journal.pone.0187605},

year  = {2018},

date = {2018-12-22},

journal = {PloS One},

volume = {12},

number = {12},

abstract = {BACKGROUND:



In 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program.

METHODS:



We conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as "being alive and receiving ART at the last clinic visit". We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables.

RESULTS:



The median follow-up time was 20.2 months (IQR 4.2-22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002).

CONCLUSION:



Retention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{BURNETT2018,

title = {Effect of TB/HIV Integration on TB and HIV indicators in Rural Ugandan Health Facilities},

author = {Sarah M BURNETT, Stella ZAWEDDE-MUYANJA, Sabine M HERMANS, Marcia R WEAVER, Robert COLEBUNDERS and Yukari C MANABE},

doi = {doi: 10.1097/QAI.0000000000001862},

year  = {2018},

date = {2018-12-15},

journal = {Journal of Acquired Immune Deficiency Syndromes},

volume = {79},

number = {5},

pages = {605–611},

abstract = {Background



WHO recommends integrating services for patients co-infected with TB and HIV. We assessed the effect of TB/HIV integration on ART initiation and TB treatment outcomes among TB/HIV co-infected patients using data collected from 14 rural health facilities during two previous TB and HIV quality of care studies.



Methods



A facility was considered to have integrated TB/HIV services if TB/HIV patients had combined treatment for both illnesses by one provider or care team at one treatment location. We analyzed the effect of integration by conducting a cross-sectional analysis of integrated and non-integrated facility periods comparing performance on ART initiation and TB treatment outcomes. We conducted logistic regression, with the patient as the unit of analysis, controlling for other intervention effects, adjusting for age and gender, and clustering by health facility.



Results



From January 2012-June 2014, 996 TB patients were registered, 97% were tested for HIV and 404 (42%) were HIV positive. Excluding transfers, 296 patients were eligible for analysis with 117 and 179 from non-integrated and integrated periods, respectively. Being treated in a facility with TB/HIV integration was associated with lower mortality (adjusted odds ratio [aOR]=0.38, 95% confidence interval [CI]=0.18–0.77), but there was no difference in the proportion initiating ART (aOR=1.34, 95% CI=0.40–4.47), with TB treatment success (aOR=1.43, 95% CI=0.73–2.82), lost to follow-up (aOR=1.64, 95% CI=0.53–5.04), or failure (aOR=1.21, 95% CI=0.34–4.32).



Conclusion



TB/HIV service integration was associated with lower mortality during TB treatment even in settings with suboptimal proportions of patients completing TB treatment and starting on ART.



Keywords: tuberculosis/HIV co-infection, anti-retroviral therapy initiation, tuberculosis treatment outcomes, mortality, Africa, south of the Sahara, Uganda},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Worodria2018b,

title = {Predictors of mortality among hospitalized patients with lower respiratory tract infections in a high HIV burden setting},

author = {William Worodria, Chang Emily, Alfred Andama, Ingvar Sanyu, Patrick Byanyima, Emmanuel Musisi, Sylvia Kaswabuli, Josephine Zawedde, Irene Ayakaka, Abdul Sessolo, Rejani Lalitha, John Lucian Davis and Laurence Huang},

doi = {doi: 10.1097/QAI.0000000000001855},

year  = {2018},

date = {2018-12-15},

journal = {J Acquir Immune Defic Syndr.},

volume = {79},

number = {5},

pages = {624–630},

abstract = {Introduction



Lower respiratory tract infections (LRTIs) are a leading cause of mortality in sub-Saharan Africa. Triaging identifies patients at high-risk of death but laboratory tests proposed for use in severity-of-illness scores are not readily available, limiting their clinical use. Our objective was to determine whether baseline characteristics in hospitalized participants with LRTI predicted increased risk of death.



Methods



This was a secondary analysis from the MIND-IHOP cohort of adults hospitalized with LRTI who underwent standardized investigations and treatment. The primary outcome was all-cause mortality at two months. Predictors of mortality were determined using multiple logistic regression.



Results



Of 1887 hospitalized participants with LRTI, 372 (19.7%) died. The median participant age was 34.3 years (Interquartile Range, IQR, 28.0–43.3 years), 978 (51.8%) were men, and 1192 (63.2%) were HIV-positive with median CD4 counts of 81 cells/µL (IQR 21–226 cells/µL). Seven hundred eleven (37.7%) participants had a microbiologically confirmed diagnosis. Temperature <35.5ºC (aOR=1.77, 95% CI=1.20–2.60; p=0.004), heart rate >120/minute (aOR=1.82, 95% CI=1.37–2.43; p<0.0001), oxygen saturation <90% (aOR=2.74, 95% CI=1.97–3.81; p<0.0001), being bed-bound (aOR=1.88, 95% CI=1.47–2.41; p<0.0001) and being HIV-positive (aOR=1.49, 95%CI=1.14–1.94; p=0.003) were independently associated with mortality at two months.



Conclusions



Having temperature <35.5°C, heart rate >120/minute, hypoxia; being HIV positive and bed-bound independently predicts mortality in participants hospitalized with LRTI. These readily-available characteristics could be used to triage patients with LRTI in low-income settings. Providing adequate oxygen, adequate intravenous fluids; and early antiretroviral therapy (in people living with HIV/AIDS) may be life-saving in hospitalized patients with LRTI.



Keywords: Predictors, Mortality, Pneumonia, HIV, sub-Saharan Africa},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Vos2018,

title = {Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir},

author = {Alinda G. Vos, Matthew F. Chersich, Kerstin Klipstein-Grobusch, Peter Zuithoff, Michelle A. Moorhouse, Samanta T. Lalla-Edward, Andrew Kambugu, N. Kumarasamy, Diederick E. Grobbee, Roos E. Barth & Willem D. Venter },

doi = {https://doi.org/10.1186/s12977-018-0460-z},

year  = {2018},

date = {2018-12-14},

journal = {Retrovirology},

volume = {15},

number = {77},

abstract = {Background



HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with low-dose stavudine or tenofovir regimens.



Methods



This is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials.gov, NCT02670772). Over 96 weeks, data were collected on fasting lipids, glucose and insulin. Insulin resistance was assessed with the HOMA-IR index and 10-year CVD risk with the Framingham risk score (FRS). A generalized linear mixed model was used to estimate trends over time.



Results



Participants were on average 35.3 years old, 57.6% female and 91.8% Black African. All lipid levels increased following treatment initiation, with the sharpest increase in the first 24 weeks of treatment. The increase in all lipid subcomponents over 96 weeks was higher among those in the stavudine than the tenofovir group. Insulin resistance increased steadily with no difference detected between study groups. FRS rose from 1.90% (1.84–1.98%) at baseline to 2.06 (1.98–2.15%) at week 96 for the total group, with no difference between treatment arms (p = 0.144). Lipid changes were more marked in Indian than African participants.



Conclusion



Lipid levels increased in both groups, with low-dose stavudine resulting in a worse lipid profile compared to tenofovir. Insulin resistance increased, with no difference between regimens. CVD risk increased over time and tended to increase more in the group on stavudine. The low CVD risk across both arms argues against routine lipid and glucose monitoring in the absence of other CVD risk factors. In high risk patients, monitoring may only be appropriate at least a year after treatment initiation.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Zawedde-Muyanja2018,

title = { Xpert® MTB/RIF associated with improved treatment initiation among patients with smear-negative tuberculosis },

author = {S. Zawedde-Muyanja, Y. C. Manabe, N. K. Sewankambo, L. Nakiyingi and D. Nakanjako},

doi = { https://doi.org/10.5588/ijtld.17.0460},

year  = {2018},

date = {2018-12-01},

journal = {International Union Against Tuberculosis and Lung Disease},

volume = {22},

number = {12},

abstract = {BACKGROUND: 

Delayed diagnosis and treatment initiation of smear-negative tuberculosis (TB) patients can lead to increased morbidity and mortality, particularly among those co-infected with the human immunodeficiency virus (HIV).



OBJECTIVE: 

To compare TB treatment initiation among smear-negative presumptive TB patients in the 6 months before and after the introduction of Xpert® MTB/RIF testing at five rural tertiary hospitals in Uganda.



METHODS: 

Patient records of the dates and results of sputum analysis were extracted from TB laboratory registers and linked to those on treatment initiation as indicated in the TB treatment registers. The proportion of smear-negative presumptive patients who initiated anti-tuberculosis treatment was compared before and after Xpert implementation using χ2 tests. Time to treatment was analysed using Kaplan-Meier survival analysis.



RESULTS: 

Records from 3658 patients were analysed, 1894 before and 1764 after the introduction of Xpert testing. After the introduction of Xpert, 25% (437/1764) of smear-negative presumptive TB patients underwent testing. The proportion initiated on anti-tuberculosis treatment increased from 5.9% (112/1894) to 10.8% (190/1764) (P < 0.01). However, 37% (32/87) of patients with a confirmed TB diagnosis did not initiate treatment. Time to TB treatment initiation improved from 8 to 3.5 days between the study periods.



CONCLUSION: 

Xpert testing was associated with improved TB treatment initiation among smear-negative presumptive TB patients. Improved utilisation and linkage to treatment could improve the impact of this test on patient-centred outcomes. },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}