@article{Hamill2018,

title = {Challenges of RPR interpretation in syphilis screening in Uganda: variability in non-treponemal results between different laboratories},

author = {Matthew M. Hamill, Kimeze J. Mbazira, Agnes N. Kiragga, Charlotte A. Gaydos, Mary Jett-Goheen, Rosalind Parkes-Ratanshi, Yukari C. Manabe, Edith Nakku-Joloba and Anne Rompalo.},

doi = {doi: 10.1097/OLQ.0000000000000883},

year  = {2018},

date = {2018-12-01},

journal = {Sexually transmitted diseases},

volume = {45},

number = {12},

pages = {829–833},

abstract = {Background



Syphilis is a cause of morbidity and mortality and is of particular concern in pregnancy in low income countries because of risks associated with maternal-fetal transmission. Ugandan national guidelines recommend a non-treponemal Rapid Plasma Reagin (RPR) followed by treponemal testing for diagnosis of syphilis. The RPR test confirms a reactive specific treponemal test, or confirms serological ‘cure’ with a 4-fold dilutional decrease; RPR is beset with technical and biological limitations making accurate diagnosis and appropriate treatment problematic. The aim of this analysis was to compare performance of RPR-testing in different laboratories.



Methods



Stored, freeze-thawed sera from 215 participants were additionally tested for RPR and dilutional titer in two different reference laboratories. Discrepant results were tested at a third reference lab which served as a tie-breaker. Equivalence in RPR titer was defined as within ≤2 fold. All patients with a reactive rapid test were treated as per Ugandan national guidelines.



Results



Of 215 sera, 97 (45.1%) were RPR reactive in clinic laboratory A, 81 (37.7%) and 65 (30.2%) were RPR reactive in labs B and C respectively. All reported positive in the lab C were positive in lab B. Discrepant results were tested in lab D. Chi square test was highly significant (p=<0.001) for difference between each dyad of labs (A&B, A&C and B&C) RPR results. There were significant differences between RPR titers by paired t-test and Wilcox rank test (p=<0.001); with up to a 3-fold difference between labs. Two one-sided test approach demonstrated non-equivalence. Agreement between labs B–D, and C–D: 48/49 (98.0%) and 35/49 (71.4%) respectively (p=<0.001). Labs B and D showed no significant difference and had equivalent RPR titers. Labs C and D had different titers (p=<0.001) and were not equivalent.



Conclusions



We found significant inter- laboratory discrepant RPR results. A 3-fold difference in results is likely to be clinically significant and could result in under- or over-treatment. These data demonstrate a key limitation of the RPR test and underline the urgent need for a more reproducible quantitative test than the current RPR for diagnosing and determining cure of syphilis.

Keywords: RPR testing, syphilis, laboratory, antenatal, Sub Saharan Africa},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Lamorde2018,

title = {A Cross-Cutting Approach to Surveillance and Laboratory Capacity as a Platform to Improve Health Security in Uganda},

author = {Mohammed Lamorde, Arthur Mpimbaza, Richard Walwema, Moses Kamya, James Kapisi, Henry Kajumbula, Asadu Sserwanga, Jane Frances Namuganga, Abel Kusemererwa, Hannington Tasimwa, Issa Makumbi, John Kayiwa, Julius Lutwama, Prosper Behumbiize, Abner Tagoola, Jane Frances Nanteza, Gilbert Aniku, Meklit Workneh, Yukari Manabe, Jeff N. Borchert, Vance Brown, Grace D. Appiah, Eric D. Mintz, Jaco Homsy, George S. Odongo, Raymond L. Ransom, Molly M. Freeman, Robyn A. Stoddard, Renee Galloway, Matthew Mikoleit, Cecilia Kato, Ronald Rosenberg, Eric C. Mossel, Paul S. Mead and Kiersten J. Kugeler},

doi = {https://doi.org/10.1089/hs.2018.0051},

year  = {2018},

date = {2018-11-27},

journal = {Health Security},

volume = {16},

number = {S1},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Bachmann2018,

title = {Importance of routine viral load monitoring: higher levels of resistance at ART failure in Uganda and Lesotho compared with Switzerland},

author = {Nadine Bachmann, Amrei von Braun, Niklaus D Labhardt, Claus Kadelka, Huldrych F Günthard, Christine Sekaggya-Wiltshire, Barbara Castelnuovo, Andrew Kambugu, Thabo I Lejone, Jürg Böni, Sabine Yerly, Matthieu Perreau, Thomas Klimkait, Roger D Kouyos, Jan Fehr, the Swiss HIV Cohort Study },

doi = {https://doi.org/10.1093/jac/dky436},

year  = {2018},

date = {2018-11-21},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {74},

number = {2},

pages = {468–472},

abstract = {Objectives



Emerging resistance to antiretroviral drugs may jeopardize the achievements of improved access to ART. We compared the prevalence of different resistance mutations in HIV-infected adults with virological failure in a cohort with regular routine viral load (VL) monitoring (Switzerland) and cohorts with limited access to VL testing (Uganda and Lesotho).



Methods



We considered individuals who had genotypic resistance testing (GRT) upon virological failure (≥1000 copies/mL) and were on ART consisting of at least one NNRTI and two NRTIs. From Lesotho, individuals with two subsequent VLs ≥1000 copies/mL despite enhanced adherence counselling (n = 58) were included in the analysis. From Uganda, individuals with a single VL ≥1000 copies/mL (n = 120) were included in the analysis. From the Swiss HIV Cohort Study (SHCS), a population without history of monotherapy or dual therapy with the first GRT upon virological failure (n = 61) was selected.



Results



We found that 50.8% of individuals in the SHCS, 72.5% in Uganda and 81.0% in Lesotho harboured HIV with high-level resistance to at least two drugs from their current regimen. Stanford resistance scores were higher in Uganda compared with Switzerland for all drugs used in first-line treatment except zidovudine and tenofovir (P < 0.01) and higher in Lesotho compared with Uganda for all drugs used in first-line treatment except zidovudine (P < 0.01).



Conclusions



Frequent VL monitoring and possibly pretreatment GRT as done in the SHCS pays off by low levels of resistance even when treatment failure occurs. The high-level resistance patterns in Lesotho compared with Uganda could reflect a selection of strains with multiple resistance during enhanced adherence counselling.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Gini2018,

title = {Validation and clinical application of a novel LC–MS method for quantification of dolutegravir in breast milk},

author = {Joshua Gini, Sujan Dilly Penchala, Alieu Amara, Elizabeth Challenger, Deirdre Egan, Catriona Waitt, Mohammed Lamorde, Catherine Orrell, Landon Myer, Saye Khoo & Laura J Else},

doi = {https://doi.org/10.4155/bio-2018-0085},

year  = {2018},

date = {2018-11-19},

journal = {Bioanalysis},

volume = {10},

number = {23},

abstract = {Aim: A novel, sensitive and reproducible method for quantification of dolutegravir (DTG) in dried breast milk spots (DBMS) was developed and validated for use in clinical studies. Its application enabled measurement of DTG pharmacokinetics in breastfeeding mothers and their infants. Results/methodology: Sample extraction was by liquid–liquid extraction using tert-butyl methy-ether, with DTG–d5 as an internal standard. DTG was eluted on a reverse phase C18 Waters XBridge (3.5 μm: 2.1 × 50 mm) column using a gradient mobile phase consisting of 0.1% formic acid in deionised water or methanol. The assay was validated over a calibration range of 10–4000 ng/ml. Conclusion: Stability, inter and intra-assay variability were acceptable according to FDA and EMA bioanalytical method guidelines. The assay is robust, accurate, precise and can be reliably applied for analysis of clinical samples in trials from low resource settings.



Keywords:

antiretroviralbreast milkclinical trialdolutegravirHIVmass spectrometrypharmacokineticsvalidation},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Bakeera-Kitaka2018,

title = {Factors Influencing the Risk of Becoming Sexually Active Among HIV Infected Adolescents in Kampala and Kisumu, East Africa},

author = {Sabrina Bakeera-Kitaka, Tom Smekens, Vicky Jespers, Eric Wobudeya, Jasna Loos, Robert Colebunders, Daniel Adipo, Adeodata Kekitiinwa, Philippa Musoke, Anne Buve & Christiana Nöstlinger },

doi = {https://doi.org/10.1007/s10461-018-2323-y},

year  = {2018},

date = {2018-11-17},

journal = {AIDS and Behavior},

pages = {1375–1386},

abstract = {About 2.1 million adolescents aged 10–19 years are living with HIV, 80% of them in sub-Saharan Africa. Early sexual activity remains an important risk factor for HIV transmission and potentially result in negative health consequences including onward transmission of sexually transmitted infections. Cross-sectional data of 580 adolescents living with HIV (ALHIV) aged 13–17 years (317 girls and 263 boys) from Kenya and Uganda were analyzed to assess factors associated with risk to become sexually active. Factors associated with risk of sexual intercourse were identified using Kaplan–Meier survival curves and Cox regression with gender-stratified bi-and multivariable models. Slightly more females (22%) than males (20%) reported they have had sex. Multivariable models showed that being aware of one’s own HIV infection, and receiving antiretroviral treatment were negatively associated with risk of becoming sexually active, while subjective norms conducive to sexuality, and girls’ poor health experience increased the risk. In the final multi-variable models, schooling was protective for girls, but not for boys. Being more popular with the opposite sex was negatively associated with the outcome variable only for girls, but not for boys. This study expands the knowledge base on factors associated with onset of sexual activity among ALHIV, potentially informing positive prevention interventions.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Reuterswärd2018,

title = {Levels of human proteins in plasma associated with acute paediatric malaria},

author = {Philippa Reuterswärd, Sofia Bergström, Judy Orikiiriza, Elisabeth Lindquist, Sven Bergström, Helene Andersson Svahn, Burcu Ayoglu, Mathias Uhlén, Mats Wahlgren, Johan Normark, Ulf Ribacke & Peter Nilsson },

doi = {https://doi.org/10.1186/s12936-018-2576-y},

year  = {2018},

date = {2018-11-15},

journal = {Malaria Journal },

volume = {17},

number = {426},

abstract = {Background



The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts.



Results



An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values < 0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values < 10−14) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values < 0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria.



Conclusion



In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Mustapha2018,

title = {Utilization of “prevention of mother-to-child transmission” of HIV services by adolescent and young mothers in Mulago Hospital, Uganda},

author = {Mariama Mustapha, Victor Musiime, Sabrina Bakeera-Kitaka, Joseph Rujumba & Nicolette Nabukeera-Barungi },

year  = {2018},

date = {2018-11-14},

journal = {BMC Infectious Diseases},

abstract = {Background



Prevention of mother to child transmission (PMTCT) has lowered the incidence of paediatric HIV globally. The risk of mother-to-child transmission of HIV (MTCT) remains high in Africa, where there is a high prevalence of pregnancy and poor health-seeking behaviour among young girls and women.



Methods



In this cross-sectional, mixed-methods study, we evaluated the utilization of PMTCT services and associated factors among adolescent and young postpartum mothers aged 15 to 24 years at a public urban referral hospital in Uganda. Both HIV-positive and HIV-negative participants were recruited. Utilization of PMTCT services was defined as use of the PMTCT cascade of services including ever testing for HIV, receiving HIV test results; If tested negative, subsequent retesting up to 14 weeks; If tested positive, Antiretroviral drugs (ARVs) for the mother, ARVs and septrin prophylaxis for infant, safe delivery, safer infant feeding, early infant diagnosis within 6 weeks, and linkage to treatment and care. Optimal utilization of PMTCT was defined as being up to date with utilization of PMTCT services for reported HIV status at the time of being interviewed. The overall proportion of participants who optimally utilized PMTCT services was determined using descriptive statistics. Qualitative data was analyzed manually using the content thematic approach.



Results



Of the 418 participants, 65 (15.5%) were HIV positive. Overall, only 126 of 418 participants (30.1%) had optimally utilized PMTCT services. However, utilization of PMTCT services was better among HIV positive mothers, with 83% (54/65) having utilized the services optimally, compared to only 20% (72/353) of the HIV negative mothers (OR 18.2 (95% CI; 9.0–36.7)). The benefits of knowing ones HIV status, health of the unborn child, and counseling and support from health workers and peers, were the major factors motivating adolescent and young mothers to utilize PMTCT services, while stigma, financial constraints, non-disclosure, and lack of partner and family support were key demotivating factors.



Conclusion



Utilization of PMTCT services by these adolescent and young mothers was suboptimal. Special consideration should be given to adolescents and young women in the design of elimination of mother to child transmission (EMTCT) programs, to improve the utilization of PMTCT services.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Bukusi2018,

title = {Mentorship and Ethics in Global Health: Fostering Scientific Integrity and Responsible Conduct of Research},

author = {Elizabeth A. Bukusi, Yukari C. Manabe and Joseph R. Zunt},

doi = {doi: 10.4269/ajtmh.18-0562},

year  = {2018},

date = {2018-11-14},

journal = {American Journal of Tropical Medicine and Hygiene},

pages = {42–47},

abstract = {Addressing ethical issues through mentorship is key to encouraging scientific integrity and increasing research capacity. Across the global health arena, mentorship requires helping mentees understand and negotiate the regulatory aspects of research—which can substantially differ even between countries with similar resources. Mentorship support spans across the research framework from obtaining ethical approval and ensuring scientific integrity, to determining authorship and disseminating study results—providing multiple opportunities to model ethical behavior for mentees. The power imbalances between the global north and south in accessing funding resources produce further challenges in setting the research agenda and for ensuring equity in the dissemination of research findings. Gender further complicates the aspiration for equity; the proportion of women in high administrative or research positions remains low. This study explores four specific mentoring case scenarios commonly encountered in the global health research field in low- and middle-income institutions.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Walimbwa2018,

title = {Drug Interactions between Dolutegravir and Artemether-Lumefantrine or Artesunate-Amodiaquine},

author = {Stephen I. Walimbwa, Mohammed Lamorde, Catriona Waitt, Julian Kaboggoza, Laura Else, Pauline Byakika-Kibwika, Alieu Amara, Joshua Gini, Markus Winterberg, Justin Chiong, Joel Tarning Saye H. Khoo},

doi = {https://doi.org/10.1128/AAC.01310-18},

year  = {2018},

date = {2018-11-12},

journal = {Antimicrobial Agents and Chemotherapy},

volume = {63},

number = {2},

abstract = {Across sub-Saharan Africa, patients with HIV on antiretrovirals often get malaria and need cotreatment with artemisinin-containing therapies. We undertook two pharmacokinetic studies in healthy volunteers, using standard adult doses of artemether-lumefantrine or artesunate-amodiaquine given with 50 mg once daily dolutegravir (DTG) to investigate the drug-drug interaction between artemether-lumefantrine or artesunate-amodiaquine and dolutegravir. The dolutegravir/artemether-lumefantrine interaction was evaluated in a two-way crossover study and measured artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine over 264 h. The dolutegravir/artesunate-amodiaquine interaction was investigated using a parallel study design due to long half-life of the amodiaquine metabolite, desethylamodiaquine and measured artesunate, amodiaquine, and desethylamodiaquine over 624 h. Noncompartmental analysis was performed, and geometric mean ratios and 90% confidence intervals were generated for evaluation of both interactions. Dolutegravir did not significantly change the maximum concentration in plasma, the time to maximum concentration, and the area under the concentration-time curve (AUC) for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine, nor did it significantly alter the AUC for artesunate, dihydroartemisinin, amodiaquine, and desethylamodiaquine. Coadministration of dolutegravir with artemether-lumefantrine resulted in a 37% decrease in DTG trough concentrations. Coadministration of dolutegravir with artesunate-amodiaquine resulted in 42 and 24% approximate decreases in the DTG trough concentrations and the AUC, respectively. The significant decreases in DTG trough concentrations with artemether-lumefantrine and artesunate-amodiaquine and dolutegravir exposure with artesunate-amodiaquine are unlikely to be of clinical significance since the DTG trough concentrations were above dolutegravir target concentrations of 300 ng/ml. Study drugs were well tolerated with no serious adverse events. Standard doses of artemether-lumefantrine and artesunate-amodiaquine should be used in patients receiving dolutegravir. (This study has been registered at ClinicalTrials.gov under identifier NCT02242799.)},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Chen2018,

title = {Paediatric immunisation and chemoprophylaxis in a Ugandan sickle cell disease clinic},

author = {Chung-Jen Chen, Sabrina Bakeera-Kitaka, Ezekiel Mupere, Philip Kasirye, Deogratias Munube, Richard Idro, Heather Hume, Betsy Pfeffer, Philip LaRussa, Nancy S Green},

doi = { https://doi.org/10.1111/jpc.14291},

year  = {2018},

date = {2018-11-09},

journal = {Journal of Paediatrics and Child Health},

volume = {55},

number = {7},

pages = {795-801},

abstract = {Aim



We aimed to assess the receipt of recommended care for young children with sickle cell disease (SCD) in a central SCD clinic in Kampala Uganda, focusing on standard vaccination and antibacterial and antimalarial prophylaxis.



Methods



A cross-sectional assessment of immunisation status and timeliness and prescribed antibacterial and antimalarial prophylaxis was performed in a sample with SCD aged ≤71 months in Mulago Hospital SCD Clinic. Government-issued immunisation cards and clinic-issued visit records for prescribed prophylaxis were reviewed.



Results



Vaccinations were documented by immunisation cards in 104 patients, mean age 31.7 months (range 3–70 months). Only 48 (46.2%) received all doses of each of the four recommended vaccine types, including pneumococcal 10-valent conjugate vaccine (pneumococcal conjugate vaccine (PCV)-10), which became available in 2014. Vaccination completion was associated with younger age and, for polio, maternal employment. PCV-10 series was completed in 54.8% of the sample and in 18.2% of those aged 48–71 months. Of children completing all vaccination types, an average 68.8% were immunised on time, defined as <60 days beyond the recommended age. Only 17 (13.5%) children were both fully and timely vaccinated. In an overlapping sample of 147 children, with a mean age of 38.4 months (4–70 months), 81.6% had ≥1 documented prescription for penicillin and/or antimalarial prophylaxis.

 

Conclusions



Standardised vaccination and antibacterial and antimalarial protective measures for young children at this central SCD clinic were incomplete, especially PCV-10 for age ≥24 months, and often late. Child age, but not general maternal demographics, were associated with vaccination and chemoprophylaxis. Clinic-based oversight may improve timely uptake of these preventative measures.

},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Kalanzi2018,

title = {Extensive dental caries in a HIV positive adult patient on ART; case report and literature review},

author = {Dunstan Kalanzi, Harriet Mayanja-Kizza, Damalie Nakanjako & Nelson K. Sewankambo },

doi = {https://doi.org/10.1186/s12903-018-0675-3},

year  = {2018},

date = {2018-11-07},

journal = {BMC Oral Health},

volume = {18},

number = {205},

abstract = {Background



The estimated number of people living with human immunodeficiency virus (HIV) (PLHIV) in Uganda is 1.5 million (7.3%). As of June 2016, 60% (898,197) of PLHIV were enrolled and receiving antiretroviral therapy (ART). In scientific literature, the effect of HIV and ART on dental caries remains equivocal. At the Prosthetics Clinic of the Department of Dentistry, Makerere University College of Health Sciences, we have seen a number of PLHIV who require replacement of missing teeth with partial or complete dentures as a result of extensive caries. Here we report a case of an HIV positive female patient with extensive dental caries resulting in complete edentulous jaws, associated with psychological stress and stigmatization.



Case presentation



A 52-year-old patient, HIV positive for fourteen (14) years and receiving antiretroviral therapy (ART) for the last four years wanted to replace her missing teeth for effective feeding and cosmetic reasons. A diagnosis of partially edentulous maxillary and mandibular arches, cervical caries of tooth # 12, 15, 25, 34 and retained roots of tooth # 11, 13, 22 and 35 was made. Following oral health education and mouth preparation, this patient received a set of removable acrylic full upper and lower dentures.



Conclusion



This case may represent the long-term effects of HIV and ART on oral health status especially tooth surfaces in some PLHIV. Further evaluation is required to ascertain if this was an isolated case or it is a common finding among HIV positive adult patients receiving long-term ART in sub-Saharan Africa. Information emerging from these studies would establish the magnitude of dental caries among PLHIV and guide the development of appropriate oral health care guidelines in the management of people living with HIV.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Muwonge2018,

title = {Short Message Service (SMS) Surveys Assessing Pre-exposure Prophylaxis (PrEP) Adherence and Sexual Behavior are Highly Acceptable Among HIV-Uninfected Members of Serodiscordant Couples in East Africa: A Mixed Methods Study},

author = {Timothy R. Muwonge, Kenneth Ngure, Elly Katabira, Nelly Mugo, Grace Kimemia, Bridget Frances O’Rourke Burns, Nicholas Musinguzi, Felix Bambia, Jared M. Baeten, Renee Heffron, Jessica E. Haberer & the Partners Mobile Adherence to PrEP (PMAP) Team},

doi = { https://doi.org/10.1007/s10461-018-2326-8},

year  = {2018},

date = {2018-11-07},

journal = {AIDS and Behavior},

volume = {23},

pages = {1267–1276},

abstract = {Short message service (SMS) surveys are a promising data collection method and were used to measure sexual behavior and adherence to HIV pre-exposure prophylaxis (PrEP) among HIV-uninfected partners of serodiscordant couples enrolled in a sub-study of the Partners Demonstration Project (an open-label study of integrated antiretroviral therapy and PrEP for HIV prevention in Kenya and Uganda). Questionnaires were completed by 142 participants after study exit. Median age was 29 years; 69% were male. Ninety-five percent (95%) felt SMS surveys were “easy” or “very easy”, 74% reported no challenges, and 72% preferred SMS surveys over in-person study visits. Qualitative interviews involving 32 participants confirmed the ease of responding to SMS surveys. Participants also indicated that surveys acted as reminders for adherence to PrEP and condom use and were experienced as support from the study. SMS surveys were generally found to be acceptable in this population and provided real-time context of PrEP use.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Mabonga2018,

title = {Complete ciprofloxacin resistance in gonococcal isolates in an urban Ugandan clinic: findings from a cross-sectional study },

author = {Emily Mabonga, Rosalind Parkes-Ratanshi, Stefan Riedel, Sheila Nabweyambo, Olive Mbabazi, Chris Taylor, Charlotte Gaydos, Yukari C Manabe},

doi = {https://doi.org/10.1177/0956462418799017},

year  = {2018},

date = {2018-11-04},

journal = {International Journal of STDs & AIDS},

volume = {30},

number = {3},

pages = {256-263},

abstract = {Antimicrobial resistance (AMR) to gonorrhoea is a threat to global health security. There have been concerns expressed that countries with high rates of disease have poor surveillance. The objectives of the study were to determine the AMR patterns of Neisseria gonorrhoeae clinical isolates to antimicrobial agents in patients with HIV or high risk of HIV acquisition, to compare the concordance of disk diffusion and agar dilution as methods for determining AMR to N. gonorrhoeae, and to describe methodological challenges to carrying out AMR testing. The study was conducted at an HIV outpatient service for at-risk populations and an outreach clinic for commercial sex workers in Kampala. Patients were offered a sexually transmitted infection screen using a polymerase chain reaction (PCR)-based assay. Samples positive for gonorrhoea were cultured. Antimicrobial susceptibility testing was performed using disk diffusion and isolates were sent to a reference laboratory for agar dilution direct susceptibility testing. Five hundred and seventy-five patients were screened. There were 33 (5.7%) patients with gonorrhoea detected by PCR. Of the 16 viable N. gonorrhoeae isolates, 100% were resistant to ciprofloxacin and tetracycline by disk diffusion and 31% exhibited reduced susceptibility to ceftriaxone and cefixime. By agar dilution, 100% of isolates were resistant to ciprofloxacin and all isolates were susceptible to ceftriaxone and cefixime. There was concordance between disk diffusion and agar dilution for ciprofloxacin and tetracycline resistance and a significant discordance for third-generation cephalosporins. More than half the women with gonorrhoea were asymptomatic and represent a potential reservoir for ongoing transmission. AMR testing of N. gonorrhoeae isolates is needed to ensure optimal treatment and prevention of antibiotic resistance progression.



Keywords

Gonorrhoea, sexually transmitted infections, antimicrobial resistance, HIV},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Davis2018,

title = {Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa Have Unknown Susceptibility to Direct-Acting Antiviral Treatments},

author = {Chris Davis, George S. Mgomella, Ana da Silva Filipe, Eric H. Frost, Genevieve Giroux, Joseph Hughes, Catherine Hogan, Pontiano Kaleebu, Gershim Asiki, John McLauchlan, Marc Niebel, Ponsiano Ocama, Cristina Pomila, Oliver G. Pybus, Jacques Pépin, Peter Simmonds, Joshua B. Singer, Vattipally B. Sreenu, Clara Wekesa, Elizabeth H. Young, Donald G. Murphy, Manj Sandhu, Emma C. Thomson},

doi = { https://doi.org/10.1002/hep.30342},

year  = {2018},

date = {2018-11-02},

journal = {Hepatology},

volume = {69},

number = {4},

pages = {1426-1441},

abstract = {The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub-Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population-based, nested case-control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next-generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR-positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well-resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Olson2018,

title = {Pulmonary Tuberculosis Is Associated With Persistent Systemic Inflammation and Decreased HIV-1 Reservoir Markers in Coinfected Ugandans},

author = {Alex Olson, Elizabeth J. Ragan, Lydia Nakiyingi, Nina Lin, Karen R. Jacobson, Jerrold J. Ellner, Yukari C. Manabe, and Manish Sagar},

doi = {doi: 10.1097/QAI.0000000000001823},

year  = {2018},

date = {2018-11-01},

journal = {J Acquir Immune Defic Syndr.},

volume = {79},

number = {3},

pages = {407-311},

abstract = {Mycobacterium tuberculosis (TB) infection induces systemic inflammation that could impact HIV-1 persistence.



Setting

HIV-1–seropositive individuals either with or without pulmonary TB disease were recruited in Kampala, Uganda.



Methods

Plasma cytokines, HIV-1 DNA, and cell-associated (ca)-RNA were compared among those coinfected with TB (cases) to those without TB (controls). TB-coinfected cases and controls were compared at presentation (n = 15 and n = 16, respectively) and at around 6 months after HIV-1 treatment initiation among those who had achieved virologic suppression (n = 6 and n = 8, respectively). At follow-up, the TB-coinfected cases had also finished TB treatment.



Results

Before treatment, the TB-coinfected cases as compared to the controls had higher levels of soluble(s)-CD163 (P = 0.0002) and interleukin-6 (P = 0.006) but lower levels of macrophage chemoattractant protein-1 (P = 0.04). After treatment, the TB-coinfected cases as compared to controls still had higher plasma s-CD163 levels (P = 0007). Controls as compared to the coinfected cases had higher ca-RNA per DNA template both at baseline (P = 0.03) and at follow-up (P = 0.07). Levels of ca-RNA per DNA copy at follow-up showed a negative correlation with baseline plasma s-CD163 (P = 0.008) and interleukin-6 (P = 0.05) levels.



Conclusions

TB disease is associated with inflammation and decreased HIV-1 RNA expression relative to the number of infected cells, both before and after viral suppression. Infections present before antiretroviral initiation impact HIV-1 latency.



Keywords: HIV-1 latency, tuberculosis, cell-associated HIV RNA, inflammation, viral transcription},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Weissberg2018,

title = {Ten years of antiretroviral therapy: Incidences, patterns and risk factors of opportunistic infections in an urban Ugandan cohort},

author = {Dana Weissberg , Frank Mubiru, Andrew Kambugu, Jan Fehr, Agnes Kiragga, Amrei von Braun, Anna Baumann, Marisa Kaelin, Christine Sekaggya-Wiltshire, Moses Kamya, Barbara Castelnuovo},

doi = {https://doi.org/10.1371/journal.pone.0206796 },

year  = {2018},

date = {2018-11-01},

journal = {PLOS},

abstract = {Background



Despite increased antiretroviral therapy (ART) coverage and the raised CD4 threshold for starting ART, opportunistic infections (OIs) are still one of the leading causes of death in sub-Saharan Africa. There are few studies from resource-limited settings on long-term reporting of OIs other than tuberculosis.



Methods



Patients starting ART between April 2004 and April 2005 were enrolled and followed-up for 10 years in Kampala, Uganda. We report incidences, patterns and risk factors using Cox proportional hazards models of OIs among all patients and among patients with CD4 cell counts >200 cells/μL.



Results



Of the 559 patients starting ART, 164 patients developed a total of 241 OIs during 10 years of follow-up. The overall incidence was highest for oral candidiasis (25.4, 95% confidence interval (CI): 20.5–31.6 per 1000 person-years of follow-up), followed by tuberculosis (15.3, 95% CI: 11.7–20.1), herpes zoster (12.3, 95% CI: 9.1–16.6) and cryptococcal meningitis (3.0, 95% CI: 1.7–5.5). Incidence rates for all OIs were highest in the first year after ART initiation and decreased with the increase of the current CD4 cell count. Factors independently associated with development of OIs were baseline nevirapine-based regimens, time-varying higher viral load, time-varying lower CD4 cell count and time-varying lower hemoglobin. In patients developing OIs at a current CD4 cell count >200 cells/μL, factors independently associated with OI development were time-varying increase in viral load and time-varying decrease in hemoglobin, whereas a baseline CD4 cell count <50 cells/μL was protective.



Conclusion



We report high early incidences of OIs, decreasing with increasing CD4 cell count and time spent on ART. Ongoing HIV replication and anemia were strong predictors for OI development independent of the CD4 cell count. Our findings support the recommendation for early initiation of ART and suggest close monitoring for OIs among patients recently started on ART, with low CD4 cell count, high viral load and anemia.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Zawedde-Muyanja2018b,

title = {Decentralisation of child tuberculosis services increases case finding and uptake of preventive therapy in Uganda},

author = {Zawedde-Muyanja, S Nakanwagi, A. Dongo, J. P. Sekadde, M. P. Nyinoburyo, R.; Ssentongo, G.  Detjen, A. K. Mugabe, F.  Nakawesi, J. Karamagi, Y. Amuge, P. Kekitiinwa, A. Graham, S. M. },

doi = {DOI: https://doi.org/10.5588/ijtld.18.0025},

year  = {2018},

date = {2018-11-01},

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

volume = {22},

number = {11},

pages = {1314-1321},

abstract = {BACKGROUND: 

A lack of capacity to diagnose tuberculosis (TB) in children at peripheral health facilities and limited contact screening and management contribute to low case finding in TB-endemic settings.



OBJECTIVE: 

To evaluate the implementation of a pilot project that strengthened diagnosis, treatment and prevention of child TB at peripheral health facilities in Uganda.



METHODS: 

In June 2015, health care workers at peripheral health facilities were trained to diagnose and treat child TB. Community health care workers were trained to screen household TB contacts. Before-and-after analysis as well as comparisons with non-intervention districts were used to evaluate impact on caseload and treatment outcomes.



RESULTS: 

By December 2016, the average number of children (age < 15 years) diagnosed with TB increased from 45 to 108 per quarter. The proportion of child TB among all TB cases increased from 8.8% to 15%, and the proportion completing treatment increased from 65% to 82%. Of 2270 child TB contacts screened, 55 (2.4%) were diagnosed with TB. Of 910 eligible child contacts, 670 (74%) started preventive therapy, 569 (85%) of whom completed therapy.



CONCLUSION: 

The strengthening of child TB services at peripheral health facilities in Uganda was associated with increased case finding, improved treatment outcomes and the successful implementation of contact screening and management. },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Byakika‑Kibwika2018,

title = {Assessment of parasite clearance following treatment of severe malaria with intravenous artesunate in Ugandan children enrolled in a randomized controlled clinical trial},

author = {Pauline Byakika‑Kibwika , Patience Nyakato, Mohammed Lamorde and Agnes N. Kiragga},

doi = {https://doi.org/10.1186/s12936‑018‑2552‑6},

year  = {2018},

date = {2018-10-30},

journal = {Malaria Journal},

volume = {17},

number = {1},

abstract = {Abstract

Background: 



Malaria control largely depends on availability of highly efficacious drugs, however, over the years, has

been threatened by emergence of drug resistance. It is, therefore, important to monitor the impact of recurrent anti‑

malarial treatment on the long‑term efficacy of anti‑malarial regimens, especially in sub‑Saharan African countries

with high malaria transmission. Evaluation of parasite clearance following treatment of severe malaria with intrave‑

nous artesunate among patients in Eastern Uganda, was performed, as a contribution to monitoring anti‑malarial

effectiveness.



Methods:



Parasite clearance data obtained from a clinical trial whose objective was to evaluate the 42‑day para‑

sitological treatment outcomes and safety following treatment of severe malaria with intravenous artesunate plus

artemisinin‑based combination therapy among patients attending Tororo District Hospital in Eastern Uganda, were

analysed. Serial blood smears were performed at 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 h, followed by 6‑hourly blood smears

post start of treatment until 6 h post the first negative blood smear when parasite clearance was achieved. Study

endpoints were; parasite clearance half‑life (the time required for parasitaemia to decrease by 50% based on the linear

portion of the parasite clearance slope) and parasite clearance time (time required for complete clearance of initial

parasitaemia).



Results: 



One hundred and fifty participants with severe malaria were enrolled. All participants were treated with

intravenous artesunate. All study participants tolerated artesunate well with rapid recovery from symptoms and ability

to take oral mediation within 24 h. No immediate adverse events were recorded. The median (IQR) number of days to

complete parasite clearance was of 2 (1–2). The median (IQR) time to clear 50% and 99% parasites was 4.8 (3.61–7.10)

and 17.55 (14.66–20.66) h, respectively. The median estimated clearance rate constant per hour was 0.32. The median

(IQR) slope half‑life was 2.15 (1.64, 2.61) h.



Conclusion: 



Parasite clearance following treatment with intravenous artesunate was rapid and adequate. This find‑

ing provides supportive evidence that resistance to artemisinins is unlikely to have emerged in this study area. Con‑

tinuous monitoring of artemisinin effectiveness for malaria treatment should be established in high malaria transmis‑

sion areas in sub‑Saharan Africa where spread of resistance would be disastrous.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Nabaggala2018,

title = {Re-engagement in HIV care following a missed visit in rural Uganda},

author = {

Maria Sarah Nabaggala, Rosalind Parkes-Ratanshi, Ronnie Kasirye, Agnes Kiragga, Barbara Castlenuovo, Ian Ochaka, Lilian Nakakawa, Diana Asiimwe Bena, Andrew Mujugira

},

doi = {doi: 10.1186/s13104-018-3865-9. },

year  = {2018},

date = {2018-10-25},

journal = {BMC Research Notes},

volume = {11},

number = {1},

pages = {762},

abstract = {Objective: 

We conducted a retrospective cohort study to assess the effect of tracking People Living with HIV (PLHIV) after missed clinic visits and factors associated with return to care in rural Uganda. We assessed retention in care among 650 HIV-infected women and men. We used univariable and multivariable generalized linear models to assess demographic and self-reported factors associated with re-engagement in HIV care.



Results: 

Of 381 PLHIV who ever missed a scheduled appointment, 68% were female and most (80%) had initiated ART. Most (70%) of those tracked returned to care. Relative to men, women (adjusted risk ratio [ARR] 1.23; 95% confidence interval (CI) 1.05-1.43; p = 0.009) were more likely to return to care after active tracking. PLHIV who missed scheduled visits for other reasons (forgetting, adequate drug supplies, or long distance to clinic) had reduced odds of return to care (ARR 0.41; 95% CI 0.28-0.59; p < 0.001). These data support close monitoring of patient retention in HIV care and active measures to re-engage those who miss an appointment. Furthermore, they highlight the need for targeted interventions to those more resistant to re-engagement such as men.



Keywords: ART; HIV; PLHIV tracking; Retention; Return to care. },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Kiwanuka2018,

title = {Retention of HIV infected pregnant and breastfeeding women on option B+ in Gomba District, Uganda: a retrospective cohort study},

author = {George Kiwanuka, Noah Kiwanuka , Fiston Muneza , Juliet Nabirye, Frederick Oporia , Magdalene A. Odikro, Barbara Castelnuovo and Rhoda K. Wanyenze },

doi = {https://doi.org/10.1186/s12879-018-3450-9 },

year  = {2018},

date = {2018-10-24},

journal = {BMC Infectious Diseases },

volume = {18},

number = {533},

abstract = {Background: 

Lifelong antiretroviral therapy for HIV infected pregnant and lactating women (Option B+) has been

rapidly scaled up but there are concerns about poor retention of women initiating treatment. However, facility-

based data could underestimate retention in the absence of measures to account for self-transfers to other facilities.

We assessed retention-in-care among women on Option B+ in Uganda, using facility data and follow-up to

ascertain transfers to other facilities.



Methods:

In a 25-month retrospective cohort analysis of routine program data, women who initiated Option B+

between March 2013 and March 2015 were tracked and interviewed quantitatively and qualitatively (in-depth interviews).

Kaplan Meier survival analysis was used to estimate time to loss-to-follow-up (LTFU) while multivariable Cox proportional

hazards regression was applied to estimate the adjusted predictors of LTFU, based on facility data. Thematic analysis was

done for qualitative data, using MAXQDA 12. Quantitative data were analyzed with STATA® 13.



Results: 

A total of 518 records were reviewed. The mean (SD) age was 26.4 (5.5) years, 289 women (55.6%) attended

primary school, and 53% (276/518) had not disclosed their HIV status to their partners. At 25 months post-ART initiation,

278 (53.7%) were LTFU based on routine facility data, with mean time to LTFU of 15.6 months. Retention was 60.2 per

1000 months of observation (pmo) (95% CI: 55.9–64.3) at 12, and 46.3/1000pmo (95% CI: 42.0–50.5) at 25 months. Overall,

237 (55%) women were successfully tracked and interviewed and 43/118 (36.4%) of those who were classified as LTFU at

facility level had self-transferred to another facility. The true 25 months post-ART initiation retention after tracking was

71.3% (169/237). Women < 25 years, aHR = 1.71 (95% CI: 1.28–2.30); those with no education, aHR = 5.55 (95% CI: 3.11–

9.92), and those who had not disclosed their status to their partners, aHR = 1.59 (95% CI: 1.16–2.19) were more likely to

be LTFU. Facilitators for Option B+ retention based on qualitative findings were adequate counselling, disclosure, and

the desire to stay alive and raise HIV-free children. Drug side effects, inadequate counselling, stigma, and unsupportive

spouses, were barriers to retention in care.



Conclusions: 

Retention under Option B+ is suboptimal and is under-estimated at health facility level. There is need to

institute mechanisms for tracking of women across facilities. Retention could be enhanced through strategies to enhance

disclosure to partners, targeting the uneducated, and those < 25 years.



Keywords: 

EMTCT, PMTCT, Retention, LTFU, HIV, Option B+},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Farr2018,

title = {Diagnostic performance of blood inflammatory markers for tuberculosis screening in people living with HIV},

author = {Katherine Farr, Resmi Ravindran, Luke Strnad, Emily Chang, Lelia H. Chaisson, Christina Yoon, William Worodria, Alfred Andama, Irene Ayakaka, Priscilla Bbosa Nalwanga, Patrick Byanyima, Nelson Kalema, Sylvia Kaswabuli, Winceslaus Katagira, Kyomugisha Denise Aman, Emmanuel Musisi, Nuwagaba Wallen Tumwine, Ingvar Sanyu, Robert Ssebunya, J. Lucian Davis, Laurence Huang, Imran H. Khan, Adithya Cattamanchi

  },

doi = {https://doi.org/10.1371/journal.pone.0206119},

year  = {2018},

date = {2018-10-23},

journal = {PLOS ONE},

volume = {13},

number = {10},

pages = { e0206119},

abstract = {Background



Approaches to screening for active tuberculosis (TB) among people living with HIV are inadequate, leading to missed diagnoses and poor implementation of preventive therapy.



Methods



Consecutive HIV-infected adults hospitalized at Mulago Hospital (Kampala, Uganda) between June 2011 and July 2013 with a cough ≥ 2 weeks were enrolled. Patients underwent extensive evaluation for pulmonary TB. Concentrations of 43 cytokines/chemokines were measured at the same time point as C-reactive protein (CRP) in banked plasma samples using commercially-available multiplex kits. Advanced classification algorithms were used to rank cytokines/chemokines for their ability to identify TB, and to model the specificity of the top-ranked cytokines/chemokines individually and in combination with sensitivity constrained to ≥ 90% as recommended for TB screening.



Results



The median plasma level of 5 biomarkers (IL-6, INF-γ, MIG, CRP, IL-18) was significantly different between patients with and without TB. With sensitivity constrained to 90%, all had low specificity with IL-6 showing the highest specificity (44%; 95% CI 37.4–49.5). Biomarker panels were found to be more valuable than any biomarker alone. A panel combining IFN-γ and IL-6 had the highest specificity (50%; 95% CI 46.7–53.3). Sensitivity remained high (>85%) for all panels among sputum smear-negative TB patients.



Conclusions



Direct measurement of unstimulated plasma cytokines/chemokines in peripheral blood is a promising approach to TB screening. Cytokine/chemokine panels retained high sensitivity for smear-negative TB and achieved improved specificity compared to individual cytokines/chemokines. These markers should be further evaluated in outpatient settings where most TB screening occurs and where other illnesses associated with systematic inflammation are less common.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Okoboi2018,

title = {Risky sexual behavior among patients on long-term antiretroviral therapy: a prospective cohort study in urban and rural Uganda},

author = {Stephen Okoboi, Barbara Castelnuovo, David M. Moore, Joseph Musaazi, Andrew Kambugu, Josephine Birungi, Pontiano Kaleebu, Mastula Nanfuka, Moses R. Kamya & Annelies Van Rie },

doi = {https://doi.org/10.1186/s12981-018-0203-1},

year  = {2018},

date = {2018-10-19},

journal = {AIDS Research and Therapy},

volume = {15},

number = {15},

abstract = {Background



While the effects of initiation of antiretroviral treatment (ART) on risky sexual behavior have been extensively studied, less is known about the long-term changes in risky sexual behavior over time in resource-poor settings.



Methods



We conducted a secondary longitudinal analysis of one rural and one urban cohort of patients who initiated ART in Uganda between April 2004 and July 2007 followed up-to 2016. Data on sexual behavior were collected every 6 months for 3.5 years in individuals on ART ≥ 4 years (baseline) when a behavioral questionnaire was introduced. Risky sexual behavior was defined as sexual intercourse with ≥ 2 partners or inconsistent or no condom use in previous 6 months. We report characteristics overall, and by cohort. We used multivariable generalized estimating equations logistic regression to assess the effects of time on ART on risky sexual behavior.



Results



Of 1012 participants, 402 (39.8%) were urban and 610 (60.2%) were rural residents. Mean age was 42.8 years (SD 8.5). Mean duration of follow-up was 51.3 months (SD 15.3), but longer for urban than rural participants (64.5 vs 36.4 months). Risky sexual behavior declined from 33.1% at baseline to 9.6% after 3.5 years of follow-up in the rural cohort (p ≤ 0.01 for the test of trend) and was unchanged from 9.7% at baseline to 9.9% after 3.5 years in the urban cohort (p = 0.51). Receiving care at a rural clinic (aOR 4.99, 95% CI 3.64–6.84); male gender (aOR 1.66, 95% CI 1.26–2.19) and being younger (aOR 5.60, 95% CI 3.80–8.25 for 18–34 years and aOR 2.34, 95% CI 1.74–3.14 for 35–44 years) were associated with increased odds of risky sexual behavior. Not being married (aOR 0.25; 95% CI 0.19–0.34), and longer time on ART (aOR 0.71 95% CI 0.67–0.76) were associated with reduced odds of risky sex.



Conclusions



We observed a decline in risky sexual behavior in rural people on long-term (≥ 4 years) ART. Rural, male and young individuals had higher odds of self-reported risky sexual behavior. ART programs should continue to emphasize risk reduction practices, especially among people receiving care in rural health facilities, males, younger individuals and those who are married.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Bakesiima2018,

title = {Dyslipidaemias in women using hormonal contraceptives: a cross sectional study in Mulago Hospital Family Planning Clinic, Kampala, Uganda},

author = {Ritah Bakesiima, Pauline Byakika-Kibwika, James K Tumwine, Joan N Kalyango, Gloria Nabaasa, Irene Najjingo, Grace S Nabaggala, Francis Olweny, Charles Karamagi},

doi = {http://dx.doi.org/10.1136/bmjopen-2018-022338},

year  = {2018},

date = {2018-10-18},

journal = {BMJ Open},

volume = {8},

number = {10},

abstract = {Objective To determine the prevalence and factors associated with dyslipidaemias in women using hormonal contraceptives.



Design Cross-sectional study



Setting Mulago Hospital, Kampala, Uganda



Participants Three hundred and eighty-four consenting women, aged 18–49 years, who had used hormonal contraceptives for at least 3 months prior to the study.



Study outcome Dyslipidaemias (defined as derangements in lipid profile levels which included total cholesterol ≥200 mg/dL, high-density lipoprotein <40 mg/dL, triglyceride >150 mg/dL or low-density lipoprotein ≥160 mg/dL) for which the prevalence and associated factors were obtained.



Results The prevalence of dyslipidaemias was 63.3% (95% CI: 58.4 to 68.1). Body mass index (BMI) (PR=1.33, 95% CI: 1.15 to 1.54, p<0.001) and use of antiretroviral therapy (ART) (PR=1.21, 95% CI: 1.03 to 1.42, p=0.020) were the factors significantly associated with dyslipidaemias.



Conclusion Dyslipidaemias were present in more than half the participants, and this puts them at risk for cardiovascular diseases. The high-risk groups were women with a BMI greater than 25 Kg/m2 and those who were on ART. Therefore, lipid profiles should be assessed in women using hormonal contraceptives in order to manage them better.



This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Zahn2018,

title = {Infectious Diseases Physicians: Improving and Protecting the Public’s Health: Why Equitable Compensation Is Critical},

author = {Matthew Zahn, Amesh A Adalja, Paul G Auwaerter, Paul J Edelson, Gail R Hansen, Noreen A Hynes, Amanda Jezek, Rodger D MacArthur, Yukari C Manabe, Colin McGoodwin, Jeffrey S Duchin},

year  = {2018},

date = {2018-10-17},

journal = {Clinical Infectious Diseases},

volume = {69},

number = {2},

pages = {Pages 352–356},

abstract = {Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees.



Keywords:

public health, ID physician workforce, compensation, value of ID physicians



Topic:

communicable diseases disease outbreaks internship and residency students, medical public health medicine nosocomial infection surveillance, medical antimicrobial stewardship workforce prevention 



},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Tugume2018,

title = {HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts},

author = {Lillian Tugume, Joshua Rhein, Kathy Huppler Hullsiek, Edward Mpoza, Reuben Kiggundu, Kenneth Ssebambulidde, Charlotte Schutz, Kabanda Taseera, Darlisha A Williams, Mahsa Abassi, Conrad Muzoora, Abdu K Musubire, Graeme Meintjes, David B Meya, David R Boulware},

doi = {https://doi.org/10.1093/infdis/jiy602 },

year  = {2018},

date = {2018-10-16},

journal = {The Journal of Infectious Diseases},

volume = {219},

number = {6},

pages = {877–883},

abstract = {Background

Cryptococcal meningitis can occur in persons with less-apparent immunosuppression. We evaluated clinical characteristics and outcomes of persons with HIV-related Cryptococcus presenting with higher CD4 counts.



Methods

We enrolled 736 participants from 2 prospective cohorts in Uganda and South Africa from November 2010 to May 2017. We compared participants with CD4 <50, 50–99, or ≥100 cells/μL by clinical characteristics, cerebrospinal fluid (CSF) parameters, and 18-week survival.



Results

Among first episode of cryptococcosis, 9% presented with CD4 ≥100 cells/μL. Participants with CD4 ≥100 cells/μL presented more often with altered mental status (52% vs 39%; P = .03) despite a 10-fold lower initial median CSF fungal burden of 7850 (interquartile range [IQR] 860–65500) versus 79000 (IQR 7400–380000) colony forming units/mL (P < .001). Participants with CD4 ≥100 cells/μL had higher median CSF levels of interferon-gamma, interleukin (IL)-6, IL-8, and IL-13, and lower monocyte chemokine, CCL2 (P < .01 for each). Death within 18 weeks occurred in 47% with CD4 <50, 35% with CD4 50–99, and 40% with CD4 ≥100 cells/μL (P = .04).



Conclusion

HIV-infected individuals developing cryptococcal meningitis with CD4 ≥100 cells/μL presented more frequently with altered mental status despite having 10-fold lower fungal burden and with greater Th2 (IL-13) immune response. Higher CD4 count was protective despite an increased propensity for immune-mediated damage, consistent with damage-response framework.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{RR2018,

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 = {10.12688/wellcomeopenres.14666.2},

year  = {2018},

date = {2018-10-12},

journal = {Welcome Open Access },

volume = {3},

number = {80},

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 = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bayigga2018,

title = {Diversity of vaginal microbiota in sub-Saharan Africa and its effects on HIV transmission and prevention},

author = {Lois Bayigga, David P.Kateete, Deborah J. Anderson, Musa Sekikubo,Damalie Nakanjako},

doi = {https://doi.org/10.1016/j.ajog.2018.10.014},

year  = {2018},

date = {2018-10-12},

journal = {American Journal of Obstetrics and Gynecology},

volume = {220},

number = {2},

pages = {155-166},

abstract = {The vaginal microbial community (“microbiota”) is a key component of the reproductive health of women, providing protection against urogenital infections. In sub-Saharan Africa, there is a high prevalence of bacterial vaginosis, a condition defined by bacterial overgrowth and a shift away from a Lactobacillus-dominated profile toward increased percentages of strict anaerobic species. Bacterial vaginosis is associated with an increased risk of HIV acquisition and transmission, as well as an increased risk of acquiring other sexually transmitted infections, preterm births, and pelvic inflammatory disease. Vaginal microbiota, rich in taxa of strict anaerobic species, disrupts the mucosal epithelial barrier through secretion of metabolites and enzymes that mediate inflammation. Advancements in next-generation sequencing technologies such as whole-genome sequencing have led to deeper profiling of the vaginal microbiome and further study of its potential role in HIV pathogenesis and treatment. Until recently data on the composition of the vaginal microbiome in sub-Saharan Africa have been limited; however, a number of studies have been published that highlight the critical role of vaginal microbiota in disease and health in African women. This article reviews these recent findings and identifies gaps in knowledge about variations in female genital commensal bacteria that could provide vital information to improve the effectiveness of interventions to prevent HIV and other sexually transmitted infections. In addition, we review the effects of pregnancy, contraception, and sexual practices on vaginal microbiome and the potential of vaginal microbiota on HIV transmission and prevention. A better understanding of the role of vaginal microbiota in host susceptibility to HIV infection and its prevention among African women could inform the development of novel local and systemic interventions to minimize new HIV infections among high-risk women.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{MacCarthy2018,

title = {“How am I going to live?”: exploring barriers to ART adherence among adolescents and young adults living with HIV in Uganda},

author = {Sarah MacCarthy, Uzaib Saya, Clare Samba, Josephine Birungi, Stephen Okoboi & Sebastian Linnemayr },

doi = {https://doi.org/10.1186/s12889-018-6048-7},

year  = {2018},

date = {2018-10-04},

journal = {BMC Public Health},

volume = {18},

number = {1158},

abstract = {Background



Studies from sub-Saharan Africa (SSA) document how barriers to ART adherence present additional complications among adolescents and young adults living with HIV. We qualitatively explored barriers to ART adherence in Uganda among individuals age 14–24 to understand the unique challenges faced by this age group.



Methods



We conducted focus group (FG) discussions with Community Advisory Board members (n = 1), health care providers (n = 2), and male and female groups of adolescents age 14–17 (n = 2) and youth age 18–24 (n = 2) in Kampala, Uganda. FGs were transcribed verbatim and translated from Luganda into English. Two investigators independently reviewed all transcripts, developed a detailed codebook, achieved a pooled Cohen’s Kappa of 0.79 and 0.80, and used a directed content analysis to identify key themes.



Results



Four barriers to ART adherence emerged: 1) poverty limited adolescents’ ability to buy food and undercut efforts to become economically independent in their transition from adolescence to adulthood; 2) school attendance limited their privacy, further disrupting ART adherence; 3) family support was unreliable, and youth often struggled with a constant change in guardianship because they had lost their biological parents to HIV. In contrast peer influence, especially among HIV-positive youth, was strong and created an important network to support ART adherence; 4) the burden of taking multiple medications daily frustrated youth, often leading to so-called ‘drug holidays.’ Adolescent and youth-specific issues around disclosure emerged across three of the four barriers.



Conclusions



To be effective, programs and policies to improve ART adherence among youth in Uganda must address the special challenges that adolescents and young adults confront in achieving optimal adherence. For example, training on budgeting and savings practices could help promote their transition to financial independence. School staff could develop strategies to help students take their medications consistently and confidentially. While challenging to extend the range of services provided by HIV clinics, successful efforts will require engaging the family, peers, and larger community of health and educational providers to support adolescents and young adults living with HIV to live longer and healthier lives.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Atherton2018,

title = {Detection of Mycobacterium tuberculosis in urine by Xpert MTB/RIF Ultra: A useful adjunctive diagnostic tool in HIV-associated tuberculosis},

author = {Rachel R. Atherton, Fiona V. Cresswell, Jayne Ellis, Caleb Skipper, Kiiza K. Tadeo, Gerald Mugumya, Vincent Wadda, David B. Meya and David R. Boulware},

doi = {https://doi.org/10.1016/j.ijid.2018.07.007},

year  = {2018},

date = {2018-10-01},

journal = {International Journal of Infectious Diseases},

volume = {75},

pages = { 92-94},

abstract = {In January 2017, the World Health Organisation recommended the Xpert® MTB/RIF Ultra assay (Ultra) for tuberculosis (TB) diagnosis. Ultra offers improved analytical sensitivity when compared with the initial Xpert® MTB/RIF (Xpert) assay for the detection of Mycobacterium tuberculosis. Ultra is therefore likely to be of particular benefit for detecting paucibacillary TB.



We present a case from Uganda demonstrating Ultra positivity in urine from an HIV-infected patient presenting with altered mental status and urinary incontinence, and no other signs of active pulmonary or extrapulmonary TB. This represents the first published instance of a diagnosis of extrapulmonary TB made on the basis of a positive urine Ultra assay.



The use of Ultra on urine may be a useful addition to the diagnostic armamentarium for disseminated TB in persons with HIV co-infection. The diagnostic accuracy of urine Ultra should be characterised further via prospective studies.



Keywords

Mycobacterium tuberculosis, Urine, Xpert MTB/RIF Ultra, Renal tuberculosis},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Ssebambulidde2018,

title = {Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis With Negative Cerebral Spinal Fluid Analysis},

author = {Kenneth Ssebambulidde, Ananta S Bangdiwala, Richard Kwizera, Tadeo Kiiza Kandole, Lillian Tugume, Reuben Kiggundu, Edward Mpoza, Edwin Nuwagira, Darlisha A Williams, Sarah M Lofgren, Mahsa Abassi, Abdu K Musubire, Fiona V Cresswell, Joshua Rhein, Conrad Muzoora, Kathy Huppler Hullsiek, David R Boulware, David B Meya, Adjunctive Sertraline for Treatment of HIV-associated Cryptococcal Meningitis Team },

doi = {https://doi.org/10.1093/cid/ciy817},

year  = {2018},

date = {2018-09-25},

journal = {Clinical Infectious Diseases},

volume = {68},

number = {12},

pages = {2094–2098},

abstract = {Background

Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies.



Methods

We evaluated 1201 human immunodeficiency virus–seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic–symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif.



Results

We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91).



Conclusions

Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity.



Clinical Trials Registration

NCT01802385.

cryptococcal meningitis, HIV, diagnosis, fungal antigen, aseptic meningitis



Topic:

polymerase chain reaction hiv meningitis cryptococcal meningitis fluconazole cerebrospinal fluid cryptococcus cryptococcal polysaccharide test 



Issue Section:

Articles and Commentaries },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{WORODRIA2018,

title = {Opportunistic Diseases Diminish the Clinical Benefit of Immediate Antiretroviral Therapy in HIV-Tuberculosis Co-infected Adults with Low CD4 counts},

author = {William WORODRIA, Victor SSEMPIJJA, Coleen HANRAHAN, Richard SSEGONJA, Abdallah MUHOFWA, Doreen MAZAPKWE, Harriet MAYANJA-KIZZA, Steven J. REYNOLDS, Robert COLEBUNDERS and Yukari C. MANABE},

doi = {doi: 10.1097/QAD.0000000000001941},

year  = {2018},

date = {2018-09-24},

journal = {AIDS},

volume = {35},

number = {15},

pages = {2141–2149},

abstract = {Introduction:



HIV-Tuberculosis (TB) co-infection remains an important cause of mortality in sub-Saharan Africa. Clinical trials have reported early (within 2 weeks of TB therapy) antiretroviral therapy (ART) reduces mortality among HIV-TB co-infected research participants with low CD4 counts, but this has not been consistently observed. We aimed to evaluate the current World Health Organization (WHO) recommendations for ART in HIV-TB co-infected patients on mortality in routine clinical settings.



Methods:



We compared two cohorts before (2008–2010) and after (2012–2013) policy change on ART timing after TB and examined the effectiveness of early versus delayed ART on mortality in HIV-TB co-infected participants with CD4 ≤100 cells/µL. We used inverse probability censoring-weighted Cox models on baseline characteristics to balance the study arms and generated hazard ratios for mortality.



Results:



Of 356 participants with CD4 counts ≤100 cells/µL, 180 were in the delayed while 176 were in the early ART cohorts. Their median age (32.5 years vs 32 years) and baseline CD4 counts (26.5 cells/µL vs 26 cells/µL) respectively were similar. There was no difference in mortality rates of both cohorts. The risk of death increased in participants with a positive Cryptococcal antigen (CrAg) test in both the early ART cohort (aHR = 2.6, 95%CI, 1.0 –6.8; P=0.045) and the delayed ART cohort (aHR = 4.2, 95%CI, 1.9–9.0; P<0.001



Conclusions:



Early ART in patients with HIV-TB co-infection was not associated with reduced risk of mortality in routine care. Asymptomatic Cryptococcal antigenemia increased the risk of mortality in both cohorts.



Keywords: Adult, HIV, Tuberculosis, Antiretroviral Therapy, Mortality},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Musinguzi2018,

title = {Comparison of short messaging service self-reported adherence with other adherence measures in a demonstration project of HIV preexposure prophylaxis in Kenya and Uganda },

author = {Nicholas Musinguzi, Timothy Muwonge , Kenneth Ngure, Elly Katabira, Nelly Mugo, Bridget Frances O'Rourke Burns , Jared M Baeten, Renee Heffron, Jessica E Haberer, Partners Mobile Adherence to PrEP (PMAP) Team

},

doi = {DOI: 10.1097/QAD.0000000000001955 },

year  = {2018},

date = {2018-09-24},

journal = {AIDS},

volume = {32},

number = {15},

pages = {2237-2245},

abstract = {Objective: Short messaging service (SMS) can collect adherence data on a frequent basis and is relatively anonymous, and therefore could potentially reduce recall and social desirability biases prevalent in other self-reported measures.



Methods: We compared SMS self-reported adherence with three self-reported adherence questions (rating of ability to adhere, frequency of doses taken, percentage of doses taken) and two objective adherence measures [electronic adherence monitoring (EAM) and plasma tenofovir levels] using data from HIV-uninfected members of serodiscordant couples enrolled in a preexposure prophylaxis demonstration project in Kenya and Uganda.



Results: Of 373 enrolled participants, 256 (69%) were male and median age at enrolment was 29 years (26, 35). Fifty-two percent were from Kenya and median education at enrolment was 10 years (7,12). Overall, median adherence was 90, 75, 85, 94 and 79%, respectively, for self-report by SMS, rating, frequency, percentage and EAM adherence. Spearman's correlation coefficient between SMS and interviewer-administered self-reported measures was 0.18 for rating and frequency, 0.22 for percentage and 0.14 for EAM (all P < 0.001). The estimated difference in average adherence between SMS and self-reported rating, frequency, percentage adherence and EAM was 8.1 (P < 0.001), 0.3 (P = 0.81), -5.2 (P < 0.001) and 9.5 (P < 0.001), respectively. Area under the receiver-operating curve assessing the ability of SMS self-report to discriminate between detectable and undetectable tenofovir was 0.51.



Conclusion: Our study found low correlation between SMS self-report and other self-reported and objective adherence measures and did not discriminate between detectable and undetectable plasma tenofovir levels. Future use of SMS self-report should explore alternative means for reducing potential biases.

},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Epiu2018,

title = {Estimating the cost and cost-effectiveness for obstetric fistula repair in hospitals in Uganda: a low income country},

author = {Isabella Epiu, Godfrey Alia, John Mukisa, Paula Tavrow, Mohammed Lamorde, Andreas Kuznik},

doi = {https://doi.org/10.1093/heapol/czy078},

year  = {2018},

date = {2018-09-24},

journal = {Health Policy and Planning},

volume = {33},

number = {9},

pages = {999–1008},

abstract = {In Africa, about 33 000 cases of obstetric fistula occur each year. Women with fistula experience debilitating incontinence of urine and/or faeces and are often socially ostracized. Worldwide, Uganda ranks third among countries with the highest burden of obstetric fistula. Obstetric fistula repair competes for scarce resources with other healthcare interventions in resource-limited settings, even though it is surgically efficacious. There is limited documentation of its cost-effectiveness in the most affected settings. We therefore sought to assess the cost-effectiveness of surgical intervention for obstetric fistula in Uganda so as to provide appropriate data for policy-makers to prioritize fistula repair and reduce women’s suffering in similarly burdened countries. We built a decision-analytic model from the perspective of Uganda’s National Health System to estimate the cost-effectiveness of vesico-vaginal and recto-vaginal fistula surgery vs a competing strategy of no surgery for Ugandan women with fistula. Long-term disability outcomes were assessed based on a lifetime Markov state-transition cohort and effectiveness of surgery. Surgical costs were estimated by micro-costing local Ugandan health resources. Disability weights associated with vesico-vaginal, recto-vaginal fistula and mortality rates among the general population in Uganda were based on published sources. The cost of providing fistula repair surgery in Uganda was estimated at $378 per procedure. For a hypothetical 20-year-old woman, surgery was estimated to decrease the lifetime disability burden from 8.53 DALYs to 1.51 DALYs, yielding a cost per DALY averted of $54. The results were robust to variations in model inputs in one-way and probabilistic sensitivity analyses. Surgery for obstetric fistula appears highly cost-effective in Uganda. In similar low-income countries, governments and non-governmental organizations need to prioritize training and strengthening surgical capacity to increase access to fistula surgical care, which would be an important step towards achieving universal health coverage.

Health policy, cost-effectiveness analysis, maternal morbidity and mortality, obstetric fistula in Uganda, low-income countries, health financing, cost analysis



Topic:

cost effectiveness pathologic fistula surgical procedures, operative uganda mortality obstetrics surgery specialty disability disability-adjusted life years health care systems low income sensitivity analysis fistula repair 



Issue Section:

Original Articles },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{vonBraun2018,

title = {High efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a CYP2B6 516 TT genotype on anti-TB treatment},

author = { Amrei von Braun, Barbara Castelnuovo, Bruno Ledergerber, Jessica Cusato, Allan Buzibye, Andrew Kambugu, Jan Fehr, Andrea Calcagno, Mohammed Lamorde, Christine Sekaggya-Wiltshire},

doi = {https://doi.org/10.1093/jac/dky379},

year  = {2018},

date = {2018-09-18},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {71},

number = {1},

pages = {135–138},

abstract = {Objectives



To report the efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults on concomitant anti-TB treatment and analyse factors associated with elevated concentrations in this specific population.



Methods



Serum efavirenz concentrations in TB/HIV-coinfected Ugandan adults on efavirenz-based ART (600 mg daily) were measured onsite at 2, 8, 12 and 24 weeks of concomitant anti-TB treatment, including rifampicin. Genetic analysis was done retrospectively through real-time PCR by allelic discrimination (CYP2B6 516G>T, rs3745274). Univariable and multivariable logistic regression analyses were done to assess factors potentially associated with elevated efavirenz serum concentrations.



Results



A total of 166 patients were included in the analysis. The median age was 34 (IQR = 30–40) years, 99 (59.6%) were male, the median CD4 cell count was 195 (IQR = 71–334) cells/mm3 and the median BMI was 19 (IQR = 17.6–21.5)  kg/m2. Almost half of all patients (82, 49.4%) had at least one efavirenz serum concentration above the reference range of 4 mg/L. The serum efavirenz concentrations of patients with genotype CYP2B6 516 TT were consistently above 4 mg/L and significantly higher than those of patients with GG/GT genotypes: CYP2B6 516 TT 9.6 mg/L (IQR = 7.3–13.3) versus CYP2B6 516 GT 3.4 mg/L (IQR = 2.1–5.1) and CYP2B6 516 GG 2.6 mg/L (IQR = 1.3–4.0) (Wilcoxon rank-sum test: P < 0.0001).



Conclusions



A large proportion of our study participants had at least one efavirenz serum concentration >4 mg/L. The CYP2B6 516 TT genotype was the strongest predictor of high concentration. Physicians should be vigilant that efavirenz serum concentrations may be elevated in patients on concomitant anti-TB treatment and that individualized care is warranted whenever possible.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Nuwagaba-Biribonwoha2018,

title = {Adolescent pregnancy at antiretroviral therapy (ART) initiation: a critical barrier to retention on ART},

author = {Harriet Nuwagaba-Biribonwoha, Agnes N Kiragga, Constantin T Yiannoutsos, Beverly S Musick, Kara K Wools-Kaloustian, Samuel Ayaya, Hilary Wolf, Emmanuel Lugina, John Ssali, Elaine J Abrams, Batya Elul, for the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa Collaboration},

doi = { https://doi.org/10.1002/jia2.25178},

year  = {2018},

date = {2018-09-18},

journal = {Journal of the International AIDS Society},

volume = {21},

number = {9},

pages = {e25178},

abstract = {Introduction

Adolescence and pregnancy are potential risk factors for loss to follow-up (LTFU) while on antiretroviral therapy (ART). We compared adolescent and adult LTFU after ART initiation to quantify the impact of age, pregnancy, and site-level factors on LTFU.



Methods

We used routine clinical data for patients initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA; 15 to 19 years) and adults (≥20 years) from 2000 to 2014 at 52 health facilities affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa collaboration. We estimated cumulative incidence (95% confidence interval, CI) of LTFU (no clinic visit for ≥6 months after ART initiation) and identified patient and site-level correlates of LTFU, using multivariable Cox proportional hazards models for all patients as well as individual age groups.



Results

A total of 138,387 patients initiated ART, including 2496 YA, 2955 OA and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and 0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation. Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA, 44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall, compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was 1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51 (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by IeDEA program. Site-level factors associated with overall lower LTFU hazard included receiving care in tertiary versus primary-care clinics aHR 0.61 (0.56 to 0.67), integrated adult and adolescent services and food ration provision aHR 0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision, having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence counselling aHR 0.61 (0.57 to 0.67).



Conclusions

Older adolescents experienced higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU among older adolescents are critically needed, particularly for female and/or pregnant adolescents.

},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Zawedde-Muyanja2018c,

title = {Anti-retroviral therapy scale-up and its impact on sex-stratified tuberculosis notification trends in Uganda},

author = {Stella Zawedde-Muyanja, Yukari C Manabe, Joseph Musaazi, Frank R Mugabe, Jennifer M Ross, Sabine Hermans},

doi = {https://doi.org/10.1002/jia2.25394},

year  = {2018},

date = {2018-09-16},

journal = {Journal of the International AIDS Society},

volume = {22},

number = {9},

pages = {e25394},

abstract = {Introduction



In order to end the tuberculosis (TB) epidemic by 2035, countries must achieve a 10% annual decline in tuberculosis incidence rates by 2025. Provision of antiretroviral therapy (ART) has been associated with population level decreases in TB notification rates. We aimed to assess whether the progressive scale-up of ART provision over the past nine years has had an effect on population level trends of TB notification in Uganda stratified by sex and HIV status.



Methods



The study area consisted of Kampala and eight surrounding districts. Annual TB notifications and mid-year populations were used to calculate notification rates per 100,000 population from the study area. Numbers alive and retained on ART were used to calculate ART coverage, overall and by sex. TB notification rates (TBNRs) overall and stratified by sex and HIV status were calculated for the period 2009 to 2017. Trends in TBNRs before and after rollout of universal ART for pregnant women in 2013 were examined using Poisson regression models. To gain insight into the trends in CD4+ T-cell counts at ART initiation over the study period, we performed a sub analysis of patient level data from the Infectious Diseases Institute clinic.



Results



From 2009 to 2017, ART coverage increased by 27.6% among men and by 35.4% among women. TBNRs declined during the same period. Overall, the average annual percentage decline in TBNRs was −3.5% (95%CI −3.7% to −3.3%), (−2.3% (95%CI −2.6% to −1.9%) in men and −5.4% (95%CI −5.7% to −5.0%) in women). ART coverage increased after 2013 but this was not associated with an accelerated decline in overall TBNRs among HIV-positive persons −3.6% before 2013 and −5.2% after 2013; p = 0.33. The proportion of patients initiating ART with CD4+ T-cell count ≤ 200 cells/mL did not decrease significantly after 2013 (42.2% to 32.2%, p = 0.05).



Conclusions



Although ART scale-up was temporally associated with a decline in TB notification rates, the achieved rates of decline are below those required to achieve the End TB Targets. Additional investments in tuberculosis control should include efforts to promote earlier care seeking and ART initiation among HIV-positive persons.

},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Bahr2018,

title = {Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.},

author = {Nathan C Bahr and Edwin Nuwagira and Emily E Evans and Fiona V Cresswell and Philip V Bystrom and Adolf Byamukama and Sarah C Bridge and Ananta S Bangdiwala and David B Meya and Claudia M Denkinger and Conrad Muzoora and David R Boulware },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Diagnostic-accuracy-of-Xpert-MTBRIF-Ultra-for-tuberculous-meningitis-in-HIV-infected-adults-a-prospective-cohort-study..pdf},

doi = {: 10.1016/S1473-3099(17)30474-7},

year  = {2018},

date = {2018-09-14},

journal = {Lancent Infectious Diseases},

volume = {18},

number = {1},

pages = {68-75},

abstract = {BACKGROUND:



WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis.

METHODS:



We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test.

FINDINGS:



From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014).

INTERPRETATION:



Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis.

FUNDING:



National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bisaso2018,

title = {A comparative study of logistic regression based machine learning techniques for prediction of early virological suppression in antiretroviral initiating HIV patients},

author = {Kuteesa R. Bisaso, Susan A. Karungi, Agnes Kiragga, Jackson K. Mukonzo & Barbara Castelnuovo },

doi = {https://doi.org/10.1186/s12911-018-0659-x},

year  = {2018},

date = {2018-09-04},

journal = {BMC Medical Informatics and Decision Making volume},

volume = {18},

number = {77},

abstract = {Background



Treatment with effective antiretroviral therapy (ART) lowers morbidity and mortality among HIV positive individuals. Effective highly active antiretroviral therapy (HAART) should lead to undetectable viral load within 6 months of initiation of therapy. Failure to achieve and maintain viral suppression may lead to development of resistance and increase the risk of viral transmission. In this paper three logistic regression based machine learning approaches are developed to predict early virological outcomes using easily measurable baseline demographic and clinical variables (age, body weight, sex, TB disease status, ART regimen, viral load, CD4 count). The predictive performance and generalizability of the approaches are compared.



Methods



The multitask temporal logistic regression (MTLR), patient specific survival prediction (PSSP) and simple logistic regression (SLR) models were developed and validated using the IDI research cohort data and predictive performance tested on an external dataset from the EFV cohort. The model calibration and discrimination plots, discriminatory measures (AUROC, F1) and overall predictive performance (brier score) were assessed.



Results



The MTLR model outperformed the PSSP and SLR models in terms of goodness of fit (RMSE = 0.053, 0.1, and 0.14 respectively), discrimination (AUROC = 0.92, 0.75 and 0.53 respectively) and general predictive performance (Brier score= 0.08, 0.19, 0.11 respectively). The predictive importance of variables varied with time after initiation of ART. The final MTLR model accurately (accuracy = 92.9%) predicted outcomes in the external (EFV cohort) dataset with satisfactory discrimination (0.878) and a low (6.9%) false positive rate.



Conclusion



Multitask Logistic regression based models are capable of accurately predicting early virological suppression using readily available baseline demographic and clinical variables and could be used to derive a risk score for use in resource limited settings.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Waitt2018b,

title = {Does U=U for breastfeeding mothers and infants? Breastfeeding by mothers on effective treatment for HIV infection in high-income settings},

author = {Catriona Waitt, Prof. Nicola Low, Prof. Philippe Van de Perre, Fiona Lyons, Prof Mona Loutfy, Karoline Aebi-Popp },

doi = {https://doi.org/10.1016/S2352-3018(18)30098-5},

year  = {2018},

date = {2018-09-01},

journal = {The Lancet HIV},

volume = {5},

number = {9},

pages = {e531-e536},

abstract = {Can the campaign Undetectable=Untransmittable (U=U), established for the sexual transmission of HIV, be applied to the transmission of HIV through breastfeeding? European AIDS Clinical Society and, to some extent, American guidelines now state that mothers with HIV who wish to breastfeed should be supported, with increased clinical and virological monitoring. This Viewpoint summarises existing evidence on transmission of HIV through breastfeeding, differences in HIV dynamics and viral load between breastmilk and plasma, and the effects of antiretroviral therapy on infants. At present, insufficient evidence exists to make clear recommendations for the required frequency of clinical and virological monitoring for mother and infant in a breastfeeding relationship or for the action to be taken in the event of viral rebound. We propose a roadmap for collaborative research to provide the missing evidence required to enable mothers who wish to breastfeed to make a fully informed choice. },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Ellis2018,

title = {Cryptococcal Meningitis and Tuberculous Meningitis Co-infection in HIV-Infected Ugandan Adults},

author = {Jayne Ellis, Fiona V Cresswell, Joshua Rhein, Kenneth Ssebambulidde, David R Boulware},

doi = {https://doi.org/10.1093/ofid/ofy193},

year  = {2018},

date = {2018-08-29},

journal = {Open Forum Infectious Diseases},

volume = {5},

number = {8},

pages = {ofy193},

abstract = {We report 5 HIV-infected Ugandan adults with cryptococcal and tuberculous (TB) meningitis co-infection. All unmasked meningitis occurred within 5 weeks of starting HIV therapy. Xpert MTB/RIF Ultra facilitated prompt diagnosis; however, 60% in-hospital mortality occurred. TB meningitis coinfection prevalence was 0.8% (5/586) among cryptococcal meningitis, 2 during second cryptococcal episodes.



Keywords:

case series, cryptococcal meningitis, HIV/AIDS, tuberculosis, tuberculous meningitis



Topic:

hiv meningitis cryptococcal meningitis adult tuberculosis tuberculous meningitis cryptococcus diagnosis hiv infections coinfection 



Issue Section:

Brief Report },

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Nasuuna2018,

title = {Low HIV viral suppression rates following the intensive adherence counseling (IAC) program for children and adolescents with viral failure in public health facilities in Uganda},

author = {Esther Nasuuna, Joanita Kigozi, Lillian Babirye, Alex Muganzi, Nelson K. Sewankambo & Damalie Nakanjako },

year  = {2018},

date = {2018-08-22},

journal = {BMC Public Health volume},

volume = {18},

pages = {1048},

abstract = {Background

The UNAIDS 90–90-90 strategy clearly stipulates that 90% of all people on antiretroviral therapy (ART) should have a suppressed viral load. Intensified adherence counselling (IAC) was recently recommended by WHO to improve viral suppression among ART-treated paediatric and adolescent clients with virological failure. This paper describes the implementation and outcomes of IAC in the first year of implementation in a public ART program, to inform strategic interventions to reach the “third 90” among children.



Methods

A retrospective chart review was conducted for all children aged 9 months to 19 years with HIV viral loads (VL) ≥ 1000 copies/ml at 15 public health facilities from June 2015–December 2016. Data on initial VL test results, IAC sessions, repeat VL test results, and ART regimen switch were abstracted and analysed for completion of IAC and viral suppression after IAC.



Results

A total of 449 children had a detectable viral load above 1000 copies/ml, after an average of 3.5 years (SD 5.8) years of ART. 192 (43%) were 10–20 years of age, and 320 (71%) were receiving Nevirapine-based ART regimen. Out of 345 (77%) who completed the recommended three IAC sessions, 62 (23%) achieved viral suppression following IAC. The mean time from 1st to 3rd IAC session was 113 (SD 153) days and 172 (50%) of the children had completed the three sessions within 200 days.



Conclusion

Suppression rates were low among ART-treated children with virological failure that completed the recommended three IAC sessions. As we move towards having 90% of ART-treated children and adolescents achieve and maintain viral suppression, there is need to re-evaluate the implementation of IAC among children and adolescents to consider both psychosocial and biological factors such as resistance testing for those with multiple detectable viral loads.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Mukisa2018,

title = {Male gender and duration of anti-tuberculosis treatment are associated with hypocholesterolemia in adult pulmonary tuberculosis patients in Kampala, Uganda },

author = {John Mukisa, Ismael Kawooya, Joan Nangendo, Annet Nalutaaya, Jean Nyamwiza, Ali Sam, Ronald Ssenyonga, William Worodria, Ezekiel Mupere

},

doi = {DOI: 10.4314/ahs.v18i3.3 },

year  = {2018},

date = {2018-08-16},

journal = {African Health Sciences},

volume = {18},

number = {3},

abstract = {Background: 

Patients with Pulmonary tuberculosis (PTB) and hypocholesterolemia have an altered immune function, delayed sputum conversion at two months and increased mortality. However, the assessment for dyslipidemias is not often done in our setting.



Methods: 

A cross-sectional study was conducted among adults at an urban TB clinic in Kampala, Uganda. We included different participants at diagnosis (0), 2, 5, 6 and 8 months of anti-TB treatment. Data was collected from a complete physical examination, a pre-tested structured questionnaire, six-hour fasting lipid profiles and random blood glucose levels.



Results: 

Of the 323 included participants, 63.5% (205/323) were males and the median age was 30 years, IQR (23-39). The prevalence of hypocholesterolemia was 43.65% (95% CI 38.3-49.2). The participants at diagnosis had the highest hypocholesterolemia prevalence, 57.3%, 95% CI (46.7-67.2); and lowest amongst those completing treatment at 6/8 months, 32.2%, 95% CI (21.6-45.2). Significant factors associated with hypocholesterolemia were: male gender (PR 1.52, 95% CI: 1.13-2.03), and duration of anti-TB treatment (0.88, 95% CI: 0.80-0.98).



Conclusion: 

Hypocholesterolemia is common among patients with PTB. The risk of hypocholesterolemia increases with being male and reduces with increased duration of treatment. There is a need for further research in lipid abnormalities in TB patients.



Keywords: 

Hypocholesterolemia, pulmonary tuberculosis, duration of anti-tuberculosis treatment, gender.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Sekaggya-Wiltshire2018,

title = {Delayed Sputum Culture Conversion in Tuberculosis-Human Immunodeficiency Virus-Coinfected Patients With Low Isoniazid and Rifampicin Concentrations },

author = {Christine Sekaggya-Wiltshire , Amrei von Braun , Mohammed Lamorde, Bruno Ledergerber , Allan Buzibye , Lars Henning  Joseph Musaazi , Ursula Gutteck , Paolo Denti , Miné de Kock , Alexander Jetter , Pauline Byakika-Kibwika , Nadia Eberhard , Joshua Matovu, Moses Joloba , Daniel Muller , Yukari C Manabe , Moses R Kamya , Natascia Corti , Andrew Kambugu , Barbara Castelnuovo , Jan S Fehr },

doi = {DOI: 10.1093/cid/ciy179 },

year  = {2018},

date = {2018-08-16},

journal = {Clin Infect Dis  .},

volume = {67},

number = {5},

pages = {708-716},

abstract = {

Background: 

The relationship between concentrations of antituberculosis drugs, sputum culture conversion, and treatment outcome remains unclear. We sought to determine the association between antituberculosis drug concentrations and sputum conversion among patients coinfected with tuberculosis and human immunodeficiency virus (HIV) and receiving first-line antituberculosis drugs.



Methods: 

We enrolled HIV-infected Ugandans with pulmonary tuberculosis. Estimation of first-line antituberculosis drug concentrations was performed 1, 2, and 4 hours after drug intake at 2, 8, and 24 weeks of tuberculosis treatment. Serial sputum cultures were performed at each visit. Time-to-event analysis was used to determine factors associated with sputum culture conversion.



Results: 

We enrolled 268 HIV-infected patients. Patients with low isoniazid and rifampicin concentrations were less likely to have sputum culture conversion before the end of tuberculosis treatment (hazard ratio, 0.54; 95% confidence interval, .37-.77; P = .001) or by the end of follow-up (0.61; .44-.85; P = .003). Patients in the highest quartile for area under the rifampicin and isoniazid concentration-time curves for were twice as likely to experience sputum conversion than those in the lowest quartile. Rifampicin and isoniazid concentrations below the thresholds and weight <55 kg were both risk factors for unfavorable tuberculosis treatment outcomes. Only 4.4% of the participants had treatment failure.



Conclusion: 

Although low antituberculosis drug concentrations did not translate to a high proportion of patients with treatment failure, the association between low concentrations of rifampicin and isoniazid and delayed culture conversion may have implications for tuberculosis transmission. Clinical Trials Registration: NCT01782950.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{vonBraun2018b,

title = {HIV-1 Drug Resistance Among Ugandan Adults Attending an Urban Out-Patient Clinic},

author = {von Braun, Amrei; Sekaggya-Wiltshire, Christine ; Bachmann, Nadine ; Ssemwanga, Deogratius; Scherrer, Alexandra U. ; Nanyonjo, Maria; Kapaata, Anne ; Kaleebu, Pontiano ; Günthard, Huldrych F.; Castelnuovo, Barbara ; Fehr, Jan, Kambugu, Andrew },

doi = {doi: 10.1097/QAI.0000000000001717},

year  = {2018},

date = {2018-08-15},

journal = {JAIDS Journal of Acquired Immune Deficiency Syndromes},

volume = {78},

number = {5},

pages = {566-573},

abstract = {Background: 

Little is known about prevalence of drug resistance among HIV-infected Ugandans, a setting with over 15 years of public sector access to antiretroviral therapy (ART) and where virological monitoring was only recently introduced.



Setting: 

This study was conducted in the adults' out-patient clinic of the Infectious Diseases Institute, Kampala, Uganda.



Methods: 

HIV genotyping was performed in ART-naive patients and in treatment-experienced patients on ART for ≥6 months with virological failure (≥1000 copies/mL).



Results: 

A total of 152 ART-naive and 2430 ART-experienced patients were included. Transmitted drug resistance was detected in 9 (5.9%) patients. After a median time on ART of 4.7 years [interquartile range: 2.5–8.7], 190 patients (7.8%) had virological failure with a median viral load of 4.4 log10 copies per milliliter (interquartile range: 3.9–4.9). In addition, 146 patients had a viral load between 51 and 999 copies per milliliter. Most patients with virological failure (142, 74.7%) were on first-line ART. For 163 (85.8%) ART-experienced patients, genotype results were available. Relevant drug-resistance mutations were observed in 135 (82.8%), of which 103 (63.2%) had resistance to 2 drug classes, and 11 (6.7%) had resistance to all drug classes available in Uganda.



Conclusion: 

The prevalence of transmitted drug resistance was lower than recently reported by the WHO. With 92% of all patients virologically suppressed on ART, the prevalence of virological failure was low when a cutoff of 1000 copies per milliliter is applied, and is in line with the third of the 90-90-90 UNAIDS targets. However, most failing patients had developed multiclass drug resistance.

},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Musisi2018,

title = {Effect of anti-retroviral therapy on oxidative stress in hospitalized HIV-infected adults with and without TB },

author = {

Emmanuel Musisi, Denis Kasozi Matovu, Andrew Bukenya, Sylvia Kaswabuli, Josephine Zawedde, Alfred Andama, Patrick Byanyima, Ingvar Sanyu, Abdul Sessolo, Emmanuel Seremba, J Lucian Davis, William Worodria, Laurence Huang, Nicholas D Walter, Harriet Mayanja-Kizza},

doi = {DOI: 10.4314/ahs.v18i3.7 },

year  = {2018},

date = {2018-08-14},

journal = {African Health Sciences},

volume = {18},

number = {3},

abstract = {Background: 

HIV infection and opportunistic infections cause oxidative stress (OS), which is associated with tissue damage. Anti-retroviral therapy (ART) is used to treat HIV and decrease the risk of opportunistic infections, but it is unclear whether ART reduces OS. Association of ART with OS was investigated.



Methods: 

We stratified a convenience sample of frozen serum or plasma from HIV-infected, ART-naïve (n=21); HIV-infected, ART-treated (n=14); HIV and PTB co-infected, ART-naïve (n=21); HIV and PTB co-infected, ART-treated (n=25) patients. Controls (n=21) were HIV-negative adults without TB symptoms. Concentration of OS markers namely: transaminases (ALT and AST), gamma glutamyl transpeptidase (GGT), albumin, total protein, malondialdehyde (MDA), vitamin C, and total anti-oxidant status (TAS) were determined.



Results: 

AST (p<0.001), GGT (p<0.001), total protein (p=0.001) and MDA (p<0.001) were higher in HIV patients compared to controls. Vitamin C (P<0.0001) and albumin (p<0.01) were lower in HIV-patients relative to controls. ART was only associated with higher albumin (p=0.001), higher GGT (p=0.02) and lower vitamin C (p=0.009). HIV and PTB co-infection was only significantly associated with higher GGT (p=0.01) and AST (p=0.03).



Conclusion: 

We identified severe OS among HIV-patients. ART was associated with both increased and reduced markers of OS hence suggesting that ART may not attenuate OS.



Keywords: 

Human immunodeficiency virus, Mycobacterium tuberculosis, Oxidative stress, anti-retroviral therapy, hospitalized patients.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Lofgren2018,

title = {A qualitative evaluation of an implementation study for cryptococcal antigen screening and treatment in Uganda},

author = {Sarah M. Lofgren, Elizabeth Nalintya, David B. Meya, David R. Boulware and Radha Rajasingham},

doi = { doi: 10.1097/MD.0000000000011722},

year  = {2018},

date = {2018-08-03},

journal = {Medicine (Baltimore)},

volume = {97},

number = {31},

pages = {e11722},

abstract = {Cryptococcal meningiti s causes 15% of AIDS-related deaths globally. Screening and preemptive treatment for cryptococcal antigen (CrAg) in the blood of persons with advanced HIV/AIDS reduces mortality. National and international HIV guidelines recommend CrAg screening; however, implementation studies and evaluations of how to integrate CrAg screening programs into existing HIV care infrastructure are lacking.



During a CrAg screening program in Kampala, Uganda, we interviewed 15 health care workers (2 coordinating research nurses and 13 clinic personnel) from 6 HIV clinics between March and April 2017, to identify barriers to implementation as well as facilitating factors for program success. The interviews were coded and themes compiled.



We found key factors for successful implementation of a CrAg screening program were: adequate supplies of fluconazole and CrAg lateral flow assay (LFA) point-of-care tests, timely patient follow-up, and quick turnaround time of laboratory results. Although both CrAg LFA kits and fluconazole are on the national formulary, stockouts are common, affecting patient care. The CrAg screening recommendation by national HIV guidelines remains integral to the success of the program, as overburdened clinics are otherwise reluctant to adopt additional screening. Collaboration with Ministries of Health for support with enforcing national guidelines, and procuring supplies is paramount to a successful CrAg screening program.



Development of a CrAg screening and treatment program within the HIV clinic infrastructure has a number of barriers. Education and training of clinic staff, along with partnership with the Ministry of Health to ensure adequate supplies, facilitated the program.



Keywords: 

cryptococcal screening, cryptococcus, field study, implementation science, qualitative research},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Seden2018,

title = {High prevalence and long duration of nervous system and psychiatric adverse drug reactions in Ugandan patients taking efavirenz 600 mg daily},

author = {Kay Seden, Daniel Kiiza, Eva Laker, Walter J Arinaitwe, Catriona Waitt, Mohammed Lamorde, Saye Khoo},

doi = {https://doi.org/10.1093/jac/dky298},

year  = {2018},

date = {2018-08-01},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {73},

number = {11},

pages = {3158–3161},

abstract = {Background



Efavirenz-related nervous system or psychiatric adverse drug reactions (ADRs) are conventionally reported to resolve soon after initiation, with incidence of dizziness at 8.5% in large clinical trials. Patients of black ethnicity are genetically at greater risk of elevated efavirenz exposure, which has been linked to nervous system toxicity.



Patients and methods



The current data derive from a prospective longitudinal observational study of adult HIV-positive outpatients taking current antiretrovirals, at three diverse clinics in central Uganda. As part of an interview about medicine use, patients were asked by trained pharmacy technicians to detail current side effects and to rate their severity on a simple visual analogue scale (1–10). Details of the reported ADRs were verified by case note review. Severity and causality of ADRs were rated by the study team using validated tools.



Results



A total of 300 patients taking efavirenz were analysed. Of these, 108 (36%, 95% CI 30.6%–41.7%) were affected by persisting nervous system/psychiatric ADRs (median duration 22 months). Dizziness affected 27.3% (95% CI 22.4%–32.8%) of patients taking efavirenz. Severity of the ADRs was rated by patients at ≥5/10 in 76 (58.5%) cases. In 95 (86%) cases, there was no record of the ADRs in the clinical notes.



Conclusions



Strategies are needed to identify and prioritize patients urgently with persisting efavirenz neurotoxicity for a switch to newer regimens as they become available.



Topic:



dizziness efavirenz adult ethnic group hiv seropositivity nervous system outpatients psychiatry uganda adverse effects of medication toxic effect anti-retroviral agents visual analogue pain scale pharmacy technicians 



Issue Section:

ORIGINAL RESEARCH

},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Thompson2018,

title = {Evolution of protease inhibitor resistance in HIV-1-infected patients failing protease inhibitor monotherapy as second-line therapy in low-income countries: an observational analysis within the EARNEST randomised trial},

author = {Jennifer A Thompson, Cissy Kityo, David Dunn, Anne Hoppe Emmanuel Ndashimye, James Hakim, Andrew Kambugu, Joep J. van Oosterhout, Jose Arribas, Peter Mugyenyi, A. Sarah, Walker, Nicholas I. Paton, for the Europe Africa Research Network for Evaluation of Second-line

Therapy (EARNEST) Trial Team},

isbn = {1058-4838},

year  = {2018},

date = {2018-07-28},

journal = {Clinical Infectious Diseases},

volume = {68},

number = {7},

abstract = {Background

Limited viral load (VL) testing in HIV-infected individuals on treatment in low-income countries often

results in late detection of treatment failure. The impact of remaining on failing second-line,

protease inhibitor (PI) containing regimens is unclear.



Methods

We retrospectively tested VL from 2,164 stored plasma samples from 386 patients randomised to

receive PI-monotherapy (ritonavir-boosted lopinavir, after initial PI+raltegravir induction) in the

EARNEST trial. Protease genotypic resistance testing was performed in samples with VL>1000

copies/ml. We assessed evolution of drug resistance mutations from virological failure (confirmed

VL>1000 copies/ml) until discontinuation of PI-monotherapy and examined associations using

Poisson and linear mixed-effects models.



Results

118 patients had a median 68(IQR 48-88) weeks on PI-monotherapy post-failure. At failure,

21/107(20%) had intermediate/high resistance to lopinavir. 40-48 weeks post-failure, 49/72(68%)

and 36/71(51%) had intermediate/high-level resistance to lopinavir and atazanavir. Most remained

susceptible to darunavir (12/72[17%] intermediate, no high resistance). Common PI mutations were

M46I, I54V, and V82A. On average, 1.7(95% CI 1.5,2.0) PI mutations developed per year; this

increased after the first mutation developed, but decreased with subsequent mutations (p<0.0001).

Modest VL changes were mainly driven by non-adherence (p=0.006) and PI-mutation development.

I47A was associated with a larger increase in log10 VL(+0.53[+0.18,+0.87], p=0.003) than other PI

mutations (+0.15[+0.07,+0.23] p<0.001; heterogeneity p=0.05).



Conclusion

Most develop intermediate/high-level lopinavir resistance within one year when lopinavir/ritonavir

is exposed to sustained VL replication without protection from other drugs. Even in this extreme

situation, annual VL testing (current WHO recommendation) would identify failure when most would

still benefit from switching to darunavir.},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Mark2018,

title = {Making Implementation Science Work for Children and Adolescents Living With HIV},

author = {Daniella Mark, Elvin Geng, Susan Vorkoper, Shaffiq Essajee, Kim Bloch, Nicola Willis, Bethany Stewart, Sabrina Bakeera-Kitaka, Nandita Sugandhi, Rachel Sturke, Kechi Achebe, B. Jane Ferguson, Marissa Vicari, Chewe Luo, Nande Putta, Grace John-Stewart, Laura Guay, Angela Mushavi, Imran Muhammad and David A. Ross, },

doi = {doi: 10.1097/QAI.0000000000001750},

year  = {2018},

date = {2018-07-11},

journal = {Journal of Acquired Immune Deficiency Syndromes (1999)},

volume = {78},

number = {1},

pages = {S58–S62},

abstract = {The global HIV response is leaving children and adolescents behind. Because of a paucity of studies on treatment and care models for these age groups, there are gaps in our understanding of how best to implement services to improve their health outcomes. Without this evidence, policymakers are left to extrapolate from adult studies, which may not be appropriate, and can lead to inefficiencies in service delivery, hampered uptake, and ineffective mechanisms to support optimal outcomes. Implementation science research seeks to investigate how interventions known to be efficacious in study settings are, or are not, routinely implemented within real-world programmes. Effective implementation science research must be a collaborative effort between government, funding agencies, investigators, and implementers, each playing a key role. Successful implementation science research in children and adolescents requires clearer policies about age of consent for services and research that conform to ethical standards but allow for rational modifications. Implementation research in these age groups also necessitates age-appropriate consultation and engagement of children, adolescents, and their caregivers. Finally, resource, systems, technology, and training must be prioritized to improve the availability and quality of age-/sex-disaggregated data. Implementation science has a clear role to play in facilitating understanding of how the multiple complex barriers to HIV services for children and adolescents prevent effective interventions from reaching more children and adolescents living with HIV, and is well positioned to redress gaps in the HIV response for these age groups. This is truer now more than ever, with urgent and ambitious 2020 global targets on the horizon and insufficient progress in these age groups to date.



Key Words: children, adolescents, HIV, implementation science, research},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}

@article{Cresswell2018b,

title = {High dose oral and intravenous rifampicin for improved survival from adult tuberculous meningitis: a phase II open-label randomised controlled trial (the RifT study)},

author = {Fiona V. Cresswell, Kenneth Ssebambulidde, Daniel Grint, Lindsey te Brake, Abdul Musabire, Rachel R. Atherton, Lillian Tugume, Conrad Muzoora, Robert Lukande, Mohammed Lamorde, Rob Aarnoutse, David Meya, David R. Boulware and Alison M. Elliott},

doi = {doi: 10.12688/wellcomeopenres.14691.1},

year  = {2018},

date = {2018-07-10},

journal = {Wellcome Open Research},

volume = {3},

abstract = { Background: 

Tuberculous meningitis (TBM) has 44% (95%CI 35-52%) in-hospital mortality with standard therapy in Uganda. Rifampicin, the cornerstone of TB therapy, has 70% oral bioavailability and ~10-20% cerebrospinal fluid (CSF) penetration.  With current WHO-recommended TB treatment containing 8-12mg/kg rifampicin, CSF rifampicin exposures frequently fall below the minimal inhibitory concentration for M. tuberculosis. Two Indonesian phase II studies, the first investigating intravenous rifampicin 600mg and the second oral rifampicin ~30mg/kg, found the interventions were safe and resulted in significantly increased CSF rifampicin exposures and a reduction in 6-month mortality in the investigational arms. Whether such improvements can be replicated in an HIV-positive population remains to be determined.



Protocol: 

We will perform a phase II, open-label randomised controlled trial, comparing higher-dose oral and intravenous rifampicin with current standard of care in a predominantly HIV-positive population. Participants will be allocated to one of three parallel arms (I:I:I): (i) intravenous rifampicin 20mg/kg for 2-weeks followed by oral rifampicin 35mg/kg for 6-weeks; (ii) oral rifampicin 35mg/kg for 8-weeks; (iii) standard of care, oral rifampicin 10mg/kg/day for 8-weeks. Primary endpoints will be: (i) pharmacokinetic parameters in plasma and CSF; (ii) safety. We will also examine the effect of higher-dose rifampicin on survival time, neurological outcomes and incidence of immune reconstitution inflammatory syndrome. We will enrol 60 adults with suspected TBM, from two hospitals in Uganda, with follow-up to 6 months post-enrolment.



Discussion: 

HIV co-infection affects the bioavailability of rifampicin in the initial days of therapy, risk of drug toxicity and drug interactions, and ultimately mortality from TBM. Our study aims to demonstrate, in a predominantly HIV-positive population, the safety and pharmacokinetic superiority of one or both investigational arms compared to current standard of care. The most favourable dose may ultimately be taken forward into an adequately powered phase III trial.



Trial registration: ISRCTN42218549 (24 th April 2018)



Keywords: 

TBM, Tuberculous Meningitis, TB, rifampicin, Ultra, HIV},

keywords = {},

pubstate = {forthcoming},

tppubtype = {article}

}