bluuebunny/crossref_metadata_2025_split huggingface dataset:
GP41 DIVERSITY IN ANTIRETROVIRAL THERAPY NAïVE AND EXPERIENCED HIV-1 SUBTYPE C-INFECTED PATIENTS IN BOTSWANA: IMPLICATIONS FOR ENFUVIRTIDE (T-20) USE
Authors: Maruapula Dorcas , Seraise Boitumelo , Einkauf Kevin , Reilly Amanda , Moyo Sikhulile , Mohammed Terence , Rowley Christopher , Musonda Rosemary , Makhema Joseph , Gaseitsiwe Simani 
Published: February 2017

BackgroundWith the expansion of HIV treatment programs in sub-Saharan Africa, there are increased cases of HIV drug resistance. In Botswana where the national HIV treatment program has been in place since 2002, patients with HIV strains resistant to the core antiretroviral classes are a reality. There is need to investigate how some of the less frequently used antiretroviral classes such as enfuvirtide (T-20) and its derivatives would fair in this population.MethodsA total of 164 samples from 129 patients initiating combination antiretroviral therapy (cART) and 35 patients failing NRTI – and NNRTI-based cART in studies conducted in Botswana were available for analysis. Viral RNA was isolated from plasma and RT-PCR targeting HIV-1 gp41 was run and the product sequenced. Sequences were edited using Sequencher and alignments were made using Clustal-X. A search on the Los Alamos HIV database yielded 106 gp41 sequences from unique Botswana patients and these were included in the analysis. The IAS-USA, 2015 Resistance Mutations update report was used to define the T-20 drug resistance mutations.ResultsA total of 154 samples were successfully sequenced, 126 from treatment naïve patients and 28 from virologic failure patients. Additionally, 106 gp41 sequences from previous studies conducted in Botswana were included in the analysis. No major T-20 was detected in any of the 260 sequences. The N42S mutation which is associated with T-20 hypersensitivity was found in (87.3%) and this is consistent with published data from HIV-1C studies. The I69V mutation (95.6%) was the most common detected HR1 polymorphism. The most common HR2 polymorphism detected was I135L (98.4%) followed by E151A (92.3%).ConclusionsThese results provide invaluable data on gp41 diversity in Botswana and show that there is no background resistance to T-20 or its derivatives. T-20 would be an alternative drug for patients failing cART in Botswana.
BASELINE BACTERIAL LOAD AND RIFAMPICIN EXPOSURE ARE ASSOCIATED TO CULTURE CONVERSION IN A TWO-MONTH STUDY OF TUBERCULOSIS
Authors: Ntinginya Nyanda , Framhein Anna , Mpagama Stella , Semvua Hadija , Kibiki Gibson , Maboko Leonard , Hoelscher Michael , Heinrich Norbert 
Published: February 2017

BackgroundEarly bactericidal activity (EBA) during the first two weeks of TB treatment is an important method for early efficacy evaluation of new anti-tuberculosis agents.MethodsWe performed an observational; two-site clinical study in Tanzania in patients with newly diagnosed pulmonary TB during the first eight weeks of standard HRZE treatment. Baseline and treatment-related covariates including X-ray, baseline bacterial load and rifampicin pharmacokinetics were analysed for their correlation to treatment success.ResultsFrom Nov 2011 to July 2013 we enrolled 74 pulmonary TB patients from Moshi (41) and Mbeya (33). Mbeya participants had a higher baseline bacterial load measured by log time to positivity (TTP) in the MGIT culture system (median 1.29; IQR 1.09–1.46vs1.58; IQR 1.44–1.87; p< 0.001) Overall, 56/68 (80%) of patients achieved a negative solid media culture, and 28/59 (47%) achieved a negative liquid culture at 8 weeks. Median time to negative on LJ culture was 45.5 days (IQR 21–56), in liquid culture 56 days. The strongest association with outcome for any covariate was found for baseline bacterial load: patients with a positive week 8 LJ culture had a median logTTP of 1.20 (IQR 0.94–1.35); patients with a negative week 8 culture had 1.48 (1.29–1.73; p=0.006). In exploratory analysis, rifampicin area under the concentration curve (AUC) was associated with shorter time to LJ culture conversion in patients who achieved negative culture, (hazard ratio 1.05, p=0.038), but not in the total population.ConclusionsThis observation EBA study using standard HZRE was successfully implemented with methodologies thus far established for the first time at the two Tanzanian sites. Baseline bacterial load was confirmed as an important predictive parameter.
TRANSLATING ETHICS GUIDELINES ON COMPENSATION FOR RESEARCH-RELATED INJURIES INTO POLICY IN LOW-INCOME COUNTRIES: LESSONS LEARNT FROM MALAWI
Authors: Kamalo Patrick , Manda-Taylor Lucinda , Rennie Stuart 
Published: February 2017

BackgroundInjury to human participants in biomedical research is a known problem and despite a number of ethical guidelines advocating compensation for research-related injuries (RRIs), African countries do not have a unified approach for compensation. In 2012, Malawi introduced a policy mandating no-fault insurance coverage for RRIs. We conducted this study to explore the challenges associated with the implementation of this policy and what lessons can be learnt from Malawi.MethodsWe conducted a qualitative case study through nine in-depth interviews with purposively sampled key stakeholders in research in Malawi: policy-makers, researchers, ethics committee members and insurers. Interviews were conducted by one researcher, recorded using a voice-recorder and later transcribed and verified for consistency. Manual data analysis was done using a word-table and pattern-matching. The study was approved by two ethics committees: in Malawi and South Africa.ResultsParticipants were in favour of compensation for RRIs through the insurance mechanism of no-fault type, although there was discordance in the understanding of the ‘no-fault’ principle. Some researchers felt this policy was instituted to punish them and stifle clinical research. In addition, we found that the local insurance industry was not in a position to cover clinical research. This deficiency in local capacity to provide insurance left some researchers feeling that Malawi would lose out by externalising hard-earned resources.ConclusionsAll stakeholders in research in Malawi view the policy mandating no-fault insurance cover for RRIs as a positive step in research governance. However, certain challenges need to be addressed, such as the understanding of the concept of no-fault and local capacity to handle clinical trial insurance. Compensation for RRIs through no-fault insurance needs to be tried in other African countries and be adopted by the African Union in order to standardise and enforce compensation in Africa, where it is ethically acceptable based on the African ethic of Ubuntu.
IMPACT OF COMMUNITY TRACING ON HIV COHORT OUTCOMES IN URBAN ZAMBIA
Authors: Munamunungu Virginia , Bolton Carolyn , Siyunda Alice , Shilimi Jacinta , Chilengi Roma , Wandeler Gilles , Vinikoor Michael 
Published: February 2017

BackgroundWe investigated the impact of community tracing as recommended in national guidelines on outcomes within a prospective HIV cohort in Zambia.MethodsHIV-positive, antiretroviral therapy-naïve adults were enrolled at 2 Lusaka clinics. Per national guidelines we collected detailed baseline patient locator information including patient phone number, address, church, and a map from the clinic to their home. Study visits were aligned with routine ART program schedules and 3 telephonic attempts were made if visits were missed. Per guidelines, a lay health worker conducted a community home visit on lost to follow-up (LTFU) patients. Transfers to other clinics and deaths were ascertained when reported by the clinic staff, patients, or family members. At one year, we measured the percentage retained, transferred out, withdrawn (stopped ART), dead, and LTFU (>6 months absent). A lay health worker went into the community to make a home visit on LTFU patients. We recorded the change in mortality after tracing. We also estimated the time and costs per patient traced.ResultsWe enrolled 795 patients (median age 34 years; 53.7% were female; median CD4 228 cell/mm3). Prior to tracing, we recorded 45 deaths, 23 transfers, 1 withdrawal, and 83 LTFU who could not be reached by phone. At 63 attempted home visits, we learnt that 9 (14.3%) had died, 5 (7.9%) had transferred, and 2 had withdrawn. We could not locate 32 (50.8%) but neighbours/family reported that 12 of these had relocated (HIV care status unknown). After successful tracing, 15 (23.8%) returned to clinic and HIV care. Community tracing increased known mortality from 5.7% to 6.8% (95% CI: 5.1–8.8%) and increased retention at 1-year from 80.9% to 82.8%. Tracing required an average of 5 person-hours and K150.00 (∼15 USD) in bus/taxi fares per patient.ConclusionsCommunity tracing was limited by patient mobility and had a modest impact on cohort mortality and retention.
PREDICTORS OF RETENTION IN CARE OF HIV-INFECTED ADULTS IN TIGRAY, ETHIOPIA: A PROSPECTIVE COHORT STUDY
Authors: Bucciardini Raffaella , Fragola Vincenzo , Abegaz Teshome , Lucattini Stefano , Halifom Atakilt , Tadesse Eskedar , Berhe Micheal , Pugliese Katherina , Castro Paola De , Terlizzi Roberta , Fucili Luca , Gregorio Massimiliano Di , Mirra Marco , Zegeye Teame , Binelli Andrea , Vella Stefano , Abraham Loko , Godefay Hagos 
Published: February 2017

BackgroundHIV/AIDS represents one of the major health challenges of Ethiopia, despite a proven record of universal access to HIV care and treatment. Long-term antiretroviral therapy (ART) retention is a key factor for personal and public health benefits. Identification of determinants of attrition is needed to design appropriate interventions.MethodsWe used data from the CASA project, a prospective, multisite study of a cohort of HIV-infected patients who started ART in seven urban and rural health facilities located in the Tigray. We analysed the retention in care and its associated determinants in over 1000 patients followed for two years. The main outcome measure was the retention in care rate, defined as the proportion of patients alive and receiving ART at the same health facility as at ART initiation. Kaplan-Meier method was used to estimate the probability of retention at different time points. Cox Proportional Hazards model with robust sandwich estimates to account for within health facility correlation was used to identify factors associated with retention.ResultsKaplan–Meier estimates of retention in care were 83.9%, 80.6% and 77.6% at 12, 18 and 24 months of follow-up, respectively. Attrition was mainly due to lost-to-follow-up and transferred-out patients. Multivariate Cox proportional hazard model showed that being male (HR 1.35, 95% CI: 1.04–1.75), CD4 count<200 (HR 1.49, 95% CI: 1.13–1.96), haemoglobin level <= 10 (HR 1.40, 95% CI: 1.11–1.76), the presence of active TB co-infection at ART initiation (HR 1.47, 95% CI: 1.04–2.08) and the type of health facility were significantly associated with attrition.ConclusionsAccording to our prospective data, combined interventions aimed to improve ART retention shall include expansion of HIV testing and earlier initiation of therapy, nutrition supplementation, early detection and treatment of TB. Observed retention differences among health facilities and according to gender suggest that innovative models of HIV care shall also be explored.
CRYPTOCOCCAL MENINGOENCEPHALITIS IN HIV-INFECTED PATIENTS IN MADAGASCAR: HIGH PREVALENCE AND LETHALITY AND THERAPEUTIC CHALLENGES
Authors: Rakotoarivelo Rivo , Raberahona Mihaja , Randriamampionona Njary , Andriamihaja Rabezanahary , Rasamoelina Tahinamandranto , Cornet Muriel , Randria Mamy Jean De Dieu , Benet Thomas , Vanhems Philippe , Andrianarivelo Mala Rakoto 
Published: February 2017

BackgroundIn Madagascar the epidemiology of cryptococcosis is poorly documented. The main objective of this study was to estimate the prevalence of Cryptococcal meningoencephalitis (CM) in Madagascar and to describe the presentation of the cases.MethodsThis is an observational transverse study conducted in the hospitals of Antananarivo and Toamasina cities. Between 3 November 2014 and 8 June 2016, HIV-infected adults presenting CD4 cell count ≤200/mm3 were selected. The crytococcocal antigen (CrAg) was screened in the blood using a lateral flow immunoassay (IMMYCrAg® LFA). If the result was positive and the patient symptomatic, CrAg was checked in the cerebrospinal fluid (CSF) and examined with India ink, and culture was performed. The isolated strains were subsequently analysed using MALDI-TOF and an antifungal susceptibility test was performed using the E-test method (BioMérieux).ResultsOverall, 118 patients were included. The mean CD4 cell count was 86.4/mm3 (SD±60.6) and 35.6% of the patients were under ARV therapy at baseline. HIV-1 viral load of 88.5% of patients was positive. We compared the clinical characteristics of patients with cryptococcal infections to those of controls without CM. Eleven cases of CM were identified corresponding to a prevalence of 15.1% (95% CI: 7.8–25.4%).Cryptococcus neoformansvar.grubii(serotype A) was isolated. Fever, headache, neck pain and night sweats were the most common signs. In 7 cases, CrAg titres in the CSF were very high (≥2560) and did not decrease even 2 months post-treatment. The Case Fatality Rate was unacceptably high (69%).ConclusionsOverall, prevalence of cryptococcal meningoencephalitis (CM) in Madagascar was very high (15.1%) compared to that observed in some Sub-Saharan African countries. The point-of-care LFA CrAg test was confirmed to be reliable and cost-effective for the diagnosis. Challenges to facilitate access to more effective molecules to treat patients with CM include heavy administrative formalities linked to drug importation and low level of priority in implementing the national control programme.
PREVALENCE AND FACTORS ASSOCIATED WITH HYPOCHOLESTEROLAEMIA AMONG ADULTS WITH PULMONARY TB AT DIAGNOSIS AND DURING TB TREATMENT IN KAMPALA
Authors: Mukisa John , Mupere Ezekiel , Worodria William 
Published: February 2017

BackgroundHypocholesterolaemia is associated with altered immune function, possible delayed conversion at two months, and increased risk of mortality. However, lipid profiles are not done routinely for tuberculosis (TB) patients and there is paucity of data regarding the prevalence of hypocholesterolaemia and its associated factors among adult bacteriologically-confirmed pulmonary tuberculosis patients.MethodsThis was a cross sectional study that consecutively enrolled 323 participants at diagnosis, 2, 5, 6 and 8 months of TB treatment, between February and April 2016. Physical examination and a structured questionnaire (administered by an interviewer) were used for data collection. Lipid profiles were determined from fasting blood samples from participants. Descriptive statistics were used to describe the patterns of dyslipidaemias and prevalence of hypocholesterolaemia. Log-binomial regression methods were used to determine the independent factors associated with hypocholesterolaemia.ResultsHypocholesterolaemia was identified in 140/323 (43.3%, 37.9–48.8) of adults with pulmonary TB with a high prevalence among those at diagnosis, 51/91 (56.0%, 45.8–66.3) but a lower prevalence among those who were at completion of treatment: 19/59 (32.2%, 20.9–44.3). On multivariate analysis, male gender (PR 1.57, 95% CI: 1.16–2.06), diabetes (PR 1.37, 95% CI: 1.05–1.78) and duration of anti TB treatment (1.12, 1.07–1.20) were associated with hypocholesterolaemia. There was no significant association between HIV infection status, presence of cavities on chest x-ray and hypocholesterolaemia at diagnosis and during anti-TB treatment in this study.ConclusionsThe overall prevalence of hypocholesterolaemia among participants was high. Males with pulmonary tuberculosis are 60% more likely to develop hypocholesterolaemia. There is a need for further research on dyslipidaemias in TB patients and policy improvements regarding assessment of these lipids and nutritional management.
ETHICAL CONSIDERATIONS IN THE HANDLING OF A COMPLAINT REPORT AGAINST A STUDY TEAM: CASE OF A CLINICAL TRIAL (EARNEST) PARTICIPANT
Authors: Kanengoni Muchineripi , Ruzario Sithembile , Ndebele Paul , Shana Melody , Tarumbiswa Fadzai , Musesengwa Rosemary , Gutsire Rutendo 
Published: February 2017

BackgroundThe major role of an ethics committee is to protect participants from harm through participating in a health research study. This includes investigating participant complaints to ensure that their wellbeing is being upheld and queries resolved satisfactorily. In this case, one clinical trial participant passed away and a report implying that her death was caused by trial medication received during participation was published by WEMOS foundation. This necessitated the National Ethics Committee (NEC) in Zimbabwe to investigate the case to understand and come up with resolutions.MethodsA case study design was used to investigate the case. Interviews with 5 conveniently selected study staff based on their involvement and roles in the study were conducted. Review of participant study records, the protocol, the WEMOS report, Serious Adverse Event reports and Data Safety and Monitoring Board reports were conducted. The investigation was used to determine which ethical principles applied and whether they were adhered to or not in the handling of the participant by the research staff.ResultsResults indicated that the research team adhered to the necessary ethical principles enshrined in the major ethical codes and local Zimbabwean research ethics regulations for the conduct of clinical trials. Investigation showed that the report was mainly based on incomplete information and contradicted the actual events at the study site. There was also no record of the participant's complaint with NEC in the complaint register. Appropriate standard of care was given to the participant.ConclusionsThe NEC continues to protect the rights of clinical trial participants by investigating complaints against study teams as their wellbeing is of primary importance. Researchers are being encouraged to adhere to best practises in conducting human participant researches. The media should also be engaged actively so that reporting is accurate to prevent incorrect information being relayed to the public.
IMPROVING THE EFFICIENCY OF AFRICAN RESEARCH ETHICS COMMITTEES AND STANDARDISING ETHICS REVIEW PROCESSES THROUGH AN AUTOMATED REVIEW PLATFORM
Authors: Mokgatla Boitumelo , Bahati Prince , Ijsselmuiden Carel 
Published: February 2017

BackgroundThe sheer amount of research being conducted in Africa, the under-resourced research ethics committees (RECs), and the lack of modern review technologies has resulted in unprecedented review timelines – with an estimated 1.5 years to get ethical clearance in many African countries. The Research for Health Innovation Organiser (RHInnO), a cloud-based ethics review platform, has ushered a new frontier of digital ethics review in Africa. It facilitates and manages the entire ethics review process. RHInnO ethics integration is estimated to reduce the review time by 12 months. In 2015, RHInnO ethics was used by 25 RECs in 8 African countries. We evaluated its impact on efficiency, data security and cost.MethodsQualitative and quantitative data was collected using an online questionnaire administered to REC administrators/chairpersons in user countries.ResultsResponses were received from 60% of RECs using RHInnO ethics. Reported areas of high impact (81%-100% of respondents) included: improved protocol submission and distribution process, improved quality of communication between RECs and researchers, improved standardisation of review process and improved data security. Reported areas of medium impact (60%-80% of respondents) included reduced REC administrator's workload and reduced RECs' administrative costs. Improved reviews of multicentre trials were reported as a low impact area by over 60% of respondents. Respondents (20%) who used RHInnO ethics for more than 2 years reported 57% reduction in review time while those who used RHInnO ethics for less than a year, (80%) reported it is too early to see the impact on reduction of review timelines.ConclusionsRHInnO ethics had high impact on data security, submission process, communication, standardisation and cost reduction. However, a long-term evaluation approach is needed to determine impact on review timelines. Integration of new monitoring and evaluation (M&E) indicators on efficiency into the platform would improve RECs capacity to conduct long-term impact analysis.
CHILD PROTECTION AND DEVELOPMENT: ADDRESSING THE PROBLEMS OF HIV/AIDS ORPHANS – A CASE STUDY IN BAHIR DAR TOWN, ETHIOPIA
Authors: Tamene Ayele 
Published: February 2017

BackgroundHIV/AIDS has continued to be a world social, economic and political threat. Recent findings indicated that currently 34 million people are living with HIV/AIDS. Sub-Saharan countries are particularly vulnerable to this pandemic. Ethiopia's HIV/AIDS epidemic pattern marked regional variations across urban and rural areas. Ethiopia which is one of the largest populations in Africa has the highest number of orphans. The proportion of orphan children due to AIDS is also alarmingly increasing in this country. It increased from 26% to 43% in Ethiopia in 2001 to 2010. The situation of AIDS orphans have become a serious problem in Ethiopia.MethodsA qualitative method of study, particularly a phenomenological approach, was used to guide the study. Data were collected through interviews, focus group discussions and case studies. In addition, a secondary review of documents such as reports, annual and strategic plans was done.ResultsThe study indicated that there are variations in the number of orphans across kebeles of the town. The Shinbit kebele has the highest number of orphans, both male and female. In Bahir Dar various forms of service are rendered to orphans living with HIV/AIDS such as psycho-social support, educational and medical support, economic strengthening through guardians, home to home support, legal support, vocational and skill development training.ConclusionsIn Bahir Dar, various forms of service are rendered to HIV/AIDS orphans such as psycho-social support, educational and medical support, economic strengthening through the guardians, legal support, vocational and skill development training. These methods of addressing HIV/ AIDS orphans form a fragmented, only need-based approach, and are far from a right-based approach as they lack institutional networking, sustainability and community ownership. Therefore, in order to meet one of the objectives of the Cross–Cutting Sectors Development Plan of the Growth and Transformation Plan, it is recommended to address the multifaceted problems of AIDS orphans in an integrated and sustainable way.