The use of chiral medicines (possessing center(s) of asymmetric carbon) may cause adverse drug reactions (ADRs). The safety assurance of these medicines is critical. We aimed to evaluate registered and commonly used anti-infective chiral medicines circulating in the Tanzanian market to establish their safety profile to protect public health. A mixed prospective-retrospective cohort study was conducted to assess the safety profile of amoxicillin, amoxicillin-clavulanic acid and ceftriaxone injection. ADRs causality assessment was conducted by using World Health Organization (WHO)-Algorithm criteria. Data were collected from 7 tertiary hospitals: Muhimbili National Hospital (MNH), Kilimanjaro Christian Medical Centre (KCMC), Bugando Medical Centre (BMC), Ligula Referral-Regional Hospital (LRRH), Kitete Referral-Regional Hospital (KRRH), Dodoma Referral-Regional Hospital (DRRH), and Mbeya Zonal-Referral Hospital (MZRH). Data were supplemented by those recorded in the WHO-Vigiflow/VigiLyze database within the same monitoring period. Data were analyzed using STATA version-15. The results were considered statistically significant when P < .05. A total of 2522 patients were enrolled in hospitals: MNH (499), KCMC (407), BMC (396), LRRH (387), KRRH (345), DRRH (249), and MZRH (239). Among those, 1197 (47.5%) were treated with ceftriaxone, 585 (23.2%) amoxicillin and 740(29.3%) amoxicillin-clavulanic acid. Out of those, 102 (4.5%) experienced adverse events (AEs), 49 (48%) were due to ceftriaxone, 37 (36.3%) amoxicillin-clavulanic acid and 16 (15.7%) amoxicillin ( P -value .012). A total of 443 participants from the enrolled and WHO-Vigiflow/VigiLyze database were experienced with ADRs. The ADRs affected mainly gastro-intestinal system 234 (53%), skin and subcutaneous tissue 85 (19%), nervous system 49 (11%), respiratory thoracic 22 (5%), and general disorders 18(4%). In this study, approximately 90% of reported AEs were ADRs possible-related to the monitored medicines, with few plausible and certain. Ceftriaxone injection caused more ADRs. Amoxicillin-clavulanic acid was associated with more ADRs than amoxicillin alone. The safety profile of these medicines is still maintained; however, comprehensive monitoring of ADRs is recommended to improve patient safety and enhance overall treatment outcomes.

In recent years, health partnerships have shared infection prevention and control innovations between United Kingdom hospitals and Low-Middle-Income Countries. However, none had focused on antimicrobial stewardship (AMS), a core component of tackling antimicrobial resistance (AMR). This paper documents an effective approach to developing a program to increase AMS capacity in four African countries: Ghana, Tanzania, Uganda, and Zambia as part of the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) program. A systematic approach was applied to assess gaps in AMS interventions and inform the development of the CwPAMS program through desk based assessments, including National Action Plans on AMR, online focus group meetings, and expert advisory group reviews. Twelve partnerships were selected for the CwPAMS program. AMS support tools were developed based on recommendations from the scoping, including an AMS checklist tool, a healthcare worker knowledge and attitudes questionnaire, and an antimicrobial prescribing app to support clinical decision-making. Training workshops on AMS were developed and delivered to volunteers in Africa and the UK using a train-the-trainer model. The tools and workshops facilitated capacity building for AMS through the generation and strengthening of knowledge, skills, commitment, structures, systems, and leadership among stakeholders in the UK and Africa. The overall average rating assigned to the program following independent evaluation using the Organisation for Economic Cooperation and Development Assistance Committee Evaluation Criteria was very good. The evaluation also highlighted that the majority of the HPs (75%) focused on AMS and/or improved prescribing practice; all HPs have developed and implemented AMS strategies, guidelines, and tools within their hospitals; and NHS staff were able to translate the knowledge and skills they had received early on in the program into clinical practice in response to COVID-19 challenges.

Abstract Introduction Under-reporting of adverse drug reactions is a major challenge in Tanzania. It is important to educate the health care providers about pharmacovigilance in order to improve the reporting rate. Objectives: We conducted a study with the objective of evaluating the impact of an educational intervention based on the knowledge on pharmacovigilance among healthcare providers in Tanzania. Methods: A pharmacovigilance e-blended learning method was used. Pre and post-test, courses were the basic concepts in Pharmacovigilance and the safety of Anti-Tuberculosis Drugs. Descriptive analyses were run to determine the proportions of the correct and wrong answers for pre and post training. Results A total of 118 (72%) completed the pre-and post-test for both the first and the second courses. There was an increase in the correct answers in the post-test to every question. The median score of pre-intervention for knowledge about basic pharmacovigilance increased from 5 (range 4–7) in pre-test to 8 (range 7–9) in post-test. The median score for anti-TB drug safety issues monitoring and management increased from 4 (range 4–6) in pre-test to 7 (range 7–9) in post-test. Conclusion The findings of this study showed that knowledge scores and correct answers were increased following an educational intervention among HCP.

BACKGROUND:Antimicrobial resistance (AMR) is a global public health concern currently mitigated by antimicrobial stewardship (AMS). Pharmacists are strategically placed to lead AMS actions that contribute to responsible use of antimicrobials; however, this is undermined by an acknowledged health leadership skills deficit. Learning from the UK's Chief Pharmaceutical Officer's Global Health (ChPOGH) Fellowship programme, the Commonwealth Pharmacists Association (CPA) is focused to develop a health leadership training program for pharmacists in eight sub-Saharan African countries. This study thus explores need-based leadership training needs for pharmacists to provide effective AMS and inform the CPA's development of a focused leadership training programme, the 'Commonwealth Partnerships in AMS, Health Leadership Programme' (CwPAMS/LP).METHODS:A mixed methods approach was undertaken. Quantitative data were collected via a survey across 8 sub-Saharan African countries and descriptively analysed. Qualitative data were collected through 5 virtual focus group discussions, held between February and July 2021, involving stakeholder pharmacists from different sectors in the 8 countries and were analysed thematically. Data were triangulated to determine priority areas for the training programme.RESULTS:The quantitative phase produced 484 survey responses. Focus groups had 40 participants from the 8 countries. Data analysis revealed a clear need for a health leadership programme, with 61% of respondents finding previous leadership training programmes highly beneficial or beneficial. A proportion of survey participants (37%) and the focus groups highlighted poor access to leadership training opportunities in their countries. Clinical pharmacy (34%) and health leadership (31%) were ranked as the two highest priority areas for further training of pharmacists. Within these priority areas, strategic thinking (65%), clinical knowledge (57%), coaching and mentoring (51%), and project management (58%) were selected as the most important.CONCLUSIONS:The study highlights the training needs of pharmacists and priority focus areas for health leadership to advance AMS within the African context. Context-specific identification of priority areas supports a needs-based approach to programme development, maximising African pharmacists' contribution to AMS for improved and sustainable patient outcomes. This study recommends incorporating conflict management, behaviour change techniques, and advocacy, amongst others, as areas of focus to train pharmacist leaders to contribute to AMS effectively.

Efficient and secure supply chains are vital for effective health services worldwide. In low- and middle-income countries, the accessibility, affordability and availability of essential medicines, including antimicrobials, remain challenging. Ineffective supply chains often cause antimicrobial shortages, leading to inappropriate use of alternative agents and increasing the risk of antimicrobial resistance. Shortages, coupled with insecure supply chains, also encourage the infiltration of substandard and falsified medicines, leading to suboptimal treatment and further promoting antimicrobial resistance. Addressing antimicrobial supply-chain issues should be considered a key component of antimicrobial stewardship programmes. We have explored the link between medicine supply chains and antimicrobial use in seven focus countries: Kenya, Malawi, Nigeria, Sierra Leone, Uganda, United Republic of Tanzania and Zambia. We explored country medicine supply-system structures, national medicine supply-chain policy documents and global study reports. Our aim was to develop evidence-based strategies to enhance the effectiveness and efficiency of the medicine supply chains in supporting antimicrobial stewardship efforts. Better management of medical supply chains involves rational selection, quantification, forecasting, procurement, storage, distribution, use and stock management of antimicrobials. Important supply-chain considerations include pooled procurement networks to ensure consistent pricing of quality-assured antimicrobials, and improved resource utilization and information exchange among relevant stakeholders. We propose adaptable recommendations for integrating medicine supply chains as an essential part of antimicrobial stewardship programmes, with a call for action at the local, regional and national levels in low- and middle-income countries.

Antimicrobial resistance (AMR) is a global health problem threatening safe, effective healthcare delivery in all countries and settings. The ability of microorganisms to become resistant to the effects of antimicrobials is an inevitable evolutionary process. The misuse and overuse of antimicrobial agents have increased the importance of a global focus on antimicrobial stewardship (AMS). This review provides insight into the current AMS landscape and identifies contemporary actors and initiatives related to AMS projects in eight African countries (Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia), which form a network of countries participating in the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme. We focus on common themes across the eight countries, including the current status of AMR, infection prevention and control, AMR implementation strategies, AMS, antimicrobial surveillance, antimicrobial use, antimicrobial consumption surveillance, a one health approach, digital health, pre-service and in-service AMR and AMS training, access to and supply of medicines, and the impact of COVID-19. Recommendations suitable for adaptation are presented, including the development of a national AMS strategy and incorporation of AMS in pharmacists’ and other healthcare professionals’ curricula for pre-service and in-service training.

Under-reporting of adverse drug events (ADEs) is a challenge facing developing countries including Tanzania. Given the high magnitude of under-reporting, it was necessary to develop and assess the effectiveness of a 'structured stimulated spontaneous safety monitoring' (SSSSM) reporting program of ADEs which aimed at strengthening pharmacovigilance system in Tanzania. A quasi-experimental design and data mining technique were used to assess the effect of intervention after the introduction of program in seven tertiary hospitals. ADEs reports were collected from a single group and compared for 18 months before (July 2017 to December, 2018) and after the program (January 2019 to June 2020). Out of 16,557 ADEs reports, 98.6% (16,332) were reported after intervention and 0.1% (23) death related to adverse drug reactions (ADRs) were reported. Reports increased from 20 to 11,637 after intervention in Dar es salaam, 49 to 316 in Kilimanjaro and 17 to 77 in Mbeya. The population-based reporting ratio per 1,000,000 inhabitants increased from 2 reports per million inhabitants in 2018 to 85 reports in 2019. The SSSSM program can increase the reporting rate of ADEs and was useful in detecting signals from all types of medicines. This was first effective developed spontaneous program to monitor medicine safety in Tanzania.

INTRODUCTION:Viral load measurement is an important gold standard for monitoring anti-retroviral treatment among people living with human immunodeficiency virus. The optimal use of the viral load results for guiding antiretroviral therapy depends on timely availability of the results at the clinic. The objective of the current study was to evaluate the turnaround time and utilization of viral load results in the clinical decision process.METHODOLOGY:This was a retrospective cohort study which involved patients receiving cART from 1 August 2018 to 31 January 2017 at three clinics in Tanzania. Data was extracted from patient files at the clinics and relevant records were kept at the viral load determining laboratory. The data were analysed with the Statistical Package for Social Sciences version 20.RESULTS:445 subjects had a viral load in test results and 88% had a viral load of > 1,000 copies/mL. The median duration on the current regimen was five years. Median time between the clinics receiving the results and communicating them to the patients was 40 days. Shorter turnaround time was observed for patients with virological failure (p = 0.003). A higher prevalence of virological failure was found in patients monitored at the Kilimanjaro Christian Medical Centre (KCMC) compared to the two primary health clinics (p = 0.04).CONCLUSIONS:The median viral load turnaround time was longer than stipulated by the national Tanzanian guidelines. Interventions that may reduce viral load turn-around-time, including point of care viral load testing, are needed to optimise monitoring of anti-retroviral therapy.

The World Health Organisation (WHO) and others have identified, as a priority, the need to improve antimicrobial stewardship (AMS) interventions as part of the effort to tackle antimicrobial resistance (AMR). An international health partnership model, the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme, was established between selected countries in Africa (Ghana, Tanzania, Zambia and Uganda) and the UK to support AMS. This was funded by UK aid under the Fleming Fund and managed by the Commonwealth Pharmacists Association (CPA) and Tropical Health and Education Trust (THET). The primary aims were to develop local AMS teams and generate antimicrobial consumption surveillance data, quality improvement initiatives, infection prevention and control (IPC) and education/training to reduce AMR. Education and training were key components in achieving this, with pharmacists taking a lead role in developing and leading AMS interventions. Pharmacist-led interventions in Ghana improved access to national antimicrobial prescribing guidelines via the CwPAMS mobile app and improved compliance with policy from 18% to 70% initially for patients with pneumonia in one outpatient clinic. Capacity development on AMS and IPC were achieved in both Tanzania and Zambia, and a train-the-trainer model on the local production of alcohol hand rub in Uganda and Zambia. The model of pharmacy health partnerships has been identified as a model with great potential to be used in other low and middle income countries (LMICs) to support tackling AMR.

Introduction: In Tanzania, the Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDEC) has implemented the Option B+ as one of the strategies to facilitate achievement of elimination of mother to child transmission of HIV. To prevent emergence of drug resistance mutations early identification of option B+ failure is critical. The emergence of drug resistance mutation and subsequent treatment failure poses a major concern for HIV program in low- and middle-income resource settings where treatment options are limited. Methodology: We recruited treatment naïve, treatment experienced HIV-1 positive pregnant women and those who had prophylaxis in their previous pregnancy in Kilimanjaro, northern Tanzania August 2016 to February 2017. Whole blood (2ml) for biochemistry, viral load and drug resistance testing were taken at baseline. ARV drug resistance testing was done on women with VL ≥ 1000 copies/ml. We used descriptive statistic and logistic regression to determine the strength of association between virologic outcome (virologic failure) and independent predictors. Results: One hundred and forty eight (148) pregnant HIV-positive women were enrolled in the study with mean age of 29.82 years (SD=6.17) from August, 2016 to February, 2017. Virologic failure was demonstrated in 34 (23%) with viral load ≥ 1,000 copies/ml. Genotyping results were available from 26 women, mutations associated with ARV resistance were detected in 23.1% (n = 6/26). Among the six women with ARV resistance mutation 4(66.7%) had high level resistance and 2(33.3%) had low level resistance. Among the 26 samples genotyped 15(58%) viruses were subtype A, while eight were subtype C (31%) and three subtypes D (11%). The most dominant drug resistance mutations against the reverse transcriptase inhibitors for the women with high level resistance were K103N, Y188L, D67N, K70R, M184V, T215F, K219EQ, and the low-level resistance was E138A. The older age was associated with virological failure compared to those who were < 20 year of age. Conclusion: Viral load testing should be done on women who were already on antiretroviral treatment on their first antenatal visit to ensure early detection of virological failure and enable clinicians to take an appropriate course of action on their management. Educational intervention on adherence should be targeted at an early stage to women with virological failure during pregnancy to reduce the emergence of HIV-1 drug resistance mutations.

BACKGROUND:Mobile communication has been found to improve antiretroviral therapy (ART) adherence among people living with HIV. In an ongoing randomized clinical trial, 2 mobile communication strategies (ie, sending SMS text messages and real-time medication monitoring [RTMM]) were used to improve adherence to ART among people living with HIV in Tanzania. We noticed remarkable discrepancies between self-reported adherence and adherence recorded by SMS text messaging or RTMM among some of the first trial participants.OBJECTIVE:Our objective was to describe these cases and the observed discrepancies in more detail, to serve as a useful illustration of some of the challenges in using mobile health in resource-limited settings.METHODS:In an ongoing randomized trial, adults living with HIV from two HIV treatment centers in Tanzania who were suspected of low levels of adherence were randomly assigned in a 1:1:1 ratio to receive (1) SMS text message reminders, (2) an RTMM device, or (3) no additional intervention to standard HIV care. During bimonthly study visits, the participants self-reported their level of adherence, received feedback about their level of adherence based on SMS text messaging or RTMM, and discussed strategies to overcome adherence problems with nurses providing HIV care. For the purpose of this report, we selected people living with HIV who had completed 5 follow-up visits and consistently reported more than 95% adherence, while SMS text messaging or RTMM recorded lower than 75% adherence. The participants were invited for a short, face-to-face in-depth interview to explore reasons for this discrepancy.RESULTS:At the time of this analysis, 26 participants had completed follow-up. Six of these evidenced the above-mentioned discrepancies, with an average adherence of 46% based on SMS text messaging or RTMM, while self-reported adherence was 98%. Five of these 6 participants insisted that their adherence to ART was good, with 4 reporting that their adherence to properly using the monitoring device was low. Three participants mentioned concerns about involuntary disclosure of HIV status as a main reason for low adherence to using the device. Two participants were still depending on other reminder cues despite receiving SMS text message or RTMM reminders. Poor network coverage caused low adherence in 1 participant.CONCLUSIONS:Psychosocial barriers were reported as importantly contributing to low adherence, both with respect to use of ART and proper use of the adherence-monitoring device. This case series illustrates that when introducing new digital adherence monitoring technology, researchers should consider psychosocial barriers and distinguish between adherence to device use and adherence to treatment.TRIAL REGISTRATION:Pan African Clinical Trials Registry PACTR201712002844286; https://tinyurl.com/y98q4p3l.

Abstract Background: There is growing evidence of high effectiveness of partner notification (PN) in reaching previously undiagnosed sexual partners. As a result, there is increasing implementation of PN in sub-Saharan Africa. Tanzania, like other countries in the region, has recently expanded PN in HIV testing services. However, this approach is unlikely to yield the expected results if not well implemented. This study aimed to identify gaps and provide recommendations to improve routine implementation of PN in Tanzania.Methods: A cross-sectional study was conducted across seven care and treatment centers (CTCs) in the Kilimanjaro region from November 2018 to April 2019. A total of 297 newly diagnosed HIV infected clients with sexual partner(s) in the past 24 months were recruited at 2 months of their CTC enrollment. Interviews using structured questionnaires were conducted. Descriptive statistics, bivariate and multivariate regression analyses were done.Results: Two-thirds (195) were females. The majority 165 (85%) of those counseled and had partner(s) not previously tested for HIV consented to PN. They all chose passive PN with 102 (62%) reporting successful HIV status disclosure to their partner(s). Reporting disclosure was associated with; being married adjusted odds ratio (aOR 5.1, 95%CI: 2.4–10.9, p < 0.001), in a relationship for > 10 years (aOR 4.9, 95%CI: 1.3–17.6, p = 0.02) and living with the partner(s) (aOR 3.4, 95%CI: 1.3–9.1, p = 0.02). Fifty-three clients (27%) of those with partners not previously tested for HIV reported partner HIV testing following PN, associated with being married (aOR 3.4, 95%CI: 1.3-9, p < 0.02) and living with the partner (aOR 4.5, 95%CI: 1.3–15, p < 0.02). Male partner(s) had lower odds of successful HIV testing (aOR 0.4, 95%CI: 0.2–0.9, p = 0.02). Thirty-seven (67%) of those tested were HIV infected.Conclusions: Detection rate of previously undiagnosed HIV infection among clients referred for HIV-testing through PN was high. However, a significant number of partners did not report for HIV testing after 2 months of index clients CTC enrollment. Initiatives to improve PN are needed with special attention towards those who are single, not living with their partners, in a relationship for < 10 years as well as male sexual partners.

Background: Pharmacovigilance is a means of ensuring drug safety and thus ensuring the risk of drug use does not outweigh the benefit. Antiretroviral therapy for HIV care and treatment has been reported to have reduced mortality and morbidity but has adverse drug reactions. These adverse drug reactions (ADR) lead to treatment failure. In 2015 in Tanzania 688,800 adults were taking ART. All health care providers are required to report all suspected adverse drug reactions seen or reported by their patients using the yellow forms that are available at all CTC centres in Tanzania. However the actual practice of reporting is not taking place. This study aimed to explore the patients’ knowledge and HIV/AIDS health care providers’ and reporting practices of adverse events of ART, with the specific objective to determine the knowledge of patients on ART adverse events and practices of health care providers on reporting of ART ADR at Kilimanjaro Christian Medical Centre (KCMC). Methods: A cross-sectional study using a semi-structured questionnaire was conducted between June to July 2016 within HIV, dermatology and infectious disease clinics at KCMC. All health care providers (HCPs) providing HIV services within these clinics completed a questionnaire. Mean and standard deviation were used to summarize the numerical data with normal distribution (age of patients) while undistributed numerical data (duration on ART) was summarized using median and range. Frequency and percentage was used to summarize categorical variables. Results: All 63 HCPs , agreed ADR reporting was necessary. Forty six (73%) were aware of the national ADR reporting system but only 32(50.8%) reported having received training on pharmacovigilance. Only 4(6.3%) of all HCPs reported to always fill ADR report forms, 27(42.9%) rarely filled the forms and 32(50.8%) reported to have never filled an ADR reporting form. Training on pharmacovigilance had positive influence towards ADR reporting. Lack of motivation, unsure on how to report, Lack of time, unavailability of reporting forms and ignorance were the major factors affecting reporting among HCP. Conclusion: Whilst the majority of HCPs were aware of the need and importance of ADR reporting and the national pharmacovigilance system, the study suggests, however, there exists an under reporting of ART adverse events. More effort is needed to strengthen the continuous reporting of ADRs by providing continuous education to health care providers that will lead to their active participation in pharmacovigilance.

BACKGROUND:Pharmacovigilance is a means of ensuring drug safety, and thus it ensures that the risks associated with medication adminstration and consumption do not outweigh the benefits. Antiretroviral therapy (ART) for HIV care and treatment has reduced mortality and morbidity, but adverse drug reactions (ADRs), which can lead to treatment failure, remain a concern. In 2015 in Tanzania, 688,800 adults were taking ART. All health-care providers are required to report all suspected ADRs seen or reported by their patients using yellow forms available at all care and treatment centres in Tanzania. However, the actual practice of reporting is not taking place. This study aimed to explore the patients' knowledge and HIV/AIDS health-care providers' reporting of ART adverse events at Kilimanjaro Christian Medical Centre (KCMC). METHODS:A cross-sectional study using a semi-structured questionnaire was conducted between June and July 2016 within HIV, dermatology, and infectious disease clinics at KCMC. All health-care providers providing HIV services within these clinics completed a questionnaire. Means and standard deviations were used to summarise the numerical data with normal distributions (age of patients), while numerical data that were not normally distributed (duration on ART) were summarised using medians and ranges. Frequencies and percentages were used to summarise categorical variables. RESULTS:All 63 health-care providers agreed that ADR reporting was necessary. Forty-six (73%) were aware of the national ADR reporting system, but only 32 (50.8%) reported having received training on pharmacovigilance. Only 4 (6.3%) of all health-care providers reported always filling the ADR report forms; 27 (42.9%) rarely filled the forms, and 32 (50.8%) reported having never filled an ADR reporting form. Training on pharmacovigilance had a positive influence on ADR reporting. Lack of motivation, uncertainty about reporting procedures, lack of time, unavailability of reporting forms, and ignorance were the major factors affecting reporting among health-care providers. CONCLUSION:The majority of health-care providers were aware of the need and importance of ADR reporting and the national pharmacovigilance system. However, ART adverse events are underreported. More effort is needed to strengthen the continuous reporting of ADRs by providing continuous education to health-care providers; this will lead to their active participation in pharmacovigilance.

BACKGROUND:Prescriptions written in daily medical practice are associated with increasing numbers of prescription writing errors. Both omission and commission errors are encountered and caused by prescribers of different cadres. Prescribing errors are associated with adverse drug events (ADEs), which are harmful to patients. This study aimed to determine the common prescription errors, the categories of prescribers who commit prescription errors, and the most prescribed drugs in the outpatient pharmacies in general practice at Kilimanjaro Christian Medical Centre (KCMC).METHODS:A prospective cross-sectional descriptive study was conducted at KCMC, a referral and teaching university hospital. All prescription dispensed on 2 June 2017 from the hospital's 2 outpatient pharmacies were reviewed, and our analysis determined the different types of prescription errors. A form designed by the authors was used to collect data from the prescription forms.RESULTS:A total of 242 prescriptions were studied, and the most common omission errors were missing patients' weight (n=231, 95.5%), missing patients' address (n=213, 88.0%), missing drug dosage (n=159, 67.1%), and commission errors were due to wrong drug strength (n=10, 2.0%). Intern doctors were leading in writing prescriptions with errors (n=352, 25.6%), followed by residents (n=199, 14.5%), registrar doctors (n=167, 12.1%), and specialists (n=45, 3.3%). The most commonly prescribed drugs were antibiotics (n=120, 17.3%), antihypertensives (n=81, 11.7%), and analgesics (n=86, 12.4%).CONCLUSION:There were significant prescription errors at the study site, hence an intervention is needed to improve skills of prescribers. Educational interventions can substantially contribute to minimising such errors. Initaiting programmes and short courses on prescription writing before medical internship at the health facility might also be helpful.

A1 Introduction to the 2nd synchronicity forum of GHRI/CHVI-funded Canadian and African HIV prevention and vaccine teams

AIDS Research and Human RetrovirusesVol. 30, No. S1 Resistance and Treatment FailureFree AccessEffectiveness of Drug Interventions Reducing Nevirapine Resistance after Single-dose Exposure for Perinatal HIV PreventionEva P. Muro, Quirine Fillekes, and David M. BurgerEva P. MuroKilimanjaro Clinical Research Institute, Moshi, Tanzania, United Republic ofSearch for more papers by this author, Quirine FillekesRadboud University Nijmegen Medical Centre, Department of Pharmacy, Nijmegen, NetherlandsSearch for more papers by this author, and David M. BurgerRadboud University Nijmegen Medical Centre, Department of Pharmacy, Nijmegen, NetherlandsSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5345.abstractAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail P22.03Background: The major disadvantage of single-dose nevirapine is the development of nevirapine resistance in mothers and infants. Co-interventions, such as short-course antiretroviral regimens in combination with single-dose nevirapine and extension of interventions, have been evaluated in this study.Methods: Systematic search of electronic databases (MEDLINE, EMBASE and Cochrane) was performed. Studies included HIV-infected, pregnant women, who were administered single-dose nevirapine for pMTCT and who were receiving an intervention to reduce nevirapine resistance. Primary outcome was the proportion of nevirapine resistance detected in plasma samples collected ≤3 months postpartum. The reducing effect of drug interventions on nevirapine resistance was assessed in meta-analyses using random effects models and the GRADE approach for quality of evidence.Results: The estimated pooled proportion of nevirapine resistance using single-dose nevirapine at labor was 31% (95%CI 7.6-54); this was reduced to 21% (95%CI 8.6-33) with addition of antepartum zidovudine. A combination of antepartum zidovudine, single-dose nevirapine and a short (<8 days) postpartum regimen resulted in a major reduction in nevirapine resistance to 0.011% (95%CI -0.11-0.13). The summary effect of 20–30 days of postpartum drug regimens combined with antepartum zidovudine and single-dose nevirapine was associated with a slightly lower incidence of nevirapine resistance, namely 0.003% (95%CI -0.054-0.060).Conclusions: Antepartum zidovudine plus antiretroviral drugs postpartum have shown to nearly eliminate nevirapine resistance. Although 20–30 days post partum regimens might be slightly more effective compared to a short (<8 days) postpartum regimen, longer term antiretroviral therapy is more complex and more challenging to implement in daily practice. The WHO guideline option A should be followed to achieve a feasible minimum risk of nevirapine resistance in regions where single-dose nevirapine is still being used.FiguresReferencesRelatedDetails Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Eva P. Muro, Quirine Fillekes, and David M. Burger.Effectiveness of Drug Interventions Reducing Nevirapine Resistance after Single-dose Exposure for Perinatal HIV Prevention.AIDS Research and Human Retroviruses.Oct 2014.A165-A166.http://doi.org/10.1089/aid.2014.5345.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download

Background:Thin layer chromatography (TLC) can be used to perform therapeutic drug monitoring in resource-limited settings, where more expensive analytical methods, such as high-performance liquid chromatography or liquid chromatography-mass spectrometry, are not feasible.Objectives:The aim of this cross-sectional study was to compare saliva concentrations of nevirapine (NVP) with self-reported adherence in patients on NVP-containing antiretroviral treatment at Kilimanjaro Christian Medical Centre, Moshi, Tanzania.Methods:HIV-infected patients using a combination of zidovudine + lamivudine + NVP, or stavudine + lamivudine + NVP, for more than 4 weeks were included. Saliva samples were collected using dental cotton rolls impregnated with citric acid (20 mg). Saliva NVP concentrations were analyzed using TLC. Adherence to ARV medication was assessed by self-reporting using the Morisky scale.Results:Of the 91 study participants, 79 (86.8%) had therapeutic saliva NVP concentrations (ie, >1.75 mg/L) and 12 (13.2%) had subtherapeutic concentrations. Self-reported adherence among the study participants was high in 62 participants (68.1%), moderate in 24 (26.4%), and low in 5 (5.5%). Fifty-seven (91.9%) of the study participants with high self-reported adherence had therapeutic saliva NVP concentrations. Of the 5 participants with low self-reported adherence, 3 had therapeutic NVP concentrations.Conclusions:A high proportion of patients had therapeutic NVP saliva concentrations as measured by TLC, which showed a good agreement with self-reported adherence.

OBJECTIVES To confirm whether 7 days of phenytoin, an enzyme inducer, would decrease the elimination half-life of single-dose nevirapine and to investigate its effect on the development of nevirapine resistance in pregnant, HIV-infected women. METHODS In a pharmacokinetic pilot trial (NCT01187719), HIV-infected, antiretroviral (ARV)-naive pregnant women ≥18 years old from Zambia and Tanzania and with CD4 cell counts >350 cells/mm(3) were randomized 1 : 1 to a control (zidovudine pre-delivery, single-dose nevirapine/zidovudine/lamivudine at delivery and zidovudine/lamivudine for 7 days post-delivery) or an intervention (control plus 184 mg of phenytoin once daily for 7 days post-delivery) group. Primary endpoints were the pharmacokinetics of and resistance to nevirapine. RESULTS Thirty-five and 37 women were allocated to the control and intervention groups, with median (IQR) ages of 27 (23-31) and 27 (23-33) years, respectively. Twenty-three and 23 women had detectable nevirapine levels at delivery and subsequent samples in the control and the intervention groups, respectively. Geometric mean (GM) (95% CI) plasma levels of nevirapine at delivery were 1.02 (0.58-1.78) mg/L and 1.14 (0.70-1.86) mg/L in the control and intervention groups, respectively (P = 0.76). One week after delivery, 0/23 (0%) and 15/22 (68%) control and intervention mothers, respectively, had undetectable levels of nevirapine (<0.05 mg/L; P<0.001). One week later, the figures were 10/21 (48%) and 18/19 (95%) mothers, respectively (P = 0.002). The GM (95% CI) half-life of nevirapine was 63.2 (52.8-75.7) versus 25.5 (21.6-30.1) h in the control group versus the intervention group (P < 0.001). New nevirapine mutations were found in 0/20 (0%) intervention-group mothers versus 1/21 (5%) control-group mothers. Overall, there was no difference in adverse events reported between the control and intervention arms (P > 0.28). CONCLUSIONS Adding 7 days of an enzyme inducer to single-dose nevirapine to prevent mother-to-child transmission of HIV significantly reduced subtherapeutic nevirapine levels by shortening the half-life of nevirapine. As prolonged subtherapeutic nevirapine dosage leads to the emergence of resistance, single-dose nevirapine could be used with phenytoin as an alternative if other ARVs were unavailable.

BACKGROUND:World Health Organization guidelines recommend zidovudine + lamivudine for 7 days from labor onset in HIV-infected women receiving single-dose nevirapine (sdNVP) to cover prolonged subtherapeutic nevirapine concentrations. Although effective, this is complicated and does not eliminate resistance; alternative strategies could add benefit. METHODS:Antiretroviral-naive HIV-infected pregnant women aged 18-40 years, with CD4 >200 cells per cubic millimeter, able to regularly attend the antenatal clinics in Moshi, Tanzania, were enrolled 1:1 by alternate allocation to receive 200 mg sdNVP alone or in combination with open-label 400-mg single-dose carbamazepine (sdNVP/CBZ) at delivery (ClinicalTrials.gov NCT00294892). The coprimary outcomes were nevirapine plasma concentrations 1 week and nevirapine resistance mutations 6 weeks postpartum. Analyses were based on those still eligible at delivery. RESULTS:Ninety-seven women were assigned to sdNVP and 95 to sdNVP/CBZ during pregnancy, of whom 75 sdNVP and 83 sdNVP/CBZ were still eligible at delivery at study sites. The median (interquartile range) nevirapine plasma concentration was 1.55 (0.88-1.84) mg/L in sdNVP (n = 61) and 1.40 (0.93-1.97) mg/L in sdNVP/CBZ (n = 72) at delivery (P = 0.91), but 1 week later was significantly lower in sdNVP/CBZ [n = 63; 0.09 (0.05-0.20) mg/L] than in sdNVP [n = 52; 0.20 (0.09-0.31) mg/L; rank-sum: P = 0.004] (geometric mean ratio: 0.64, 95% confidence interval: 0.43 to 0.96; P = 0.03). Six weeks postpartum, nevirapine mutations were observed in 11 of 52 (21%) in sdNVP and 6 of 55 (11%) in sdNVP/CBZ (odds ratio = 0.46, 95% confidence interval: 0.16 to 1.34; P = 0.15). CONCLUSIONS:Addition of single-dose carbamazepine to sdNVP at labor onset in HIV-infected, pregnant women did not affect nevirapine plasma concentration at delivery, but significantly reduced it 1 week postpartum, with a trend toward fewer nevirapine resistance mutations.