58 research outputs found

    Rapid HIV-1 drug resistance testing in a resource limited setting: the Pan Degenerate Amplification and Adaptation assay (PANDAA)

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    Introduction: pre-treatment drug resistance (PDR) can compromise the 3rd 95-95-95 global target for viral load suppression. The high complexity and cost of genotyping assays limits routine testing in many resource limited settings (RLS). We assessed the performance of a rapid HIV-1 drug resistance assay, the Pan Degenerate Amplification and Adaptation (PANDAA) assay when screening for significant HIV-1 drug resistance mutations (DRMs) such as K65R, K103NS, M184VI, Y181C and G190A. Methods: we used previously generated amplicons from a cross-sectional study conducted between October 2018 and February 2020 of HIV-1 infected antiretroviral therapy (ART)-na√Įve or those reinitiating 1st line ART (18 years or older). The performance of the PANDAA assay in screening K65R, K103NS, M184VI, Y181C, and G190A mutations compared to the reference assay, Sanger sequencing was evaluated by Cohen¬īs kappa coefficient on Stata version 14 (StataCorp LP, College Station, TX, USA). Results: one hundred and twenty samples previously characterized by Sanger sequencing were assessed using PANDAA. PDR was found in 14% (17/120). PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was higher at 13% (16/120) than PDR to nucleotide reverse transcriptase inhibitors (NRTIs), 3% (3/120). The PANDAA assay showed a strong agreement with the reference assay, i.e. Sanger sequencing for all five target DRMs (kappa (95%CI); 0.93(0.78-0.98)) and NNRTI DRMs (kappa (95%CI); 0.93(0.77-0.980), and a perfect agreement for NRTI DRMs (kappa (95%CI); 1.00(0.54-1.00)). Conclusion: the PANDAA assay is a simple and rapid method to identify significant HIV DRMs in plasma samples as an alternative to Sanger sequencing in many RLS

    A Scoping Review of Gut Microbiome and Bifidobacterium Research in Zimbabwe:Implications for Future Studies

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    Background: Gut microbiota play a key role in host health, with certain Bifidobacterium strains critical for immune development. The healthy gut of breastfed infants is dominated by these pioneer microbes, especially the strains that feed on human milk oligosaccharides.Objective: This is a scoping review of gut microbiome research from Zimbabwe. It focuses on distribution and dynamic changes of bifidobacteria, and milk components that promote growth of microbes in infants, together with the distribution of associated gut microbes in adults.Design: Online databases were searched for publications from 2000 to 2023.Results and Analysis: Fourteen publications on microbiota of infants and adults were included in this scoping review. Most were cross-sectional, while three were clinical trials/cohort protocols. Publications focused on pediatrics (78.5%), pregnant women (14.3%), and men (7.2%). Zimbabwe has a high burden of HIV; hence 35.7% of study populations were delineated by HIV status. The laboratory methods used included shotgun metagenomics (62%) or 16S rRNA gene amplicon sequencing. Almost 85% of the studies focused on total microbiome profiles and rarely reported the distribution of different Bifidobacterium species and variants. None of the papers studied human breast milk composition. There were reports of reduced abundance of beneficial genera in pregnant women, children, and adolescents living with HIV. Additionally, gut microbiota was reported to be poorly predictive of child growth and vaccine response, though this was not conclusive.Conclusion: There are few studies that characterize the gut microbiome by Zimbabwe-based researchers. However, studies on strain level diversity of Bifidobacterium and other key microbes, and their role in health during and beyond infancy, lag behind in Zimbabwe and other low- and middle-income countries. Such cohorts are needed to inform future mechanistic studies and downstream translational work such as next-generation probiotics and prebiotics

    An analysis of the COVID-19 laboratory dataset at AiBST Laboratory in Harare, Zimbabwe, 2020

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    Introduction: coronavirus disease 2019 (COVID-19) has become a major public health problem and has spread rapidly around the globe since its first identification in Wuhan, China, in December 2019. Zimbabwe reported its first case on the 20th March 2020, and since then the disease has spread to almost every part of the country. Laboratory testing is important in controlling this pandemic. However, few studies have focused on assessing trends of SARS-CoV-2 laboratory data. We described SARS-CoV-2 data from African Institute of Biomedical Science and Technology (AiBST) Laboratory in Harare, Zimbabwe. Methods: a retrospective record review of secondary SARS-CoV-2 data from AiBST Laboratory in Harare between May to September 2020 was done. Epi Info TM 7.2.2.6 was used to generate frequencies, proportions and conduct bivariate analysis. Results: a total of 6,535 SARS-CoV-2 laboratory records were analysed. The median age of the patients was 36 years and 55% (3594/6535) were males. There was an increase in average analytical turn-around time (TAT) of SARS-CoV-2 results from May to August 2020. Analytical and preanalytical TAT remained above 2 days from August to September. Males were 1.18 times at risk of being SARS-CoV-2 infected than females (p<0.05). The risk of being SARS-CoV-2 infected increased with age from 1.06 in the 11-20 age group to 1.45 in the 41-50 age group. Conclusion: COVID-19 poses a greater threat to the older age groups and to men. The delayed TAT of SARS-CoV-2 results limits the efforts to control the pandemic. Decentralization of testing to provincial and district level would help improve result TAT

    Drug resistance in children at virological failure in a rural KwaZulu-Natal, South Africa, cohort.

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    BACKGROUND: Better understanding of drug resistance patterns in HIV-infected children on antiretroviral therapy (ART) is required to inform public health policies in high prevalence settings. The aim of this study was to characterise the acquired drug resistance in HIV-infected children failing first-line ART in a decentralised rural HIV programme. METHODS: Plasma samples were collected from 101 paediatric patients (‚ȧ15¬†yrs of age) identified as failing ART. RNA was extracted from the plasma, reverse transcribed and a 1.3¬†kb region of the pol gene was amplified and sequenced using Sanger sequencing protocols. Sequences were edited in Geneious and drug resistance mutations were identified using the RegaDB and the Stanford resistance algorithms. The prevalence and frequency of mutations were analysed together with selected clinical and demographic data in STATA v11. RESULTS: A total of 101 children were enrolled and 89 (88%) were successfully genotyped; 73 on a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen and 16 on a protease inhibitor (PI)-based regimen at the time of genotyping. The majority of patients on an NNRTI regimen (80%) had both nucleoside reverse-transcriptase inhibitor (NRTI) and NNRTI resistance mutations. M184V and K103N were the most common mutations amongst children on NNRTI-based and M184V among children on PI-based regimens. 30.1% had one or more thymidine analogue mutation (TAM) and 6% had ‚Č•3 TAMs. Only one child on a PI-based regimen harboured a major PI resistance mutation. CONCLUSIONS: Whilst the patterns of resistance were largely predictable, the few complex resistance patterns seen with NNRTI-based regimens and the absence of major PI mutations in children failing PI-based regimens suggest the need for wider access to genotypic resistance testing in this setting

    Tenofovir, Lamivudine and Dolutegravir (TLD) among Rural Adolescents in Zimbabwe, a Cautionary Tale.

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    Tenofovir disoproxil fumarate, lamivudine and dolutegravir (TLD) as a safe and more effective single daily dose regimen is rolling out in Africa for people living with HIV. Although access to viral load (VL) testing is improving, patients may still be transitioned to TLD with virological failure and potential drug resistance. We reviewed annual VL test results of 390 children and adolescents who had enrolled in a community-based antiretroviral therapy programme in rural Zimbabwe between 2018 and 2019. VL testing was done by the near point of care Simplified Amplification-based Assays (Diagnostics for the Real World, Sunnyvale California) at Chidamoyo Christian Hospital. Rate of virological suppression (VS) on TLD (VL<1000 copies/ml) was assessed. Overall, 184 children and adolescents on TLD were enrolled in this study. The median (IQR) age was 15 (11-19) years, above half of the participants were female (57%). Prior to switching to TLD, rate of VS was 76% (139/184). After a median (IQR) duration of 6.9 (5.5-9.1) months on TLD, VS was observed in 95% (174/184) of the participants. Of the 10 participants with VL ‚Č•1000 copies/ml on TLD, 90% (9/10) were failing on their previous regimens, 6/9 (67%) having been on boosted protease inhibitor- based regimens. A high rate (95%) of VS was observed among children and adolescents on TLD in rural Zimbabwe. TLD may address the problems of virologic failure and emergence of resistance in Africa. However, longer follow up might be needed to ascertain sustained VS in this vulnerable population

    Southern African Treatment Resistance Network (SATuRN) RegaDB HIV drug resistance and clinical management database: supporting patient management, surveillance and research in southern Africa

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    Substantial amounts of data have been generated from patient management and academic exercises designed to better understand the human immunodeficiency virus (HIV) epidemic and design interventions to control it. A number of specialized databases have been designed to manage huge data sets from HIV cohort, vaccine, host genomic and drug resistance studies. Besides databases from cohort studies, most of the online databases contain limited curated data and are thus sequence repositories. HIV drug resistance has been shown to have a great potential to derail the progress made thus far through antiretroviral therapy. Thus, a lot of resources have been invested in generating drug resistance data for patient management and surveillance purposes. Unfortunately, most of the data currently available relate to subtype B even though >60% of the epidemic is caused by HIV-1 subtype C. A consortium of clinicians, scientists, public health experts and policy markers working in southern Africa came together and formed a network, the Southern African Treatment and Resistance Network (SATuRN), with the aim of increasing curated HIV-1 subtype C and tuberculosis drug resistance data. This article describes the HIV-1 data curation process using the SATuRN Rega database. The data curation is a manual and time-consuming process done by clinical, laboratory and data curation specialists. Access to the highly curated data sets is through applications that are reviewed by the SATuRN executive committee. Examples of research outputs from the analysis of the curated data include trends in the level of transmitted drug resistance in South Africa, analysis of the levels of acquired resistance among patients failing therapy and factors associated with the absence of genotypic evidence of drug resistance among patients failing therapy. All these studies have been important for informing first- and second-line therapy. This database is a free password-protected open source database available on www.bioafrica.net

    Increasing HIV-1 Drug Resistance Between 2010 and 2012 in Adults Participating in Population-Based HIV Surveillance in Rural KwaZulu-Natal, South Africa.

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    As more human immunodeficiency virus (HIV)-infected patients access combination antiretroviral therapy (cART), higher proportions of newly infected patients may be infected with drug-resistant viruses. Regular surveillance of transmitted drug resistance (TDR) is required in southern Africa where high rates of transmission persist despite rapid expansion of ART. Dried blood spot samples from cART-naive participants from two rounds of an annual population-based HIV surveillance program in rural KwaZulu-Natal were tested for HIV RNA, and samples with HIV RNA >10,000 copies/ml were genotyped for drug resistance. The 2009 surveillance of drug resistance mutation (SDRM) list was used for drug resistance interpretation. The data were added to previously published data from the same program, and the Ōá(2) test for trend was used to test for trend in estimated prevalence of any TDR. Seven hundred and one participants' data were analyzed: 67 (2010), 381 (2011), and 253 (2012). No TDR was detected in 2010. Years 2011 and 2012 had 18 participants with SDRMs 4.7% and 7.1%, respectively (p‚ÄČ=‚ÄČ.02, Ōá(2) test for trend). The nonnucleoside reverse transcriptase inhibitor mutation, K103N, was the most common mutation, occurring in 27 (3.8%) of the participants, while nucleoside reverse transcriptase inhibitor (NRTI) SDRMs were detected in 10 (1.4%) of the participants, of whom eight had only a single NRTI SDRM. The increase in levels of drug resistance observed in this population could be a signal of increasing transmission of drug-resistant HIV. Thus, continued surveillance is critical to inform public health policies around HIV treatment and prevention

    Clinic-based SAMBA-II vs centralized laboratory viral load assays among HIV-1 infected children, adolescents and young adults in rural Zimbabwe: A randomized controlled trial.

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    BACKGROUND In Zimbabwe, children, adolescents and young adults living with HIV (CALWH) who are on public health antiretroviral therapy (ART) have inadequate viral load (VL) suppression. We assessed whether a clinic-based VL monitoring could decrease 12-month virologic failure rates among these CALWH. METHODS The study was registered on ClinicalTrials.gov: NCT03986099. CALWH in care at Chidamoyo Christian Hospital (CCH) and 8 rural outreach sites (ROS) on long-term community-based ART were randomized (1:1) to 6 monthly VL monitoring by COBAS¬ģAmpliprep¬ģ/Taqman48¬ģ HIV-1 at the provincial referral laboratory (PRL) as per standard of care (SOC) or by the clinic-based SAMBA II assay, Diagnostics for the Real World, at CCH. VL suppression, turn-around-time (TAT) for VL results, drug switching and drug resistance in second-line failure were assessed at 12 months. RESULTS Of 390 CALWH enrolled 347 (89%) completed 12 months follow-up. Median (IQR) age and ART duration were 14.1 (9.7-18.2) and 6.4 (3.7-7.9) years, respectively. Over half (57%) of the participants were female. At enrolment, 78 (20%) had VL ‚Č•1,000 copies/ml and VL suppression of 80% was unchanged after 12 months, with no significant difference between the SOC (81%) and the clinic-based (80%) arms (p = 0.528). Median (IQR) months to confirmatory VL result at CCH vs PRL was 4.0 (2.1-4.4) vs 4.5 (3.5-6.3) respectively; p = 0.027 at 12 months. Drug switching was documented among 26/347 (7%) participants with no difference between the median (IQR) time to switch in SOC vs clinic-based arms (5.1 (3.9-10.0) months vs 4.4 (2.5-8.4) respectively; p = 0.569). Out of 24 confirmed second-line failures, only 4/19 (21%) had protease inhibitor resistance. CONCLUSION In rural Zimbabwe, the clinic-based SAMBA II assay was able to provide confirmatory VL results faster than the SOC VL assay at the PRL. However, this rapid TAT did not allow for a more efficient drug switch among these CALWH

    Implementing antiretroviral resistance testing in a primary health care HIV treatment programme in rural KwaZulu-Natal, South Africa: early experiences, achievements and challenges.

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    BACKGROUND: Antiretroviral drug resistance is becoming increasingly common with the expansion of human immunodeficiency virus (HIV) treatment programmes in high prevalence settings. Genotypic resistance testing could have benefit in guiding individual-level treatment decisions but successful models for delivering resistance testing in low- and middle-income countries have not been reported. METHODS: An HIV Treatment Failure Clinic model was implemented within a large primary health care HIV treatment programme in northern KwaZulu-Natal, South Africa. Genotypic resistance testing was offered to adults (‚Č•16 years) with virological failure on first-line antiretroviral therapy (one viral load >1000 copies/ml after at least 12 months on a standard first-line regimen). A genotypic resistance test report was generated with treatment recommendations from a specialist HIV clinician and sent to medical officers at the clinics who were responsible for patient management. A quantitative process evaluation was conducted to determine how the model was implemented and to provide feedback regarding barriers and challenges to delivery. RESULTS: A total of 508 specimens were submitted for genotyping between 8 April 2011 and 31 January 2013; in 438 cases (86.2%) a complete genotype report with recommendations from the specialist clinician was sent to the medical officer. The median turnaround time from specimen collection to receipt of final report was 18 days (interquartile range (IQR) 13-29). In 114 (26.0%) cases the recommended treatment differed from what would be given in the absence of drug resistance testing. In the majority of cases (n‚ÄČ=‚ÄČ315, 71.9%), the subsequent treatment prescribed was in line with the recommendations of the report. CONCLUSIONS: Genotypic resistance testing was successfully implemented in this large primary health care HIV programme and the system functioned well enough for the results to influence clinical management decisions in real time. Further research will explore the impact and cost-effectiveness of different implementation models in different settings

    Implementation of Antibody Rapid Diagnostic Testing versus Real-Time Reverse Transcription-PCR Sample Pooling in the Screening of COVID-19: a Case of Different Testing Strategies in Africa

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    COVID-19 has wreaked havoc across the globe, although cases in Africa remain lower than 50 other regions but they are gradually on an upward trajectory. To date, COVID-19 cases have 51 been reported in 54 countries. However, due to limited SARS-COV-2 rRT-PCR testing 52 capacity and scarcity of testing reagents, it is probable that the total number of cases could 53 far exceed published statistics. In this viewpoint, using Ghana, Malawi, South Africa and 54 Zimbabwe as examples of countries that have implemented different testing strategies, we 55 argue that the implementation of sample pooling for rRT-PCR over antibody rapid diagnostic 56 testing could have a greater impact in assessing disease burden. Sample pooling offers huge 57 advantages compared to single test rRT-PCR, as it lowers experimental costs, personnel 58 time, reduces burnout and analytical run-times. Africa is already strained in terms of testing 59 resources for COVID-19, hence cheaper alternative ways need to be implemented to 60 conserve resources, maximise on mass testing and reduce transmission in the wider 61 population
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