Browsing by Author "van Zyl, Gert"

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    Better virological outcomes among people living with human immunodeficiency virus (HIV) initiating early antiretroviral Tteatment (CD4 Counts ≥500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) trial in South Africa
    (Oxford University Press, 2020-01-16) Fatti, Geoffrey; Grimwood, Ashraf; Nachega, Jean B.; Nelson, Jenna A.; LaSorda, Kelsea; van Zyl, Gert; Grobbelaar, Nelis; Ayles, Helen; Hayes, Richard; Beyers, Nulda; Fidler, Sarah; Bock, Peter
    Background: There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. Methods: This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. Results: The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200-499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12-.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200-499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). Conclusions: Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/µL. Clinical trials registration: NCT01900977.
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    PhyloPi: An affordable, purpose built phylogenetic pipeline for the HIV drug resistance testing facility
    (Public Library of Science, 2019-03-05) Bester, Phillip Armand; De Vries, Andrie; Riekert, Stephanus; Steegen, Kim; van Zyl, Gert; Goedhals, Dominique
    Introduction: Phylogenetic analysis plays a crucial role in quality control in the HIV drug resistance testing laboratory. If previous patient sequence data is available sample swaps can be detected and investigated. As Antiretroviral treatment coverage is increasing in many developing countries, so is the need for HIV drug resistance testing. In countries with multiple languages, transcription errors are easily made with patient identifiers. Here a self-contained blastn integrated phylogenetic pipeline can be especially useful. Even though our pipeline can run on any unix based system, a Raspberry Pi 3 is used here as a very affordable and integrated solution. Performance benchmarks: The computational capability of this single board computer is demonstrated as well as the utility thereof in the HIV drug resistance laboratory. Benchmarking analysis against a large public database shows excellent time performance with minimal user intervention. This pipeline also contains utilities to find previous sequences as well as phylogenetic analysis and a graphical sequence mapping utility against the pol area of the HIV HXB2 reference genome. Sequence data from the Los Alamos HIV database was analyzed for inter- and intra-patient diversity and logistic regression was conducted on the calculated genetic distances. These findings show that allowable clustering and genetic distance between viral sequences from different patients is very dependent on subtype as well as the area of the viral genome being analyzed. Availability: The Raspberry Pi image for PhyloPi, source code of the pipeline, sequence data, bash-, python- and R-scripts for the logistic regression, benchmarking as well as helper scripts are available at http://scholar.ufs.ac.za:8080/xmlui/handle/11660/7638 and https://github.com/ArmandBester/phylopi. The PhyloPi image and the source code are published under the GPLv3 license. A demo version of the PhyloPi pipeline is available at http://phylopi.hpc.ufs.ac.za/.
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    Rapid emergence of resistance to antiretroviral treatment after undisclosed prior exposure : a case report
    (AOSIS Publishing, 2019) Rossouw, Theresa M.; Van Dyk, Gisela; van Zyl, Gert
    Introduction: Patients who disengaged from care may present as therapy naïve for antiretroviral treatment (ART) initiation at a different site, without being recognised as being at an increased risk of rapid treatment failure and HIV drug resistance. Patient presentation: A 43-year-old woman, who gave no prior history of ART, was initiated on a standard first-line regimen of TDF, FTC and EFV. She had a poor response to treatment with evidence of treatment failure at 12 months. Management and outcome: HIV-1 drug resistance tests showed no pre-treatment HIVDR mutations, but revealed high-level drug resistance to all component drugs at 12 months. On investigation, viral load (VL) was recorded in 2012 and 2013, providing evidence of prior ART use. Conclusion: Linkage of patient therapy and laboratory information to unique patient identifiers may allow health-care workers to identify patients who previously received ART and disengaged from care. This will enable differentiated care when these patients reinitiate ART, which should involve expedited VL testing and more rapid transition to definitive second-line ART.