Dr Zinhle Cindi graduates with PhD – 30 March 2023 – at UCT

19 Aug 2023
zinhle_cindi_graduation
19 Aug 2023

Zinhle Cindi graduated with an MSc (Med) Human Genetics from UCT in 2018 and joined the Division of Clinical Pharmacology in 2019. For her Fogarty HATTP-funded PhD thesis (supervised by A/Prof P Sinxadi (UCT), Prof G Maartens (UCT) and Prof D Haas (Vanderbilt University)), she conducted a series of genome-wide association studies in a subset of participants enrolled in the ADVANCE clinical trial (NCT03122262), investigating how genetic differences influence blood concentrations of modern antiretroviral drugs, dolutegravir and tenofovir, and how they affect weight gain associated with these drugs. 

Dr Zinhle Cindi with her supervisor Associate Professor Phumla Sinxadi
Dr Zinhle Cindi with her supervisor Associate Professor Phumla Sinxadi

Her findings improved the understanding of genetic determinants of dolutegravir plasma exposure in an African population, which included identifying a novel association with a variant in UGT1A1, a gene which encodes the drug metabolizing enzyme for dolutegravir (Cindi et al, J Infect Dis 2022). She also observed novel associations with tenofovir exposure (Cindi et al, Pharmacogenet Genomics 2023) and weight gain (Cindi et al, J Acquir Immune Defic Syndr 2021), which require validation in other studies or populations.

To date, these are the largest studies that have investigated associations between genetic variants and drug exposure of modern antiretrovirals in an African population. As dolutegravir and tenofovir form part of the preferred first- or second-line regimens for treating HIV, these data aid in the understanding of pharmacogenetics of dolutegravir and tenofovir among people of African descent.

Zinhle is currently a pursuing a 2-year postdoctoral fellowship at the University of Pennsylvania. She is supervised by A/Prof P Sinxadi, Prof D Haas and Prof M Ritchie. She is partially funded by the Fogarty-HATTP grant and Profs Haas and Ritchie’s NIH-RO1 grant. She is investigating the association of polygenic risk scores and drug-induced liver injury in the AIDS Clinical Trials Group cohort.

The full citations for the 3 manuscripts from the PhD are listed below:

  1. Cindi Z, Kawuma AN, Maartens G, Bradford Y, Venter F, Sokhela S, Chandiwana N, Wasmann RE, Denti P, Wiesner L, Ritchie MD, Haas DW, Sinxadi P. Pharmacogenetics of Dolutegravir Plasma Exposure Among Southern Africans With Human Immunodeficiency Virus. J Infect Dis. 2022 Nov 1;226(9):1616-1625. doi: 10.1093/infdis/jiac174. PubMed PMID: 35512135; PubMed Central PMCID: PMC9624457.
  2. Cindi Z, Kawuma AN, Maartens G, Bradford Y, Sokhela S, Chandiwana N, Venter WDF, Wasmann RE, Denti P, Wiesner L, Ritchie MD, Haas DW, Sinxadi P. Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV. Pharmacogenet Genomics. 2023 Jun 1;33(4):79-87. doi: 10.1097/FPC.0000000000000495. Epub 2023 Mar 6. PMID: 37098852; PMCID: PMC10154044.
  3. Cindi Z, Maartens G, Bradford Y, Venter WDF, Sokhela S, Chandiwana NC, Haas DW, Sinxadi P. Genetic Associations with Weight Gain among South Africans who Initiated Dolutegravir-Containing and Tenofovir-Containing Regimens. J Acquir Immune Defic Syndr. 2021 Jul 1;87(3):1002-1009. doi: 10.1097/QAI.0000000000002661. PubMed PMID: 33625064; PubMed Central PMCID: PMC8192425.
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