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3. Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study

Author

Wolter, Nicole, Jassat, Waasila, Walaza, Sibongile, Welch, Richard, Moultrie, Harry, Groome, Michelle, Amoako, Daniel Gyamfi, Everatt, Josie, Bhiman, Jinal N, Scheepers, Cathrine, Tebeila, Naume, Chiwandire, Nicola, du Plessis, Mignon, Govender, Nevashan, Ismail, Arshad, Glass, Allison, Mlisana, Koleka, Stevens, Wendy, Treurnicht, Florette K, Makatini, Zinhle, Hsiao, Nei-yuan, Parboosing, Raveen, Wadula, Jeannette, Hussey, Hannah, Davies, Mary-Ann, Boulle, Andrew, von Gottberg, Anne, and Cohen, Cheryl

Published
2022
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4. Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa

Author

Wolter, Nicole, Jassat, Waasila, Walaza, Sibongile, Welch, Richard, Moultrie, Harry, Groome, Michelle J., Amoako, Daniel Gyamfi, Everatt, Josie, Bhiman, Jinal N., Scheepers, Cathrine, Tebeila, Naume, Chiwandire, Nicola, du Plessis, Mignon, Govender, Nevashan, Ismail, Arshad, Glass, Allison, Mlisana, Koleka, Stevens, Wendy, Treurnicht, Florette K., Subramoney, Kathleen, Makatini, Zinhle, Hsiao, Nei-yuan, Parboosing, Raveen, Wadula, Jeannette, Hussey, Hannah, Davies, Mary-Ann, Boulle, Andrew, von Gottberg, Anne, and Cohen, Cheryl

Published
2022
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6. Patterns of HIV-1 Drug Resistance Observed Through Geospatial Analysis of Routine Diagnostic Testing in KwaZulu-Natal, South Africa.

Author

Gounder, Lilishia, Khan, Aabida, Manasa, Justen, Lessells, Richard, Tomita, Andrew, Pillay, Melendhran, Manyana, Sontaga C., Govender, Subitha, Francois, Kerri-Lee, Moodley, Pravi, Msomi, Nokukhanya, Govender, Kerusha, Parboosing, Raveen, Moyo, Sikhulile, Naidoo, Kogieleum, and Chimukangara, Benjamin

Subjects
NON-nucleoside reverse transcriptase inhibitors, GEOGRAPHIC information systems, ROUTINE diagnostic tests, DRUG resistance, HIV
Abstract

HIV-1 drug resistance (HIVDR) impedes treatment and control of HIV-1, especially in high-prevalence settings such as KwaZulu-Natal (KZN) province, South Africa. This study merged routine HIV-1 genotypic resistance test (GRT) data with Geographic Information Systems coordinates to assess patterns and geographic distribution of HIVDR in KZN, among ART-experienced adults with virological failure. We curated 3133 GRT records generated between 1 January 2018 and 30 June 2022, which includes the early phase of dolutegravir (DTG) rollout, of which 2735 (87.30%) had HIVDR. Of the 2735, major protease, nucleoside, and non-nucleoside reverse transcriptase inhibitor mutations were detected in 41.24%, 84.97% and 88.08% of GRTs, respectively. Additional genotyping of HIV-1 integrase for 41/3133 (1.31%) GRTs showed that 17/41 (41.46%) had integrase strand transfer inhibitor resistance. Notably, of 26 patients on DTG with integrase genotyping, 9 (34.62%) had DTG-associated resistance mutations. Dual- or triple-class resistance was observed in four of every five GRTs. The odds of HIVDR increased significantly with age, with ≥60 years having 5 times higher odds of HIVDR compared to 18–29 years (p = 0.001). We identified geospatial differences in the burden of HIVDR, providing proof of concept that this could be used for data-driven public health decision making. Ongoing real-time HIVDR surveillance is essential for evaluating the outcomes of the updated South African HIV treatment programme. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Geospatial and temporal mapping of detectable HIV-1 viral loads amid dolutegravir rollout in KwaZulu-Natal, South Africa

Author

Gounder, Lilishia, primary, Tomita, Andrew, additional, Lessells, Richard, additional, Moodley, Sandrini, additional, Francois, Kerri-Lee, additional, Khan, Aabida, additional, Pillay, Melendhran, additional, Manyana, Sontaga C., additional, Govender, Subitha, additional, Govender, Kerusha, additional, Moodley, Pravi, additional, Parboosing, Raveen, additional, Msomi, Nokukhanya, additional, Tanser, Frank, additional, Naidoo, Kogieleum, additional, and Chimukangara, Benjamin, additional

Published
2024
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15. Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages in South Africa

Author

Wolter, Nicole, primary, Jassat, Waasila, additional, Walaza, Sibongile, additional, Welch, Richard, additional, Moultrie, Harry, additional, Groome, Michelle, additional, Amoako, Daniel, additional, Everatt, Josie, additional, Bhiman, Jinal, additional, Scheepers, Cathrine, additional, Tebeila, Naume, additional, Chiwandire, Nicola, additional, du Plessis, Mignon, additional, Govender, Nevashan, additional, Ismail, Arshad, additional, Glass, Allison, additional, Mlisana, Koleka, additional, Stevens, Wendy, additional, Treurnicht, Florette, additional, Subramoney, Kathleen, additional, Makatini, Zinhle, additional, Hsiao, Marvin, additional, Parboosing, Raveen, additional, Wadula, Jeanette, additional, Hussey, Hannah, additional, Davies, Mary-Ann, additional, Boulle, Andrew, additional, von Gottberg, Anne, additional, and Cohen, Cheryl, additional

Published
2022
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18. Active targeting of CD4+T lymphocytes by PEI-capped, peptide-functionalized gold nanoparticles

Author

0000-0001-6707-4555, Ncobeni, Nomfundo, de la Torre, Beatriz G., Albericio, Fernando, Kruger, Hendrik G., Parboosing, Raveen, 0000-0001-6707-4555, Ncobeni, Nomfundo, de la Torre, Beatriz G., Albericio, Fernando, Kruger, Hendrik G., and Parboosing, Raveen

Abstract

Active targeting is a promising approach for the treatment of viral infections. In particular, site-specific formulations for the treatment of HIV infection may overcome challenges associated with current ARV regimens. In this study we explored active targeting by synthesizing a gold nanoparticle construct decorated with an anti-CD4 cyclic peptide. The aim was to demonstrate selectivity of the system for the CD4 receptor and to deliver the RNA payload into T-lymphocytes. Colloidal gold nanoparticles functionalized withN-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) were formed by a one-pot synthesis method where thiol modified polyethyleneimine (PEI) was mixed with chloroauric acid. PEI-SPDP AuNPs (gold nanoparticles) were conjugated to an anti-CD4 peptide and loaded with RNA. We measured toxicity and uptake using TZM-bl and HeLa cells. Our findings show that the nanoparticles bind selectively to CD4 + cells. UV-vis characterisation of the nanoparticles revealed a surface plasmon resonance (SPR) peak at 527 nm, corresponding to a 6 nm diameter. HRTEM of the complete nanoparticles visualised circular shaped particles with average diameter of ∼7 nm. The polydispersity index was calculated to be 0.08, indicating monodispersity of complete NPS in solution. Through the pyridine-2-thione assay each nanoparticle was calculated to carry 1.37 × 105SPDP molecules available for peptide binding. Flow cytometry showed that 13.6% of TZM-bl cells, and 0.14% of HeLa cells retained fluorescence after an overnight incubation, an indication of system binding. No internal RNA delivery was demonstrated. Further work is required to improve internalization.

Published
2022

23. Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa

Author

Wolter, Nicole, primary, Jassat, Waasila, additional, Walaza, Sibongile, additional, Welch, Richard, additional, Moultrie, Harry, additional, Groome, Michelle, additional, Amoako, Daniel Gyamfi, additional, Everatt, Josie, additional, Bhiman, Jinal N., additional, Scheepers, Cathrine, additional, Tebeila, Naume, additional, Chiwandire, Nicola, additional, du Plessis, Mignon, additional, Govender, Nevashan, additional, Ismail, Arshad, additional, Glass, Allison, additional, Mlisana, Koleka, additional, Stevens, Wendy, additional, Treurnicht, Florette K., additional, Makatini, Zinhle, additional, Hsiao, Nei-yuan, additional, Parboosing, Raveen, additional, Wadula, Jeannette, additional, Hussey, Hannah, additional, Davies, Mary-Ann, additional, Boulle, Andrew, additional, von Gottberg, Anne, additional, and Cohen, Cheryl, additional

Published
2021
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27. A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission

Author

Samuel, Reshmi, Paredes, Roger, Parboosing, Raveen, Moodley, Pravi, Singh, Lavanya, Naidoo, Anneta, Gordon, Michelle, Universitat Autònoma de Barcelona, and Universitat de Vic - Universitat Central de Catalunya. Càtedra de la Sida i Malalties Relacionades

Subjects
Adult, Mother to child transmission, Nevirapine, Anti-HIV Agents, Mothers, HIV Infections, Emtricitabine, Deoxycytidine, Drug Administration Schedule, South Africa, Zidovudine, Pregnancy, immune system diseases, Antiretroviral Therapy, Highly Active, Virology, Drug Resistance, Viral, HIV drug resistance, medicine, Humans, Pregnancy Complications, Infectious, Child, Tenofovir, Pre partum, Research Articles, Post partum, business.industry, Postpartum Period, virus diseases, Sequence Analysis, DNA, Viral Load, Sida -- Tractament, Infectious Disease Transmission, Vertical, Infectious Diseases, Mutation, HIV-1, Reverse Transcriptase Inhibitors, Gestation, Vertical transmission, Female, vertical transmission, business, Research Article, medicine.drug
Abstract

Although the rates of vertical transmission of HIV in the developing world have improved to around 3% in countries like South Africa, resistance to antiretrovirals (ARV) used in Prevention of Mother-to-Child transmission (pMTCT) strategies may thwart such outcomes and affect the efficacy of future ARV regimens in mothers and children. This study conducted in Durban, South Africa, between 2010 and 2013 found a high rate of nevirapine (NVP) resistance among women receiving Zidovudine (AZT) from 14 weeks gestation, single dose nevirapine (sd NVP) at the onset of labor and a single dose of coformulated Tenofovir/Emtricitabine (TDF/FTC) postpartum. Using Sanger sequencing, high and intermediate levels of nevirapine (NVP) resistance were detected in 15/44 (34%) and in 1/44 (2%) of women tested, respectively. Most subjects selected the K103N mutation (22% (10/45) of all patients and 66% (10/15) of those with high-level NVP resistance). Such rate of NVP resistance is comparable to studies where only sd NVP was used. In conclusion, a post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum sd NVP to prevent mother-tochild HIV-1 transmission.

Published
2021

28. Active targeting of CD4 + T lymphocytes by PEI-capped, peptide-functionalized gold nanoparticles.

Author

Ncobeni, Nomfundo, de la Torre, Beatriz G, Albericio, Fernando, Kruger, Hendrik G, and Parboosing, Raveen

Subjects
GOLD nanoparticles, T cells, COLLOIDAL gold, SURFACE plasmon resonance, CD4 antigen
Abstract

Active targeting is a promising approach for the treatment of viral infections. In particular, site-specific formulations for the treatment of HIV infection may overcome challenges associated with current ARV regimens. In this study we explored active targeting by synthesizing a gold nanoparticle construct decorated with an anti-CD4 cyclic peptide. The aim was to demonstrate selectivity of the system for the CD4 receptor and to deliver the RNA payload into T-lymphocytes. Colloidal gold nanoparticles functionalized with N -succinimidyl 3-(2-pyridyldithio) propionate (SPDP) were formed by a one-pot synthesis method where thiol modified polyethyleneimine (PEI) was mixed with chloroauric acid. PEI-SPDP AuNPs (gold nanoparticles) were conjugated to an anti-CD4 peptide and loaded with RNA. We measured toxicity and uptake using TZM-bl and HeLa cells. Our findings show that the nanoparticles bind selectively to CD4 + cells. UVâ€"vis characterisation of the nanoparticles revealed a surface plasmon resonance (SPR) peak at 527 nm, corresponding to a 6 nm diameter. HRTEM of the complete nanoparticles visualised circular shaped particles with average diameter of ∼7 nm. The polydispersity index was calculated to be 0.08, indicating monodispersity of complete NPS in solution. Through the pyridine-2-thione assay each nanoparticle was calculated to carry 1.37 × 105 SPDP molecules available for peptide binding. Flow cytometry showed that 13.6% of TZM-bl cells, and 0.14% of HeLa cells retained fluorescence after an overnight incubation, an indication of system binding. No internal RNA delivery was demonstrated. Further work is required to improve internalization. [ABSTRACT FROM AUTHOR]

Published
2022
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37. siRNAs and Viruses: The good, the Bad and the Way Forward

Author

Soobramoney, Cassandra and Parboosing, Raveen

Abstract

There are no available antivirals for many viruses or strains, while current antivirals arelimited by toxicity and drug resistance. Therefore, alternative strategies, such as RNA interference(RNAi) are required. RNAi suppresses gene expression of any mRNA, making it an attractive candidatefor antiviral therapeutics. Studies have evaluated siRNAs in a range of viruses, with someshowing promising results. However, issues with stability and delivery of siRNAs remain. These issuesmay be minimized by modifying the siRNA structure, using an efficient delivery vector andtargeting multiple regions of a virus's genome in a single dose. Finding these solutions could acceleratethe progress of RNAi-based antivirals. This review highlights selected examples of antiviralsiRNAs, limitations of RNAi and strategies to overcome these limitations

Published
2022
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42. HIV-1 drug resistance by ultra-deep sequencing following short course zidovudine, single-dose nevirapine, and single-dose tenofovir with emtricitabine for prevention of mother-to-child transmission

Author

Samuel, Reshmi, Noguera-Julian, Marc, Paredes, Roger, Parboosing, Raveen, Moodley, Pravi, Singh, Lavanya, Naidoo, Anneta, Gordon, Michelle, and Universitat Autònoma de Barcelona

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Nevirapine, Anti-HIV Agents, viruses, PMTCT, HIV Infections, Drug resistance, Emtricitabine, 03 medical and health sciences, Zidovudine, 0302 clinical medicine, Pregnancy, immune system diseases, Internal medicine, Drug Resistance, Viral, HIV drug resistance, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, HIV vertical transmission, Pregnancy Complications, Infectious, Tenofovir, Basic and Translational Science, Reverse-transcriptase inhibitor, business.industry, Infant, Newborn, virus diseases, Viral Load, biochemical phenomena, metabolism, and nutrition, medicine.disease, Infectious Disease Transmission, Vertical, 030104 developmental biology, Infectious Diseases, Mutation, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, HIV-1, Drug Therapy, Combination, Female, business, Viral load, medicine.drug
Abstract

Supplemental Digital Content is Available in the Text., Antiretroviral drug resistance following pMTCT strategies remains a significant problem. With rapid advancements in next generation sequencing technologies, there is more focus on HIV drug-resistant variants of low frequency, or the so-called minority variants. In South Africa, AZT monotherapy for pMTCT, similar to World Health Organization option A, has been used since 2008. In 2010, a single dose of co-formulated TDF/FTC was included in the strategy for prevention of resistance conferred by single-dose nevirapine (sd NVP). The study was conducted in KwaZulu-Natal, South Africa, among pMTCT participants who received AZT monotherapy from 14 weeks of gestation, intrapartum AZT and sd NVP, and postpartum sd TDF/FTC. Twenty-six specimens collected at 6 weeks post-delivery were successfully sequenced using 454 ultra-deep sequencing. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected in 17 of 26 (65%) patients, 2 (7%) had Thymidine analogue mutations, and 3 (11%) had K65R. Of the 17 patients with NNRTI resistance, 11 (65%) had high-level NNRTI resistance, whereas 6 (35%) had intermediate NNRTI resistance. The levels of NNRTI resistance are much higher than would be expected, given the inclusion of antepartum AZT and postpartum TDF/FTC. This high level of NNRTI resistance could impact future NNRTI-containing treatment for a large proportion of pMTCT-exposed women. The detection of Thymidine analogue mutations highlights the need to understand the clinical impact of these on AZT-containing antiretroviral treatment in women exposed to AZT monotherapy.

Published
2016

44. Potential inhibition of HIV-1 encapsidation by oligoribonucleotide–dendrimer nanoparticle complexes

Author

Parboosing,Raveen, Chonco,Louis, de la Mata,Javier, Govender,Thavendran, Maguire,Glenn, Kruger,Gert, Parboosing,Raveen, Chonco,Louis, de la Mata,Javier, Govender,Thavendran, Maguire,Glenn, and Kruger,Gert

Abstract

Raveen Parboosing,1,2 Louis Chonco,1,2 Francisco Javier de la Mata,3,4 Thavendran Govender,5 Glenn EM Maguire,5 Hendrik G Kruger5 1Department of Virology, University of KwaZulu-Natal, 2National Health Laboratory Service, Durban, South Africa; 3Organic and Inorganic Chemistry Department, University of Alcalá, Alcalá de Henares, 4Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; 5Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, South Africa Background: Encapsidation, the process during which the genomic RNA of HIV is packaged into viral particles, is an attractive target for antiviral therapy. This study explores a novel nanotechnology-based strategy to inhibit HIV encapsidation by an RNA decoy mechanism. The design of the 16-mer oligoribonucleotide (RNA) decoy is based on the sequence of stem loop 3 (SL3) of the HIV packaging signal (Ψ). Recognition of the packaging signal is essential to the encapsidation process. It is theorized that the decoy RNA, by mimicking the packaging signal, will disrupt HIV packaging if efficiently delivered into lymphocytes by complexation with a carbosilane dendrimer. The aim of the study is to measure the uptake, toxicity, and antiviral activity of the dendrimer–RNA nanocomplex. Materials and methods: A dendriplex was formed between cationic carbosilane dendrimers and the RNA decoy. Uptake of the fluorescein-labeled RNA into MT4 lymphocytes was determined by flow cytometry and confocal microscopy. The cytoprotective effect (50% effective concentration [EC50]) and the effect on HIV replication were determined in vitro by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and viral load measurements, respectively. Results: Flow cytometry and confocal imaging demonstrated efficient transfection of lymphocytes. The dendriplex containing the Ψ decoy showed some activity (EC50 =3.20 µM, sel

Published
2017

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