Analyses of HIV‐1 integrase gene sequences among treatment‐naive patients in the Eastern Cape, South Africa

2020 ◽  
Vol 92 (8) ◽  
pp. 1165-1172
Author(s):  
Tennison Onoriode Digban ◽  
Benson Chucks Iweriebor ◽  
Larry Chikwelu Obi ◽  
Uchechuwku Nwodo ◽  
Anthony Ifeanyi Okoh
Keyword(s):  
South Africa ◽  
Eastern Cape ◽  
Gene Sequences ◽  
Integrase Gene ◽  
Treatment Naïve ◽  
Hiv 1

HIV-1 drug resistance surveillance among parturient women on anti-retroviral therapy in the Eastern Cape, South Africa: Implications for elimination of mother-to-child transmission

2019 ◽  
Vol 117 ◽  
pp. 89-95 ◽  
Author(s):  
Oladele Vincent Adeniyi ◽  
Chikwelu Larry Obi ◽  
Daniel Ter Goon ◽  
Benson Iweriebor ◽  
Anthony Idowu Ajayi ◽  
...  
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Eastern Cape ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
Mother To Child ◽  
Hiv 1

Molecular Genetics and the Incidence of Transmitted Drug Resistance Among Pre-Treatment HIV-1 Infected Patients in the Eastern Cape, South Africa

2019 ◽  
Vol 17 (5) ◽  
pp. 335-342
Author(s):  
Tennison Onoriode Digban ◽  
Benson Chucks Iweriebor ◽  
Larry Chikwelu Obi ◽  
Uchechuwku Nwodo ◽  
Anthony Ifeanyi Okoh
Keyword(s):  
South Africa ◽  
Drug Resistance ◽  
Transmitted Drug Resistance ◽  
Eastern Cape ◽  
Resistance Mutations ◽  
Subtype C ◽  
Drug Resistance Mutations ◽  
Combined Antiretroviral Therapy ◽  
Pre Treatment ◽  
Hiv 1

Background: Transmitted drug resistance (TDR) remains a significant threat to Human immunodeficiency virus (HIV) infected patients that are not exposed to antiretroviral treatment. Although, combined antiretroviral therapy (cART) has reduced deaths among infected individuals, emergence of drug resistance is gradually on rise. Objective: To determine the drug resistance mutations and subtypes of HIV-1 among pre-treatment patients in the Eastern Cape of South Africa. Methods: Viral RNA was extracted from blood samples of 70 pre-treatment HIV-1 patients while partial pol gene fragment amplification was achieved with specific primers by RT-PCR followed by nested PCR and positive amplicons were sequenced utilizing ABI Prism 316 genetic sequencer. Drug resistance mutations (DRMs) analysis was performed by submitting the generated sequences to Stanford HIV drug resistance database. Results: Viral DNA was successful for 66 (94.3%) samples of which 52 edited sequences were obtained from the protease and 44 reverse transcriptase sequences were also fully edited. Four major protease inhibitor (PI) related mutations (I54V, V82A/L, L76V and L90M) were observed in seven patients while several other minor and accessory PIs were also identified. A total of 11(25.0%) patients had NRTIs related mutations while NNRTIs were observed among 14(31.8%) patients. K103N/S, V106M and M184V were the most common mutations identified among the viral sequences. Phylogenetic analysis of the partial pol gene indicated all sequences clustered with subtype C. Conclusions: This study indicates that HIV-1 subtype C still predominates and responsible for driving the epidemic in the Eastern Cape of South Africa with slow rise in the occurrence of transmitted drug resistance.

Variability of the HIV-1 3′ polypurine tract (3′PPT) region and implication in integrase inhibitor resistance

2019 ◽  
Vol 74 (12) ◽  
pp. 3440-3444 ◽  
Author(s):  
Isabelle Malet ◽  
Olivier Delelis ◽  
Thuy Nguyen ◽  
Valentin Leducq ◽  
Besma Abdi ◽  
...  
Keyword(s):  
Rapid Change ◽  
Rare Event ◽  
Integration Step ◽  
Integrase Gene ◽  
Polypurine Tract ◽  
Treatment Naïve ◽  
High Level ◽  
Hiv 1 ◽  
Level Resistance

Abstract Background Integrase strand-transfer inhibitors (INSTIs) are efficient at impairing retroviral integration, which is a critical step in HIV-1 replication. To date, resistance to these compounds has been explained by mutations in the viral protein integrase, which catalyses the integration step. Recently, it has been shown that selected mutations in the 3′ polypurine tract (3′PPT), a sequence involved in the reverse transcription mechanism, result in high-level resistance to these compounds. This observation was reinforced by the description of a patient who failed INSTI treatment by selecting mutations in the 3′PPT sequence. Methods Sequences of the 3′PPT region were analysed in 30706 treatment-naive patients from the public Los Alamos database belonging to six different subtypes and, in parallel, in 107 patients failing INSTI treatment. Results The analysis showed that the sequences of patients failing INSTI treatment, in the same way as those of treatment-naive patients, are very well conserved regardless of the presence or absence of resistance mutations in the integrase gene. Conclusions This study confirms that the selection of a mutation in the 3′PPT region conferring high-level resistance to INSTIs is a rare event. It would require a particular in vivo context and especially a long enough time to be selected, this exposure time being generally reduced by the rapid change of treatment in the case of virological failure. Larger-scale studies in patients with INSTI treatment failure are needed to determine whether the 3′PPT region can play an important role in vivo in INSTI resistance.

Chemokine Coreceptor Usage Among HIV-1 Drug-Naive Patients Residing in the Rural Eastern Cape, South Africa

2020 ◽  
Vol 36 (8) ◽  
pp. 688-696
Author(s):  
Tennison Onoriode Digban ◽  
Benson Chucks Iweriebor ◽  
Uchechukwu U. Nwodo ◽  
Anthony Ifeanyi Okoh ◽  
Larry Chikwelu Obi
Keyword(s):  
South Africa ◽  
Coreceptor Usage ◽  
Eastern Cape ◽  
Drug Naïve ◽  
Hiv 1

Genetic Characterization of HIV-1 Subtype A1/C/D/B/K Unique Recombinant Form from Eastern Cape, South Africa

2020 ◽  
Author(s):  
Oladele Vincent Adeniyi ◽  
Chikwelu Larry Obi ◽  
Daniel Ter Goon ◽  
Benson Iweriebor ◽  
Wezile Chitha ◽  
...  
Keyword(s):  
South Africa ◽  
Genetic Characterization ◽  
Recombinant Form ◽  
Eastern Cape ◽  
Unique Recombinant Form ◽  
Hiv 1

scholarly journals Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals after First-Line Antiretroviral Therapy Failure in South Africa

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Kerri J. Penrose ◽  
Carole L. Wallis ◽  
Chanson J. Brumme ◽  
Kristen A. Hamanishi ◽  
Kelley C. Gordon ◽  
...  
Keyword(s):  
South Africa ◽  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Plasma Concentrations ◽  
Cross Resistance ◽  
Subtype C ◽  
First Line ◽  
Nnrti Mutation ◽  
Treatment Naïve ◽  
Hiv 1

ABSTRACT A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and nevirapine (NVP)-resistant viruses that could be transmitted is not well defined. We investigated DPV cross-resistance of subtype C HIV-1 from individuals on failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa. Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml and with HIV-1 containing at least one non-nucleoside reverse transcriptase (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was determined for recombinant HIV-1LAI containing bulk-amplified, plasma-derived, full-length reverse transcriptase sequences. Fold change (FC) values were calculated compared with a composite 50% inhibitory concentration (IC50) from 12 recombinant subtype C HIV-1LAI plasma-derived viruses from treatment-naive individuals in South Africa. A total of 25/100 (25%) samples showed >500-FCs to DPV compared to treatment-naive samples with IC50s exceeding the maximum DPV concentration tested (132 ng/ml). A total of 66/100 (66%) samples displayed 3- to 306-FCs, with a median IC50 of 17.6 ng/ml. Only 9/100 (9%) samples were susceptible to DPV (FC < 3). Mutations L100I and K103N were significantly more frequent in samples with >500-fold resistance to DPV compared to samples with a ≤500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from individuals on failing first-line ART in South Africa exhibited ≥3-fold cross-resistance to DPV. This level of resistance exceeds expected plasma concentrations, but very high genital tract DPV concentrations from DPV ring use could block viral replication. It is critically important to assess the frequency of transmitted and selected DPV resistance in individuals using the DPV ring.

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