University of Sussex
Browse
1/1
2 files

Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART

journal contribution
posted on 2023-06-09, 15:36 authored by Anne Derache, Collins IwujiCollins Iwuji, Siva Danaviah, Jennifer Giandhari, Anne-Geneviève Marcelin, Vincent Calvez, Tulio de Oliveira, François Dabis, Deenan Pillay, Ravindra K Gupta
Objectives: The WHO recently recommended the use of a new first-line ART containing dolutegravir. We investigated the efficacy of NRTI backbones (tenofovir or abacavir with a cytosine analogue) in low- and middleincome countries where there is significant prior exposure to antiretrovirals and drug resistance to NRTIs. Methods: Within the treatment-as-prevention study in South Africa, we selected participants with available nextgeneration sequencing (NGS) data for the HIV-1 pol gene at trial entry; they were either ART initiators (n" 1193) or already established on ART (n" 94). NGS of the HIV-1 pol gene was carried out using MiSeq technology; reverse transcriptase drug resistance mutations (DRMs) were detected at 5% (DRM5%) and 20% (DRM20%) for all 1287 participants. Genotypic susceptibility was assessed using the Stanford HIVDB resistance interpretation algorithm. Results: NRTI DRM20% and DRM5% were detected among 5/1193 (0.4%) and 9/1193 (0.8%) of ART initiators, respectively. There was tenofovir exposure in 73/94 (77.7%) of those established on ART, with full susceptibility to abacavir in 57/94 (60.6%) and 56/94 (59.6%) for DRM20% and DRM5%, respectively, while 67/94 (71.3%) and 64/94 (68.1%) were fully susceptible to tenofovir, respectively. The differences between tenofovir and abacavir were not statistically significant at the 20% or 5% variant level (P" 0.16 and 0.29, respectively). NGS detection of variants at the 5% level increased detection of K65R in both naive and treated groups. One of 607 integrase sequences carried a DRM20% (Q148R). Conclusions: Dolutegravir with a cytosine analogue plus tenofovir or abacavir appears to have similar efficacy in South Africans naive to ART. NGS should be considered in HIV drug resistance surveillance.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Antimicrobial Chemotherapy

ISSN

0305-7453

Publisher

Oxford University Press

Issue

2

Volume

74

Page range

473-479

Department affiliated with

  • Global Health and Infection Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-10-23

First Open Access (FOA) Date

2018-12-07

First Compliant Deposit (FCD) Date

2018-12-07

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC