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

Derache, Anne, Iwuji, Collins C, Danaviah, Siva, Giandhari, Jennifer, Marcelin, Anne-Geneviève, Calvez, Vincent, de Oliveira, Tulio, Dabis, François, Pillay, Deenan and Gupta, Ravindra K (2019) 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 of Antimicrobial Chemotherapy, 74 (2). pp. 473-479. ISSN 0305-7453

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Abstract

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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0643 Communicable diseases and public health > RA0644 Individual diseases or groups of diseases, A-Z > RA0644.A25 AIDS. HIV infections
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Depositing User: Deborah Miller
Date Deposited: 23 Oct 2018 15:43
Last Modified: 11 Jul 2019 16:15
URI: http://sro.sussex.ac.uk/id/eprint/79659

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