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
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 middle-income 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 next-generation 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
|---|---|
| Enthalten in: |
The Journal of antimicrobial chemotherapy - 74(2019), 2 vom: 01. Feb., Seite 473-479 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Derache, Anne [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.05.2020 Date Revised 08.04.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/jac/dky428 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM290136202 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM290136202 | ||
| 003 | DE-627 | ||
| 005 | 20240408231938.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/jac/dky428 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1369.xml |
| 035 | |a (DE-627)NLM290136202 | ||
| 035 | |a (NLM)30380053 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Derache, Anne |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.05.2020 | ||
| 500 | |a Date Revised 08.04.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 middle-income countries where there is significant prior exposure to antiretrovirals and drug resistance to NRTIs | ||
| 520 | |a Methods: Within the treatment-as-prevention study in South Africa, we selected participants with available next-generation 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Dideoxynucleosides |2 NLM | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a HIV Integrase Inhibitors |2 NLM | |
| 650 | 7 | |a Heterocyclic Compounds, 3-Ring |2 NLM | |
| 650 | 7 | |a Oxazines |2 NLM | |
| 650 | 7 | |a Piperazines |2 NLM | |
| 650 | 7 | |a Pyridones |2 NLM | |
| 650 | 7 | |a Cytosine |2 NLM | |
| 650 | 7 | |a 8J337D1HZY |2 NLM | |
| 650 | 7 | |a Tenofovir |2 NLM | |
| 650 | 7 | |a 99YXE507IL |2 NLM | |
| 650 | 7 | |a dolutegravir |2 NLM | |
| 650 | 7 | |a DKO1W9H7M1 |2 NLM | |
| 650 | 7 | |a abacavir |2 NLM | |
| 650 | 7 | |a WR2TIP26VS |2 NLM | |
| 700 | 1 | |a Iwuji, Collins C |e verfasserin |4 aut | |
| 700 | 1 | |a Danaviah, Siva |e verfasserin |4 aut | |
| 700 | 1 | |a Giandhari, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Marcelin, Anne-Geneviève |e verfasserin |4 aut | |
| 700 | 1 | |a Calvez, Vincent |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira, Tulio |e verfasserin |4 aut | |
| 700 | 1 | |a Dabis, François |e verfasserin |4 aut | |
| 700 | 1 | |a Pillay, Deenan |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Ravindra K |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of antimicrobial chemotherapy |d 1981 |g 74(2019), 2 vom: 01. Feb., Seite 473-479 |w (DE-627)NLM000017701 |x 1460-2091 |7 nnns |
| 773 | 1 | 8 | |g volume:74 |g year:2019 |g number:2 |g day:01 |g month:02 |g pages:473-479 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/jac/dky428 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 74 |j 2019 |e 2 |b 01 |c 02 |h 473-479 | ||