Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen

Keene, Claire; Griesel, Rulan; Zhao, Ying; Gcwabe, Zimasa; Sayed, Kaneez; Hill, Andrew; Cassidy, Tali; Ngwenya, Olina; Jackson, Amanda; Zyl, Gert van; Schutz, Charlotte; Goliath, René; Flowers, Tracy; Goemaere, Eric; Wiesner, Lubbe; Simmons, Bryony; Maartens, Gary; Meintjes, Graeme

doi:10.1097/qad.0000000000002936

Cited by 42 publications

(43 citation statements)

References 30 publications

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“…High levels of NRTI resistance were also reported in other studies conducted in Haiti (40.5%) [24] and Zambia (12%) [25 & ]. Although findings from recent studies [26,27,28 & ] show high levels of viral suppression among patients receiving DTG or PI despite resistance to TDF, there are limited data on the efficacy of ART when ABC effectiveness is compromised. Therefore, caution is warranted to closely monitor treatment response in young infants as well as accelerating access to paediatric formulations to newer drugs.…”

Section: Andandmentioning

confidence: 99%

“…). The proportion of countries meeting the target of having at least 5% of patients on secondline ART increased from 45% (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) in 2017 to 56% (14 of 25) in 2020. Overall, most countries reported sub-optimal performance in preventing HIVDR, indicating the need to strengthen the quality and monitoring systems and implement sustainable solutions.…”

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confidence: 99%

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Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence

Bertagnolio

Jordan

Girón

et al. 2022

Current Opinion in HIV and AIDS

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Purpose of reviewThis review summarises the latest information of the epidemiology of HIV drug resistance (HIVDR) in lowand middle-income countries and the updated WHO global strategy for HIVDR surveillance and monitoring. Recent findingsFinding from recent national-representative surveys show a rise in pretreatment drug resistance (PDR) to reverse transcriptase inhibitors and especially to the class of nonnucleoside reverse transcriptase inhibitors. Levels of PDR are especially high in infants <18 months and adults reporting prior exposure to antiretrovirals. Although viral suppression rates are generally high and increasing among adults on antiretroviral therapy, those with unsuppressed viremia have high levels of acquired drug resistance (ADR). Programmatic data on HIVDR to integrase-transfer-inhibitor resistance is scarce, highlighting the need to increase integrase-inhibitors resistance surveillance. As the landscape of HIV prevention, treatment and monitoring evolves, WHO has also adapted its strategy to effectively support countries in preventing and monitoring the emergence of HIVDR. This includes new survey methods for monitoring resistance emerging from patients diagnosed with HIV while on preexposure prophylaxis, and a laboratory-based ADR survey leveraging on remnant viral load specimens which are expected to strengthen dolutegravir-resistance surveillance.

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Section: Andandmentioning

confidence: 99%

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confidence: 99%

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence

Bertagnolio

Jordan

Girón

et al. 2022

Current Opinion in HIV and AIDS

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“…The efficacy of protease inhibitors or DTG in the presence of a compromised TDF or ZDV-based NRTI backbone has been attributed to residual activity of the NRTIs, the high genetic barrier of protease inhibitors or DTG and an antagonistic effect of the M184V mutation, which causes hypersusceptibility of HIV to ZDV and TDF [5][6][7][8]. There is, however, limited direct evidence to guide recycling of ABC.…”

mentioning

confidence: 99%

Impact of nucleos(t)ide reverse transcriptase inhibitor resistance on dolutegravir and protease-inhibitor-based regimens in children and adolescents in Kenya

Kingwara

Inzaule

Momanyi

et al. 2021

Aids

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We assessed the impact of using dolutegravir or a protease inhibitor with an inactive nucleoside-reverse transcriptase inhibitor (NRTI) in children and adolescents. We observed high-levels of viral suppression among those on tenofovir–lamivudine–dolutegravir even in presence of an inactive NRTI backbone but lower levels among those on protease inhibitors, especially those retained on an inactive abacavir. Although tenofovir may be recycled with dolutegravir, more studies are needed to determine if abacavir can be reused with dolutegravir or protease inhibitors.

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“…While findings from a recent study investigating effects of recycling TDF in second-line TLD regimen and a larger randomized non-inferiority trial (i.e. NADIA trial) showed successful viral outcomes on DTG-based treatment (including in patients with prior extensive NRTI resistance), the long-term impact of pre-existing NRTI resistance on outcomes with standardised DTG-based regimens remains unclear [ 25 , 26 ]. Despite high occurrence of XTC drug resistance (as shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

et al. 2021

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Background Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa. Methods We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG. Results From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7–96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1–97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3–97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs). Conclusions Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens.

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Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen

Cited by 42 publications

References 30 publications

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence

Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence

Impact of nucleos(t)ide reverse transcriptase inhibitor resistance on dolutegravir and protease-inhibitor-based regimens in children and adolescents in Kenya

Acquired HIV drug resistance and virologic monitoring in a HIV hyper-endemic setting in KwaZulu-Natal Province, South Africa

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