Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

Villa, Giovanni; Phillips, Richard Odame; Smith, Colette; Stockdale, Alexander; Ruggiero, Alessandra; Beloukas, Apostolos; Appiah, Lambert; Chadwick, David; Geretti, Anna María

doi:10.1093/jac/dky281

Cited by 8 publications

(8 citation statements)

References 41 publications

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“…In Western and Central Africa, CRF02_AG has been the predominant HIV-1 subtype (Hemelaar et al, 2019). Consistent with previous studies (Delgado et al, 2008;Nii-Trebi et al, 2013Martin-Odoom et al, 2018;Villa et al, 2018;Deletsu et al, 2020;Obeng et al, 2020), we report CRF02_AG as the predominant (70%) HIV-1 subtype in this study population from Ghana.…”

Section: Discussionsupporting

confidence: 92%

“…We report a high frequency of major mutations associated with resistance to NRTI (57%) and NNRTI (75%) in PLWH receiving ART. The pattern and frequency of the most common mutations, such as M184V/I, K103N, T215F/Y, G190A/S, P225H, Y181C, and V106A were consistent with reports from Ghana and other sub-Saharan African countries (Hamers et al, 2012;Nii-Trebi et al, 2013;Martin-Odoom et al, 2018;Villa et al, 2018;World Health Organization, 2019;Deletsu et al, 2020). The non-polymorphic mutation K103N is selected in patients receiving Nevirapine or Efavirenz and reduces susceptibility to these drugs (Melikian et al, 2014).…”

Section: Discussionsupporting

confidence: 80%

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High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study

Parbie

Abana²,

Kushitor³

et al. 2022

Front. Microbiol.

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Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS “95-95-95” target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)—M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)—K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTI-based antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 80%

High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study

Parbie

Abana²,

Kushitor³

et al. 2022

Front. Microbiol.

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“…We noted a relatively high prevalence of tenofovir RAMs in this group, with 21/65 (32%) patients showing K65R, K70E/G/N, L74I/V, or Y115F. As previously observed by us [34] and others [30], the highly mutated virus strains did not show evidence of impaired fitness given the high viral loads and low CD4 cell counts. Tenofovir remains a key component of firstand second-line ART in sub-Saharan Africa, including forthcoming regimens with dolutegravir.…”

Section: Discussionsupporting

confidence: 80%

“…Detection of RAMs by population sequencing might have failed to detect low-frequency variants. However, we previously documented that in a population long established on NNRTI-based ART deep sequencing affords a rather modest increase in yield [34].…”

Section: Discussionmentioning

confidence: 98%

Determining virological suppression and resuppression by point-of-care viral load testing in a HIV care setting in sub-Saharan Africa

et al. 2020

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Background: This prospective pilot study explored same-day point-of-care viral load testing in a setting in Ghana that has yet to implement virological monitoring of antiretroviral therapy (ART). Methods: Consecutive patients accessing outpatient care while on ART underwent HIV-1 RNA quantification by Xpert. Those with viraemia at the first measurement (T0) received immediate adherence counselling and were reassessed 8 weeks later (T1). Predictors of virological status were determined by logistic regression analysis. Drug resistance-associated mutations (RAMs) were detected by Sanger sequencing. Findings: At T0, participants had received treatment for a median of 8¢9 years; 297/333 (89¢2%) were on NNRTI-based ART. The viral load was 40 copies/mL in 164/333 (49¢2%) patients and 1000 copies/mL in 71/ 333 (21¢3%). In the latter group, 50/65 (76¢9%) and 55/65 (84¢6%) harboured NRTI and NNRTI RAMs, respectively, and 27/65 (41¢5%) had 1 tenofovir RAM. Among 150/164 (91¢5%) viraemic patients that reattended at T1, 32/150 (21¢3%) showed resuppression <40 copies/mL, comprising 1/65 (1¢5%) subjects with T0 viral load 1000 copies/mL and 31/85 (36¢5%) subjects with lower levels. A T0 viral load 1000 copies/mL and detection of RAMs predicted ongoing T1 viraemia independently of self-reported adherence levels. Among participants with T0 viral load 1000 copies/mL, 23/65 (35¢4%) showed resuppression <1000 copies/mL; the response was more likely among those with higher adherence levels and no RAMs. Interpretation: Same-day point-of-care viral load testing was feasible and revealed poor virological control and suboptimal resuppression rates despite adherence counselling. Controlled studies should determine optimal triaging modalities for same-day versus deferred viral load testing.

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“…Finally, as previously reported [10,26,27], the most frequent NRTI resistance mutations among B subtypes belonged to the thymidine analogue mutation (TAM) group (revertant mutants at codon 215, followed by M41L), which are long-term persistent mutations in ART-naive individuals [28]. Conversely, in non-B strains, the main resistance mutation was M184V, which is selected in the course of previous WHO-recommended first-line ART regimens when administered in the absence of virological monitoring [29,30]. Hence, the presence of M184V in GRT of patients naive to ART migrants from sub-Saharan Africa could indicate a possible circulation of this mutation and, as a consequence, the need of specific interventions in this setting to counteract this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment HIV drug Resistance and Treatment Failure in Non-Italian HIV-1-Infected Patients Enrolled in ARCA

et al. 2019

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Background An increase in pretreatment drug resistance (PDR) to first-line antiretroviral therapy (ART) in low-income countries has been recently described. Herein we analyse the prevalence of PDR and risk of virological failure (VF) over time among migrants to Italy enrolled in ARCA. Methods HIV-1 sequences from ART-naive patients of non-Italian nationality were retrieved from ARCA database from 1998 to 2017. PDR was defined by at least one mutation from the reference 2009 WHO surveillance list. Results Protease/reverse transcriptase sequences from 1,155 patients, mainly migrants from sub-Saharan Africa (SSA; 42%), followed by Latin America (LA; 25%) and Western countries (WE; 21%), were included. PDR was detected in 8.6% of sequences (13.1% versus 5.8% for B and non-B strains, respectively; P<0.001), 2.1% of patients carried a PDR for protease inhibitors (PIs; 2.1% versus 2.3%; P=0.893), 3.9% for nucleoside/ nucleotide reverse transcriptase inhibitors (NRTIs; 6.8% versus 2.1%; P<0.001) and 4.3% for non-nucleoside/ nucleotide reverse transcriptase inhibitors (NNRTIs; 6.3% versus 3.1%; P=0.013). Overall, prevalence of PDR over the years remained stable, while it decreased for PIs in LA (P=0.021) and for NRTIs (P=0.020) among migrants from WE. Having more than one class of PDR (P=0.015 versus absence of PDR), higher viral load at diagnosis (P=0.008) and being migrants from SSA (P=0.001 versus WE) were predictive of VF, while a recent calendar year of diagnosis (P<0.001) was protective for VF. Conclusions PDR appeared to be stable over the years in migrants to Italy enrolled in ARCA; however, it still remains an important cause of VF together with viral load at diagnosis.

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Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

Cited by 8 publications

References 41 publications

High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study

High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study

Determining virological suppression and resuppression by point-of-care viral load testing in a HIV care setting in sub-Saharan Africa

Pretreatment HIV drug Resistance and Treatment Failure in Non-Italian HIV-1-Infected Patients Enrolled in ARCA

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