Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan

Chang, Sui‐Yuan; Lin, Pei-Yu; Cheng, Chien-Lin; Chen, Mao-Yuan; Sun, Hsin‐Yun; Hsieh, Szu‐Min; Sheng, Wang-Huei; Su, Yi‐Ching; Su, Li‐Hsin; Chang, Shu-Fang; Liu, Wen-Chun; Hung, Chien‐Ching; Chang, Shan‐Chwen

doi:10.1038/srep35779

Cited by 27 publications

(28 citation statements)

References 34 publications

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“…The fact that only 0.6% of samples analyzed had INSTIs major RAMs suggests that there will be a lesser likelihood of resistance to INSTIs in Cameroon and that INSTIs will be effective for HIV-infected Cameroonians. Similar trends were observed in other countries in Africa [13,34,[43][44][45], Asia [46][47][48][49][50][51], Europe [52][53][54], and South America [55] where studies showed a low frequency of INSTIs major RAMs.…”

Section: Discussionsupporting

confidence: 82%

Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

Acharya

Tagny

Mbanya

et al. 2020

IJMS

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Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3′polypurine tract (3′-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3′-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3′23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3′-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had ≥1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3′-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3′-PPT sequences could reveal treatment failure etiology.

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Section: Discussionsupporting

confidence: 82%

Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

Acharya

Tagny

Mbanya

et al. 2020

IJMS

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“…However, INSTI polymorphic substitutions were not rare, and those who had INSTI polymorphic substitutions were more likely to have a higher HIV viral load and syphilis infection. The absence of INSTI resistance-associated mutations in this study is similar to the CORONET study [ 9 ], the Italian Cohort of Antiretroviral Naive study group [ 15 ], the National Taiwan University Hospital Study [ 8 ] and the epidemiological surveillance study of the European SPREAD programme in 2006–2007 [ 5 ], in which primary resistance to INSTIs was rare.…”

Section: Discussionsupporting

confidence: 79%

“…Our study could not be compared to those reported from northern Taiwan [ 3 , 8 ]. In the study of Lai et al [ 3 ], they reported that the prevalence of INSTI mutation was 3.2%.…”

Section: Discussionmentioning

confidence: 85%

“…With the increasing use of INSTIs and subsequently treatment failure to INSTIs, the risk of TDR to INSTIs is expected to increase, especially in treatment-experienced patients who are not receiving suppressive antiretroviral drugs [ 7 , 8 ]. However, despite the increasing use of INSTIs, few cases of transmission of INSTI resistance in treatment-naïve HIV-1 infected patients were reported in the SPREAD study [ 5 ] and northern Taiwan [ 3 , 8 ]. Minor resistance mutations or polymorphisms have been reported to occur more often in non-B subtype HIV infections compared to subtype B infections [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan

Tsai

Chen

et al. 2018

Oncotarget

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The use of antiretroviral therapy has reduced rates of mortality and morbidity in patients with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS). However, transmission of drug-resistant strains poses a challenge to control the spread of HIV-1. Primary resistance to integrase strand-transfer inhibitors (INSTIs) is rare despite their increased use. The prevalence of transmitted drug resistance (TDR) to INSTIs was 0.9% in northern Taiwan. This study was to analyse the prevalence and risk factors of TDR to INSTIs in southern Taiwan. In this study, we enrolled antiretroviral treatment-naïve HIV-1-infected subjects who underwent voluntary counselling and testing from 2013 to 2016 in southern Taiwan. Genotypic drug resistance, coreceptor tropism (CRT) and INSTI resistance were determined. Logistic regression was used to analyse the risk factors for INSTI polymorphic substitution. Sequences were obtained from 184 consecutive individuals, of whom 96.7% were men who have sex with men and 3.3% were heterosexual. Of the patients, 10% (19/183) had hepatitis B and 33.3% (61/183) had syphilis infection. Subtype B HIV-1 strains were found in 96.1% of the patients. Fifteen patients (8.4%, 15/178) harboured nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors or protease inhibitors resistance. CCR-5 coreceptors were used by 71.4% (130/184) of the patients. None of the patients had INSTI resistance-associated mutations, however 16 patients had INSTI polymorphic substitutions, and they were associated with a higher HIV viral load (p = 0.03, OR 2.4, CI 1.1–5.3) and syphilis infection (p = 0.03, OR 3.7, CI 1.1–12.0). In conclusion, no signature INSTI resistance-associated mutations were detected in our cohort. Continued monitoring of TDR to INSTI is needed due to the increased use of INSTIs.

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“…Genotypic resistance assays were neither offered free-of-charge or routinely determined before cART initiation, although surveillance data suggested that the prevalence of transmitted drug resistance of HIV-1 to at least one antiretroviral was in the range of 10–15%; instead, the assays were performed at Taiwan CDC or a few designated hospitals for patients with virological failure and PVL >1000 copies/mL [12–14]. The national HIV treatment guidelines had increased the CD4 cell count threshold for cART initiation from 350 to 500 cells/mm 3 in September 2013 [11], which was further revised to treat all HIV-positive patients irrespective of CD4 cell count in June 2016.…”

Section: Methodsmentioning

confidence: 99%

Trends and outcomes of late initiation of combination antiretroviral therapy driven by late presentation among HIV-positive Taiwanese patients in the era of treatment scale-up

Lin

Cheng

et al. 2017

PLoS ONE

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ObjectivesThe international and national HIV treatment guidelines in 2016 have focused on scaling up access to combination antiretroviral therapy (cART). We aimed to assess the trends and treatment outcomes of late cART initiation in Taiwan.MethodsBetween June 2012 and May 2016, we retrospectively included antiretroviral-naive HIV-positive adults who initiated cART. Late initiation was defined as when cART was initiated in patients with a CD4 count <200 cells/mm3 or having experienced AIDS-defining illnesses. The treatment outcomes were assessed up to 6 months after starting cART.ResultsWe included 3655 HIV-positive patients, and the majority of the patients were male (95.4%) with a median age of 31 years and initiated non-nucleoside reverse-transcriptase inhibitor-containing regimens (87.0%). The median CD4 count at cART initiation increased from 207 cells/mm3 in 2012 to 298 cells/mm3 in 2016, and the overall proportion of late cART initiation decreased from 49.1% in 2012 to 29.0% in 2016 (P for trend <0.001). Late cART initiation mainly resulted from late presentation for HIV care and was associated with older age (per 1-year increase, adjusted odds ratio [AOR], 1.05; 95% CI, 1.04–1.06), HBsAg seropositivity (AOR, 1.31; 95% CI, 1.04–1.64), HIV care in central and southern Taiwan, initiating cART in earlier year, non-intravenous drug users (AOR, 1.96; 95% CI, 1.33–2.86), and negative hepatitis C serostatus (AOR, 1.47; 95% CI, 1.04–2.08). Compared with non-late initiators, late initiators had a higher rate of all-cause mortality (1.7% vs. 0.3%) and regimen modification due to virological failure (7.1% vs. 2.6%). The predicting factors of all-cause mortality were late cART initiation (adjusted hazard ratio [AHR], 5.40; 95% CI, 2.14–13.65) and older age (AHR, 1.06; 95% CI, 1.03–1.10).ConclusionsWhile the proportion of late cART initiation decreased over time in Taiwan, late initiation remained in a substantial proportion of HIV-positive patients. The late initiators had higher risk for poor outcomes. The need for strategies to earlier detection of HIV infection and expediting cART initiation should be highlighted, especially among the older population.

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Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan

Cited by 27 publications

References 34 publications

Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

Variability in HIV-1 Integrase Gene and 3′-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan

Trends and outcomes of late initiation of combination antiretroviral therapy driven by late presentation among HIV-positive Taiwanese patients in the era of treatment scale-up

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