Abstract
Background
Domestic data on antiretroviral drug (ARV) resistance are limited, while alterations in ARV resistance are expected as the incidence of human immunodeficiency virus (HIV) infection increases. We evaluated the ten-year change in ARV resistance in people with HIV (PWH) in Korea.
Materials and Methods
Adults aged ≥19 years and diagnosed with HIV infection between January 2010 and December 2020 at a 750-bed municipal hospital were retrospectively reviewed. Data on clinical characteristics and resistance mutation test results were collected. The study population was divided into three-year intervals according to diagnosed year and their clinical characteristics were compared.
Results
A total of 248 PWH were analyzed, and ARV resistance was detected in 30 of them (12.1%). Resistance was detected most frequently in PWH aged ≤29 years (16, 6.5%), and the median percentage of resistance detection per year was 14.3% (interquartile range, 12.7 - 16.1). The trend of the overall prevalence of ARV resistance mutations slightly decreased and then increased over time (15.3% in 2012 - 2014, 9.6% in 2015 - 2017, and 12.9% in 2018 - 2020). The prevalence of the non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance markedly decreased over time (15.3% in 2012 - 2014, 8.7% in 2015 - 2017, and 2.4% in 2018-2020), while that of protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI) increased from 0 until 2018 to 3.5% and 8.2% in 2018 - 2020, respectively.
Conclusion
The trend of NNRTI resistance has decreased over time, and resistance to PIs and INSTIs increased from 2018. Therefore, continuous monitoring of ARV resistance pattern is necessary.
Keywords: Human immunodeficiency virus, Antiretroviral agents, Resistance, Epidemiology, Korea
Graphical Abstract
Introduction
Treatment guidelines for human immunodeficiency virus (HIV) infection now recommend that antiretroviral treatment (ART) must be initiated immediately or as soon as possible after HIV diagnosis regardless of the CD4+ T cell count for decreasing the morbidity caused by opportunistic infections and mortality and preventing transmission [1,2,3,4]. International guidelines also recommended pre-exposure prophylaxis (PrEP) for high-risk groups for preventing the infection [1,2,3]. In 2017, the Korean Society of Acquired Immunodeficiency Syndrome recommended the PrEP [5]. These treatment and prevention strategies are now applied worldwide, resulting in a well-controlled state for most patients with HIV infection. Because the importance of rapid initiation of ART has been emphasized [6], and the use of effective antiretroviral drug (ARV) combination is essential, information regarding recent resistance epidemiology is needed for appropriate empirical selection of ARV.
Although early treatment and active prophylaxis strategies are effective, the increased use of ARVs could lead to increased resistance to them [7,8,9]. Based on the HIV drug resistance report 2021 by the World Health Organization (WHO), after initiating ART, patients (2014 - 2020) with previous ARV exposure are at a greater risk of ARV resistance than ARV naïve patients [10]. As ARV resistance could make HIV treatment ineffective, the WHO has developed a revised strategy for the assessment and prevention of HIV drug resistance since 2004. This report suggests that surveys should include sections on pretreatment and acquired HIV drug resistance [11]. In Korea, 4.8% of V118I mutation was reported in 42 ARV-naïve HIV patients in 2007 [12]; however, recent ten-year data on HIV drug resistance are limited. The present study aimed to investigate the ten-year trend of ARV resistance in newly diagnosed ARV-naïve patients with HIV and contribute to an effective response to HIV drug resistance in Korea.
Materials and Methods
1. Study design and data collection
All adults aged ≥19 years who were newly diagnosed with HIV infection between January 2010 and December 2020 at a 750-bed municipal hospital with two infectious disease specialists were included. Clinical data were retrospectively collected from electronic medical records. Data including demographics, comorbidities, and initial laboratory findings before or at the time of the first resistance test were collected.
The initial state of an HIV-infected person was evaluated using non-specific laboratory data including complete blood count, hepatic and renal function tests, and HIV-specific laboratory data including CD4+ T cell count and HIV RNA quantification by real-time reverse transcription polymerase chain reaction (PCR). Results of HIV drug resistance mutation sequencing by PCR (AB 3500xL Dx genetic analyzer, Applied biosystem, Waltham, MA, USA) for each ARV class (nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], protease inhibitor [PI], and integrase strand transfer inhibitor [INSTI]) were reviewed, and data on gene mutation and actual resistance to each medication were collected and analyzed based on the HIV drug resistance database of Stanford University, Stanford, CA, USA [13].
The first test results from each patient were collected, and the enrolled patients were then divided into resistance and no resistance group based on their laboratory findings of ARV resistance. In patients with ARV resistant mutation, it was confirmed whether there was an ARV change in consideration of the resistance mutation. Because resistance tests for INSTI began only after May 30, 2018, at the research center, resistance data for this class were restricted. ARV resistance was defined based on the test results.
2. Ethics statement
The study protocol was reviewed and approved by the Institutional Review Board (IRB) of Boramae Medical Center (No. 20-2021-80), and the need for informed consent was waived because of the retrospective nature of the study. All personal identifiers of the participants were anonymized prior to data processing. This study was conducted in compliance with the principles of the Declaration of Helsinki.
3. Statistical analysis
Resistance mutations were organized by year and ARV classes. In addition, the gene mutations detected throughout the entire study period were analyzed.
The study population was divided into three-year intervals according to diagnosed year and their clinical characteristics were compared. Kruskal-Wallis test, Chi-square test and Fisher’s exact test were used appropriately. The patients were also divided into resistant and non-resistant groups. In the resistant group, the resistance trends were analyzed by year and class of medication. Data regarding each drug, and each mutation were collected from both groups. A chi-square test or Fisher’s exact test was used to compare categorical variables, and Student’s t test was used to compare continuous variables. Kruskal-Wallis test were used for continuous variables when comparing three separate groups. The Cochran-Armitage trend test was used to analyze the prevalence of the resistance mutations trends of ARVs over time. In all analyses, a P-value <0.05 was considered statistically significant. Statistical analyses were performed using IBM SPSS Statistics (version 28.0, IBM, Armonk, NY, USA).
Results
1. Clinical characteristics of HIV-infected persons with ARV resistance mutation
A total of 336 patients were screened, and 248 were included in the analysis. A total of 86 patients were excluded, including 41 with low viral titers, 24 who were diagnosed with HIV before 2010, 19 who were diagnosed with HIV in other institutions and had no resistance mutation results, and two under 19 years of age. When the clinical characteristics were compared every 3 years by diagnosis year from 2012, median age became younger from 36 to 29 without statistical significance (Table 1). There was no statistically different prevalence of comorbidities except decreased incidence of lymphoma (3/59 [5.1%] in 2012 - 2014, and 0/104 [0.0%] and 0/85 [0.0%] in 2015 - 2020, P = 0.013). Previous history of ART has been increased without statistical significance (1/59 [1.7%] in 2012 - 2014, 1/104 [1.0%] in 2015 - 2017, and 4/85 [4.7%] in 2018 - 2020, P = 0.281), and there was no significant difference in CD4+ T cell count (median {interquartile range [IQR]}, 264 [60 - 473]/mm3 in 2012 - 2014, 261 [124 - 419]/mm3 in 2015-2017, and 231 [84 - 341]/mm3 in 2018 - 2020; P = 0.177) and HIV viral load (median [IQR], 64,407 [25,508 - 183,076] copies/mL in 2012 - 2014, 38,717 [11,636 - 133,834] copies/mL in 2015 - 2017, and 49,789 [12,080 - 177,297] copies/mL in 2018 - 2020; P = 0.417).
Table 1. Baseline characteristics of newly diagnosed people with human immunodeficiency virus during 2012 - 2020.
| Characteristics | Year | Total (n = 248) | P-valuea | |||
|---|---|---|---|---|---|---|
| 2012 - 2014 (n = 59) | 2015 - 2017 (n = 104) | 2018 - 2020 (n = 85) | ||||
| Age (median, IQR) | 36 (28 - 48) | 30 (24 - 46) | 29 (26 - 39) | 31 (25 - 44) | 0.148 | |
| Male, n (%) | 55 (93.2) | 99 (95.2) | 80 (94.1) | 234 (94.4) | 0.832 | |
| Comorbidity, n (%) | 9 (15.3) | 18 (17.3) | 8 (9.4) | 35 (14.1) | 0.288 | |
| Diabetes mellitus | 1 (1.7) | 5 (4.8) | 2 (2.4) | 8 (3.2) | 0.594 | |
| Hypertension | 4 (6.8) | 7 (6.7) | 1 (1.2) | 12 (4.8) | 0.139 | |
| Chronic hepatitis B | 1 (1.7) | 5 (4.8) | 2 (2.4) | 8 (3.2) | 0.594 | |
| Chronic hepatitis C | 1 (1.7) | 1 (1.0) | 2 (2.4) | 4 (1.6) | 0.825 | |
| Liver cirrhosis | 0 (0.0) | 1 (1.0) | 0 (0.0) | 1 (0.4) | 0.999 | |
| Solid organ tumor | 0 (0.0) | 1 (1.0) | 2 (2.4) | 3 (1.2) | 0.611 | |
| Lymphoma | 3 (5.1) | 0 (0.0) | 0 (0.0) | 3 (1.2) | 0.013 | |
| Resistance mutation, n (%) | 9 (15.3) | 10 (9.6) | 11 (12.9) | 30 (12.1) | 0.545 | |
| Any Mutation, n (%) | 35 (59.3) | 61 (58.7) | 54 (63.5) | 150 (60.5) | 0.775 | |
| Laboratory results (median, IQR) | ||||||
| White blood cell count, /mm3 | 5,070 (3,990 - 6,210) | 5,090 (4,048 - 6,220) | 5,170 (4,125 - 6,770) | 5,120 (4,073 - 6,400) | 0.470 | |
| CD4+ T cell count, /mm3 | 264 (60 - 473) | 261 (124 - 419) | 231 (84 - 341) | 251 (113 - 399) | 0.177 | |
| HIV RNA, copies/mL | 64,407 (25,508 - 183,076) | 38,717 (11,636 - 133,834) | 49,789 (12,080 - 177,297) | 49,041 (13,359 - 160,000) | 0.417 | |
Values are counts (%) or median (interquartile range) as indicated.
aKruskal-Wallis test for continuous variables, Chi-square or Fisher’s exact test for categorical variables.
IQR, interquartile range; HIV, human immunodeficiency virus.
Overall patients were divided both resistance and no resistance group, and baseline characteristics were also analyzed (Table 2). ARV resistance mutations were detected in 30/248 (12.1%) patients, and there was no significant difference in CD4+ T cell count (median [IQR], 233 [47 - 402]/mm3 vs. 256 [116 - 399]/mm3; P = 0.856) between resistant and non-resistant groups and HIV viral load (median [IQR], 60,320 [15,441 - 408,928] copies/mL vs. 48,815 [13,280 - 152,005] copies/mL; P = 0.218) between the two groups. Other characteristics, including age, sex, comorbidities, and laboratory findings, were not significantly different between the two groups, except for the incidence of lymphoma (2/30 [6.7%] vs. 1/218 [0.5%], P = 0.039). ART was administered to 6 patients within 12 days before testing for ARV- resistance mutations, and ART resistance was not detected in them.
Table 2. Baseline characteristics of newly diagnosed people with HIV according to anti-retroviral resistance results during 2012 - 2020.
| Characteristics | Resistance (n = 30) | No resistance (n = 218) | P | |
|---|---|---|---|---|
| Age (median, IQR) | 28 (23 - 44) | 31 (26 - 44) | 0.279 | |
| Male, n (%) | 28 (93.3) | 206 (94.5) | 0.524 | |
| Comorbidity, n (%) | 5 (16.7) | 30 (13.8) | 0.421 | |
| Diabetes mellitus | 2 (6.7) | 6 (2.8) | 0.250 | |
| Hypertension | 0 (0.0) | 12 (5.5) | 0.205 | |
| CVD | 0 (0.0) | 3 (1.4) | 0.678 | |
| Chronic hepatitis B | 1 (3.3) | 7 (3.2) | 0.649 | |
| Chronic hepatitis C | 0 (0.0) | 4 (1.8) | 0.595 | |
| Liver cirrhosis | 0 (0.0) | 1 (0.5) | 0.879 | |
| Solid organ tumor | 0 (0.0) | 3 (1.4) | 0.678 | |
| Lymphoma | 2 (6.7) | 1 (0.5) | 0.039 | |
| Previous ART history, n (%) | 0 (0.0) | 6 (2.8) | 0.457 | |
| Laboratory results (median, IQR) | ||||
| White blood cell count, /mm3 | 4,530 (3,363 - 6,078) | 5,170 (4,138 - 6,415) | 0.138 | |
| CD4+ T cell count, /mm3 | 233 (47 - 402) | 256 (116 - 399) | 0.856 | |
| HIV RNA, copies/mL | 60,320 (15,441 - 408,928) | 48,815 (13,280 - 152,005) | 0.218 | |
| AST, IU/L | 27 (22 - 41) | 25 (21 - 33) | 0.604 | |
| ALT, IU/L | 29 (15 - 46) | 23 (17 - 34) | 0.173 | |
| Albumin, g/dL | 4.2 (3.9 - 4.5) | 4.3 (3.8 - 4.5) | 0.776 | |
| Creatinine mg/dL | 0.80 (0.70 - 0.86) | 0.79 (0.72 - 0.88) | 0.598 | |
Values are counts (%) or median (interquartile range) as indicated.
HIV, human immunodeficiency virus; IQR, interquartile range; CVD, cardiovascular diseases; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
2. Overall resistance mutation trends of ARVs
The number of patients with ARV resistance, regardless of the ARV class, showed little difference per year (median [IQR], 4 [3,4,5]) (Fig. 1). Resistance was detected most frequently in patients aged ≤29 years (16 patients, 6.5%). The median percentage of resistance detected per year was 14.3% (IQR, 12.7 - 16.1%). NNRTI resistance was most frequently detected from 2010 to 2020, but its frequency decreased after 2017 (Fig. 1). PI or INSTI resistance was most frequently identified in 2019 and 2020. Resistance to only one class of ARV was detected in 27 (10.9%) patients and resistance to two classes of ARVs were detected in three (1.2%) patients. Mutations to three or more ARV classes were not detected.
Figure 1. Antiretroviral agent resistance mutation trends in Korea between 2012 and 2020 according to drug classes.
ARV, antiretroviral drug; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transfer inhibitor.
The trend of the overall prevalence of ARV resistance mutations slightly decreased and then increased over time (15.3% in 2012 - 2014, 9.6% in 2015 - 2017, and 12.9% in 2018 - 2020; P = 0.387) (Fig. 2). The prevalence of the NNRTI resistance markedly decreased over time (15.3% in 2012 - 2014, 8.7% in 2015 - 2017, and 2.4% in 2018-2020; P = 0.002), however, there was only a slight change in that of NRTI (1.7% in 2012 - 2014, 1.9% in 2015 - 2017, and 1.2% in 2018 - 2020; P = 0.391) (Fig. 2). The prevalence of the PI resistance was only detected in 2018 - 2020 (0.0% in 2012 - 2014 and in 2015 - 2017, and 3.5% in 2018 - 2020; P = 0.980), and the prevalence of the INSTI resistance could not be analyzed due to its initiation time. Interestingly, only the decreased prevalence of the NNRTI was clinically significant.
Figure 2. The prevalence of antiretroviral drug resistance mutations between 2012 and 2020.
The prevalence of INSTI resistance mutation was calculated from May 30, 2018, to December 31, 2020.
NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transfer inhibitor.
Among the 30 patients with ARV resistance mutations, 28 were started on ART at our research hospital and two did not re-visit. Fifteen patients underwent ART before the resistance results were reported and there was no change in the ART regimen after resistance mutations were found. Although the effects of resistance mutations were uncertain in 13 patients beginning ART after confirmation of the results, there was no difference in the initial regimen selection compared to that in patients without resistance mutations diagnosed during a similar period, and no case that ART strategy was changed due to the resistant mutation results. All 28 patients had been prescribed a single pill regimen since 2015. Details of the resistance mutations, classes and ARVs of resistance, and effects of treatment on individual patients are described in Supplementary Table 1.
3. Resistance mutation trends of ARVs: NRTI
Resistance to NRTI was detected in 4/248 (1.6%) patients, and NRTI single class resistance was detected only in two patients (Fig. 1). Among the 2 patients with NRTI single class resistance, L74I mutation, which resulted in resistance to didanosine and abacavir (ABC), was found in a patient, and T215D mutation, which resulted in resistance to zidovudine (ZDV) and stavudine (d4T), was identified in the other patient (Supplementary Table 1). T215S mutation was detected in two patients with K103N mutation for NNRTI resistance. These patients were resistant to ZDV and d4T (NRTI), and delavirdine (DLV), nevirapine (NVP), and efavirenz (EFV) (NNRTI).
4. Resistance mutation trends of ARVs: NNRTI
The proportion of resistance to NNRTI was the highest (20/248 [8.1%]), and all patients with resistance to two ARV classes had resistance to NNRTI (Fig. 1). Resistance to DLV, NVP, and EFV was detected in nine patients (Supplementary Table 1), including seven with K103N mutation and two with K101Q, K103R, and Y181C mutations. Simultaneous K101Q and K103R mutations were detected in a patient.
Resistance to DLV and NVP was detected in seven patients (Supplementary Table 1). V108I, V179D, V179E, and K238T mutations were detected in each patient, and both V179D and V179E mutations were found in a patient. Resistance to NVP and EFV was identified in four patients. V179E mutation was detected in two patients, and two different sets of mutations were observed in another two patients (K103N and K103S; K103R and V179D). There were no patients with resistance to DLV and EFV or single ARV.
5. Resistance mutation trends of ARVs: PI and INSTI
Resistances to PI (3/248 [1.2%]) and INSTI (6/248 [2.4%]) were less detected, but the prevalence rates increased after 2018. Only nelfinavir resistance was identified in three patients, but the mutations were different: A71T and M46L mutations in two patients and M46I mutation in a patient (Supplementary Table 1). E157Q mutation was detected in all patients with INSTI resistance with potential low-level resistance to elvitegravir (EVG) and raltegravir (RAL) (Supplementary Table 1). Only a patient had resistance to both INSTI and NNRTI with E157Q, K103R, and V179D mutations. This patient also had additional NVP and EFV mutations. The overall INSTI resistance rate was 2.4%. However, the true percentage of INSTI resistance was 8.2% (6/73) because the resistance test for INSTI was initiated only after 2018 in the study hospital. Moreover, the number of patients with INSTI resistance has increased. After 2018, resistances to PI and INSTI increased, while resistance to NNRTI decreased.
Discussion
The WHO regularly reports global HIV drug resistance; however, Korea has been classified as a country in which such data are not available [10]. A previous report has suggested approximately 4.8% of V118I mutations in 42 ARV-naïve HIV patients in Korea in 2007 [12]. The present study confirmed different results, possibly due to the dramatic changes in the treatment and prevention strategy and increase in the HIV incidence between the study period. Moreover, this study found that the resistance trends have changed within the 10- year study period.
The WHO has reported the overall prevalence of HIV drug resistance during the period from 2014 to 2020 in people with HIV before initiating ART (5.4% for NRTI, 12.9% for NNRTI [EFV or NVP], 0.4% for PI [atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir], and 0.6% for INSTI) [10]. In the present study, the proportions of ARV resistance were different in Korea (1.6% for NRTI, 8.1% for NNRTI, 1.2% for PI, and 8.2% for possible low-level resistance to INSTI). NRTI and NNRTI resistance rates were lower than those worldwide and decreased over the years (Fig. 1). The proportions of resistance to PI and INSTI were higher, especially a resistance of 8.2% for INSTI was observed after 2018. The possible low-level resistance to EVG and RAL was high when compared to the prevalence of resistance to other ARVs, and given the widespread use of these drugs, continued careful monitoring is necessary. In the prevalence of ARV resistance mutations over time, resistance mutations of the NNRTI markedly decreased from 15.3% in 2012 - 2014 to 2.4% in 2018 - 2020, and that of the PI (3.5%) was detected for the first time in 2018 - 2020 (Fig. 2). A recent study on the trends in ARV resistance from another region of Korea reported the increased overtime prevalence of NNRTI resistance from 1.5% in 2011 - 2013 to 6.0% in 2017 - 2019 but no significant change of PI resistance (detailed numeric data were not shown) [14]. Although these studies were conducted in different regions of Korea, the markedly different resistance trends within the same country suggest the need for a large-scale, multicenter study.
Mechanisms of NRTI resistance are known to involve two pathways: impairment of analog incorporation and removal of the NRTI from terminated DNA [7,15]. It is important to evaluate NRTI resistance trends because NRTI is the essential back bone of ART regimens [1,2,3,4]. The worldwide NRTI mutation rate was 5.4% [10], but in the present study, NRTI resistance was detected in only 1.4% of the patients, and all of those were ARV-naïve (Fig. 1). M184V is a representative mutation for impairment of analog, resulting in lamivudine (3TC) resistance [7,15,16] and is often reported with L74V and Y115F mutations in patients with ABC resistance [16,17]. In our result, there was no detected M184V mutation and 3TC resistance; L74I mutation likely associated with ABC resistance [18] was detected in only a patient (Supplementary Table 1). T215 revertants related to virological failure to ZDV or d4T [19] were found in three patients, and a patient with T215 revertants had T215D and K103N mutations simultaneously. Thus, the frequency of NRTI mutations decreased, and most of the ARVs to which resistance was detected in this study are not routinely recommended for ART [1,2]; however, T215 revertants in treatment-naïve patients still need to be considered because of the relatively higher frequency of occurrence.
Resistance to NNRTI is the most frequently detected ARV resistance worldwide [10], and the present study also revealed the high frequency of NNRTI resistance (Fig. 1); however, after 2018, the overall and single detection rates of NNRTI resistance reduced. K103N, the most common mutation and frequently selected by EFV [7,20,21], was the one with the highest frequency, and K103R was detected in only a patient after 2018 (Supplementary Table 1). Y181C, a mutation most frequently selected by NVP [7,19], was detected in only a patient after 2018. Other mutations were less frequent and were not detected after 2018, which could be due to the decreased prescription of NNRTIs.
Resistances to PI and INSTI were detected less frequently [10]. In the present, the overall PI or INSTI resistance rate was low, but the frequency was found to be increasing. After 2019, all detected resistance were to PI and INSTI (Fig. 1). However, the occurrence of A71T with M46L mutations or M46I single mutations was most frequently detected; resistance to nelfinavir was detected in patients with these mutations. Resistance to boosted PI, known to have a higher resistance barrier [21], was not detected. Only E157Q mutation was detected in six patients and reported possible low-level resistance to EVG or RAL (Supplementary Table 1). E157Q mutation is reported to be a natural polymorphism detected in HIV patients (1 - 10%) and dolutegravir (DTG) resistance could be elevated 10-fold in patients with E157Q and R263K mutations [22]. Therefore, the increased frequency of E157Q mutation could be a potential risk factor for increased DTG resistance in patients in Korea.
The selection of empirical ARV changed during the study period according to the development of the drug [23]. Maybe, therefore, in the group with resistance mutation, there was no case of confirmed resistance mutation to the selected empirical ARV. However, since it was confirmed in this study that the resistance mutation trend has changed, it is necessary to continuously monitor how the resistance pattern changes.
This study has some limitations. First, the sample size was small, and the study was restricted to a single center. In Korea, 10,522 Koreans were newly diagnosed with HIV infection during the study period [24]. Only 2.4% of the patients were analyzed in this study. Moreover, most patients lived in Seoul or Gyeonggi-do, and although half of the population in Korea lives in this area, the generalization of the resistance trends from these areas to the rest of the country should be performed cautiously. Second, the HIV drug resistance database of Stanford University used in this study is one of the algorithms widely used worldwide. However, different interpretations of ARV resistance are possible in other algorithms. To aid the reader`s understanding, high-level reduced susceptibility and reduced susceptibility to ARVs have been highlighted in bold underlined text and bold text, respectively, in Supplementary Table 1.
In conclusion, the trend of the overall prevalence of ARV resistance mutations slightly decreased and then increased over time in Korean people with HIV (15.3% in 2012 - 2014, 9.6% in 2015 - 2017, and 12.9% in 2018 - 2020). The trend of NNRTI resistance markedly decreased over time (15.3% in 2012 - 2014, 8.7% in 2015 - 2017, and 2.4% in 2018 - 2020), and in 2018 - 2020, the prevalence of resistance PIs and INSTIs exceeded those of NNRTI. Continuous monitoring for the pattern of ARV resistance is necessary.
ACKNOWLEDGMENTS
This study was presented as an abstract at The Korean Society for AIDS 2021, virtual, November 19, 2021 (Abstract number P-16) and received the best abstract award.
Footnotes
Funding: None.
Conflict of Interest: No conflict of interest.
- Conceptualization: EL.
- Data curation: SMO.
- Formal analysis: SMO, EL.
- Methodology: SMO, EL.
- Supervision: JHB, SWP, EL.
- Writing – original draft: SMO.
- Writing – review & editing: SMO, JHB, SWP, EL.
SUPPLEMENTARY MATERIAL
The effects of antiretroviral drug resistance mutations on treatment change
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Supplementary Materials
The effects of antiretroviral drug resistance mutations on treatment change