Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong, China : Infectious Diseases & Immunity

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Pre-treatment Drug Resistance Could Impact the 96-Week Antiretroviral Efficacy in Treatment-Naive HIV-1–Infected Patients in Guangdong, China

Guo, Pengle; Lan, Yun; Li, Quanmin; Ling, Xuemei; Li, Junbin; Tang, Xiaoping; Hu, Fengyu; Cai, Weiping; Li, Linghua

Author Information
Infectious Diseases & Immunity: October 2022 - Volume 2 - Issue 4 - p 233-238
doi: 10.1097/ID9.0000000000000069
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Abstract

Introduction

The global HIV infection situation remains a challenge. In Western and Central Africa, 6.1 million people were still living with HIV/AIDS in 2016.[1] In China, the total number of people living with HIV/AIDS by the end of August 2018 was 841,478,[2] with more than 10,000 new cases being reported every month. Over the last 30 years, antiretroviral therapy (ART) has become the most effective way to control the progress of HIV, improve the quality of life of patients, and prolong the life span of people living with HIV. The initiation of ART has been recommended in all HIV-1–infected people at any CD4+ T-cell count since 2015.[3] Moreover, in 2014, United Nations program on AIDS/HIV launched the ambitious 90-90-90 treatment targets: 90% of those infected by HIV-1 must be diagnosed, 90% of those diagnosed must be on ART, and 90% of those on treatment must have a fully suppressed viral load (VL).[4] However, drug resistance has always been an important factor affecting the efficacy of ART.

At present, there are many new drugs with high gene resistance barriers, such as integrase inhibitors, which are recommended as the first-line ART regimen in newly diagnosed HIV-infected people, according to many guidelines. However, in resource-limited countries, such as China, efavirenz (EFV) is still the preferred drug, and almost 70% of patients with HIV chose 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus EFV/nevirapine as the initial treatment. The drug resistance barrier of non-NRTIs (NNRTIs) is low, but there is a high pre-treatment drug resistance (PDR) rate (15.9%).[5] In some places, the problem of PDR is severe. It has been reported that approximately 10% of newly diagnosed patients with HIV in Europe carry PDR mutations.[6,7] In Central, South, and Southwest China, the overall drug resistance rates were higher than 5% (the moderate drug resistance warning line proposed by the World Health Organization [WHO]).[8] Pretreatment drug resistance can compromise the response to ART, leading to virologic failure (VF). However, whether it is necessary to detect PDR before ART to guide the selection of antiretroviral drugs is still controversial in China because the ratio of PDR is considered low and the PDR assay is expensive and time-consuming. In this study, we retrospectively detected the drug resistance sites in the blood samples of patients with HIV in the Guangdong Province of China, taken before they underwent ART, and analyzed their impact on the efficacy of ART after 96 weeks, providing evidence for the detection of PDR in patients with initial ART in resource-limited countries.

Methods

Ethics approval

This study was approved by the ethics committee of Guangzhou Eighth People’s Hospital (approval number: 201815106), and each participant signed a written consent form.

Study design

This was a retrospective cohort study that implemented a PDR assay after collecting all blood samples, aiming to investigate the prevalence of PDR and determine its impact on the efficacy of ART. The main outcome was the proportion of VF, defined as 2 consecutive quantitative VLs (≥7 and ≤30 days apart) of more than 400 copies/mL at week 24 (or thereafter after ART) during the 96-week observation frame, and the secondary outcome was the change in CD4+ T cells and CD4+ T/CD8+ T ratio at the 96th week after ART.

Patients

PDR was retrospectively assayed in 1936 HIV-1–infected treatment-naive patients, whose blood samples were collected before initiating ART in the clinic of the infectious department, Guangzhou Eighth People’s Hospital, between August 2018 and December 2019. The inclusion criteria were: patients who were diagnosed with HIV infection[9]; at least 16 years old and naive to ART; ART was initiated within 2 weeks after HIV diagnosis; and provided signed informed consent, agreed to follow-up, and share data. The exclusion criteria are as follows: patients who have previously taken other anti-HIV or HBV drugs, patients who have used immunopotentiator or suppressor drugs during the past 3 months, and patients who could not start ART because of various reasons. Of these, 125 patients had PDR (PDR arm). Patients without PDR were randomly selected at a ratio of 1:1 as the control arm (non-PDR arm) according to a computer-generated allocation schedule. Patients in both arms were retrospectively followed up for 96 weeks. CD4+ T-cell counts were collected before ART and at the 12th, 24th, 48th, 72nd, and 96th weeks after ART. The HIV-RNA VL was tested at the 24th, 48th, and 96th weeks after ART.

CD4+ T-cell count

CD4+ T and CD8+ T cells from fresh whole blood of patients were quantified via flow cytometry using a Beckman Coulter FC500 (San Diego, CA, USA).

HIV-RNA VL

HIV-1 RNA was extracted from blood plasma using a QIAamp Viral RNA Mini Kit (Qiagen, Germany) and quantified using a Roche Cobas Ampliprep/Cobas TaqMan HIV-1 v2.0 Assay (Indianapolis, IN, USA).

HIV subtype and genotypic resistance assay

Total RNA was extracted and the HIV-1 reverse transcriptase (RT) and protease genes were amplified (the primer sequences used are available upon request because they are the targets of the most common antiretroviral drugs in China, including NRTIs, NNRTIs, and protease inhibitors (PIs). Integrase genes were not tested because integrase inhibitors are rarely used in China. The sub-genotypes were identified via phylogenetic analysis using Bioedit software (downloaded freely from https://bioedit.software,informer.com/7.2/) and MEGA5 software (downloaded freely from https://www.megasoftware.net/dload_win_gui) with the standard strains selected from the Los Alamos HIV database (https://www.hiv.lanl.gov/content/sequence/HIV/COMPENDIUM/2018compendium.html). Drug resistance mutation sites were identified using the Stanford HIV-resistant database HIVdb program, version 8.8 (https://hivdb.stanford.edu/).

Statistical analysis

Differences between arms were evaluated using Student t test for continuous variables with normal distribution, and the non-parametric Mann-Whitney test for the variables with skewed distribution. Comparisons between categorical variables were performed using the χ2 test and Fisher exact test. Statistical tests were performed using GraphPad Prism version 5.0a and SPSS Statistics 20.0. P values were less than 0.05 were considered significant.

Results

Pretreatment drug resistance rate

A total of 1936 cases were enrolled. Mutations of PDR genes were detected in 125 cases, showing a drug resistance rate of 6.46% (125/1936). Single-drug resistance accounted for 96.80% of resistant cases (121/125), with 11.20% (14/125), 64.00% (80/125), and 21.60% (27/125) participants exhibiting PDR to NRTIs, NNRTIs, and PIs, respectively. Dual drug resistance accounted for 3.20% (4/125), with 0.80% (1/125) and 2.40% (3/125) participants exhibiting PDR to NNRTIs + PIs and NRTIs + NNRTIs, respectively. The distribution of drug resistance mutation sites is shown in Table 1.

Table 1 - Distribution of DRM sites in the 125 cases
PI-related DRM NRTI-related DRM NNRTI-related DRM
sites n (%) sites n (%) sites n (%)
Q58E 17 (53.1) M184V 3 (13.6) V179E 230 (55.0)
M46L 5 (15.6) L210W 3 (13.6) V179D 85 (20.3)
L10F 3 (9.4) T215S 3 (13.6) E138G 31 (7.4)
L33F 3 (9.4) K70Q 2 (9.1) V106I 22 (5.3)
K43T 1 (3.1) V75I 2 (9.1) K103N 10 (2.4)
M46I 1 (3.1) T215A 2 (9.1) V179T 8 (1.9)
N88S 1 (3.1) D67N 1 (4.5) E138A 7 (1.7)
L90M 1 (3.1) K70E 1 (4.5) Y181C 5 (1.2)
Total 32 (100.0) V75A 1 (4.5) K103Q 4 (1.0)
V106I 1 (4.5) A98G 3 (0.7)
T215D 1 (4.5) G190A 3 (0.7)
T215N 1 (4.5) V106M 2 (0.5)
K219N 1 (4.5) E138K 2 (0.5)
Total 22 (100.0) L100M 1 (0.2)
K101E 1 (0.2)
V179L 1 (0.2)
Y181V 1 (0.2)
H221Y 1 (0.2)
K238T 1 (0.2)
Total 418 (100.0)
DRM: Drug resistance mutation; PI: Protease inhibitor; NRTI: Nucleoside reverse transcriptase inhibitor; NNRTI: Non-nucleoside reverse transcriptase inhibitor. Blank means no data.

Characteristics of the study population

During the retrospective 96-week follow-up of 125 patients in the PDR arm, 3 patients were lost to follow-up and 14 patients were transferred to other treatment sites (therefore, HIV-RNA or CD4+ T-cell count could not be collected). The remaining 108 patients were included in the further analyses. In the control arm, 3 patients were lost to follow-up and 10 shifted treatment sites; the remaining 112 cases were included in the further analyses [Figure 1]. The baseline characteristics of the study population included in the study are shown in Table 2. There were no significant differences in the baseline age, sex composition, education level, acquisition route, CD4+ T-cell counts, and ART regimen between the 2 arms. However, the genotype composition was more complex in the PDR arm, with less common subtypes (such as CRF07_BC and CRF01_AE), more unique recombinant forms (URF), and other uncommon subtypes.

F1
Figure 1:
Subject disposition in the study. ART: Antiretroviral therapy; PDR: Pretreatment drug resistance.
Table 2 - Baseline characteristics of patients in the PDR arm and the non-PDR arm
Parameter PDR (n = 108) non-PDR (n = 112) Statistical value P
Age (years, mean ± SD) 39.7 ± 12.9 41.2 ± 13.3 t = −0.828 0.409
Male [n (%)] 95 (88.0) 100 (89.3) χ 2 = 0.168 0.682
Acquisition route [n (%)] χ 2 = 1.411 0.290
 Sexual 102 (94.4) 102 (91.1)
 Other 6 (5.6) 10 (8.9)
Degree of education [n (%)] χ 2 = 0.056 0.885
 High school and above 72 (66.7) 76 (67.9)
 Below high school 36 (33.3) 36 (32.1)
CD4+ T-cell counts (cells/μL, mean ± SD) 231.3 ± 190.6 230.7 ± 159.8 t = 0.024 0.981
Viral sub-type based on PR/RT sequences [n (%)] χ 2 = 18.283 0.075
 CRF07_BC 22 (20.4) 38 (33.9) χ 2 = 5.125 0.032
 CRF01_AE 31 (28.7) 43 (38.4) χ 2 = 2.197 0.152
 CRF55_01B 17 (15.7) 12 (10.7) χ 2 = 1.043 0.320
 CRF08_BC 2 (1.9) 0 / /
 B 15 (13.9) 8 (7.1) χ 2 = 2.354 0.176
 CRF59_01B 2 (1.9) 2 (1.8) / /
 C 2 (1.9) 1 (0.9) / /
 G 2 (1.9) 0 / /
 CRF67_01B 0 1 (0.9) / /
 CRF68_01B 1 (0.9) 0 / /
 CRF12_BF 1 (0.9) 0 / /
 URF 13 (12.0) 7 (6.3) χ 2 = 3.111 0.107
ART regimen [n (%)] χ 2 = 5.106 0.277
 2NRTIs + EFV/NVP 80 (74.1) 85 (75.9) χ 2 = 0.098 0.756
 2NRTIs + LPV/r 6 (5.6) 10 (8.9) χ 2 = 0.785 0.442
 2NRTIs + DTG/RAL 18 (16.7) 17 (15.2) χ 2 = 0.055 0.853
 2NRTIs 3 (2.8) 0 / /
 3TC + DTG 1 (0.9) 0 / /
PDR: Pretreatment drug resistance; SD: Standard deviation; PR/ RT: Protease-reverse transcriptase; ART: Antiretroviral therapy; NRTIs: Nucleoside reverse transcriptase inhibitors; EFV: Efavirenz; NVP: Nevirapine; LPV/r: Lopinavir/ritonavir; DTG: Dolutegravir; RAL: Raltegravir; 3TC: Lamivudine; “/”: Not applicable.

Patients whose ART regiments include the resistant drug

Among the 108 patients with PDR mutations, 52 patients (48.1%, con-PDR arm) were found using an ART regimen containing the resistant drug. Most of the con-PDR patients chose the treatment regimen containing 2 NRTIs and EFV, with 3 (5.8%), 47 (90.4%), 1 (1.9%), and 1 (1.9%) patients whose ART regiments include the resistant drug to NRTIs, NNRTIs, PIs, and NRTIs + NNRTIs, respectively.

Antiretroviral outcomes

After ART initiation, 7 patients (6.5%, 7/108) in the PDR arm, 3 patients (5.8%, 3/52) in the con-PDR arm, and 1 patient (0.9%, 1/112) in the non-PDR arm developed VF during the 96-week observation period. There was a significant difference in the VF rate between the PDR and non-PDR arms (χ2 = 4.901, P = 0.029), as shown in Table 3. As for the CD4+ T-cell count, the non-PDR arm (median, 386.6 cells/μL) showed a greater increase compared with the PDR arm (median, 319.1 cells/μL; t = 2.448, P = 0.015) or con-PDR arm (median, 325.1 cells/μL; t = 1.821, P = 0.070) at 12 weeks after ART. However, there was no significant difference observed in the CD4+ T-cell count of the non-PDR arm from the 24th week after ART onward when compared with the PDR arm or con-PDR arm [Figure 2]. A similar change was found in the ratio of CD4+ T cells and CD8+ T cells in the PDR arm or the con-PDR arm versus the non-PDR arm from baseline through 96 weeks after ART (data not shown). Among the 7 patients who developed VF, 2 were dual drug resistant, 3 were resistant to NNRTIs (2 patients had a V106I mutation, while 1 patient had a K101E mutation), and the other 2 were resistant to PIs (Q58E mutations). It is worth noting that the initial levels of CD4+ T cells of these 7 patients was very low, with a median of 22 cells/μL, and 6 of the 7 patients initiated with the ART regimen of 3TC + TDF + EFV.

Table 3 - Antiretroviral effect among three arms during the 96-week observation period after ART
Variables non-PDR (n = 112) PDR (n = 108) Statistical valuea P a con-PDR (n = 52) Statistical valueb P b
VF [n (%)] 1 (0.9) 7 (6.5) χ 2 = 4.901 0.029 3 (5.8) χ 2 = 3.549 0.095
Increases in CD4+ T-cell count (cells/μL, mean ± SD) 250.9 ± 145.1 233.1 ± 181.1 t = −0.784 0.434 225.2 ± 201.9 t = −0.909 0.365
Increase in CD4/CD8 ratio (mean ± SD) 0.37 ± 0.31 0.31 ± 0.27 t = −1.375 0.171 0.29 ± 0.21 t = −1.338 0.183
aRepresents the comparison between the non-PDR and PDR arms.
bRepresents the comparison between the non-PDR and con-PDR arms.
ART: Antiretroviral therapy; PDR: Pretreatment drug resistance; VF: Virologic failure; SD: Standard deviation.

F2
Figure 2:
Changes in CD4+ T-cell count from baseline to 96 weeks after ART. (A) The CD4+ T-cell counts from the PDR arm and non-PDR arm at different treatment points as compared through the Mann-Whitney U test. (B) The CD4+ T-cell counts from the con-PDR arm and non-PDR arm at different time points as compared through the Mann-Whitney U test. *P < 0.05. ART: Antiretroviral therapy; PDR: Pretreatment drug resistance.

Discussion

It is crucial to monitor PDR in patients receiving ART, concomitant with ART expansion, and the treat-all strategy. It has been reported that the prevalence of PDR to NNRTI is approximately 10% (the WHO threshold for changing first-line ART) in southern and eastern Africa and Latin America,[10] increasing substantially every year. In this way, the success of the achievement of the third 90 target may be compromised, especially in resource-limited areas, where NNRTI is still recommended as a first-line therapy. Recommendations to detect HIV PDR before the initiation of ART have been issued by the WHO since 2008[11] and European guidelines in 2017.[12]

Pretreatment drug resistance mutations were found in 3.6% of the 5627 HIV cases in China in 2015,[13] 10.8% of the cases in Chongqing in 2022,[14] 11.5% of the cases in Tianjin in 2020,[15] and 4.9% among cases of men who have sex with men (MSM) in 19 cities in 2010.[16] In our study, the prevalence of PDR was 6.46%, which was above the moderate drug resistance warning line and those reported in previous studies. Meanwhile, the prevalence of pre-treatment NNRTI resistance was 4.13% (80/1936), near the WHO moderate threshold of 5%, highlighting the need for close surveillance of PDR in China.

Among the patient genotypes included in the study, CRF01_AE and CRF07_BC were the dominant, consistent with previous studies.[5,14] However, in the PDR arm, these 2 major genotypes accounted for only 49% of the cases. A majority of the genotypes were other uncommon types, especially CRF55_01B (15.4%, 16/104), sub-type B (13.5%, 14/104), and URFs (12.5%, 13/104). CRF55_01B has disseminated widely among MSM in major cities in southern, eastern, and central China.[17] It has been reported that 79.01% of CRF55_01B-infected patients carried mutations conferring lower or higher drug resistance to any of the three classes of ART drugs.[18] In addition, there were many recombinant virus strains and new recombinant virus strains that have not been reported (URF) in our data. It was observed that the genotypic distribution of the HIV-1 virus was more complex in the PDR arm, which may lead to an active cross transmission among different genotypes of HIV; therefore, the need to prevent and control the HIV situation in Guangdong, China, is still of great importance.

The effect of PDR on ART efficacy has not yet been determined. Some studies believe that PDR is not correlated with VF or survival rate,[5,19] but others believe that PDR is related to VF.[20–22] In our study, there were more cases of treatment failure in the PDR arm, where PDR affected the CD4+ T-cell counts at 12 weeks after ART. This suggests the profound impact of PDR on ART in patients with HIV. The con-PDR arm, which used the drug-resistant site regimen, was not significantly related to VF compared with the PDR arm during the 96-week observation period. This might be due to bias from the small number of cases. Further studies are needed to clarify whether the use of regimens containing drug-resistant sites has an impact on the efficacy of ART.

In our study, it seems that the prevalence of viral failure is high in PDR individuals, no matter whether they received ART regiments including resistant drugs or not. This also makes sense, because most of our patients used NNRTIs, which had the lowest gene resistance barrier. This suggested that we should choose drugs with higher gene resistance barrier and avoid using NNRTIs, when there was PDR, even if no resistance to NNRTIs in the resistance site. This was consistent with the previous research that PDR significantly increased the risk of virological failure of EFV-based ART.[23] This can also explain the difference between genotype resistance and phenotypic resistance.

Moreover, it seemed that HIV patients with dual drug resistance, low initial CD4+ T-cell count, using NNRTIs regimen, and resistance to PIs may have a predisposition to VF. Unfortunately, the number of cases is too small to carry out regression analysis for these influencing factors, which requires further study.

In general, PDR, with a diversified genotype distribution, increases annually and affects the virologic response and immune reconstitution of ART in patients with HIV. It is therefore necessary to closely monitor PDR and select a rational ART regimen following this phenomenon in patients with HIV.

Our study also had many limitations, because it was a retrospective study. The number of cases in PDR group and the number of people who reached the main outcome were small, and further research was needed. Because the NRTIs and NNRTIs were chosen as the ART regimen by most patients, the pre-treatment resistance of integrase inhibitors was not tested in our study.

Acknowledgments

The authors thank the patients who participated in our study.

Author Contributions

Weiping Cai, Linghua Li, and Xiaoping Tang designed and directed the study. Pengle Guo, Yun Lan, and Fengyu Hu performed experiments. Quanmin Li, Xuemei Ling, Junbin Li, and Pengle Guo followed up on patients, collected samples, and recorded data. Linghua Li and Pengle Guo analyzed the data and wrote the manuscript. All authors revised the manuscript and approved the final version of the manuscript.

Funding

The study was supported by the Major National Science and Technology Projects during the 13th 5-year plan period (2017ZX10202101-003, 2017ZX10202102-003-004), and the Guangzhou Science and Technology Innovation Committee project (new strategy for functional cure of AIDS–clinical and basic research, 201803040002), and Guangzhou basic research program on people’s Livelihood Science and technology (No. 202002020005).

Conflicts of Interest

None.

References

1. UNAIDS. Fact Sheet-world AIDS day 2021. Available from: http://www.unaids.org/sites/default/files/media_asset/UNAIDS_FactSheet_en.pdf. Accessed January 25, 2022.
2. National Center for AIDS/STD Control and Prevention, China CDC. Update on the AIDS/STD epidemic in China in July, 2018. Chin J AIDS STD 2018;24:965. doi:10.13419/j.cnki.aids.2018.09.01.
3. World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, WHO. Available from: www.who.int/entity/hiv/pub/guidelines/earlyrelease-arv/en/. Accessed January 25, 2022.
4. Bain LE, Nkoke C, Noubiap JJN. UNAIDS 90-90-90 targets to end the AIDS epidemic by 2020 are not realistic: comment on “Can the UNAIDS 90-90-90 target be achieved? A systematic analysis of national HIV treatment cascades”. BMJ Glob Health 2017;2:e000227. doi:10.1136/bmjgh-2016-000227.
5. Keita A, Sereme Y, Pillet S, et al. Impact of HIV-1 primary drug resistance on the efficacy of a first-line antiretroviral regimen in the blood of newly diagnosed individuals in Bamako, Mali. J Antimicrob Chemother 2019;74(1):165–171. doi:10.1093/jac/dky382.
6. Tostevin A, White E, Dunn D, et al. Recent trends and patterns in HIV-1 transmitted drug resistance in the United Kingdom. HIV Med 2017;18(3):204–213. doi:10.1111/hiv.12414.
7. Hofstra LM, Sauvageot N, Albert J, et al. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe. Clin Infect Dis 2016;62(5):655–663. doi:10.1093/cid/civ963.
8. Liu D, Feng M, Liu M. Primary drug resistance of human immunodeficiency virus (HIV) among the treatment-naive individuals with HIV in China: a meta-analysis. Beijing Da Xue Xue Bao Yi Xue Ban 2015;47:474–482.
9. AIDS and Hepatitis C Professional arm, Society of Infectious Diseases, Chinese Medical Association, Chinese Center for Disease Control and Prevention. Chinese guidelines for diagnosis and treatment of HIV/AIDS (version 2018). Zhonghua Nei Ke Za Zhi 2018;57(12):867–884.
10. Gupta RK, Gregson J, Parkin N, et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect Dis 2018;18(3):346–355. doi:10.1016/S1473-3099(17)30702-8.
11. Bennett DE, Myatt M, Bertagnolio S, et al. Recommendations for surveillance of transmitted HIV drug resistance in countries scaling up antiretroviral treatment. Antivir Ther 2008;13:25–36.
12. European AIDS Clinical Society. EACS guidelines for the clinical management and treatment of HIV-infected adults. v9.0, October 2017. Available from: https://www.eacsociety.org/files/guidelines_9.0-english.pdf. Accessed January 21, 2022.
13. Zhao S, Feng Y, Hu J, et al. Prevalence of transmitted HIV drug resistance in antiretroviral treatment naïve newly diagnosed individuals in China. Sci Rep 2018;8(1):12273. doi:10.1038/s41598-018-29202-2.
14. Liu M, He XQ, Deng RN, et al. Pretreatment drug resistance in people living with HIV: a large retrospective cohort study in Chongqing, China. HIV Med 2022;23(Suppl 1):95–105. doi:10.1111/hiv.13253.
15. Zeng R, Ren D, Gong X, et al. HIV-1 genetic diversity and high prevalence of retreatment drug resistance in Tianjin, China. AIDS Res Hum Retroviruses 2020;36(10):852–861. doi:10.1089/AID.2020.0056.
16. Yang J, Xing H, Niu J, et al. The emergence of HIV-1 primary drug resistance genotypes among treatment-naïve men who have sex with men in high-prevalence areas in China. Arch Virol 2013;158(4):839–844. doi:10.1007/s00705-012-1557-7.
17. Gan M, Zheng S, Hao J, et al. The prevalence of CRF55_01B among HIV-1 strain and its connection with traffic development in China. Emerg Microbes Infect 2021;10(1):256–265. doi:10.1080/22221751.2021.1884004.
18. Lan Y, Xin R, Cai W, et al. Characteristics of drug resistance in HIV-1 CRF55_01B from ART-experienced patients in Guangdong, China. J Antimicrob Chemother 2020;75(7):1925–1931. doi:10.1093/jac/dkaa116.
19. Zeng R, Ren D, Gong X, et al. HIV-1 genetic diversity and high prevalence of pretreatment drug resistance in Tianjin, China. AIDS Res Hum Retroviruses 2020;36(10):852–861. doi:10.1089/AID.2020.0056.
20. Neuhann F, de Forest A, Heger E, et al. Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi. AIDS Res Ther 2020;17(1):22. doi:10.1186/s12981-020-00282-3.
21. Soria J, Mugruza R, Levine M, et al. Pretreatment HIV drug resistance and virologic outcomes to first-line antiretroviral therapy in Peru. AIDS Res Hum Retroviruses 2019;35(2):150–154. doi:10.1089/AID.2018.0239.
22. Bavaro DF, Di Carlo D, Rossetti B, et al. Pretreatment HIV drug resistance and treatment failure in non-Italian HIV-1–infected patients enrolled in ARCA. Antivir Ther 2020;25(2):61–71. doi:10.3851/IMP3349.
23. Hermans LE, Hofstra LM, Schuurman R, et al. HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment—week 96 results from the ITREMA trial. AIDS 2022;36(7):923–931. doi:10.1097/QAD.0000000000003182.
Keywords:

Prevalence; Pretreatment drug resistance; Antiretroviral therapy; Virologic failure

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