UNIVERSA MEDICINA
Univ Med 2025.
44:57-64
pISSN: 1907-3062 / eISSN: 2407-2230 DOI: https://doi.
org/10.
18051/UnivMed.
ORIGINAL ARTICLE
HIVAc1 drugAcresistance mutations and related risk factors among HIVAc1Acpositive individuals receiving first-line antiretroviral therapy Dwitya Elvira1* .
Sri Puji Rahayuningsih2 .
Rizka Nadia2 , and Raveinal Masri1 Division of Allergy and Clinical Immunology.
Department of Internal Medicine.
Medical Faculty.
Andalas University/M.
Djamil Hospital.
Padang.
West Sumatera.
Indonesia Department of Internal Medicine.
Medical Faculty.
Andalas University/M.
Djamil Hospital.
Padang.
West Sumatera.
Indonesia * Correspondence Author:
dwityaelvira@med.
Date of first submission.
January 2, 2025 Date of final revised submission.
March 21, 2025 Date of acceptance.
March 26, 2025 Cite this article as: Elvira D.
Rahayuningsih SP.
Nadia R.
Masri R.
HIVAc1 drugAcresistance mutations and related risk factors among HIVAc1Acpositive individuals receiving first-line antiretroviral Univ Med 2025.
44:57-64
ABSTRACT
BACKGROUND
Acquired immunodeficiency syndrome (AIDS) remains a global health issue.
Antiretroviral therapy (ART) controls HIV progression, but widespread use had led to drug resistance mutations (DRM.
such as M184V and K103N, compromising treatment efficacy.
This study assessed the prevalence of these mutations and identified associated risk factors in patients with first-line nucleoside reverse transcriptase inhibitor (NRTI)-based ART.
METHODS
A cross-sectional study was conducted involving 80 HIV patients aged > 18 years who had been on NRTI and non-NRTI (NNRTI) therapy for >6 months.
Data included sociodemographic characteristics.
ART adherence, opportunistic infections, viral load.
CD4 count, treatment duration.
ART regimen, and presence of M184V and/or K103N mutations.
Genetic analysis was performed and statistical associations were assessed using simple and multivariate logistic regression.
RESULTS
M184V and/or K103N mutations were detected in 8 patients .
%), significantly associated with poor ART adherence .
<0.
, detectable viral load .
<0.
and male gender .
=0.
, but not with age .
=0.
, body mass index .
=0.
, opportunistic infections .
=0.
CD4 count .
=0.
, and treatment duration .
=0.
Multivariate logistic regression analysis showed that poor ART adherence was associated with a decreased risk of mutations compared to good adherence (OR = 0.
73, 95% CI:0.
and male patients had a 10-fold higher risk compared to females (OR = 10.
03, 95% CI:1.
CONCLUSION
This study demonstrated that male gender was significantly associated with an increased risk of mutations, while poor ART adherence showed an unexpected inverse association.
Strengthening adherence support programs remains essential to preventing drug resistance mutations and ensuring treatment efficacy.
Keywords: ART, adherence, drug resistance mutation.
HIV Copyright@Author.
- https://univmed.
org/ejurnal/index.
php/medicina/article/view/1677 Elvira D ,Rahayuningsih SP.
Nadia R, et al
INTRODUCTION
Acquired immunodeficiency syndrome (AIDS) remains a global health issue.
According to World Health Organization (WHO) data, an 9 million people worldwide were living with human immunodeficiency virus (HIV), 3 million new cases and 630,000 deaths from HIV-related causes in 2023.
In Indonesia, the number of HIV infections continues to rise annually, with an estimated 543,100 individuals living with HIV in 2020.
West Sumatra ranks eighth nationally in cumulative HIV and AIDS cases, with 3,338 HIV cases and 2,087 AIDS cases recorded as of 2019.
The WHO and the Joint United Nations Program on HIV/AIDS (UNAIDS) have set a global objective to end the AIDS pandemic as a public health threat by 2030.
This goal follows the "95-95-95" strategy: ensuring that 95% of people living with HIV are aware of their status, that 95% of diagnosed individuals receive antiretroviral therapy (ART), and that 95% of those on ART achieve viral suppression.
To achieve this target, the WHO recommended in 2016 that all HIV patients should receive immediate ART upon .
Combination ART has proven to be highly effective in suppressing viral load and reducing HIV transmission compared to .
With advancements in ART, life expectancy among people living with HIV has significantly improved.
However, long-term therapy increases the risk of drug-related side effects and treatment failure.
Additionally.
HIV drug resistance has emerged as a major challenge to epidemic control, as it compromises the effectiveness of ART and increases the risk of treatment failure and the transmission of resistant .
A meta-analysis of ART failure rates in China reported a treatment failure rate of approximately 4%, which is lower than rates observed in Haiti .
%).
Ethiopia .
3%), and Uganda .
%).
study by Kurniawan et al.
found that around 7% of patients experienced virological failure .
efined as a viral load >400 copies/mL), while research by Fibriani et al.
reported a similar rate Treatment failure can lead to the development of ART resistance, increasing the risk of mortality due to drug resistance mutations (DRM.
Antiretroviral therapy resistance is influenced by both viral and host factors.
The HIV virus has a high mutation rate, while host-related factors include low drug susceptibility .
egimen potency and toxicit.
, suboptimal drug selection .
nappropriate regimen, incorrect dosage, low drug potency, poor absorption, and drug interaction.
, delays in drug delivery, and .
Antiretroviral therapy resistance can negatively impact treatment response, increase mortality rates, and complicate disease management, requiring careful consideration to prevent further treatment failure.
According to the WHO.
ART resistance is defined by the presence of one or more mutations in the HIV genome that reduce the effectiveness of specific antiretroviral drugs in inhibiting viral .
A single mutation can confer resistance to certain ART drugs of the nucleoside reverse transcriptase inhibitor (NRTI) class, such as lamivudine, or of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class.
Zuo et al.
reported that the M184V mutation leads to lamivudine resistance, while the K103N mutation is the most frequently observed NNRTIassociated mutation at 54.
Zou et al.
found that the most common NRTI resistance mutation was M184V .
04%), while NNRTI resistance was most frequently associated with K103N .
90%).
These mutations allow the virus to replicate despite ART, leading to increased HIV RNA levels and treatment failure.
Previous studies have demonstrated that M184V and K103N mutations contribute to ART resistance, with a relatively high prevalence in certain countries, such as China.
The risk of developing drug resistance mutations (DRM.
depends on several factors, including the ART regimen used and its duration.
However, results from previous studies on ART resistance have shown variability, depending on the studied population.
ART regimen, and adherence patterns.
The heterogeneous nature of these studies makes summarizing and interpreting the evidence regarding acquired drug resistance (ADR) The present study aimed to analyze the risk factors contributing to the development of M184V and K103N mutations and identify the most dominant risk factor in a local Indonesian Universa Medicina.
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HIV-drug resistance mutation risk factor
METHODS
Research design A cross-sectional study was conducted at the Voluntary and Counseling Testing (VCT) clinic of Dr.
Djamil-Hospital Padang, from January to June 2022.
Research subjects A total of 80 patients were included in the Patient were included if they were aged > 18 years and had been receiving NRTI and/or NNRTI therapy for more than 6 months.
The exclusion criteria were patients with hepatitis B or hepatitis C co-infection, active pulmonary tuberculosis, autoimmune disease, or undergoing radiotherapy or chemotherapy.
The selected sample was divided into two groups, namely patients with M184V and/or K103N mutations and those without mutations.
Data collection Data collected included age, gender.
BMI.
ART regimen, opportunistic infections, viral load.
CD4 count, treatment duration.
ART adherence, and presence of M184V and/or K103N mutations.
Blood specimens were obtained through venipuncture and processed for genetic analysis.
HIV genotyping and drug resistance mutations (M184V and K103N) The HIV antiretroviral drug resistance mutations (DRM.
M184V and K103N were examined using a 5-mL venous blood sample from each subject.
The examination was conducted by means of the RT-PCR technique, with first round primers consisting of forward primer 5'tYAGRGARCTYAATAARAGAACTCA-3' (RT):
5'CCTCITTYTTGCATAYTTYCCTGTT-3'.
Second round primers comprised forward primer (RT):
5'TTYTgARGTYCARYTAGGRATACC-3' (RT):
5'GGYTCtGRTatGRATATGTCCA3'.
Data in the form of presence or absence of mutation of either one or both of these SNPs were tabulated and the respective percentages Statistical analysis The obtained data were processed using the IBM statistical package for the social sciences (SPSS) and analyzed using simple logistic regression test for bivariate analysis to assess the association between independent variables .
ge, gender.
BMI.
ART regimen, opportunistic infections, viral load.
CD4 count, treatment duration, and ART adherenc.
and the presence of M184V and/or K103N mutations.
Variables with p-value <0.
25 were further analyzed using multivariate logistic regression to determine the most dominant risk factors.
A p-value of < 0.
was considered statistically significant.
Ethical clearance This study was approved by the Health Research Ethics Committee of Dr.
Djamil Hospital under No.
LB.
02/5.
7/157/2022.
Table 1.
Characteristics of study participants .
Characteristics Age .
<35 Ou35 Gender Male Female Body mass index Underweight Normal Overweight Obese Separate drugs Yes Comorbidity / opportunistic Yes Viral load Detectable Undetectable CD4 .
ells/mm.
<200 >200 Treatment duration .
<12 Ou12
Therapy regimen
AZT 3TC EFV
AZT 3TC NVP
EFV/FTC TDF
TDF 3TC EFV
TDF 3TC NVP
M184V and/ or K103N mutation Present Absent Note: 3TC: lamivudine.
AZT: zidovudine.
EFV: efavirenz.
FTC: emtricitabine.
NVP: nevirapine.
Elvira D ,Rahayuningsih SP.
Nadia R, et al Furthermore, 65 subjects .
3%) did not receive separate ART drugs and 51 subjects .
8%) did not have complications in the form of opportunistic infections, such as tuberculosis and A total of 45 subjects .
showed no detectable viral load and 55 subjects .
8%) had a CD4 count of >200 cells/mm3.
Most of the subjects, namely 73 people .
3%), had received treatment for Ou12 months and 46 subjects .
5%) consumed EFV FTC TDF.
Only 8 subjects .
0%) had M184V and/ or K103N mutations (Table .
Risk factors of M184V and/or K103N Simple logistic regression was conducted to assess the association between demographic characteristics, treatment history, and the presence of M184V and/or K103N mutations.
The results indicated a statistically significant association for male gender .
= 0.
, detectable viral load .
<0.
, and poor ART adherence .
<0.
contrast, other variables, including age.
BMI, opportunistic infections.
CD4 count, and treatment duration, showed no significant association (>0.
(Table .
Based on the simple logistic regression, variables with a p-value of < 0.
25 included gender.
ART adherence, and viral load, which were selected for multivariate logistic regression.
All three variables were included in the initial model (Table .
Gender .
=0.
and poor ART adherence .
=0.
remained significantly associated with the risk of developing the M184V and/or K103N mutations, whereas viral load was found to be non-significantly associated .
= .
as shown in Table 3.
The results indicate that male individuals have a 10.
03 times higher risk of developing these mutations compared to females (OR = 10.
03, 95% CI: 1.
Additionally, poor ART adherence was significantly associated with a decreased risk of mutation compared to good adherence (OR = 0.
95% CI: 0.
Table 2.
Association of risk factors with M184V and/or K103N mutations Variable Age <35 years Ou35 years Gender Male Female BMI Underweight Normal Overweight Obese Poor ART adherence Yes Opportunistic infections Yes Viral Load Detectable Undetectable CD4 Count .
ells/mm.
<200 Ou200 Duration of ART .
<12 Ou12 M184V and/ or K103N mutation Mutation No mutation OR .
% CI) p-value 410 .
--*
<0.
Undefined <0.
Undefined *OR is undefined for some variables because at least one cell in the 2x2 table contains zero, making the calculation unreliable Universa Medicina.
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HIV-drug resistance mutation risk factor Table 3.
Multivariate logistic regression for M184V and/or K103N mutations Variable Gender
ART Adherence Viral Load
95% CI
Undefined 033 - 97.
012 - 0.
----
DISCUSSION