scholarly journals Involvement of the Genetic Diversity of HIV-1 in the Virological Treatment Failure of First Line Antiretroviral in Kinshasa

2017 ◽  
Vol 07 (01) ◽  
pp. 23-33
Author(s):  
Erick Ntambwe Kamangu ◽  
Richard Lunganza Kalala ◽  
Georges Lelo Mvumbi ◽  
Dolores Vaira ◽  
Marie-Pierre Hayette
2020 ◽  
Author(s):  
Behailu Tariku Derseh ◽  
Belay Shewayerga ◽  
Abinet Dagnaw ◽  
Elyas Admasu Basha

Abstract Background Nowadays Human Immuno-deficiency Virus (HIV) is one of the devastating and prevalent viruses affecting the globe without a cure. Highly Active Antiretroviral Therapy (HAART) significantly reduced the morbidity and mortality of patients with HIV infection. Although there is increasing global use of antiretroviral therapy (ART) for the treatment of HIV/AIDs, the global trends in ART failure are growing. In developing countries including Ethiopia, particularly in our study settings, information related to the magnitude and correlates of virological treatment failure is scarce. Thus, this study aimed at assessing the magnitude of virological treatment failure and associated factors among HIV reactive adults at selected hospitals of North Shoa, Amhara Region, Ethiopia. Methods a facility-based cross-sectional study was conducted among 498 study participants who started their first-line HAART from August 2005 to December 2018. Data were collected from patients’ charts and face-to-face interviews using a structured questionnaire. The bivariable analysis was executed to select candidate predictor variables at a p-value of less than 0.2. Multivariable logistic regression (forward stepwise, conditional) analysis was used to identify factors associated with virologic failure at a significant level of 5%. Model adequacy check was done by Hosmer and Lemeshow (p = 0.57) and Naglkerke R Square (0.46) was calculated to express the variability of virological failure by predictors. Result More than half 290 (58.2%) of the study participants were females. The median age at ART initiation was 40 years with an interquartile range (IQR) of 15 years. The median duration of virologic failure since initiation of treatment was 96 months (IQR) of 72. The magnitude of virological treatment failure was 10.24% (95% CI: 7.57% − 12.91%). Poor ART drug adherence (AOR = 4.54; 95% CI: 2.09, 9.87), CD4 count less than 250 cell/µl (AOR = 24.88; 95% CI: 11.73, 52.81) and Poor Quality of Life (QoL) (AOR = 2.65; 95% CI: 1.12, 6.25) were independent predictors of virologic failure. Conclusion The magnitude of Virologic ART treatment failure in this study was relatively high. Poor ART drug adherence, patients’ having lower CD4 count and poorer quality of life were predictors of treatment failure. Thus, an intervention programs that enriches patients’ health-related quality of life should be implemented. Moreover, counseling that supplements the importance of drug adherence and reduction of risks that lower CD4 counts should be given emphasis which in turn helps to prevent first-line ART treatment failure.


2019 ◽  
Vol 2 (2) ◽  

Introduction: Highly active antiretroviral therapy (HAART) played a critical role in the medical management of HIV infected individuals by restoring the immune function and minimizes HIV related outcomes. But treatment failure minimized these advantages and leads to an increment of morbidity and mortality with poor quality of life in all HIV patients. Objective: The aim of this study was to assess the virological treatment failure and its determinant factors of patients on first line HAART at five commandant Hospitals, Ethiopia. Methods: A Retrospective hospital based study design was used to determine magnitude of treatment/virology failure and its determinant factors, among HIV positive adults enrolled to HAART program at five commandant Hospitals from February 1 to May 30, 2018. Data abstracted from patient charts or electronic data base was cleaned, coded, entered and analyzed using EPI data version 3.1 and SPSS version 23 statistical software package. Descriptive statistics, proportion of treatment failure cases among those diagnosed to have treatment failure was calculated. Bi-variate and multiple logistic regressions were used to analysis association between the outcome and the independent variables were taken as significant at P<0.05 (2 tail test) and 95% confidence intervals (CIs). Result: Among the 326 participants enrolled, 229(70.2%) were males. The mean ages were 36.84 years (SD+7.716) years and the median months on HAART from initiation were 81.50 months. A total of 75(23%) participants were found to have treatment failure among those 50(15.3%) immunological failure, 7(2.1%) virological failure and 16(4.9%) all Treatment failure (VF, IF&CF in one). The mean CD4 T-cells at base line and at study time were 213.3 cells/ µl. Long duration on treatment (AOR= 4.231, 95% CI: 1.453-12.320) , IPT cycle (AOR = 3.060, 95% CI: 1.388-6.746), Type of drug AZT based therapy (AOR= 2.572, 95% CI: 1.357-4.875), experience of PEP (AOR=7.950, 95% CI: 1.945-66.915) and lost to follow up (AOR= 9.104, 95% CI: 2.973-27.873) were found to be significant predictors of treatment/virologic failure and showed positive odds ratio. Conclusion: This study demonstrates high treatment /virologic failure and the determinant factors of treatment/virologic failures among HAART first line adult are still changing. Therefore, evidence-based intervention and early detection of treatment failure must be made to further identify the potential causes and set standardized protective mechanisms of treatment/virologic failures.


2000 ◽  
Vol 44 (9) ◽  
pp. 2475-2484 ◽  
Author(s):  
Lee T. Bacheler ◽  
Elizabeth D. Anton ◽  
Phil Kudish ◽  
David Baker ◽  
Julie Bunville ◽  
...  

ABSTRACT Efavirenz is a potent and selective nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Nucleotide sequence analyses of the protease and RT genes (coding region for amino acids 1 to 229) of multiple cloned HIV-1 genomes from virus found in the plasma of patients in phase II clinical studies of efavirenz combination therapy were undertaken in order to identify the spectrum of mutations in plasma-borne HIV-1 associated with virological treatment failure. A K103N substitution was the HIV-1 RT gene mutation most frequently observed among plasma samples from patients for whom combination therapy including efavirenz failed, occurring in at least 90% of cases of efavirenz-indinavir or efavirenz-zidovudine (ZDV)-lamivudine (3TC) treatment failure. V108I and P225H mutations were observed frequently, predominantly in viral genomes that also contained other nonnucleoside RT inhibitor (NNRTI) resistance mutations. L100I, K101E, K101Q, Y188H, Y188L, G190S, G190A, and G190E mutations were also observed. V106A, Y181C, and Y188C mutations, which have been associated with high levels of resistance to other NNRTIs, were rare in the patient samples in this study, both before and after exposure to efavirenz. The spectrum of mutations observed in cases of virological treatment failure was similar for patients initially dosed with efavirenz at 200, 400, or 600 mg once a day and for patients treated with efavirenz in combination with indinavir, stavudine, or ZDV-3TC. The proportion of patients carrying NNRTI resistance mutations, usually K103N, increased dramatically at the time of initial viral load rebound in cases of treatment failure after exposure to efavirenz. Viruses with multiple, linked NNRTI mutations, especially K103N-V108I and K103N-P225H double mutants, accumulated more slowly following the emergence of K103N mutant viruses.


2020 ◽  
Author(s):  
Behailu Tariku Derseh ◽  
Belay Shewayerga ◽  
Abinet Dagnaw ◽  
Elyas Admasu Basha

Abstract Background: Nowadays Human Immuno-deficiency Virus (HIV) is one of the devastating and prevalent virus affecting the globe without a cure. Highly Active Antiretroviral Therapy (HAART) significantly reduced the morbidity and mortality of patients with HIV infection. Although there is increasing global use of antiretroviral therapy (ART) for the treatment of HIV/AIDs, the global trends in ART failure is growing. In developing countries including Ethiopia, particularly in our study settings, information related to magnitude and correlates of virological treatment failure is scarce. Thus, this study aimed at assessing the magnitude of virological treatment failure and associated factors among HIV reactive adults at selected hospitals of north Shoa, Amhara Region, Ethiopia.Methods: a facility based cross-sectional study was conducted among 498 study participants who started their first-line HAART from August 2005 to December 2018. Data were collected from patients’ charts and face-to-face interviews using a structured questionnaire. Bivariable analysis was executed to select candidate predictor variables at a p-value less than 0.2. Multivariable logistic regression (forward stepwise, conditional) analysis was used to identify factors associated with virologic failure at significant level of 5%. Model adequacy check was done by Hosmer and Lemshow (p = 0.57) and Naglkerke R Square (0.46) was calculated to express the variability of virological failure by predictors.Result: More than half 290 (58.2%) of study participants were females. The median age at ART initiation was 40 years with an interquartile range (IQR) of 15 years. The median duration of virologic failure since initiation of treatment was 96 months (IQR) of 72. The magnitude of virological treatment failure was 10.24% (95% CI: 7.57% - 12.91%). Poor ART drug adherence (AOR = 4.54; 95% CI: 2.09, 9.87), CD4 count less than 250 cell/μl (AOR = 24.88; 95% CI: 11.73, 52.81) and Poor Quality of Life (QoL) (AOR = 2.65; 95% CI: 1.12, 6.25) were independent predictors of virologic failure. Conclusion: The magnitude of Virologic ART treatment failure in this study was relatively high. Poor ART drug adherence, patients’ having lower CD4 count and poorer quality of life were predictors of treatment failure. Thus, intervention program that enrich patients’ health related quality of life should be implemented. Moreover, counselling that supplement the importance of drug adherence and reduction of risks that lowers CD4 counts should be given emphasis which in turn helps to prevent first-line ART treatment failure.


2020 ◽  
Author(s):  
Nafisa Ahmed Ibrahim ◽  
Khalid A Enan ◽  
Mahdi Mustafa Yagoup ◽  
Wafa Ibrahim Elhag

Abstract Objective: Small number of people on antiretroviral therapy and their virological status in Sudan is lacking. This study aimed to determine the viral load for adult HIV-1 patients who were on antiretroviral therapy for 12+/- 3 months attending different Voluntary Counseling Testing and treatment centers (VCT/ART) in Khartoum state, Sudan.Results: out of 112 adult HIV-1 patients included in this study, only 17.9% (20/112) showed unsuppressed viral load (treatment failure). The majority of them from Omdurman VCT/ART center 80% (16/20), followed by Khartoum VCT/ART center 15% (3/20), Bahri VCT/ART center 5% (1/20) and non from Elban Gadeid VCT/ART center. All of them were on the first line of treatment. Most of them 30% (6/20) on 39-48 years old age group, the majority of them 55%(11/20) on stage 3 WHO clinical staging.


2020 ◽  
Vol 18 (3) ◽  
pp. 210-218
Author(s):  
Guolong Yu ◽  
Yan Li ◽  
Xuhe Huang ◽  
Pingping Zhou ◽  
Jin Yan ◽  
...  

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.


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