scholarly journals Limited HIV-1 Subtype C nef 3′PPT Variation in Combination Antiretroviral Therapy Naïve and Experienced People Living with HIV in Botswana

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1027
Author(s):  
Kaelo K. Seatla ◽  
Dorcas Maruapula ◽  
Wonderful T. Choga ◽  
Olorato Morerinyane ◽  
Shahin Lockman ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Real World ◽  
People Living With Hiv ◽  
Whole Genome ◽  
Combination Antiretroviral Therapy ◽  
Subtype C ◽  
Gene Sequences ◽  
Genome Sequences ◽  
Cart Analysis ◽  
Hiv 1

Dolutegravir (DTG) is a potent anti-HIV drug that is used to treat HIV globally. There have been reports of mutations in the HIV-1 3′-polypurine tract (3′PPT) of the nef gene, contributing to DTG failure; however, there are limited ‘real-world’ data on this. In addition, there is a knowledge gap on the variability of 3′PPT residues in patients receiving combination antiretroviral therapy (cART) with and without viral load (VL) suppression. HIV-1 subtype C (HIV-1C) whole-genome sequences from cART naïve and experienced individuals were generated using next-generation sequencing. The nef gene sequences were trimmed from the generated whole-genome sequences using standard bioinformatics tools. In addition, we generated separate integrase and nef gene sequences by Sanger sequencing of plasma samples from individuals with virologic failure (VF) while on a DTG/raltegravir (RAL)-based cART. Analysis of 3′PPT residues was performed, and comparison of proportions computed using Pearson’s chi-square test with p-values < 0.05 was considered statistically significant. A total of 6009 HIV-1C full genome sequences were generated and had a median log10 HIV-1 VL (Q1, Q3) copies/mL of 1.60 (1.60, 2.60). A total of 12 matching integrase and nef gene sequences from therapy-experienced participants failing DTG/ RAL-based cART were generated. HIV-1C 3′PPT nef gene sequences from therapy-experienced patients failing DTG cART (n = 12), cART naïve individuals (n = 1263), and individuals on cART with and without virological suppression (n = 4696) all had a highly conserved 3′PPT motif with no statistically significant differences identified. Our study confirms the high conservation of the HIV-1 nef gene 3′PPT motif in ‘real-world’ patients and showed no differences in the motif according to VL suppression or INSTI-based cART failure. Future studies should explore other HIV-1 regions outside of the pol gene for associations with DTG failure.

Classes of Antiretrovirals

2017 ◽  
Author(s):  
Benjamin Young
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Suppression ◽  
Hiv Protease ◽  
People Living With Hiv ◽  
Hiv Integrase ◽  
Combination Antiretroviral Therapy ◽  
Entry Inhibitors ◽  
Asymptomatic Individuals ◽  
Living With Hiv ◽  
Hiv 1

Results of the randomized, international INSIGHT START clinical trial provide definitive proof of the benefit of antiretroviral therapy initiation in asymptomatic individuals with CD4+ counts greater than 500 cells/mm3. There are six different classes of antiretroviral agents: two types of reverse transcriptase inhibitors, two types of entry inhibitors, one class of inhibitors of HIV protease, and one class of inhibitors of HIV integrase. Combination antiretroviral therapy is recommended for all people living with HIV. The primary goal of combination antiretroviral therapy is to achieve viral suppression. Each antiretroviral class targets a unique step in the replication cycle of HIV-1.

scholarly journals Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children

2020 ◽  
Vol 101 (12) ◽  
pp. 1289-1299
Author(s):  
Sanjeev Kumar ◽  
Himanshu Batra ◽  
Swarandeep Singh ◽  
Himanshi Chawla ◽  
Ravinder Singh ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Antibody Responses ◽  
Combination Antiretroviral Therapy ◽  
Subtype C ◽  
Effector Functions ◽  
Cart Initiation ◽  
Immunodeficiency Virus ◽  
Hiv 1

Protective antibody responses to human immunodeficiency virus (HIV)-1 infection evolve only in a fraction of infected individuals by developing broadly neutralizing antibodies (bnAbs) and/or effector functions such as antibody-dependent cellular cytotoxicity (ADCC). HIV-1 chronically infected adults and children on combination antiretroviral therapy (cART) showed a reduction in ADCC activity and improvement in HIV-1 specific neutralizing antibody (nAb) responses. Early initiation of cART in infected adults is found to be beneficial in reducing the viral load and delaying disease progression. Herein, we longitudinally evaluated the effect of cART on HIV-1 specific plasma ADCC and nAb responses in a cohort of 20 perinatally HIV-1 subtype-C infected infants and children ≤2 years of age, pre-cART and up to 1 year post-cART initiation. Significant reductions in HIV-1 specific plasma ADCC responses to subtype-C and subtype-B viruses and improvement in HIV-1 neutralization were observed in HIV-1 infected children 1 year post-cART initiation. A positive correlation between reduction in viral load and the loss of ADCC response was observed. This study provides information aiding the understanding of the effects of early initiation of cART on antibody effector functions and viral neutralization in HIV-1 infected children, which needs to be further evaluated in large cohorts of HIV-1 infected children on cART to plan future intervention strategies.

scholarly journals Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil

2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  
Keyword(s):  
Drug Resistance ◽  
People Living With Hiv ◽  
Resistance Mutations ◽  
Subtype C ◽  
Viral Loads ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Low Prevalence ◽  
Living With Hiv ◽  
Hiv 1

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

scholarly journals HIV‐1 Reverse Transcriptase Connection Domain Mutations: Dynamics of Emergence and Implications for Success of Combination Antiretroviral Therapy

2010 ◽  
Vol 51 (5) ◽  
pp. 620-628 ◽  
Author(s):  
Viktor von Wyl ◽  
Maryam Ehteshami ◽  
Lisa M. Demeter ◽  
Philippe Bürgisser ◽  
Monique Nijhuis ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Reverse Transcriptase ◽  
Combination Antiretroviral Therapy ◽  
Hiv 1
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