Identification and differential expression of serotransferrin and apolipoprotein A-I in the plasma of HIV-1 patients treated with first-line antiretroviral therapy

Abstract Background Plasma proteins are known to interfere the drug metabolism during therapy. As limited information is available regarding the role of plasma proteins in HIV drug resistance during ART in HIV/AIDS patients, the present study aimed to identify and characterize the differentially expressed plasma proteins in the drug resistant and drug respondent groups of HIV-1 infected patients with > 6 years of first line ART. Methods Four-drug resistant (treatment failure) and four-drug respondent (treatment responder) patients were selected for plasma proteomic analysis based on viral load and drug resistance associated mutations from a cohort study designed on the first line ART patients who were enrolled in the antiretroviral therapy center, Sarojini Naidu Medical College, Agra, India from December 2009 to November 2016. After depleting high abundant proteins, plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3–10. Spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein data base using the internal Mascot. Gene ontology study was completed through STRING v.11 and Panther15.0. Results Out of eight spots from 2D gel samples analyzed by MALDITOF/TOF, two proteins were found to have significant score (> 56) after Flex analysis. These two proteins were identified to be apolipoprotein A1 and serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. Apolipoprotein-A1 and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes. Conclusion Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.

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Identification and differential expression of serotransferrin and apolipoprotein A-I in the plasma of HIV-1 patients treated with first-line antiretroviral therapy

10.21203/rs.3.rs-33825/v1 ◽

2020 ◽

Author(s):

Sushanta Kumar Barik ◽

Keshar Kunja Mohanty ◽

Ashok Kumar Mohanty ◽

Preeti Rawat ◽

G Gopal ◽

...

Keyword(s):

Gene Ontology ◽

Plasma Proteins ◽

Time Of Flight ◽

Drug Resistant ◽

First Line ◽

Maldi Tof ◽

Apolipoprotein A ◽

Respondent Group ◽

Resistant Group ◽

Hiv 1

Abstract Background As plasma proteins were involved in drug metabolism, the aim of the study was to identify and characterize the plasma proteins of the drug resistant and drug respondent groups of HIV-1 infected first line ART patients with > 6 years in therapy. Methods Plasma proteomics analysis of the four drug-resistant (treatment failure) and four drug respondent (treatment responder) groups were conducted. High abundant plasma proteins like albumin and globulin were depleted from plasma through Aurum serum mini kit (Bio-Rad, USA). Plasma proteins were resolved using two-dimensional gel electrophoresis on IPG strips, pH range of 3–10. Eight protein spots were selected in the gel based on the density of staining which was common in the drug resistant and drug respondent groups separately. The fold change of each spot was calculated using image-J. Each protein spot was identified using the matrix assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) after tryptic digestion. Peptide peaks were identified through flex analysis version 3.3, and a search against a protein database using the internal mascot search engine. Gene ontology study was completed through STRING v.11 and Panther 15.0. Results Out of eight spots from 2D gel of drug respondent and drug resistant samples analyzed by MALDI TOF/TOF, two proteins were found to have significant score (i;e > 56) after Flex analysis. These two proteins were identified to be apolipoproteinA1 and Serotransferrin. The fold change expression of these two proteins were analyzed in drug resistant and drug respondent group. ApolipoproteinA1and serotransferrin were observed to be expressed 1.76 and 1.13-fold more respectively in drug respondent group compared to drug resistant group. The gene ontology analysis revealed the involvement of these two proteins in various important physiological processes. Conclusion Apolipoprotein A-I and serotransferrin were found to be expressed more in drug respondent group compared to drug resistant group.

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OC 8450 ABSENCE OF MINORITY HIV-1 DRUG-RESISTANT VARIANTS FOLLOWING MOTHER-TO-CHILD TRANSMISSION DOES NOT PREDICT VIROLOGIC SUCCESS OF FIRST-LINE ANTIRETROVIRAL THERAPY

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.15 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A6.3-A7

Author(s):

Cissy Kityo ◽

Tobias Rinke De Wit ◽

Immaculate Nankya ◽

Sheilla Balinda ◽

Kim Sigaloff ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Mutation Frequency ◽

Drug Resistant ◽

Mother To Child Transmission ◽

Child Transmission ◽

First Line ◽

Group I ◽

Mother To Child ◽

Hiv 1

BackgroundAlthough minority HIV-1 drug-resistant HIV-1 variants may be selected under antiretroviral pressure, leading to therapy failure, their clinical significance remains controversial. This is particularly relevant in the case of prevention of mother-to-child transmission (MTCT), where transmitted drug resistance can affect treatment outcomes.MethodsAn ultrasensitive HIV-1 genotyping assay based on deep sequencing (DEEPGENHIV) with a 1% mutation frequency sensitivity, was used to quantify MTCT drug-resistant variants in 38 prenatally HIV-infected children experiencing (Group I, n=27) or not (Group II, n=11) virologic failure 12 months after initiating first-line antiretroviral therapy (ART) as part of a paediatric cohort in Uganda.ResultsInfants were infected with subtype A(n=20), D(n=16) or C(n=2) HIV-1 strains, distributed equally between both patients’ groups. Similarly, no significant difference was observed in intra-patient HIV-1 diversity among viruses obtained from Group I or II individuals at baseline. DEEPGENHIV was able to detect all the mutations originally detected in samples obtained from four control patients in Group II, where drug resistance was identified at baseline using Sanger sequencing, e.g. K65R (78% mutation frequency), K103N (47%), or M184V (85%). More importantly, a series of low abundance (<20% detection limit of Sanger) primary and compensatory mutations associated with resistance to PIs (D30N, Q48V), NRTIs (D67N, K219Q), or NNRTIs (L100I, K103N) were identified in both groups of patients, although just a few seem to have been selected and became majority variants after 12 or 24 months of ART.ConclusionDEEPGENHIV improves the detection of minority viral variants in infants following MTCT; however, most of the emergent HIV-1 drug resistance mutations were not present at low frequency at baseline in subjects failing ART, most likely being generated and selected following exposure to treatment. Further studies, using this or other ultrasensitive assays, are needed to better understand the transmission, dynamics and overall evolution of minority drug-resistant viruses in MTCT.

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Factors Influencing HIV Drug Resistance among Pregnant Women in Luanda, Angola: Findings from a Cross-Sectional Study

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010029 ◽

2021 ◽

Vol 6 (1) ◽

pp. 29

Author(s):

Cruz S. Sebastião ◽

Joana Morais ◽

Miguel Brito

Keyword(s):

Drug Resistance ◽

Pregnant Women ◽

Rural Areas ◽

Cross Sectional Study ◽

Drug Resistant ◽

Sectional Study ◽

Cross Sectional ◽

Hiv Drug Resistance ◽

Hiv 1 ◽

High Educational

The increase in HIV infection and drug-resistant strains is an important public health concern, especially in resource-limited settings. However, the identification of factors related to the propagation of infectious diseases represents a crucial target offering an opportunity to reduce health care costs as well as deepening the focus on preventing infection in high-risk groups. In this study, we investigate the factors related to drug resistance among HIV-infected pregnant women in Luanda, the capital city of Angola. This was a part of a cross-sectional study conducted with 42 HIV-positive pregnant women. A blood sample was collected, and HIV-1 genotyping was carried out using an in-house method. Multivariate analyses were performed to determine the interaction between sociodemographic characteristics and drug resistance. HIV drug resistance was detected in 44.1% of the studied population. High probabilities of drug resistance were observed for HIV-infected pregnant women living in rural areas (AOR: 2.73; 95% CI: 0.50–14.9) with high educational level (AOR: 6.27; 95% CI: 0.77–51.2) and comorbidities (AOR: 5.47; 95% CI: 0.28–106) and infected with a HIV-1 non-B subtype other than subtype C (AOR: 1.60; 95% CI: 0.25–10.3). The present study reports high HIV drug resistance. Furthermore, older-age, rural areas, high educational levels, unemployed status, having comorbidities, and HIV-1 subtypes were factors related to drug resistance. These factors impact on drug susceptibility and need to be urgently addressed in order to promote health education campaigns able to prevent the spread of drug-resistant HIV strains in Angola.

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Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy

AIDS ◽

10.1097/qad.0b013e32835b0f59 ◽

2013 ◽

Vol 27 (4) ◽

pp. 553-561 ◽

Cited By ~ 17

Author(s):

Mary-Ann A. Etiebet ◽

James Shepherd ◽

Rebecca G. Nowak ◽

Man Charurat ◽

Harry Chang ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

First Line ◽

Hiv 1

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Primary HIV drug resistance among newly HIV type-1 diagnosed patients in St. Petersburg

HIV Infection and Immunosuppressive Disorders ◽

10.22328/2077-9828-2021-13-1-70-79 ◽

2021 ◽

Vol 13 (1) ◽

pp. 70-79

Author(s):

Thierry Ingabire ◽

A. V. Semenov ◽

E. V. Esaulenko ◽

E. B. Zueva ◽

A. N. Schemelev ◽

...

Keyword(s):

Drug Resistance ◽

Reverse Transcriptase ◽

Direct Sequencing ◽

Population Level ◽

Multidrug Resistant ◽

Antiretroviral Drugs ◽

Drug Resistant ◽

Resistant Virus ◽

Primary Drug Resistance ◽

Hiv 1

There is concern that the widespread use of antiretroviral drugs (ARV) to treat human immunodeficiency virus 1 (HIV-1) infection may result in the emergence of transmission of drug-resistant virus among persons newly infected with HIV-1. Russia is one of a growing number of countries in the world where drug-resistant HIV is becoming a serious health problem because it has the potential to compromise the efficacy of antiretroviral therapy (ART) at the population level.Materials and methods. We performed a genetic analysis of the HIV-1 plasma derived pol gene among the newly diagnosed ART-naïve HIV-1 infected patients during the period from November 2018 to October 2019 in the St. Petersburg Clinical Infectious Diseases Hospital named after S.P. Botkin. We used reverse transcriptase polymerase chain reaction (RT-PCR) followed by direct sequencing of PCR products to determine the prevalence of primary drug resistance (PDR) conferring mutations. HIV-1 genotypes were determined by phylogenetic analysis.Results. The predominant HIV-1 subtype was A1 (87.2%), followed by B (11.8%) and CRF06_cpx (1%). The overall prevalence of PDR was 11%. Virus with known resistance-conferring mutations to any nucleoside reverse transcriptase inhibitors (NRTIs) was found in 8 individuals, to any non NRTIs in 5 subjects, and to any protease inhibitors in 1 case. Multidrug-resistant virus was identified in 2 individuals (2%).Conclusion. The distribution of HIV-1 genotypes in St. Petersburg, Russia is diverse. The emerging prevalence of PDR in ART-naïve patients demonstrates the significance of constant monitoring due to the challenges it presents towards treatment.

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