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

BMC Infectious Diseases ◽

10.1186/s12879-020-05610-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Sushanta Kumar Barik ◽

Keshar Kunja Mohanty ◽

Ashok Kumar Mohanty ◽

Preeti Rawat ◽

G. Gopal ◽

...

Keyword(s):

Drug Resistance ◽

Gene Ontology ◽

Plasma Proteins ◽

Apolipoprotein A1 ◽

Drug Resistant ◽

First Line ◽

Apolipoprotein A ◽

Respondent Group ◽

Resistant Group ◽

Hiv 1

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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Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals: A Systematic Review of Detection Methods, Prevalence, and Clinical Impact

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz650 ◽

2019 ◽

Vol 221 (10) ◽

pp. 1584-1597 ◽

Cited By ~ 11

Author(s):

Herbert A Mbunkah ◽

Silvia Bertagnolio ◽

Raph L Hamers ◽

Gillian Hunt ◽

Seth Inzaule ◽

...

Keyword(s):

Transcriptase Inhibitor ◽

Clinical Impact ◽

Detection Methods ◽

Resistance Testing ◽

Drug Resistant ◽

First Line ◽

Antiretroviral Drug ◽

Drug Naïve ◽

The Impact ◽

Hiv 1

Abstract Background The presence of high-abundance drug-resistant HIV-1 jeopardizes success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) at levels <15%–25% of the virus population in antiretroviral (ARV) drug-naive individuals remains controversial. Methods We systematically reviewed 103 studies assessing prevalence, detection methods, technical and clinical detection cutoffs, and clinical significance of LA-DRVs in antiretroviral drug-naive adults. Results In total, 14 919 ARV drug-naive individuals were included. Prevalence of LA-DRVs (ie, proportion of individuals harboring LA-DRVs) was 0%–100%. Technical detection cutoffs showed a 4 log range (0.001%–10%); 42/103 (40.8%) studies investigating the impact of LA-DRVs on ART; 25 studies included only individuals on first-line nonnucleoside reverse transcriptase inhibitor-based ART regimens. Eleven of those 25 studies (44.0%) reported a significantly association between preexisting LA-DRVs and risk of virological failure whereas 14/25 (56.0%) did not. Conclusions Comparability of the 103 studies is hampered by high heterogeneity of the studies’ designs and use of different methods to detect LA-DRVs. Thus, evaluating clinical impact of LA-DRVs on first-line ART remains challenging. We, the WHO HIVResNet working group, defined central areas of future investigations to guide further efforts to implement ultrasensitive resistance testing in routine settings.

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Faculty Opinions recommendation of Second-line antiretroviral treatment successfully resuppresses drug-resistant HIV-1 after first-line failure: prospective cohort in Sub-Saharan Africa.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717097881.792402848 ◽

2012 ◽

Author(s):

Simon Portsmouth

Keyword(s):

Prospective Cohort ◽

Antiretroviral Treatment ◽

Sub Saharan Africa ◽

Drug Resistant ◽

Second Line ◽

First Line ◽

Sub Saharan ◽

Hiv 1

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Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy

African Journal of Laboratory Medicine ◽

10.4102/ajlm.v7i1.708 ◽

2018 ◽

Vol 7 (1) ◽

Cited By ~ 2

Author(s):

Zhiyong Zhou ◽

Kevin Tang ◽

Guoqing Zhang ◽

Nellie Wadonda-Kabondo ◽

Kundai Moyo ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Drug Resistant ◽

Subtype C ◽

First Line ◽

Hiv 1

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Second-Line Antiretroviral Treatment Successfully Resuppresses Drug-Resistant HIV-1 After First-Line Failure: Prospective Cohort in Sub-Saharan Africa

The Journal of Infectious Diseases ◽

10.1093/infdis/jis261 ◽

2012 ◽

Vol 205 (11) ◽

pp. 1739-1744 ◽

Cited By ~ 46

Author(s):

K. C. E. Sigaloff ◽

R. L. Hamers ◽

C. L. Wallis ◽

C. Kityo ◽

M. Siwale ◽

...

Keyword(s):

Prospective Cohort ◽

Antiretroviral Treatment ◽

Sub Saharan Africa ◽

Drug Resistant ◽

Second Line ◽

First Line ◽

Sub Saharan ◽

Hiv 1

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Drug Resistant Tuberculosis in Diabetes Mellitus: A Retrospective Study from South India

Tropical Doctor ◽

10.1177/004947550303300311 ◽

2003 ◽

Vol 33 (3) ◽

pp. 154-156 ◽

Cited By ~ 18

Author(s):

H S Subhash ◽

I Ashwin ◽

U Mukundan ◽

D Danda ◽

G John ◽

...

Keyword(s):

Diabetes Mellitus ◽

Drug Therapy ◽

South India ◽

Tertiary Care ◽

Drug Resistant ◽

First Line ◽

Drug Resistant Tuberculosis ◽

Duration Of Diabetes ◽

Resistant Tuberculosis ◽

Resistant Group

This study was conducted in a tertiary care teaching hospital in south India to evaluate the association of drug resistant tuberculosis (TB) in diabetic subjects. There were: 361 subjects with positive mycobacterial culture and susceptibility tests results over a 3-year period; 267 (74%) acid-fast bacillus smear positive; and 94 (26%) smear negative cases. One hundred and seventy-seven (49%) had resistant isolates to any one first line anti TB drugs (resistant group) and 184 (51%) had isolates sensitive to all drugs (non-resistant group). In the resistant and non-resistant subjects the mean duration of TB symptoms was, respectively, 22 months and 4.5 months, past history of TB 126 (71%) and 48 (26%), past anti TB drug therapy 126 (71%) and 47 (25%), inadequate anti TB drug therapy 42 (24%) and 23 (13%), HIV positive six and 13 subjects. There were 72 diabetic subjects [35 and 37, respectively] with a duration of diabetes 5.8 ± 7.5 years and 3.7 ± 5.0 years in the resistant and non-resistant groups. Twenty-six per cent of the diabetic subjects (19/72) had multi-drug resistant TB. Drug resistance to first line anti-TB drugs was not found to be associated with diagnosis or duration of diabetes mellitus.

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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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