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Research article
HariOm Singh
National AIDS Research Institute
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The multidrug resistance protein, MDR1 is involved in the transport of numerous drugs. Polymorphism of MDR1 is linked with the treatment outcome. Antiretroviral (ARV) regimen is being used to manage the progression of HIV infection. Ethnic disparities have been observed in the distribution of MDR1 genotypes.
Methods: MDR1 polymorphisms (1236 C/T, 3435 C/T) was genotyped in 34 HIV-infected individuals with ARV-associated hepatotoxicity, 131 HIV-infected individuals without ARV-associated hepatotoxicity, and one-fifty-five healthy individuals by utilization of PCR-RFLP.
Results: The incidence of haplotype TC of MDR1 was found to be more in HIV infected individuals with hepatotoxicity than the non-hepatotoxic ones, thus indicating a greater risk for hepatotoxicity severity (OR=1.96, P=0.06). Whereas the haplotypes TT and CC were found to be linked with a reduced risk for hepatotoxicity severity (OR= 0.16, P=0.006; OR= 0.46, P=0.06). A higher occurrence of MDR1 1236TT genotype was seen among patients with hepatotoxicity who consumed alcohol (28.6% versus 14.8%, OR=1.50). In patients with hepatotoxicity on nevirapine, there was an increased incidence of MDR1 1236TT genotype in contrast with efavirenz (21.7% versus 9.1%, OR=2.11). In HIV-infected people on nevirapine, the incidence of MDR1 1236CT, 1236TT genotypes was found to be more as compared to the ones on efavirenz (43.7% versus 33.3%, OR=1.66; 12.6% versus 8.3%, OR=1.96). Also a higher occurrence of MDR1 1236TT genotype was found in the hepatotoxicity cases on nevirapine, who consume alcohol as compared to the alcohol nonusers on nevirapine (40.0% versus 16.67%, OR=2.21).
Conclusion: Haplotype TC was associated with the increased severity of hepatotoxicity because of synergistic effect. In the HIV infected individuals on nevirapine who consume alcohol, the presence of MDR1 1236TT and 3435CT genotypes may have a combined effect on vulnerability to hepatotoxicity severity and progression of HIV infection.
Keywords
ARV-associated hepatotoxicity, Genetic predisposition, NNRTI regimen, Multidrug-resistant-1, HIV Infected Individuals
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CURRENT STATUS: Under Review
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Posted 06 Nov, 2020
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Reviewer #1 agreed
On 22 Nov, 2020
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On 29 Sep, 2020
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A new preprint design is coming!
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This preprint is under consideration at BMC Infectious Diseases. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
HariOm Singh
National AIDS Research Institute
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 06 Nov, 2020
No community comments so far
Reviewer #1 agreed
On 22 Nov, 2020
Reviewers invited
Invitations sent on 18 Nov, 2020
Editor assigned
On 30 Sep, 2020
Submission checks complete
On 29 Sep, 2020
Editor invited
On 29 Sep, 2020
First submitted
On 25 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The multidrug resistance protein, MDR1 is involved in the transport of numerous drugs. Polymorphism of MDR1 is linked with the treatment outcome. Antiretroviral (ARV) regimen is being used to manage the progression of HIV infection. Ethnic disparities have been observed in the distribution of MDR1 genotypes.
Methods: MDR1 polymorphisms (1236 C/T, 3435 C/T) was genotyped in 34 HIV-infected individuals with ARV-associated hepatotoxicity, 131 HIV-infected individuals without ARV-associated hepatotoxicity, and one-fifty-five healthy individuals by utilization of PCR-RFLP.
Results: The incidence of haplotype TC of MDR1 was found to be more in HIV infected individuals with hepatotoxicity than the non-hepatotoxic ones, thus indicating a greater risk for hepatotoxicity severity (OR=1.96, P=0.06). Whereas the haplotypes TT and CC were found to be linked with a reduced risk for hepatotoxicity severity (OR= 0.16, P=0.006; OR= 0.46, P=0.06). A higher occurrence of MDR1 1236TT genotype was seen among patients with hepatotoxicity who consumed alcohol (28.6% versus 14.8%, OR=1.50). In patients with hepatotoxicity on nevirapine, there was an increased incidence of MDR1 1236TT genotype in contrast with efavirenz (21.7% versus 9.1%, OR=2.11). In HIV-infected people on nevirapine, the incidence of MDR1 1236CT, 1236TT genotypes was found to be more as compared to the ones on efavirenz (43.7% versus 33.3%, OR=1.66; 12.6% versus 8.3%, OR=1.96). Also a higher occurrence of MDR1 1236TT genotype was found in the hepatotoxicity cases on nevirapine, who consume alcohol as compared to the alcohol nonusers on nevirapine (40.0% versus 16.67%, OR=2.21).
Conclusion: Haplotype TC was associated with the increased severity of hepatotoxicity because of synergistic effect. In the HIV infected individuals on nevirapine who consume alcohol, the presence of MDR1 1236TT and 3435CT genotypes may have a combined effect on vulnerability to hepatotoxicity severity and progression of HIV infection.
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