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Positive and negative drug selection pressures on the N348I connection domain mutation: new insights from in vivo data
- Source :
- Antiviral therapy. 15(2)
- Publication Year :
- 2010
-
Abstract
- Background There is conflicting evidence on specific reverse transcriptase inhibitors to which the N348I mutation in the connection domain of HIV type-1 reverse transcriptase confers resistance. Here, we examined associations between the emergence of N348I and anti-retroviral history in a large clinical database. Methods We analysed 5,353 resistance tests (that were sequenced beyond codon 348) among 2,266 antiretroviral-experienced patients. Associations between N348I and individual antiretroviral drug exposure were estimated using a matched case-control approach. Cases were defined as the first resistance test where N348I was detected; for each case, the 10 closest (in calendar time) N348N tests were selected as controls. Odds ratios (ORs) adjusted for effects of all other drugs were estimated by conditional logistic regression. Results N348I was detected in 198 (8.7%) cases. Drugs that were statistically significantly positively associated with N348I were efavirenz (OR 1.55, 95% confidence interval [CI] 1.08–2.23; P=0.017) and nevirapine (OR 2.06, 95% CI 1.49–2.85; PConclusions This is the first clinical evidence to suggest that efavirenz might select for N348I in addition to nevirapine, that stavudine might select for N348I in addition to zidovudine and that TDF might protect against the mutation.
- Subjects :
- Drug
Cyclopropanes
Anti-HIV Agents
media_common.quotation_subject
Human immunodeficiency virus (HIV)
Organophosphonates
Biology
medicine.disease_cause
Drug Administration Schedule
Domain (software engineering)
In vivo
Databases, Genetic
Drug Resistance, Viral
medicine
Humans
Pharmacology (medical)
Nevirapine
3 azido 3 deoxythymidine
Tenofovir
Selection (genetic algorithm)
media_common
Pharmacology
Genetics
Adenine
Reverse transcriptase
HIV Reverse Transcriptase
Benzoxazines
Stavudine
Infectious Diseases
Logistic Models
Alkynes
Case-Control Studies
Mutation (genetic algorithm)
Mutation
HIV-1
Reverse Transcriptase Inhibitors
Drug Therapy, Combination
Zidovudine
Subjects
Details
- ISSN :
- 20402058
- Volume :
- 15
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Antiviral therapy
- Accession number :
- edsair.doi.dedup.....c98136d416a288847331380b488b2e9a