The relationship between resistance and adherence in drug-naive individuals initiating HAART is specific to individual drug classes

Lily W Y Tam, Celia K S Chui, Chanson J. Brumme, David Bangsberg, Julio S G Montaner, Robert S. Hogg, P. Richard Harrigan

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada. Plasma samples with plasma viral load > 1000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables. The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50% per additional mutation. At 80%-90% adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95% confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0,95% CI: 3.3 to 10.9; P < 0.0001) compared with the ≥95% refill reference group. In a multivariate model, individuals with <95% refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95% CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95% CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of ≥95% refills with consistently detectable drug levels. Adherence-resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs. The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.

Original languageEnglish (US)
Pages (from-to)266-271
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume49
Issue number3
DOIs
StatePublished - Nov 2008
Externally publishedYes

Fingerprint

Reverse Transcriptase Inhibitors
Lamivudine
Highly Active Antiretroviral Therapy
Drug Resistance
Confidence Intervals
Protease Inhibitors
Pharmaceutical Preparations
Mutation
HIV
British Columbia
Mutation Rate
Viral Load
Nucleosides
Canada
Prescriptions
HIV-1
Outcome Assessment (Health Care)

Keywords

  • Adherence
  • HAART
  • HIV-1 drug resistance
  • Mutations

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

The relationship between resistance and adherence in drug-naive individuals initiating HAART is specific to individual drug classes. / Tam, Lily W Y; Chui, Celia K S; Brumme, Chanson J.; Bangsberg, David; Montaner, Julio S G; Hogg, Robert S.; Harrigan, P. Richard.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 49, No. 3, 11.2008, p. 266-271.

Research output: Contribution to journalArticle

Tam, Lily W Y ; Chui, Celia K S ; Brumme, Chanson J. ; Bangsberg, David ; Montaner, Julio S G ; Hogg, Robert S. ; Harrigan, P. Richard. / The relationship between resistance and adherence in drug-naive individuals initiating HAART is specific to individual drug classes. In: Journal of Acquired Immune Deficiency Syndromes. 2008 ; Vol. 49, No. 3. pp. 266-271.
@article{ecc11fe0f86148039a5b2337a5904921,
title = "The relationship between resistance and adherence in drug-naive individuals initiating HAART is specific to individual drug classes",
abstract = "To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada. Plasma samples with plasma viral load > 1000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables. The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50{\%} per additional mutation. At 80{\%}-90{\%} adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95{\%} confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0,95{\%} CI: 3.3 to 10.9; P < 0.0001) compared with the ≥95{\%} refill reference group. In a multivariate model, individuals with <95{\%} refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95{\%} CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95{\%} CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of ≥95{\%} refills with consistently detectable drug levels. Adherence-resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs. The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.",
keywords = "Adherence, HAART, HIV-1 drug resistance, Mutations",
author = "Tam, {Lily W Y} and Chui, {Celia K S} and Brumme, {Chanson J.} and David Bangsberg and Montaner, {Julio S G} and Hogg, {Robert S.} and Harrigan, {P. Richard}",
year = "2008",
month = "11",
doi = "10.1097/QAI.0b013e318189a753",
language = "English (US)",
volume = "49",
pages = "266--271",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - The relationship between resistance and adherence in drug-naive individuals initiating HAART is specific to individual drug classes

AU - Tam, Lily W Y

AU - Chui, Celia K S

AU - Brumme, Chanson J.

AU - Bangsberg, David

AU - Montaner, Julio S G

AU - Hogg, Robert S.

AU - Harrigan, P. Richard

PY - 2008/11

Y1 - 2008/11

N2 - To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada. Plasma samples with plasma viral load > 1000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables. The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50% per additional mutation. At 80%-90% adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95% confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0,95% CI: 3.3 to 10.9; P < 0.0001) compared with the ≥95% refill reference group. In a multivariate model, individuals with <95% refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95% CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95% CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of ≥95% refills with consistently detectable drug levels. Adherence-resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs. The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.

AB - To investigate the relationship between HIV-1 drug resistance and adherence and the accumulation rate of resistance mutations in 1191 HIV-infected, antiretroviral-naive adults initiating highly active antiretroviral therapy in British Columbia, Canada. Plasma samples with plasma viral load > 1000 copies per milliliter collected within 30 months of follow-up were genotyped for drug resistance. Adherence was estimated using prescription refills and plasma drug levels. The primary outcome measure was time to detection of drug resistance. Cox proportional hazard regression was used to calculate hazard ratios (HRs) associated with baseline variables. The accumulation rates of multiple primary and secondary mutations were similar in patients initiating highly active antiretroviral therapy with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor (NNRTI). Rates decreased approximately 50% per additional mutation. At 80%-90% adherence based on refills, there was greater risk of detecting lamivudine (3TC) [HR 3.0, 95% confidence interval (CI): 1.9 to 4.7; P < 0.0001] and NNRTI mutations (HR 6.0,95% CI: 3.3 to 10.9; P < 0.0001) compared with the ≥95% refill reference group. In a multivariate model, individuals with <95% refills and consistently detectable plasma drug levels were at increased risk for 3TC (HR 4.5, 95% CI: 2.6 to 7.9; P = 0.0001) and NNRTI resistance (HR 7.0, 95% CI: 3.4 to 14.5; P = 0.0001) compared with the reference group of ≥95% refills with consistently detectable drug levels. Adherence-resistance relationships were much weaker for protease inhibitors and nucleoside reverse transcriptase inhibitors as there was little variance in HRs among the different adherence strata compared with 3TC and NNRTIs. The relationships between resistance, adherence, and mutation accumulation differ between HIV drug classes.

KW - Adherence

KW - HAART

KW - HIV-1 drug resistance

KW - Mutations

UR - http://www.scopus.com/inward/record.url?scp=58149146880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149146880&partnerID=8YFLogxK

U2 - 10.1097/QAI.0b013e318189a753

DO - 10.1097/QAI.0b013e318189a753

M3 - Article

C2 - 18845950

AN - SCOPUS:58149146880

VL - 49

SP - 266

EP - 271

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 3

ER -