The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time

Viviane D. Lima, Richard Harrigan, David Bangsberg, Robert S. Hogg, Robert Gross, Benita Yip, Julio S G Montaner

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

OBJECTIVE:: To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens. METHODS:: Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N ≤ 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective. RESULTS:: The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value <0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and boosted protease inhibitor-based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality. CONCLUSIONS:: Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.

Original languageEnglish (US)
Pages (from-to)529-536
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume50
Issue number5
DOIs
StatePublished - Apr 2009
Externally publishedYes

Fingerprint

efavirenz
Highly Active Antiretroviral Therapy
Reverse Transcriptase Inhibitors
Mortality
Confidence Intervals
Lopinavir
Nevirapine
Ritonavir
Protease Inhibitors
Survival
Pharmaceutical Preparations

Keywords

  • Adherence
  • Boosted PI
  • HAART
  • Marginal structural models
  • Mortality
  • NNRTI

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time. / Lima, Viviane D.; Harrigan, Richard; Bangsberg, David; Hogg, Robert S.; Gross, Robert; Yip, Benita; Montaner, Julio S G.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 50, No. 5, 04.2009, p. 529-536.

Research output: Contribution to journalArticle

Lima, Viviane D. ; Harrigan, Richard ; Bangsberg, David ; Hogg, Robert S. ; Gross, Robert ; Yip, Benita ; Montaner, Julio S G. / The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time. In: Journal of Acquired Immune Deficiency Syndromes. 2009 ; Vol. 50, No. 5. pp. 529-536.
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T1 - The combined effect of modern highly active antiretroviral therapy regimens and adherence on mortality over time

AU - Lima, Viviane D.

AU - Harrigan, Richard

AU - Bangsberg, David

AU - Hogg, Robert S.

AU - Gross, Robert

AU - Yip, Benita

AU - Montaner, Julio S G

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N2 - OBJECTIVE:: To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens. METHODS:: Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N ≤ 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective. RESULTS:: The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value <0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and boosted protease inhibitor-based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality. CONCLUSIONS:: Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.

AB - OBJECTIVE:: To characterize the impact of longitudinal adherence on survival in drug-naive individuals starting currently recommended highly active antiretroviral therapy (HAART) regimens. METHODS:: Eligible study participants initiated HAART between January 2000 and November 2004 and were followed until November 2005 (N ≤ 903). HAART regimens contained efavirenz, nevirapine, or ritonavir-boosted atazanavir or lopinavir. Marginal structural modeling was used to address our objective. RESULTS:: The all-cause mortality was 11%. Individual adherence decreased significantly over time, with the mean adherence shifting from 79% within the first 6 months of starting HAART to 72% within the 24- to 30-month period (P value <0.01). Nonadherence over time (<95%) was strongly associated with higher risk of mortality (hazard ratio: 3.13; 95% confidence interval (CI): 1.95 to 5.05). Nonadherent (<95%) patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and boosted protease inhibitor-based regimens were, respectively, 3.61 times (95% CI: 2.15 to 6.06) and 3.25 times (95% CI: 1.63 to 6.49) more likely to die than adherent patients. Within the NNRTI-based regimens, nonadherent individuals on efavirenz were at a higher risk of mortality. CONCLUSIONS:: Incomplete adherence to modern HAART over time was strongly associated with increased mortality, and patients on efavirenz-based NNRTI therapies were particularly at a higher risk if nonadherent. These results highlight the need to develop further strategies to help sustain high levels of adherence on a long-term basis.

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KW - Boosted PI

KW - HAART

KW - Marginal structural models

KW - Mortality

KW - NNRTI

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