Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008.

Abstract

BACKGROUND:

Adverse effects of combination antiretroviral therapy (CART) commonly result in treatment modification and poor adherence.

METHODS:

We investigated predictors of toxicity-related treatment modification during the first year of CART in 1318 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from the Swiss HIV Cohort Study who began treatment between January 1, 2005, and June 30, 2008.

RESULTS:

The total rate of treatment modification was 41.5 (95% confidence interval [CI], 37.6-45.8) per 100 person-years. Of these, switches or discontinuations because of drug toxicity occurred at a rate of 22.4 (95% CI, 19.5-25.6) per 100 person-years. The most frequent toxic effects were gastrointestinal tract intolerance (28.9%), hypersensitivity (18.3%), central nervous system adverse events (17.3%), and hepatic events (11.5%). In the multivariate analysis, combined zidovudine and lamivudine (hazard ratio [HR], 2.71 [95% CI, 1.95-3.83]; P < .001), nevirapine (1.95 [1.01-3.81]; P = .050), comedication for an opportunistic infection (2.24 [1.19-4.21]; P = .01), advanced age (1.21 [1.03-1.40] per 10-year increase; P = .02), female sex (1.68 [1.14-2.48]; P = .009), nonwhite ethnicity (1.71 [1.18-2.47]; P = .005), higher baseline CD4 cell count (1.19 [1.10-1.28] per 100/microL increase; P < .001), and HIV-RNA of more than 5.0 log(10) copies/mL (1.47 [1.10-1.97]; P = .009) were associated with higher rates of treatment modification. Almost 90% of individuals with treatment-limiting toxic effects were switched to a new regimen, and 85% achieved virologic suppression to less than 50 copies/mL at 12 months compared with 87% of those continuing CART (P = .56).

CONCLUSIONS:

Drug toxicity remains a frequent reason for treatment modification; however, it does not affect treatment success. Close monitoring and management of adverse effects and drug-drug interactions are crucial for the durability of CART.

• Authors: Luigia Elzi, Catia Marzolini, Hansjakob Furrer, Bruno Ledergerber, Matthias Cavassini, Bernard Hirschel, Pietro Vernazza, Enos Bernasconi, Rainer Weber, Manuel Battegay, Swiss HIV Cohort Study
• Journal: Archives of internal medicine (Arch Intern Med) Vol. 170 Issue 1 Pg. 57-65 (Jan 11 2010) ISSN: 1538-3679 [Electronic] United States
• PMID: 20065200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Anti-HIV Agents
• Benzoxazines
• Cyclopropanes
• Dideoxynucleosides
• Oligopeptides
• Organophosphonates
• Pyridines
• Pyrimidinones
• Deoxycytidine
• Lopinavir
• Lamivudine
• Zidovudine
• Atazanavir Sulfate
• Nevirapine
• Tenofovir
• Emtricitabine
• Adenine
• efavirenz
• abacavir

Topics

• AIDS-Related Opportunistic Infections (drug therapy, epidemiology)
• Adenine (administration & dosage, adverse effects, analogs & derivatives)
• Adult
• Alkynes
• Anti-HIV Agents (administration & dosage, adverse effects)
• Atazanavir Sulfate
• Benzoxazines (administration & dosage, adverse effects)
• Cyclopropanes
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Dideoxynucleosides (administration & dosage, adverse effects)
• Drug Therapy, Combination
• Emtricitabine
• Female
• HIV Infections (drug therapy, epidemiology)
• Humans
• Lamivudine (administration & dosage, adverse effects)
• Lopinavir
• Male
• Middle Aged
• Nevirapine (administration & dosage, adverse effects)
• Oligopeptides (administration & dosage, adverse effects)
• Organophosphonates (administration & dosage, adverse effects)
• Proportional Hazards Models
• Prospective Studies
• Pyridines (administration & dosage, adverse effects)
• Pyrimidinones (administration & dosage, adverse effects)
• Risk Factors
• Switzerland (epidemiology)
• Tenofovir
• Zidovudine (administration & dosage, adverse effects)