Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008.
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.
Elzi
Luigia
L
University Hospital Basel, Switzerland.
Marzolini
Catia
C
Furrer
Hansjakob
H
Ledergerber
Bruno
B
Cavassini
Matthias
M
Hirschel
Bernard
B
Vernazza
Pietro
P
Bernasconi
Enos
E
Weber
Rainer
R
Battegay
Manuel
M
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000453:epidemiology; D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology; D000068698:Tenofovir; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects; D000099227:Abacavir
D000225:Adenine; D000480:Alkynes; D019380:Anti-HIV Agents; D000069446:Atazanavir Sulfate; D048588:Benzoxazines; D003521:Cyclopropanes; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D000068679:Emtricitabine; D019259:Lamivudine; D061466:Lopinavir; D019829:Nevirapine; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D011744:Pyrimidinones; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir; C098320:efavirenz