Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study

Publication

Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study

Journal Paper/Review - Sep 11, 2015

Yang Wan-Lin, Swiss HIV Cohort Study (SHCS), Günthard Huldrych F, Ledergerber Bruno, Held Leonhard, Vernazza Pietro, Bernasconi Enos, Cavassini Matthias, Battegay Manuel, Hirzel Cédric, Aubert Vincent, Klimkait Thomas, Yerly Sabine, Shah Cyril, Böni Jürg, Scherrer Alexandra U, Kouyos Roger D, Swiss HIV Cohort Study SHCS

Citation

Yang W, Swiss HIV Cohort Study (SHCS), Günthard H, Ledergerber B, Held L, Vernazza P, Bernasconi E, Cavassini M, Battegay M, Hirzel C, Aubert V, Klimkait T, Yerly S, Shah C, Böni J, Scherrer A, Kouyos R, Swiss HIV Cohort Study SHCS. Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study. J Antimicrob Chemother 2015

Type

Journal Paper/Review (English)

Journal

J Antimicrob Chemother 2015

Publication Date

Sep 11, 2015

Issn Electronic

1460-2091

Brief description/objective

BACKGROUND
The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare.

METHODS
We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency.

RESULTS
Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02).

CONCLUSIONS
Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.