This work was presented in part at (1) the first Italian Conference on AIDS and Retroviruses, Milan, Italy, 24–26 May 2009 [Infection 2009; 37 (SII): 22]; (2) the 12th European AIDS Conference, Cologne, Germany, 11–14 November 2009 [HIV Medicine 2009; 10 (Suppl. 2): PE3.4/10]; (3) the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy, 17–20 July 2011 (Abstract CDB343).
Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues†
Article first published online: 13 MAY 2013
© 2013 British HIV Association
Volume 14, Issue 9, pages 571–577, October 2013
How to Cite
Santoro, M., Sabin, C., Forbici, F., Bansi, L., Dunn, D., Fearnhill, E., Boumis, E., Nicastri, E., Antinori, A., Palamara, G., Callegaro, A., Francisci, D., Zoncada, A., Maggiolo, F., Zazzi, M., Perno, C., Ceccherini-Silberstein, F. and Mussini, C. (2013), Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues. HIV Medicine, 14: 571–577. doi: 10.1111/hiv.12044
- Issue published online: 4 SEP 2013
- Article first published online: 13 MAY 2013
- Manuscript Accepted: 19 MAR 2013
- European Commission Framework 7 Programme
- European AIDS Treatment Network
- Italian Ministry of Health. Grant Number: 40H78
- AVIRALIA foundation
- VI AIDS Research Program of the Ministry of Health. Grant Number: 30G.58
- first-line regimen;
- genotypic resistance test;
- resistance to reverse transcriptase inhibitors;
- virological failure
We evaluated the emergence of drug resistance in patients failing first-line regimens containing one nonnucleoside reverse transcriptase inhibitor (NNRTI) administered with zidovudine (ZDV) + lamivudine (the ZDV group) or non-thymidine analogues (non-TAs) (tenofovir or abacavir, + lamivudine or emtricitabine; the non-TA group).
Three hundred HIV-1-infected patients failing a first-line NNRTI-containing regimen (nevirapine, n = 148; efavirenz, n = 152) were included in the analysis. Virological failure was defined as viraemia ≥ 400 HIV-1 RNA copies/mL for the first time at least 6 months after starting the NNRTI-based regimen. For each patient, a genotypic resistance test at failure was available. The presence of drug-resistance mutations in HIV-1 reverse transcriptase was evaluated by comparing patients treated with NNRTI + zidovudine + lamivudine vs. those treated with NNRTI + non-TA.
A total of 208 patients were failing with NNRTI + zidovudine + lamivudine and 92 with NNRTI + non-TA. No significant differences were observed between the non-TA group and the ZDV group regarding the time of virological failure [median (interquartile range): 12 (8–25) vs. 13 (9–32) months, respectively; P = 0.119] and viraemia [median (interquartile range): 4.0 (3.2–4.9) vs. 4.0 (3.3–4.7) log10 copies/mL, respectively; P = 0.894]. Resistance to reverse transcriptase inhibitors (RTIs) occurred at a significant lower frequency in the non-TA group than in the ZDV group (54.3 vs. 75.5%, respectively; P = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non-TA group compared with the ZDV group. As expected, the mutation K65R was found only in the non-TA group (18.5%; P < 0.001).
At first-line regimen failure, a lower prevalence of RTI resistance was found in patients treated with NNRTI + non-TA compared with those treated with NNRTI + zidovudine + lamivudine. These results confirm that the choice of backbone may influence the prevalence of drug resistance at virological failure.