Drug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues

TitleDrug-resistance development differs between HIV-1-infected patients failing first-line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues
Publication TypeJournal Article
Year of Publication2013
AuthorsSantoro MM, Sabin CA, Forbici F., Bansi L, Dunn DT, Fearnhill E, Boumis E, Nicastri E., Antinori AM, Palamara G, Callegaro A, Francisci D, Zoncada A, Maggiolo F, Zazzi M, Perno CF, Ceccherini-Silberstein F., Mussini C
JournalHIV Med
Volume14
Pagination571-7
Date Published2013-10
ISBN Number1464-2662
Accession Number23668660
KeywordsAdenine/analogs & derivatives/pharmacology/therapeutic use, Adult, Anti-HIV Agents/pharmacology/*therapeutic use, Antiretroviral Therapy, Highly Active/adverse effects, CD4 Lymphocyte Count, Deoxycytidine/analogs & derivatives/pharmacology/therapeutic use, Dideoxynucleosides/pharmacology/therapeutic use, Drug Combinations, Drug Resistance, Viral/*drug effects/genetics, Emtricitabine, Female, first-line regimen, genotypic resistance test, HIV Infections/*drug therapy/virology, HIV Reverse Transcriptase/*adverse effects/therapeutic use, HIV-1/*drug effects/genetics, Humans, Lamivudine/pharmacology/therapeutic use, Male, Middle Aged, Organophosphonates/pharmacology/therapeutic use, resistance to reverse transcriptase inhibitors, Tenofovir, Thymidine/analogs & derivatives/*pharmacology/therapeutic use, Treatment Failure, Viral Load, Virological failure, Zidovudine/pharmacology/therapeutic use
Abstract

OBJECTIVES: 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). METHODS: 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. RESULTS: 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) log(1)(0) 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). CONCLUSIONS: 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.

Short TitleHIV medicine
Alternate JournalHIV medicine