Drug‐resistance development differs between HIV‐1‐infected patients failing first‐line antiretroviral therapy containing nonnucleoside reverse transcriptase inhibitors with and without thymidine analogues1. Issue 9 (13th May 2013)

• Record Type: Journal Article
• Authors: Santoro, MM; 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, CF; Ceccherini‐Silberstein, F; Mussini, C
• Is Part Of: HIV medicine. Volume 14:Issue 9(2013:Oct.)
• Page Start: 571
• Page End: 577
• Publication Date: 2013-05-13
• Subjects: HIV infections -- Treatment -- Periodicals; HIV-positive persons -- Periodicals; HIV infections -- Treatment -- Decision making -- Periodicals; 616.9792
• DOI: 10.1111/hiv.12044
• Languages: English
• ISSNs: 1464-2662

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hiv12044-sec-0001" sec-type="section"> <title>Objectives</title> <p>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).</p> </sec> <sec id="hiv12044-sec-0002" sec-type="section"> <title>Methods</title> <p>Three hundred HIV‐1‐infected patients failing a first‐line NNRTI‐containing regimen (nevirapine, <italic>n</italic> = 148; efavirenz, <italic>n</italic> = 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 <italic>vs.</italic> those treated with NNRTI + non‐TA.</p> </sec> <sec id="hiv12044-sec-0003" sec-type="section"> <title>Results</title> <p>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) <italic>vs.</italic> 13 (9–32) months, respectively; <italic>P</italic> = 0.119] and viraemia [median (interquartile range): 4.0 (3.2–4.9) <italic>vs.</italic> 4.0 (3.3–4.7) log<sub>10</sub> copies/mL, respectively; <italic>P</italic> = 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 <italic>vs.</italic> 75.5%, respectively; <italic>P</italic> = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 <italic>vs.</italic> 74.0%, respectively; <italic>P</italic> = 0.002) and of the nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V (23.9 <italic>vs.</italic> 63.5%, respectively; <italic>P</italic> < 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%; <italic>P</italic> < 0.001).</p> </sec> <sec id="hiv12044-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>