TY - JOUR
T1 - Impact of the M184V resistance mutation on virological efficacy and durability of lamivudine-based dual antiretroviral regimens as maintenance therapy in individuals with suppressed HIV-1 RNA: A cohort study
AU - Gagliardini, Roberta
AU - Ciccullo, Arturo
AU - Borghetti, Alberto
AU - Maggiolo, Franco
AU - Bartolozzi, Dario
AU - Borghi, Vanni
AU - Pecorari, Monica
AU - Di Biagio, Antonio
AU - Callegaro, Anna Paola
AU - Bruzzone, Bianca
AU - Saladini, Francesco
AU - Paolucci, Stefania
AU - Maserati, Renato
AU - Zazzi, Maurizio
AU - Di Giambenedetto, Simona
AU - De Luca, Andrea
PY - 2018
Y1 - 2018
N2 - Background. Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. Methods. We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. Results. Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (P = .016). Conclusions. Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.
AB - Background. Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. Methods. We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. Results. Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6-97.2) without M184V and 87.8% (95% CI, 78.4-97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51-199 copies/mL) was 79.8% (95% CI, 67.8%-91.8%) with M184V vs 90.1% (95% CI, 84.0%-96.2%) without M184V (P = .016). Conclusions. Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.
KW - Dual therapy
KW - Integrase inhibitors
KW - Lamivudine
KW - M184V
KW - NRTI mutations
KW - Neurology (clinical)
KW - Oncology
KW - Dual therapy
KW - Integrase inhibitors
KW - Lamivudine
KW - M184V
KW - NRTI mutations
KW - Neurology (clinical)
KW - Oncology
UR - https://publicatt.unicatt.it/handle/10807/127189
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85054077551&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054077551&origin=inward
U2 - 10.1093/ofid/ofy113
DO - 10.1093/ofid/ofy113
M3 - Article
SN - 2328-8957
VL - 5
SP - 1
EP - 8
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 6
ER -