Risk factors for HIV-1 resistance associated mutations in patients after first-line antiretroviral treatment in Buenos Aires
E. Cordova1,2, C. Acuipil1,2, E. Loiza1,2, N. Porteiro1,2, H. Mingrone1,2
1Infectious Diseases ´F. Muñiz´ Hospital, Outpatient Care Unit, Buenos Aires, Argentina, 2IDEAA Foundation, Buenos Aires, Argentina
Background: The prevalence of HIV-1 resistance associated mutations (RAMs) patterns after antiretroviral failure depends on several factors and varies across different studies. We aimed to analyze RAMs patterns after failure of first-line antiretroviral treatment in Buenos Aires.
Methods: Patients failing first-line treatment with a genotypic test performed from 2000 to 2009 were selected from Outpatient Care Unit Muñiz Hospital cohort (MHOBA), Buenos Aires, Argentina. RAMs were analyzed according to IAS/USA Panel 2009.
Results: N=86. Median baseline viral load: 5.11log (IQR 4.7-5.5). Median baseline CD4 T-cell count: 120 (IQR 46-205). Initial antiretroviral regimen: NNTRI: 81% (EFV 74%), PI: 16%, Triple-NRTI: 2%. Among NRTI: 3TC/AZT (34%), 3TC/D4T (52%). HIV-1 subtype B: 10/22 (45%), BF 11/22 (50%), other 1/22 (5%). Most frequent NRTI-RAMs: M184V 79%, M41L 21%, K70R 17%, T215F 14%. Frequency of TAMs: 49% (AZT=50%; D4T=48%; p=0.8). K65R was only present in 2%, with no association with D4T-exposure. Among those exposed to NNRTI: K103N 59%, G190A 26%, K101E 21%, P225H 21%. Comparing failure of an EFV and NVP-containing regimen: K103N 71% vs. 17% (p=0.0001); Y181C 4% vs. 50% (p=0.0001). Maximal response to etravirine (weighted mutation score): 67% (EFV=75%; NVP=44%; p< 0.001). This difference was not observed with an AZT-containing regimen. More frequent major PI-RAMs: L90M 35%. Etravirine maximal response, isolated M184V and ≤1 NTRI-RAM were associated with a shorter duration of virological failure (months/median) (11 vs. 19, p=0.02), (15 vs. 26, p< 0.001) and (10 vs. 22.5, p< 0.001) respectively. Baseline CD4 T-cell count < 200 was associated with more NTRI-RAMs (median): 2 (IQR 1-3) vs. 1 (IQR 1-2) (p=0.03).
Conclusions: A high frequency of NTRI-RAMs was observed. NNTRI-RAMs differed from patients on EFV- or NVP-containing regimen. Long-term virological failure and low baseline CD4 were associated with a higher frequency of NTRI-RAMs. Genotypic tests are useful tools for the management of patients with first-line treatment failure.
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