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Mutations at Codons 10 and 36 of Protease Region in Absence of Primary Mutations May Correlate with Virological Outcome in Naive Patients Starting a PI-Containing HAART Regimen C. F. PERNO*1, A. D'ARMINIO-MONFORTE2, A. COZZI-LEPRI3, C. BALOTTA1, F. FORBICI2, A. BERTOLI2, P. PEZZOTTI2, G. FACCHI2, L. MONNO4, G. ANGARANO4, P. BOTTURA5, V. VULLO1, A. CARGNEL2, M. CAPOBIANCHI, G. IPPOLITO1, and M. MORONI2 for the I.CO.N.A. Study Group. 1Rome, Italy; 2Milan, Italy; 3London, UK; 4Bari, Italy; and 5Varese, Italy We studied the potential correlation between mutations (M) in reverse transcriptase (RT) or protease (PR) region and virological outcome in 130 patients (pts) belonging to the italian multicenter I.CO.N.A cohort, naive at baseline and treated with PI-containing HAART regimens. HIV-RNA from plasma at baseline was extracted, amplified and sequenced by using a Perkin Elmer kit. End-point was virological failure (VF) i.e. HIV RNA> 500 copies/ml at 24 weeks from the beginning of HAART, or therapy discontinuation because of VF. Logistic regression was performed. Covariates included were: baseline HIV-RNA and CD4+ counts, no. of NRTI M (score 1 assigned to 41, 62, 67, 70, 75, 184, 210, 215, 219), no. of NNRTI M (score 1 if 98,101,103,106,108), no. of PI M (score=1 if 10 or 36). The analysis is consistent with Data Analysis Plan of the HIV Resistance Collaborative Group. At baseline, 5 pts (3.8%) and 2 pts (1.5%) had 1 and 2 NRTI M respectively. Seven (5.4%) had 1 NNRTI M and 1 (0.8%) had 2 NNRTI M. Thirty-one pts (23.8%) had a M at either codon 10 or 36 of PR region and 4 pts (3.1%) had both. Thirty-six out of 130 pts (27.7%) showed VF at 24 weeks. Multivariate odds ratios -OR- (95% CI) of VF from fitting the logistic regression are as follows: HIV-RNA 1.50 (0.8-2.82, p=0.2), CD4 0.87 (0.68-1.12 p=0.29), no. NRTI M (1 extra M) 0.44 (0.07-2.74 p=0.38), no. NNRTI M (1 extra M) 1.99 (0.50-7.91 p=0.33), no. PR M (1 extra M) 2.13 (1.07-4.24 p=0.03). None of the individual M conferred higher risk of VF in these pts, including all other secondary mutations found in this cohort (20,33, 60, 63, 71 and 77). However, in absence of primary PR M, the risk of VF in pts with M at both codons 10 and 36 was higher than that of pts without them. Conclusions: Data suggest that virological outcome may be affected by the presence of selected secondary mutations in PR before starting PI-including HAART. Key Words: genotype, protease inhibitors, resistance |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |