D'Arminio-Monforte A, Cozzi-Lepri A, Balotta C, Forbici F, Violin M, Bertoli A, Facchi G, Colangeli V, Vincenti A, De Luca A, Soscia F, Ippolito G, Perno CF; Conference on Retroviruses and Opportunistic Infections.

Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 176 (abstract no. 447).

ICONA Study Group, Italy.

Background: The objective was to study the prevalence of 3TC-related mutations and heir relation to the virological outcome in 249 previously naive patients (pts) treated with 3TC-containing HAART. Methods: Plasma from 249 naive pts belonging to the I.C.O.N.A. cohort was sequenced at baseline. Mutations associated with reduced susceptibility to NRTIs, NNRTIs and PIs were counted, with focus on 3TC mutations E44D, V118I and M184I/V. Virological success (VS) was defined as at least one 'on-treatment' HIV RNA <500 copies/mL by week 32; time to VS was calculated as the first time pt viral load (VL) decreased <500 copies/ml while on the original treatment and related to the presence of 3TC-related mutations by multivariate Cox analysis including baseline VL, CD4, and NRTI, NNRTI and PI mutations as cofactors. Results: Median VL and CD4 count at baseline were 4.92 log10 copies/mL (range: 2.76-6.64) and 210 cells/ mm3 (range: 1-1225); 160 (68.4%) pts carried no mutations in reverse transcriptase or protease, while 89 pts carried either E44D mutation (1, 0.4%), M184V (2, 0.8%), or V118I (9, 3.6%). None carried >1 3TC-related mutation. Mutations associated with other NRTIs, NNRTIs and PIs were present in 5 pts (2.0%: M41L, A62V, D67N, T69D, L210W, T215Y, and K219Q, one each), 10 pts (4.0%: A98G n = 1, K101I/E n = 2, K103R n = 2, V106I n = 2, V108I n = 1, V179D n = 2) and 74 pts (29.7%: L10F/I/V, M36I, M46L, I54V, and V82I), respectively. Despite the presence of 3TC-related mutations, 10/10 (100%) pts with either E44D or V118I achieved VS, compared to 152/239 (63.6%) without these mutations (two-tailed Fisher exact test, p = 0.02). Of the two patients carrying M184V mutation, one, carrying M184V alone, failed to achieve VS and the other, who also carried mutations L210W, M41L, T215Y, I54V, and V82A, reached the endpoint. The adjusted RH of VS were RH = 0.43, 95% CI: 0.06-3.13, comparing patients with and without the M184V mutation, and RH = 1.19, 95% CI: 0.61-2.33, comparing patients with and without the E44D or V118I mutations. Conclusions: A moderate prevalence of mutations E44D/V118I conferring limited resistance to 3TC was detected in this large cohort of drug-naive pts. These mutations do not seem to impair virological response to 3TC- containing HAART.

Publication Types:

• Meeting Abstracts

Keywords:

• Acquired Immunodeficiency Syndrome
• Anti-HIV Agents
• Antiretroviral Therapy, Highly Active
• Base Sequence
• CD4 Lymphocyte Count
• Drug Therapy, Combination
• HIV
• HIV Infections
• HIV Protease
• HIV Protease Inhibitors
• HIV Seropositivity
• Humans
• Lamivudine
• Mutation
• Prevalence
• RNA-Directed DNA Polymerase
• Viral Load
• drug therapy
• genetics
• reverse transcriptase, Human immunodeficiency virus 1
• therapy

Other ID:

• GWAIDS0006734

UI: 102244230

From Meeting Abstracts