14th International HIV Drug Resistance Workshop 7-11 June 2005, Québec City, Canada

RELATION BETWEEN THE ANTIRETROVIRAL ACTIVITY OF DIDANOSINE (DDI) AND THE NUMBER OF REVERSE TRANSCRIPTASE (RT) MUTATIONS: DINAM STUDY

Antivir Ther. 10, Suppl 1:S26 (abstract no. 24)

JL Blanco, A Biglia, M Arnedo, E de Lazzari, J Mallolas, E Martinez, M Lonca, M Laguno, M Larrousse, A Leon, A Milinkovic, F Garcia, JM Miro, JA Arnaiz, T Pumarola, JM Gatell
Infectious Diseases Service. Hospital Clinic, Hospital de dia de Infecciones, Hospital Clinic, Barcelona, Spain

BACKGROUND: Didanosine may retain substantial antiretroviral activity despite the presence of RT mutations. We have investigated the effectiveness of adding ddI to a stable failing antiretroviral (ARV) therapy on plasma viral load (VL), and its relation with the baseline number of different clusters of RT mutations.

METHODS: Consecutive patients failing to an ARV regimen not containing ddI and with VL above 1000 copies/ml were eligible for the study. After a genotypic and virtual phenotype resistance testing, ddI (Videx EC 400 mg or 250 mg qd according to body weight) was added to the failing therapy. A clinical, immunological, and virological evaluation was performed at baseline and at weeks 2 and 4. Thereafter the ARV regimen was optimized according to resistance test results.

RESULTS: Forty patients were included. Mean (range) baseline PVL and CD4+ lymphocytes were 4560 copies/mL (IQR 2810–14900) and 405 cells/mm³ (IQR 290–505) respectively. At weeks 2 and 4 the median HIV RNA reduction was 0.73 and 0.67 log₁₀ respectively. At week 4 the proportion of patients with a drop VL>0.5 log, >1 log or with PVL<200 copies/ml was 63%, 30% and 24% respectively. Mean rise in CD4+ cell count at week 4 was 53 cells/mm³. At baseline, the median number RT, nucleoside-associated mutations (NAMs) or thymidine-associated mutations (TAMs) were 4.3 and 3 respectively. Relations between number of mutations in each studied cluster (RT/NAMs/TAMs) and median log₁₀ drop HIV RNA level were: RT mutations: 0–2: -1.37; 3–4: -0.67; 5: -0.35; and 6–7: -0.50. NAMs mutations: 0–1: -1.18; 2: 0.88; 3: -0.67; 4: 0.63; and 5–6: -0.47. TAMs mutation : 0–1: -1.18; 2: 0.88; 3: -0.67; 4: -0.35; 5: -0.11 log. We did not find differences in comparing patients with two different pathways of TAMs. VL drop was statistically significant (P<0.05) compared with baseline when the number of baseline mutations /RT, NAMs or TAMs) was less than four. Median drop of VL in the three patients harbouring 74V+65R was -0.02 log compared with –0.69 log in the remaining 37 patients (P<0.05). VL drop was similar irrespective of the pathways of TAMs (41L,210W,215Y vs 67N,70R, 215F, 219E/Q).

CONCLUSION: ddI retains significant antiretroviral activity when the number of RT, TAMs or NAMs is less than four except when both the 74V and 65R are present.

PRESENTING AUTHOR: JL Blanco

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2005-06-07
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