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

E-184V STUDY: IMMUNOLOGICAL AND VIROLOGICAL CORRELATES OF HIV-1 REPLICATIVE CAPACITY

Antivir Ther. 10, Suppl 1:S175 (abstract no. 160)

N Gianotti¹, S Menzo², A Danise¹, L Galli¹, G Schira¹, A Galli¹, M Mammarella¹, M Clementi¹, A Lazzarin¹ and A Castagna^1
1Università Vita-Salute San Raffaele, Milano, Italy; ²Università Politecnica delle Marche, Ancona, Italy

AIM: The pilot, randomized E-184V study showed that, in patients failing in the presence of the 184V mutation and requesting treatment interruption (TI), lamivudine monotherapy (3TC) allows a slower CD4+ decline and disease progression, along with a smaller viral rebound, compared to TI. We investigated the correlation between the viral replicative capacity (RC) and the immunological and virological changes during the study period.

METHODS: HIV-infected adults, requesting TI with CD4+>500/µl, HIV-RNA >1000 copies/ml, an ongoing lamivudine-including HAART, and documented 184V mutation, were enrolled. Protocol failure was defined as immunologic failure (CD4+<350/µl) and/or clinical failure (occurrence of B or C CDC events) within 48 weeks. In the first consecutive 31 enrolled patients, HIV-1 RC of each clone was measured as p24Ag production by each recombinant clone after 4 days in culture. RCs of clones from week 24 (or study discontinuation) were compared with those from the baseline, as RC₂₄/RC_BL ratio. Correlations were tested using the Spearman rank correlation coefficient. LOCF (last observation carried forward) technique was applied for patients who discontinued the study before week 24. Continuous variables are presented as medians (interquartile ranges).

RESULTS: At baseline, CD4+ cells/µl, CD4+%, and log₁₀ copies/ml HIV-RNA were 603 (498–741), 32.0 (25.9–35.8), and 3.79 (3.39–4.24) in TI-arm and 522 (426–599), 25.2 (21.1–29.9), and 3.66 (3.39–3.97) in 3TC-arm, with no statistical difference between arms, except for CD4+% (P=0.016). RC was 474 (110–1680) and 760 (312–1750) pg/ml in TI- and 3TC-arm (P=not significant). The RC24/RCBL was 11.42 (2.4-57.1) and 1.14 (1-1.28) in TI- and 3TC-arm (P=0.0006). Patients with protocol failure before week 24 had a greater RC recovery compared to those without it (P=0.045). The RC24/RCBL correlated with the CD4+ counts and CD4+% decrease at week 24 (r=-0.46, P=0.01 and r=-0.55, P=0.001, respectively), and with the CD4+% decline at week 48 (r=-0.55, P=0.001). No correlation was found between RC24/RCBL and (i) baseline CD4+ counts, CD4+%, and HIV-RNA, (ii) 24-weeks increase in HIV-RNA (iii) 48-weeks changes in CD4+ counts and HIV-RNA.

CONCLUSIONS: RC recovery is lower in patients treated with lamivudine monotherapy than in those undergoing TI. CD4+ decline observed during the study is at least partially explained by changes in HIV-1 RC.

PRESENTING AUTHOR: N Gianotti

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2005-06-07
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