421-W. Virological and Immunological Benefit of a Salvage Therapy that Includes Kaletra plus Fortovase Preceded or not by Antiretroviral Therapy Interruption (TI) in Advanced HIV-Infected Patients (6-Month-Follow-up)

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Session 61 Poster Session
Antiretroviral Chemotherapy in Previously Treated Individuals
Session Time: 4:30-6:30 pm
Room 4E-F

421-W.

Virological and Immunological Benefit of a Salvage Therapy that Includes Kaletra plus Fortovase Preceded or not by Antiretroviral Therapy Interruption (TI) in Advanced HIV-Infected Patients (6-Month-Follow-up)
L. Ruiz*¹, E. Ribera², A. Bonjoch1¹, J. Martinez-Picado¹, M. Díaz², J. Romeu¹, S. Marfil¹, E. Negredo¹, J. García-Prado¹, C. Tural¹, T. Puig1¹, G. Sirera¹, and B. Clotet¹
¹IrsiCaixa Fndn. and Lluita contra la SIDA Fndn., Univ. Hosp. Germans Trias i Pujol, Badalona, Spain and ²Hosp. Vall d’Hebron, Barcelona, Spain

Objective: Our objective was to assess in a prospective, open, randomised study the virological efficacy of a Mega-HAART salvage therapy which includes Kaletra+Fortovase+3TC+ABC+ddI, preceded (group A) or not (group B) by a 3-month antiretroviral TI in HIV-infected patients with virological failure.
Methods: Patients with plasma viral load (pVL) >1000 copies/mL (twice consecutively), virological failure to more than 2 HAARTs and resistant mutations to all 3 classes of drugs prior to study entry were eligible. pVL and CD4 were determined in group A monthly during off therapy and every 3 months thereafter, whereas in group B these parameters were measured every 3 months. Genotypic testing was performed at the study entry in both groups and at the start of ST in group a by using Trugene HIV-Kit in RNA.
Results: A total of 46 patients (22 in group A and 24 in group B) were included into the study. Clinical complications were not observed. The mean number of drugs previously received was of 8 (5 - 13) for a median time of 5.7 years (2.8 - 14). Mean pVL was of 4.3±0.6 log₁₀ in group A and of 4.3±0.7 log₁₀ in group B at baseline. CD4 counts were of 396±189 cells/mm³ and 322±165 cells/mm³ in group A and group B, respectively. pVL increased a mean of 0.9 log₁₀ copies/mL and CD4 decreased 131 cells/mm³ after 3 months off therapy in group A. The mean number of drug-resistance mutations were 10.8±4.8 group A and 9.7± 5.4 (group B). The number of drug-resistance mutations at the start of ST decreased to 3.8±4.2 in group A. Results at 24 weeks: ST was well tolerated. A mean increase of 144 and 80 cells/mm³ were produced in group A and group B, respectively. 47% of the patients in group A and 36% in group B reached a pVL < 80 copies/mL (p=NS). Patients with pVL<20,000 copies/mL at baseline had a better response (<80 copies/mL) than those with pVL above this limit (p=0.016). In group A, the mutant virus population of 64% (13/20) of the patients interrupatienting therapy complete or partially reverted to WT according to the genotype analysis. Overall, the number of prior regimens, CD4 or number of drug-resistance mutations at baseline were not associated with a better virological response. In a multivariate analysis the presence of L10I/V in the protease gene was the only factor associated with a poorer response (p=0.02).
Conclusions: Dual PI salvage therapy including Kaletra+Fortovase appears to be active in heavily pretreated patients at week 24. A prior 3 months of therapy discontinuation does not seem to affect the virological and immunological outcome in heavily treated HIV-infected patients.