Science

Intensification therapy with saquinavir soft gelatine capsules (SQV-SGC)/Ritonavir (RTV), once a day in patients with lack of response to HAART with saquinavir hard capsules (SQV-HGC).

History:

The strategies for the treatment of the HIV require a combination of power with a comfortable dosage. Saquinavir in hard capsules is hardly absobed, and the trough levels in plasma stay under the CI90 for the wild strains, what leads to a lack of effectiveness and to the selection of resistant

strains. The inhibiting effect of the ritonavir on the CYP34A can be used to improve the pharmakinetic profile of the saquinavir.

Aim:

To check if patients with a lack of response to HAART with SQV-HGC, 600mg TID, can be rescued by changing the SQV-HGC for SQV-SGC/RTV, 1600/200mg once a day.

Methods:

Three consecutive patients with a lack of response (viral charge > 1000 copies/mL) to HAART with SQV-HGC were included. SQV-HGC was changed for SQV-SGC/RTV, 1600/200mg once a day, and at the same time, the same two analogues of nucleosids, at least until the week 3. At the basal moment after 3,12 and 24 weeks, some clinical, virological and biological evaluations were made, and the plasmatic trough and the peak levels of saquinavir were measured. Plasmatic concentrations of saquinavir and ritonavir were simultaneously determined by means of a new method of high pressure liquid chromatography (HPLC) developed and validated in our pharmakinetic laboratory.

Results:

18 patients were included, although 2 of them were retired in the first 2 months because of a gastrointestinal intolerance, and 12 patients completed a monitoring of 3 months. At the beginning, the average viral charge in plasma was of 3869 copies/mL (interval from 957 to 8750), the previous average exposition to SQV-HGC of 31 months (from 24 to 48 months), the average number of previous antiretroviral treatments of 3 (from 1 to 7), and the plasmatic trough levels of saquinavir were lower than 0,05-0,01mcg/mL (the CI90 of saquinavir for the wild type of HIV) in every patient. The average increase of the total number of CD4/mL cells was < 65 at the 12th week. In weeks 3 and 12, the average trough levels of saquinavir in plasma were of 0,4157 and 0,284 respectively,