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Many studies have demonstrated that the long-term, virological, immunological and clinical effectiveness of highly active antiretroviral therapy (HAART) is mainly related to durable suppression of viral replication. Among the specific antiretroviral agents available today, nelfinavir has been widely used in the last 3 years. This open label, non comparative, retrospective study on 307 patients living with HIV aimed to evaluate the effectiveness of an antiretroviral (ART) regimen including nelfinavir as first-line HAART in terms of rate and durability of viro-immunological response. Most patients, 258/307 (84%), were pre-treated whereas only 49/307 (16%) were treatment naive. The median baseline CD4 cell count was 223 cells/mm3 for naive patients and 317 cells/mm3 for experienced patients whereas median HIV RNA values were 2,500 and 82,000 copies/ml for experienced and naive patients respectively. Median times spent on nelfinavir were 839 and 897 days for experienced and naive patients respectively, with 171/258 pre-treated patients (66%) remaining on nelfinavir-based therapy up to 24 months. Overall, the mean CD4 increase was 196 cells/mm3 with a relevant increment of 165 in experienced patients and 367 cells/mm3 in naive patients (p<0.01). The mean viral load variation in naive patients was -2.22 log10 and in experienced patients -0.53 log10 (p<0.01). In conclusion, nelfinavir, as part of HAART, demonstrated long-term benefit (almost two-thirds of patients stayed on nelfinavir up to 24 months). The response rate in patients naive to antiretroviral therapy was better than for experienced patients. Although there were some differences related to the baseline CD4 level, the overall response rate was good, supporting the role of nelfinavir in HAART.

The pharmacokinetics of nelfinavir tablets (A) and an oral simplified nelfinavir suspension (B) were studied. Twelve healthy volunteers randomly received either five 250-mg nelfinavir tablets or a simplified oral suspension obtained from tablets dissolved in water (nelfinavir 1250 mg in 100 mL of water) in a single dose before being crossed over to the second treatment after a one-week washout period. Blood samples were drawn up to 24 h after drug administration. Nelfinavir concentrations in plasma were analyzed by a specific and validated reverse-phase high-performance liquid chromatography assay (HPLC) with UV detection, and pharmacokinetic values were determined. For the AUC(0-infinity) with means+/-SD of 31.71+/-7.85, 30.88+/-10.28 (microg/L) respectively for treatments B and A, the ratio (F(B/A)) was of 1.1 with a C.I. of 0.90-1.24. For Cmax with means+/-SD of 3.1+/-0.6 (treatment B) and 3.2+/-0.8 mg/mL (treatment A), the ratio was 1.0. with C.I. of 0.92-1.08. The two treatments evidenced no significant differences in AUC(0-inifnity) and Cmax values and the two-one sided t-test showed that the two preparations are bioequivalent. There was no significant difference in Tmax between the liquid and tablets. Nelfinavir suspension might be a option for treating HIV-infected patients with swallowing disturbances or compliance problems.