VIRACEPT« (nelfinavir mesylate):

NEW STUDIES SHOW REAL-LIFE ADVANTAGES OF VIRACEPT IN EFFICACY, TOLERABILITY, DRUG RESISTANCE AND CONVENIENCE

New data on the protease inhibitor VIRACEPTÔ (nelfinavir mesylate) continue to expand the scientific database supporting VIRACEPT potency, tolerability, convenience and first-line use, according to new data presented at the 7th European Conference on Clinical Aspects and Treatment of HIV-Infection in Lisbon.

A 96-week study exploring enhanced dosing convenience for patients found that VIRACEPT therapy produces the same degree of efficacy and tolerability in a convenient twice-daily (BID) dose as in its standard three-times daily dose.

Focusing on how VIRACEPT benefits patients in real-world settings, studies also showed that VIRACEPT therapy resulted in the highest rates of HIV suppression, the lowest rates of discontinuation due to adverse effects, and the fewest viral mutations leading to therapeutic failure and cross-resistance when compared with other protease inhibitors.

 

VIRACEPT Twice a Day Equally Effective and More Convenient

Data from a prospective, randomized study led by Dr. Peterson1 of Agouron Pharmaceuticals, La Jolla, CA, showed that a regimen consisting of VIRACEPT, d4T and 3TC was as effective with VIRACEPT in a BID as in a TID dose. The study involved 554 patients na´ve to 3TC therapy, with no therapy involving nucleoside analogues during the prior 6 months.

VIRACEPT was administered 1250mg BID to 344 patients and 750mg TID to 210 patients, with d4T and 3TC administered in standard doses to both groups. Analysis of the data by different statistical approaches consistently showed that VIRACEPT administered twice daily was equally effective to VIRACEPT three-times daily during 96 weeks of therapy. The two VIRACEPT doses were similar in pharmacokinetics, providing equally favorable exposure to the drug. Both doses were also equally well-tolerated.

Only four cases of fat redistribution disorders were reported during the initial 48-week study period in each treatment group

 

VIRACEPT Best Initial Anti-HIV Drug

Dr. Easterbrook2 of the King’s College Hospital, Chelsea and Westminster Hospital, London, presented a retrospective study involving the initial treatment of 690 HIV-infected patients in real-life clinical settings with one of the following drugs or drug combinations: VIRACEPT, indinavir, ritonavir, INVIRASE« (saquinavir mesylate, or saquinavir HGC), INVIRASE combined with ritonavir, and the non-nucleoside reverse transcriptase inhibitor, nevirapine.

The study found that, at the end of the first 6 months of treatment, VIRACEPT had suppressed viral loads below the detectable limit (<500 copies/mL) in the highest percentage of patients while leading to the lowest rate of discontinuation of all the regimens studied.

Viral load suppression and discontinuation with initial anti-HIV regimens are summarized below:

 

Drug(s)

N

Rate of Viral Load Suppression below Detectable Limit
(<500 copies/mL)

Rate of Discontinuation

VIRACEPT

109

81%

17%

Indinavir

189

76%

25%

Ritonavir

42

76%

40%

Nevirapine

122

73%

27%

Ritonavir/Saquinavir HGC

45

71%

31%

Saquinavir HGC

183

35%

52%


VIRACEPT Best-Tolerated Protease Inhibitor

Dr. Bonfanti3 of the CISAI Group, Italy, presented a study closely supporting Dr. Easterbrook’s in regard to tolerability and discontinuation rates. Involving 1,209 patients in conjunction with 10 Italian Departments of Health, this prospective, multicenter, cohort study compared five protease inhibitor regimens: VIRACEPT, indinavir, ritonavir, INVIRASE, and combination INVIRASE/ritonavir.

The average age of the patients was 37.1 years (SD 8) and the average CD4 cell count at enrollment was 253 cells/mm3 (SD 192). The study, initiated in 1997, has found that the two drugs with the lowest rates of discontinuation due to adverse effects were VIRACEPT and saquinavir HGC. VIRACEPT has also had the lowest incidence of grade 3-4 adverse effects.

Adverse events and discontinuation rates of the various regimens are summarized below:

Drug(s)

AE-Related Discontinuations

Adverse Effects, Grades 3-4*

Adverse Effects,
All Grades*

VIRACEPT

23%

0.45

7.78

Saquinavir HGC

22%

0.79

3.29

Ritonavir/SQV-HGC

26%

1.75

7.97

Indinavir

38%

1.24

5.94

Ritonavir

48%

2.25

8.96

*Incidence/person-month

VIRACEPT Highly Effective In Suppressing Viral Loads Of Treatment-Na´ve Patients

Dr. Estrada4 of the Unidad de Enfermedades Infecciosas, Hospital ClÝnico de San Carlos, Madrid, presented data from a retrospective, non-comparative study involving 26 HIV-infected, treatment-na´ve patients. The data showed that VIRACEPT-based regimens suppressed fully 96% of patients’ HIV viral load below the detectable limit (<400 copies/mL) at 24 weeks of therapy. The VIRACEPT-based regimens also increased CD4 cell count, as summarized in the table below:

Parameter

12 weeks

24 weeks

Viral load
< 400 copies/mL
(% of patients)

65.3%

96.1%

CD4+ increase (mean)
(cells/mm3)

+35 cells

+47 cells

 

The regimens consisted of VIRACEPT in a dose of 1250mg BID and two nucleoside analogues (NAs) in standard doses. The patients (of whom 23 were male) had a mean age of 39 (SD 9 years), an initial viral load of 4.15 log10 (SD 1.05), and a mean initial CD4 count of 303 cells/mm3 (range 8-864). No serious adverse effects, opportunistic infections, or other AIDS-related complications were reported in the study.

 

VIRACEPT Less Likely To Induce Drug Resistance

Dr. Harder5 of the Institute of Medical Microbiology, Christian-Albrechts University in Kiel, Germany, presented data from a retrospective study comparing VIRACEPT and indinavir in regard to the inducement of drug resistance.

The study involved 23 patients who, failing previous treatment with reverse transcriptase inhibitors (RTIs), went on to receive therapy with two RTIs (at least one of which was new) and either VIRACEPT or indinavir (IDV). Before the start of the new treatment, the patients were homogeneous in regard to the frequency of resistance-related mutations.

After the new regimens were started, mutations linked to therapeutic failure occurred significantly more often with IDV-based than VIRACEPT-based regimens (P=.01). The affected codons were mostly those involving secondary mutations (protease inhibitor-related codons 20, 48, 63, 71, 77, 90), connoting cross-resistance between IDV and other protease inhibitors. Primary mutations were relatively infrequent.

1. Peterson A et al. A comparison of the long-term antiviral efficacy of BID and TID dosing of nelfinavir in combination with stavudine (D4T) and lamivudine (3TC) beyond 48 weeks.
2. Easterbrook PJ et al. Comparison of virological, immunological and clinical response to
nevirapine (NVP) and five different initial protease inhibitor (PI) treatment regimens.

3. Bonfanti P et al. Adverse reaction in patients treated with PIs: a prospective multicentre study.
4. Estrada V et al. Nelvinavir-based antiretroviral therapy is highly effective on na´ve
patients.

5. Harder T et al. Emergence and stability of point mutations at the HIV-1 protease (PRT) and reverse transcriptase (RT) loci in response to HAART containing indinavir or nelfinavir.