Once-daily Double-boosted Protease Inhibitor Regimen of Atazanavir, Saquinavir, and Ritonavir: 60-week Efficacy and Metabolic Effects

HIV patients who have experienced treatment failure on one or more HAART regimens require new regimens that can effectively and safely suppress their virus.

At the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007), Thai researchers presented results from a study of the efficacy and metabolic effects of a once-daily double-boosted protease inhibitor (PI) regimen of atazanavir (Reyataz) and saquinavir soft-gel capsules with low dose ritonavir (Norvir) for salvage therapy in patients who had treatment failure with nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral therapy. (Soft-gel saquinavir was formerly sold as Fortovase in the U.S., but was withdrawn from the market in favor of the Invirase hard-gel formulation).

This was a prospective study that enrolled patients at the Bamrasnaradura Infectious Diseases Institute in Bangkok, Thailand, between May 2005 and August 2005.

The doses given were atazanavir 300 mg/day, saquinavir 1600 mg/day and ritonavir 100 mg/day. Plasma HIV RNA, CD4 cell counts, and lipid profiles were monitored every 12 weeks through 60 weeks.

Results

• Of 24 patients enrolled, 58% were male; the mean age was 37.4 years.

• The mean baseline CD4 cell count was 179 cells/mm3 and the median HIV viral load was 41,600 copies/mL.

• The median duration of prior antiretroviral therapy was 30 months.

• The patterns of baseline NRTI resistance mutations were TAMs+M184V (92%) and TAMs+Q151M (8%); all patients had NNRTI resistance mutation(s).

• At 60 weeks, 18 (75%) and 14 (58%) patients achieved undetectable HIV RNA < 400 and < 50 copies/mL, respectively.

• At 12, 24, 36, 48, and 60 weeks, mean CD4 cell counts were 265, 298, 342, 353, and 389 cells/mm3, respectively.

• At 60 weeks, the following metabolic outcomes were observed:

- 12 (50%) had total cholesterol > 200 mg/dL;
- 15 (63%) had LDL >130 mg/dL;
- 9 (38%) had LDL >160 mg/dL;
- 2 (8%) had triglycerides > 400 mg/dL;
- 3 (13%) patients had HDL < 35 mg/dL.

• Five (21%) patients needed to commence or increase their dosage of lipid-lowering medications.

Conclusion

In conclusion, the study authors wrote, "A once-daily regimen of atazanavir/saquinavir/ritonavir 300/1600/100 mg/day for salvage therapy in NRTI/NNRTI experienced HIV-infected patients with limited options for a second-line antiretroviral therapy has favorable efficacy."

However, they added, "long-term metabolic complications, particularly hypercholesterolemia, is common and should be closely monitored."

Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand, Faculty of Medicine, Srinakharinwirot University, Nakornnayok, Thailand, Chonburi Hospital, Ministry of Public Health, Chon Buri, Thailand, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

08/24/07

Reference
W Manosuthi, A Chaovavanich, W Prasithsirikul, and others. Once-daily double-boosted protease inhibitor regimen of atazanavir, saquinavir, and ritonavir: 60-week efficacy and metabolic effects. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney, Australia. Abstract (poster) TUPEB070.