Pilot study of saquinavir and lopinavir/ritonavir twice daily in protease inhibitor-naive HIV-positive patients.
OBJECTIVE
Protease inhibitor (PI)-naive patients may have limited reverse transcriptase inhibitor (RTI) options due to resistance and/or toxicity. Effective, well-tolerated nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens are therefore needed.


METHODS
This prospective study evaluated the efficacy and safety of saquinavir/lopinavir/ritonavir (1000/400/100 mg bid) in PI-naive patients over 48 weeks. The regimen could be intensified with NRTIs if patients did not achieve virologic suppression by 12 weeks. The primary study endpoint was virologic suppression at 48 weeks. Additional study objectives included assessment of safety, CD4 cell counts, blood lipids, PI trough levels, and anthropometrics.


RESULTS
Of the 20 PI-naive study participants, 16 completed 48 weeks of study treatment, with no discontinuations attributed to virologic failure. Fourteen of 16 patients achieved virologic suppression with only the PIs; 2 patients required tenofovir intensification to achieve complete suppression. Median CD4 counts increased significantly over 48 weeks. Adverse events were generally mild and manageable. Extreme lipid elevations were uncommon, although moderate lipid elevations occurred in the majority of patients. Most patients reported some degree of central fat accumulation.


CONCLUSIONS
Our study demonstrates that saquinavir/lopinavir/ritonavir 1000/400/100 mg bid with tenofovir intensification is a potent nucleoside-sparing regimen for PI-naive patients, associated with durable HIV suppression and improved CD4 cell counts. Fat accumulation and metabolic changes observed in this study warrant confirmation from ongoing trials.
CRI of New England, Boston and Springfield, MA, USA. jhellinger@tufts-nemc.org
James
J
Hellinger
Calvin
C
Cohen
Anne
A
Morris
Sandy
S
Sheble-Hall
Danielle
D
Gordon
Clarissa
C
Foy
Lenore
L
Jackson-Pope
Abby
A
Shevitz
Erno
E
van Schaic
D000328:Adult; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D019258:Saquinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D019562:Viral Load
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019258:Saquinavir; D019438:Ritonavir