HIV and Hepatitis.com Coverage of the 15th
Conference on Retroviruses and Opportunistic Infections (CROI 2008) February
3 - 6, 2008, Boston, MA
The
material posted on HIV and Hepatitis.com about CROI 2008 is not approved by
nor is it a part of CROI 2008.
Efficacy
and Safety of Dual Protease Inhibitor Regimens for the Treatment of Antiretroviral-naive
HIV Patients
Lexiva
Tablet
Invirase
Tablet
Reyataz
Capsule
Antiretroviral
therapy comprised of 2 protease
inhibitors (PI) alone has been proposed for use in treatment-naive patients
as a means of avoiding exposure to other drug classes, which may reduce the risk
of side effects and viral resistance. However, experience with dual-PI regimens
in treatment-naive individuals is limited.
In
this randomized pilot trial, conducted at multiple medical centers in France,
61 antiretroviral-naive participants were assigned to receive 1 of the following
regimens:
•
Arm 1: fosamprenavir (Lexiva)
700 mg twice daily + atazanavir (Reyataz)
300 mg once daily boosted with ritonavir (Norvir) 100 mg twice daily;
•
Arm 2: saquinavir (Invirase)
1500 mg once daily + atazanavir 300 mg once daily boosted with ritonavir 100 mg
once daily.
All
participants had a baseline HIV viral load of 10,000 to 750,000 copies/mL, a CD4
cell count above 200 cells/mm3, and no evidence of PI resistance. At baseline,
both arms were well matched, with a median viral load of 4.8 log copies/mL and
a median CD4 count of 271 cells/mm3.
The primary efficacy endpoint was
early virological response, defined as viral load < 50 copies/mL at week 16.
Any antiretroviral therapy modification before week 16 was considered a failure.
To challenge conventional HAART,
each regimen had to demonstrate an early response rate of at least 50%. Therapy
was changed for patients who still had a viral load above 400 copies/mL at week
16 or above 50 copies/mL at week 24.
Results
•
8 of 61 patients (13.1%) had their therapy modified before week 16:
•
2 in each arm due to adverse events;
•
2 in Arm 2 with an un-protocoled saquinavir dose increase;
•
2 in Arm 1 due to poor adherence or insufficient viral load reduction.
•
At week 16, 12 of 30 participants (40.0%) in Arm 1 and 13 of 31 (41.9%) in Arm
2 achieved viral load < 50 copies/mL.
•
Median viral load decreases were 3.1 and 2.9 log copies/mL in Arm 1 and Arm 2,
respectively.
•
At week 24, 14 of 30 patients (46.7%) in Arm 1 and 13 of 31 (41.9%) in Arm 2 had
a viral load < 50 copies/mL.
•
At week 24, the overall median CD4 count had increased by 149 cells/mm3.
•
Baseline viral load was the only significant predictor of virological suppression
< 50 copies/mL at week 16:
•
63.6% for those below the 50,000 copies/mL baseline cut-off;
•
15.8% for those above this cut-off level (P = 0.003).
•
No major genotypic mutations in the HIV protease were observed.
Conclusion
Based
on these results, the investigators noted that despite good tolerability and adequate
drug levels, "neither dual-PI regimen reached the specified threshold of
early efficacy."
In conclusion, they stated, "This insufficient
antiviral potency restricts the potential use of these regimens in antiretroviral-naive
patients to those with low to intermediate viral load."
Efficacy
and Safety of Dual Protease Inhibitor Regimens for the Treatment of Antiretroviral-naive
HIV Patients 
Results
