Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT.
BACKGROUND
Once-daily (QD) ritonavir 100 mg-boosted fosamprenavir 1400 mg (FPV/r100) or atazanavir 300 mg (ATV/r100), plus tenofovir/emtricitabine (TDF/FTC) 300 mg/200 mg, have not been compared as initial antiretroviral treatment. To address this data gap, we conducted an open-label, multicenter 48-week study (ALERT) in 106 antiretroviral-naïve, HIV-infected patients (median HIV-1 RNA 4.9 log10 copies/mL; CD4+ count 191 cells/mm3) randomly assigned to the FPV/r100 or ATV/r100 regimens.


RESULTS
At baseline, the FPV/r100 or ATV/r100 arms were well-matched for HIV-1 RNA (median, 4.9 log10 copies/mL [both]), CD4+ count (mean, 176 vs 205 cells/mm3). At week 48, intent-to-treat: missing/discontinuation = failure analysis showed similar responses to FPV/r100 and ATV/r100 (HIV-1 RNA < 50 copies/mL: 75% (40/53) vs 83% (44/53), p = 0.34 [Cochran-Mantel-Haenszel test]); mean CD4+ count change-from-baseline: +170 vs +183 cells/mm3, p = 0.398 [Wilcoxon rank sum test]). Fasting total/LDL/HDL-cholesterol changes-from-baseline were also similar, although week 48 median fasting triglycerides were higher with FPV/r100 (150 vs 131 mg/dL). FPV/r100-treated patients experienced fewer treatment-related grade 2-4 adverse events (15% vs 57%), with differences driven by ATV-related hyperbilirubinemia. Three patients discontinued TDF/FTC because their GFR decreased to <50 mL/min.


CONCLUSIONS
The all-QD regimens of FPV/r100 and ATV/r100, plus TDF/FTC, provided similar virologic, CD4+ response, and fasting total/LDL/HDL-cholesterol changes through 48 weeks. Fewer FPV/r100-treated patients experienced treatment-related grade 2-4 adverse events.
Smith
Kimberly Y
KY
Section of Infectious Diseases, Rush University Medical Center, Chicago, Illinois, USA.
Weinberg
Winkler G
WG
Infectious Diseases Service, Kaiser Permanente, Atlanta, Georgia, USA.
DeJesus
Edwin
E
Orlando Immunology Center Research Facility, Orlando Immunology Center, Orlando, Florida, USA.
Fischl
Margaret A
MA
AIDS Clinical Research Unit, University of Miami, Miami, Florida, USA.
Liao
Qiming
Q
Infectious Diseases, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Ross
Lisa L
LL
Infectious Diseases, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Pakes
Gary E
GE
Infectious Diseases, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Pappa
Keith A
KA
Infectious Diseases, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Lancaster
C Tracey
CT
Infectious Diseases, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.