A
3-drug Class HAART Strategy Is Not Superior to a 2-drug Class Strategy for Immunologic
or Clinical Outcomes There
are scant clinical data regarding the long-term consequences of initiating therapy
with a protease inhibitor (PI), a non nucleoside reverse transcriptase inhibitor
(NNRTI) or a PI plus an NNRTI. In
the current study, presented by Dr. Roger MacArthur of Wayne State University
at the 16th International AIDS Conference in Toronto this week, 1397 treatment-naïve
persons were randomized 1:1:1 to 1) PI + NRTIs, 2) NNRTI + NRTIs, or 3) PI + NNRTI
+ NRTI(s). Primary
endpoints were a composite of AIDS events, death, and CD4+ cell count decline
to <200 cells/mm3 (PI vs NNRTI comparison); and CD4+ cell count change after
32 months (3-class vs combined 2-class comparison) Results
- Median age was 38 years;
21% were female; 54% were black, 17% were Latino. Median CD4+ cell count was 163
cells/mm3. Median follow-up was 5 years.
- 302
persons developed an AIDS event or died; 188 died; 388 developed the composite
clinical/CD4+ cell count endpoint.
- NNRTI
vs PI hazard ratios (HRs) for the composite endpoint, AIDS or death, and virologic
failure (VF) (HIV RNA >1000 copies/mL after 4 months) were 1.02, 1.07, and
0.66, respectively.
- Mean
increases in CD4+ cell counts after 32 months were 227 and 234 cells/mm3 for the
combined 2-class and 3-class strategies (p=0.62), respectively.
- HRs
(3-class vs combined 2-class) for AIDS or death and VF were 1.14 and 0.87, respectively.
- HRs (3-class
vs combined 2-class) for AIDS or death and VF were similar for persons with baseline
CD4+ cell counts <200 and >200 cells/mm3 (p=ns for interaction).
- Persons
assigned the 3-class arm discontinued therapy due to toxicity more than those
assigned the 2-class arms (HR=1.58, p<0.01).
Based
on these findings, the authors conclude, “NNRTI-based and PI-based strategies
for initial therapy do not differ for a composite outcome based on CD4+ cell count
decline, AIDS events, and death after a median follow-up of 5 years.” “The
NNRTI strategy was superior virologically to the PI-based strategy.” “A
3-class strategy is not superior to a 2-class strategy for immunologic or clinical
outcomes, and is associated with more drug toxicity.” Wayne
State University, Infectious Diseases, Detroit, United States, University of Illinois,
Infectious Diseases, Chicago, United States, University of Minnesota, Biostatistics,
Minneapolis, United States, Yale University, Infectious Diseases, New Haven, United
States, Temple University, Infectious Diseases, Philadelphia, United States, Southern
New Jersey AIDS Clinical Trials, Camden, United States, Social & Scientific
Systems, Silver Spring, United States, NIH/NIAID, Division of AIDS, Bethesda,
United States. 08/15/06 Reference
R
D MacArthur, R M Novak, G Peng, and others (for the CPCRA 058 Study Team and the
Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Long-term
clinical and immunologic outcomes are similar in HIV-infected persons randomized
to NNRTI vs PI vs NNRTI+PI-based antiretroviral regimens as initial therapy: results
of the CPCRA 058 first study. 16th International AIDS Conference. August 13-18,
2006. Toronto, Canada. Abstract TUAB0102
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