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HIV & AIDS
Figure 5: Combined Efficacy—Percentage of Patients with
Figure 3 shows the marked difference in viral response (in both BENCHMRK
HIV RNA <400 copies/ml at Week 16 by Baseline HIV RNA and
1 and BENCHMRK 2) between R+OBT (upper curves) and P+OBT (lower
CD4 Cell Count
curves). Partial data for week 24 showed equivalent responsiveness.
Subgroup Figures 4a and 4b summarize the (essentially identical) responses of
n% of patients
patients in BENCHMRK 1 (see Figure 4a) and BENCHMRK 2 (see Figure 4b)
Overall efficacy data 447 79
with respect to CD4 count (upper panel) and viral load (lower panel).
230 43
Within each panel, the upper curve refers to R+OBT patients and the lower
Baseline plasma HIV RNA (copies/ml)
curve to P+OBT.
288 88
< 100,000
155 55
159 64
Efficacy was also analyzed as a function of baseline viral load as well as CD4
> 100,000
75 19
cell counts (see Figure 5), with significantly greater efficacy in the R+OBT
Baseline CD4 cell counts (cells/mm
3
)
group compared with the P+OBT group for all entry groups. Adverse
experiences were comparable.
140 63
< 50
75 24
168 86
> 50 and < 200
82 46
Positioned as they are in an entirely new
> 200
138 88
73 59 class of therapeutics, IN inhibitors will no
0 20 40 60 80 100
doubt join existing or future drugs in
combination therapy for HIV disease.
Raltegravir + OBT Placebo + OBT
drug in each of the three classes of ARTs: nucleoside reverse transcriptase Resistance
inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), Retroviruses continuously reinvent themselves, adapting to changes in
and protease inhibitors (PIs). Selected ARTs that were investigational at conditions such as emerging host immunity or the introduction of drugs to
study entry were permitted in the OBT. Patients had to have HIV loads over interfere with replication. Given the phenomenal speed and carelessness of
1,000 RNA copies/ml. The pre-determined end-point was at 16 weeks of unedited transcription of RNA by RT, resistant mutations inevitably emerge,
therapy with measurement of HIV RNA and CD4 cell count and analysis of as they do in vitro.
20
Some will have phenotypes that confer a survival
adverse experiences. The combined results of the two identical trials were advantage in the new milieu. There is no reason to suppose that an IN
based on 699 randomized patients. Four hundred and sixty-two entered the inhibitor is exempt from such developments in the long term. Positioned as
raltegravir + OBT (R+OBT) arm and 237 the placebo + OBT (P+OBT) arm. they are in an entirely new class of therapeutics, IN inhibitors will no doubt
The mean entry CD4 counts were equivalent (151 per mm
3
in R+OBT versus join existing or future drugs in combination therapy for HIV disease. In this
158 per mm
3
in P+OBT). The geometric mean viral loads were also way, the emergence of resistant strains will be better suppressed, and
equivalent at ~400,000 RNA copies/ml in each group. The patients had surviving strains will be even less likely to be fully replication-competent,
many years of prior ART (median 10 years). with a commensurately large improvement in outlook for the patient. ■
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16 US INFECTIOUS DISEASE 2007
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