A combination antiretroviral regimen
consisting of lopinavir/ritonavir (Kaletra) plus the
integrase inhibitor raltegravir (Isentress) without
nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) works as well as
a traditional three-drug cocktail, according to findings from the PROGRESS
study presented this week at the Eighteenth International AIDS Conference in
Highly active antiretroviral
therapy, or HAART, traditionally includes a protease inhibitor or
non-nucleoside reverse transcriptase inhibitor (NNRTI), plus a 'backbone' of
two NRTIs. But nucleoside/nucleotide drugs can cause long-term toxicities, and
development of new classes of HIV entry and integrase inhibitors has allowed
more flexibility in constructing potent regimens.
Jacques Reynes and fellow investigators with the
international PROGRESS study performed a head-to-head comparison of a
traditional three-drug HAART regimen and a two-drug NRTI-sparing regimen.
In this open-label Phase III trial, 206 previously
untreated participants were randomly assigned to receive lopinavir/ritonavir (400/100 mg twice daily) in combination with either 400 mg
twice-daily raltegravir or the once-daily tenofovir/emtricitabine NRTI coformulation
The two study groups were similar at baseline. Most
participants (about 85%) were men, the average age was 49 years and three-quarters
were white. All had plasma viral load greater than 1000 copies/ml (mean about
20,000 copies/ml) and the average CD4 count was about 300
About 9% of study participants dropped out for various
reasons, about equally distributed between the two arms. Two individuals in
each group stopped early due to side-effects, whilst one in the raltegravir
group and two in the tenofovir/emtricitabine group did so due to virological
An intent-to-treat analysis at 48 weeks found that
similar proportions of people in both arms achieved viral load below 40
copies/ml: 83% in the raltegravir group and 85% in the tenofovir/emtricitabine
group. The minimal difference between the groups indicated that the
NRTI-sparing combination was non-inferior to the traditional HAART regimen.
The researchers did not report results according to
whether patients started treatment with high or low viral load, which has been
shown to affect response to raltegravir in some prior studies.
CD4 cell gains were slightly smaller in the
raltegravir group compared with the tenofovir/emtricitabine group
– 215 vs 245
– but again the difference was
not statistically significant.
Both study regimens were generally well-tolerated. The
most common side-effects, occurring with similar frequency in the raltegravir
and tenofovir/emtricitabine arms, were diarrhoea (8% vs 13%, respectively) and
elevated cholesterol (8% vs 5%, respectively). One person in each arm showed
evidence of drug-resistance mutations.
The researchers acknowledged that 48 weeks might not
be long enough to detect long-term problems, and follow-up will continue
through to 96 weeks.
PROGRESS investigators concluded that lopinavir/ritonavir plus raltegravir
"resulted in non-inferior efficacy and similar tolerability", compared
with the three-drug traditional antiretroviral regimen, and suggested that a
two-drug NRTI-sparing regimen "can provide an alternative approach to
treatment of antiretroviral-naive patients".