regimen based on raltegravir and ritonavir-boosted darunavir is as safe and
effective as a traditional nucleoside-based HIV treatment combination,
according to the results of a small US study presented to the Sixth International
AIDS Society conference (IAS 2011) in Rome.
Patients taking the
nucleoside-sparing regimen were just as likely as those taking tenofovir/FTC (Truvada) with ritonavir-boosted
darunavir (Prezista) to have an
undetectable viral load after six months of therapy. Increases in CD4 cell counts
were comparable between the two regimens, which also had a similar impact
“The NRTI [nucleoside
reverse transcriptase inhibitor] sparing regimen of raltegravir and
darunavir/ritonavir achieved similar safety and efficacy as tenofovir/FTC and
darunavir/ritonavir and could provide an alternative approach in the treatment
of antiretroviral-naive patients,” comment the investigators.
A second study showed that a two-drug nucleoside-sparing regimen consisting of once-daily maraviroc and ritonavir-boosted atazanavir also had good antiviral efficacy, but a small number of patients experienced a low level rebound in their viral load between weeks 24 and 48.
However a third study showed that maraviroc could be dosed once daily with the ritonavir-boosted protease inhibotor lopinavir, darunavir or atazanavir.
has dramatically improved the life expectancy of many HIV-positive patients.
However, it can cause long-term side-effects, many of which appear to be caused
by drugs in the NRTI class of anti-HIV medications.
triple-drug HIV therapy has been based on a backbone of two NRTI drugs.
Investigators from the
US RADAR study wanted to see if the NRTIs could be replaced with the integrase
inhibitor raltegravir (Isentress), a drug which has been shown to be a safe and effective therapy
for both treatment-experienced and therapy-naive individuals.
designed a study involving 80 patients. All were starting HIV treatment for the
first time and had a viral load above 5000 copies/ml.
The patients were
randomised into two arms. Individuals in the first arm were treated with the
nucleoside-sparing regimen of raltegravir and the protease inhibitor
darunavir/ritonavir. Patients in the second arm received Truvada combined with darunavir/ritonavir.
The primary outcome of
the study was the proportion of patients with an undetectable viral load after
24 weeks. Information was also gathered on CD4 cell changes and the impact of
the alternative regimens on lipid levels.
Most of the patients
(75%) were men, their average age was 42 years, and 38% were white. There were
no significant differences between the two study arms, and at baseline the
patients had a median CD4 cell count of 261 cells/mm3 and an average
viral load of 4.72 log10 copies/ml.
After 24 weeks of
therapy, 86% of patients in the NRTI-sparing arm had achieved a viral load
below 50 copies/ml, compared to 87% of individuals treated with Truvada.
changes at six months were also comparable between the two study arms, the median increase
for the raltegravir-treated patients being 149 cells/mm3, compared to
an increase of 125 cells/mm3 for patients taking the traditional
regimens had a similar impact on lipid profiles and kidney function.
Three patients in the
raltegravir arm stopped therapy compared to five individuals in the Truvada arm.
Serious adverse events
occurred in three of the patients taking the nucleoside-sparing regimen as well
as in one person treated with Truvada.
There were two virological failures among the raltegravir-treated patients, but
none in those taking an NRTI backbone. However, none of these differences was
The investigators were
encouraged by these findings. The study will continue until week 48, but the
researchers were aware that its findings are limited by the small sample size.
They conclude, “a larger, appropriately powered study is warranted. Such a
study (ANRS 143/NEAT 001; estimated enrolment 800 patients) is underway.”