Antiretroviral combinations based on an
integrase inhibitor are superior to other first-line HIV treatment regimens,
according to the results of a meta-analysis published in the open access
journal PLoS One. The study also showed
the benefits of integrase inhibitor-containing regimens for people changing HIV
therapy after virological failure. However, switching to an integrase inhibitor
was not supported for people whose existing therapy was suppressing viral
“The addition of the integrase inhibitor class
to our armamentarium has strengthened cART [combination antiretroviral therapy]
regimens, and further rational use can preserve future therapeutic options,”
write the authors.
Integrase inhibitors are a class of
anti-HIV drug that prevent the integration of the virus into CD4 cells. The
first integrase inhibitor to be approved was raltegravir (Isentress). Other drugs in this class have been, or are being,
developed. Elvitegravir has been licenced in the United States and clinical
studies involving dolutegravir are well advanced.
Originally envisaged as a therapy for
people with previous experience of HIV treatment and drug-resistant strains of HIV,
integrase inhibitors are also considered an option for individuals who are starting antiretroviral therapy.
However, the precise benefits of therapy
with an integrase inhibitor are unclear. Investigators from Belgium and the
Netherlands therefore performed a systematic review and meta-analysis of
current evidence for the use of integrase inhibitors in a variety of patient populations.
Studies published or presented between 2006
and 2012 were included in the study if they compared the virological efficacy
of a regimen containing an integrase inhibitor to that of a combination based
on a different class of antiretrovirals.
The effectiveness of integrase inhibitors
was examined in three patient populations: treatment-naive individuals; people
changing therapy due to virologic failure; and those switching treatment in the
context of a suppressed viral load.
A total of 16 studies met the inclusion
The meta-analysis was performed using
modified intent-to-treat (mITT), on-treatment (OT) and as-treated (AT)
A review of the ten studies involving treatment-naive
patients showed that use of an integrase inhibitor achieved better virologic
outcomes. These reached significance in the mITT (OR = 0.71; 95% CI, 0.59-0.86)
and OT (OR = 0.63; 95% CI, 0.47-0.84) analyses. The AT data showed a
non-significant trend favouring integrase inhibitor-containing regimens (OR =
0.86; 95% CI, 0.61-1.22).
A sub-analysis compared first-line
integrase inhibitor-based therapy to treatment based on the non-nucleoside
reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva,
also in Atripla). Both the mITT
(OR = 0.67; 95% CI, 0.54-0.84) and OT (OR = 0.59; 95% CI, 0.43-0.81) data
showed the superiority of the combinations that included an integrase
inhibitor. The investigators suggest this superiority was due to the good
toxicity and safety profile of integrase inhibitors.
Results from three studies involving
treatment-experienced patients with virological failure were included examined
by the investigators. The mITT results favoured the use of an integrase
inhibitor (OR = 0.27; 95% CI, 0.11-0.66). Meta-analysis of two studies using
both OT data (OR = 0.28; 95% CI, 0.20-0.38) and AT data (OR = 0.16; 95% CI,
0.04-0.61) confirmed this finding.
Next, the investigators turned their
attention to outcomes among treatment-experienced patients who had an
undetectable viral load when they switched to an integrase inhibitor. Three
studies were included in this meta-analysis. In the mITT analysis, there was a
non-significant trend suggesting the inferiority of integrase inhibitor-based
therapy (OR = 1.43; 95% CI, 0.89-2.31). The AT analysis clearly showed
inferiority of integrase inhibitors (OR = 1.73; 95% CI, 1.01-2.97) when
patients were switching from boosted protease inhibitors.
“Based on the meta-analysis, treatment with
INIs [integrase inhibitors] in combination with dual NRTIs [nucleoside reverse
transcriptase inhibitors] showed to be more beneficial for treatment-naïve
patients compared to other currently used treatment strategies,” conclude the
authors. “Also in treatment-experienced patients with virological failure, use
of INIs proved to be beneficial as well. However, in successfully treated
patients…switching a high genetic barrier drug towards INI was not supported.”