www.hivandhepatitis.com

IAS 2013: Raltegravir/Etravirine Dual Regimen Maintains Viral Suppression

A regimen of raltegravir (Isentress) plus etravirine (Intelence) without NRTIs or protease inhibitors was able to keep HIV in check after switching from a standard regimen if patients did not have pre-existing NNRTI resistance, researchers reported at the recent 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) in Kuala Lumpur.

Standard antiretroviral therapy (ART) regimens consist of 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus a third drug -- either a non-nucleoside reverse transcriptase inhibitor (NNRTI, a protease inhibitor (PI), or an integrase inhibitor. Such regimens are highly effective, but NRTIs and PIs can cause a variety of side effects, prompting exploration of NRTI- and PI-free alternatives.

Ruxandra Calin from Hôpital Pitié-Salpêtrière and colleagues evaluated the virological efficacy of raltegravir plus etravirine as a maintenance regimen for people with suppressed HIV viral load (<50 copies/mL) who wished to switch from their current standard ART combination.

Raltegravir and etravirine both have favorable toxicity profiles and present a lower risk of drug-drug interactions compared to other antiretrovirals, the researchers noted as background. However, this combination warrants caution because raltegravir has a relatively low genetic barrier to resistance, especially in people with extensive treatment experience.

This observational study enrolled 91 participants at a single center in Paris starting in January 2008. The median age was about 54 years and they had been on ART for a median of 17 years. During this time they had tried a median of 10 regimens and had suppressed viral load (<200 copies/mL) for a median of 4 years. The median baseline CD4 T-cell count was high at 558 cells/mm³, but many had previous advanced immune suppression, with a median nadir (lowest-ever) count of 166 cells/mm³.

Participants switched from a NNRTI- or PI-based regimen containing NRTIs to a dual regimen of 400 mg twice-daily raltegravir plus 200 mg twice- daily etravirine.

The primary endpoint was maintenance of viral suppression, with treatment failure defined as 2 consecutive viral load measurements above 50 copies/mL. The median duration of follow-up was 11.5 months, during which 65 patients reached the 6-month endpoint and 48 reached the 12-month endpoint.

Results

• The main reasons for switching regimens were metabolic abnormalities or lipodystrophy (21%), desire for treatment simplification (10%), kidney toxicity (9%), gastrointestinal toxicity (9%), bone toxicity (7%), liver toxicity (6%), and neurological side effects (6%).
• In a per protocol analysis, 98% of participant maintained viral suppression at 6 months and 92% did so at 12 months after switching.
• 21 people (23%) stopped taking raltegravir/etravirine, including 3 due to virological failure and 5 due to possibly related side effects.
• 1 person experienced virological failure by month 6, and 2 more did so by month 12.
• The 3 patients (3%) with virological failure all had a history of previous NNRTI use, though not NNRTI treatment failure.
• 1 of these patients had pre-existing etravirine resistance mutations (K103N and Y181C) and 1 had a mutation (V179I) "impacting, but not compromising" etravirine activity.
• 2 participants acquired NNRTI resistance mutations (P225H and V72I) after virological failure, 1 of whom also acquired an integrase resistance mutation (N155H).

Based on these findings, the researchers concluded, "Dual therapy with raltegravir plus etravirine represents a potentially safe NRTI/PI-sparing strategy in virologically suppressed patients with sensitive strains."

However, they cautioned, "Before switching clinicians should check for potential prior resistance to NNRTIs." A larger prospective study of this approach is currently underway.

8/14/13

Reference

R Calin, M-A Valantin, A Simon, et al. Raltegravir/etravirine dual therapy as a virologically safe treatment option in suppressed HIV-1-infected patients without previous NNRTI failure. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WEPE516.