No Benefits for Protease Inhibitor Plus Raltegravir As Second Line in HIV

A recent study showed that treatment with a protease inhibitor plus raltegravir offered no benefit over a protease inhibitor plus nucleoside reverse-transcriptase inhibitor (NRTI) regimen in patients with HIV.

James G. Hakim, MD, from the University of Zimbabwe Clinical Research Centre, Harare, and colleagues published the results of their study November 3, 2017, in the Lancet Infectious Diseases.

“Taking into account the higher cost of raltegravir, the absence of clear advantages of protease inhibitor plus raltegravir seen in any trial and the failure to show non-inferiority consistently across all analyses after 144 weeks of treatment in this trial suggest that there is no compelling reason for national programmes to adopt this combination as the standardized second-line therapy in the public health approach to antiretroviral therapy,” the authors write.

For patients with HIV, World Health Organization (WHO) guidelines currently recommend 2 NRTIs and a boosted protease inhibitor for second-line treatment antiretroviral therapy (ART), and suggest a protease inhibitor plus raltegravir as an alternative regimen.

According to Dr. Hakim and colleagues, however, resistance to NRTIs occurs after virological failure of first-line treatment in low-income countries, and this may affect future treatment options.

The researchers therefore conducted the EARNEST trial to investigate alternatives for second-line treatment. They wanted to determine whether the WHO-recommended regimen offers any benefit to patients with HIV over the standard protease inhibitor plus 2 NRTIs regimen.

The trial enrolled 1277 patients with HIV who had extensive resistance at randomization; 95% of patients had at least 1 NRTI mutation, and 59% had no active NRTIs.

Patients were randomly assigned to receive either: a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus 2 or 3 NRTIs (protease inhibitor plus NRTI group); a protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group); or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group).

The researchers followed the patients for 144 weeks.

Despite extensive NRTI resistance, the researchers found that the protease inhibitor plus NRTI group performed better than the other non-NRTI groups, with 86% of 426 patients having viral loads of less than 400 copies per mL by week 144, compared with 81% patients in the protease inhibitor plus raltegravir group, and 78% patients in the protease inhibitor monotherapy group.

“There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification,” the authors add.

The results of this study have important implications for the selection of second-line therapy in the public health approach to ART.

“The good longer-term outcomes with the combination of a protease inhibitor (in this case lopinavir) with 2 NRTIs provides support for this regimen as the WHO-recommended preferred second-line combination,” the authors conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.