Isentress HD in clinical trials

In a two-year trial called Oncemrk, researchers in Canada and other countries compared a regimen containing the older formulation of raltegravir (Isentress) to a regimen containing the new formulation of raltegravir (Isentress HD). Analysing the data after one year, researchers found that Isentress HD was roughly equivalent in effectiveness and safety to the older formulation.

Study details

Researchers randomly assigned HIV-positive adults who had never previously been treated, in a 2:1 ratio, to one of the following regimens:

• Isentress HD 1,200 mg (taken once daily) + Truvada (tenofovir + FTC) – 533 people
• Isentress 400 mg (taken twice daily) + Truvada – 269 people

The average profile of participants upon entering the study was as follows:

• 85% men, 15% women
• age – 34 years
• history of AIDS – 12%
• co-infected with hepatitis B or C viruses – 3%
• HIV viral load – 36,000 copies/mL; 28% of participants had a viral load greater than 100,000 copies/mL
• CD4+ count – 390 cells/mm³

Results—Changes to viral loads and CD4+ cell counts

Both regimens were highly effective and viral loads fell rapidly in the study regardless of which formulation of raltegravir was used. For instance, by the fourth week of the study the following proportions of participants had a viral load less than 40 copies/mL:

• Isentress HD-based regimen – 54%
• a regimen based on the older formulation of raltegravir – 52%

By the 24^th week of the study the figures were as follows:

• Isentress HD-based regimen – 87%
• a regimen based on the older formulation of raltegravir – 87%

By the 48^th week of the study the figures were as follows:

• Isentress HD-based regimen – 89%
• a regimen based on the older formulation of raltegravir – 88%

Among participants who entered the study with a viral load greater than 100,000 copies/mL, the figures at week 48 were as follows:

• Isentress HD-based regimen – 87%
• a regimen based on the older formulation of raltegravir – 84%

Increases in CD4+ cell counts

Overall, CD4+ cell counts increased by an additional 230 cells/mm³ at the end of the study. This meant that on average a person’s cell count had moved from almost 400 cells at the start of the study to about 600 cells/mm³ at week 48.

Based on these results, the new formulation of raltegravir is roughly equivalent to the older formulation. The technical term for this is non-inferior.

Sub-analyses of the study found that both study regimens were similarly effective in men, women and people of different ethno-cultural groups.

Adverse events

Side effects are common during the first few days or weeks of a new regimen. Integrase inhibitor–based regimens are generally well tolerated and adverse effects tend to fade over time.

Overall, the distribution of drug-related adverse effects were as follows:

• Isentress HD-based regimen – 25%
• a regimen based on the older formulation of raltegravir – 26%

The most common side effects associated with Isentress HD are as follows:

• difficulty falling asleep
• headache
• dizziness
• nausea
• fatigue

However, in general, these side effects were less common in people who used Isentress HD compared to the older formulation of raltegravir.

More detailed information on Isentress HD, including uncommon side effects, will appear in a CATIE factsheet that is being developed on this drug.

There were three deaths in the study, none of which appeared to be related to the use of the study medicines. Instead, the deaths were likely related to underlying disease processes (immunological dysfunction and deficiency) caused by HIV. The deaths were distributed as follows:

• Isentress HD-based regimen – lymphoma (diagnosed on the 36^th day of the study); tuberculosis (diagnosed on the 7^th day of the study)
• a regimen based on the older formulation of raltegravir – multiple life-threatening infections occurring on the 17^th day of the study

Summary

Regimens based on the new or old formulation of raltegravir appear to be equally effective in people who have not previously taken HIV treatment. Both regimens were generally safe.

—Sean R. Hosein

REFERENCES:

1. Cahn P, Kaplan R, Sax P, et al. Raltegravir 1200 mg once daily is non-inferior to raltegravir 400 mg twice daily, in combination with tenofovir/emtricitabine, in treatment-naïve HIV-1-infected subjects: week 48 results. In: Program and abstracts of the 21st International AIDS Conference (AIDS 2016), Durban, South Africa, 18-22 July 2016. Abstract FRAB0103LB.
2. Cahn P, Kaplan R, Sax P, et al. Subgroup analyses from Oncemrk, a phase III study of raltegravir 1200 mg once daily vs. raltegravir 400 mg twice daily; in combination with tenofovir/emtricitabine, in treatment-naïve HIV-1-infected subjects. In: Program and abstracts the International Congress on Drug Therapy in HIV infection, 23-26 October 2016. Abstract 3514101.