Raltegravir: Long-Term Results

Knowledge about the long-term safety and effectiveness of potent combination HIV therapy (commonly called ART or HAART) is essential particularly if HIV-positive people are expected to take these medicines for the rest of their life. As mentioned earlier, raltegravir is the first integrase inhibitor approved for use by HIV-positive people. Long-term clinical trials with this drug continue. In one trial, researchers are comparing regimens based on raltegravir to those based on efavirenz (Sustiva and in Atripla). After four years of study, both combinations demonstrated good overall anti-HIV activity, although results appear to be better with raltegravir.

Study Details

Researchers randomly assigned 281 HIV-positive volunteers to receive raltegravir and 281 others to receive efavirenz. No participant had previously taken anti-HIV drugs. All participants also received tenofovir + FTC (Truvada).

The average profile of participants when they enrolled in the study was as follows:

• 81% men, 19% women
• age -- 37 years
• CD4+ cell count -- 200 cells
• viral load -- 100,000 copies/ml
• 6% were co-infected with hepatitis C virus (HCV)

Results -- Effectiveness

Here are the proportions of participants who had a viral load less than 50 copies/ml at different points in time:

Year 1

• raltegravir -- 86%
• efavirenz -- 82%

Year 2

• raltegravir -- 81%
• efavirenz -- 79%

Year 3

• raltegravir -- 78%
• efavirenz -- 70%

Year 4

• raltegravir -- 76%
• efavirenz -- 67%

These results suggest that raltegravir is no worse than efavirenz (the technical term for this is "non-inferior") over the short term. Moreover, over the long term there is the possibility that raltegravir may be superior to efavirenz.

Among participants whose viral load at the start of the study was more than 100,000 copies/ml, here are the proportions who had a suppressed viral load four years later:

• raltegravir -- 89%
• efavirenz -- 89%

Changes in CD4+ Cell Counts

In general, raltegravir users had slightly greater CD4+ cell counts throughout the study. By the fourth year of the study, changes in CD4+ counts (compared to their values at the start of the study) were as follows:

• raltegravir -- 361 more CD4+ cells
• efavirenz -- 301 more CD4+ cells

Dropouts

Participants left the clinical trial for several reasons, distributed as follows:

Raltegravir

Overall, 20% of participants prematurely left the study.

• 5 people left because their regimen failed
• nurses could no longer contact 8 people
• 13 people left because of adverse events
• 32 people left for a variety of other reasons

Efavirenz

Overall, 30% of participants prematurely left the study.

• 8 people left because their regimen failed
• nurses could no longer contact 17 people
• 26 people left because of adverse events
• 34 people left for a variety of other reasons

Factors such as gender and race did not affect the results of the study.

Changes in Lipids and Blood Sugar

In general, efavirenz users had statistically significant increases in the following assessments of lipids and glucose in the blood:

• total cholesterol
• good cholesterol (HDL-C)
• bad cholesterol (LDL-C)
• triglycerides
• glucose

However, a change in the ratio of total cholesterol to HDL-C among efavirenz users was not statistically significant. This ratio is useful in predicting the risk for cardiovascular disease.