Not only can ViiV Healthcare’s Selzentry (maraviroc) increase the chances of achieving an undetectable viral load in treatment-experienced people living with HIV, but it can also contribute to greater improvements in CD4 counts. This is the main conclusion of a study published online December 9 by the Journal of Acquired Immune Deficiency Syndromes, which also showed that such CD4 gains are associated with a lower risk of developing a new AIDS-related opportunistic infection or a drop in CD4s to a level below 200.

There has been growing interest in the observation that CCR5 inhibitors—such as Selzentry—achieve higher-than-usual CD4 gains, an important finding for people with advanced, drug-resistant HIV disease. In studies conducted thus far, people receiving an entry inhibitor plus an optimized background regimen (OBR) gained more CD4 cells than people receiving a placebo plus OBR.

Data from large clinical trials are needed to further explore this potential benefit, notably to figure out whether Selzentry improves CD4s because it is more likely to reduce viral load to undetectable levels compared with those taking placebo plus OBR, or because the drug potentially has unique CD4-boosting attributes. Moreover, it is necessary to determine whether the CD4 cell advantage among those being treated with Selzentry—and potentially other CCR5-blocking agents—actually contributes to longer, disease-free survival.

David Asmuth, MD, from the University of California in Davis, and his colleagues conducted an analysis of two Selzentry studies, MOTIVATE-1 and MOTIVATE-2, to address these lingering questions. Both trials compared Selzentry to a placebo, and both were combined with an OBR.

Asmuth’s team found that people taking Selzentry gained significantly more CD4 cells than those taking a placebo. The placebo group gained on average about 24 CD4 cells over the course of the study, while those receiving Selzentry once daily gained 92 cells and those receiving it twice daily gained 103 cells.

The difference in CD4s between the two groups wasn’t surprising, given that significantly more people on Selzentry also achieved an undetectable viral load. In turn, Asmuth’s team explored whether they would get a similar result if they only looked at people who achieved a viral load of less than 50 copies at least once. Again, the difference remained—people who received Selzentry plus OBR gained, on average, 26 more CD4 cells than people on a placebo plus OBR by week 48 of treatment.

Though the MOTIVATE studies were not designed to look at differences in the development of opportunistic infections, the authors found that current CD4 count was associated with a 20 percent reduction for every 25 cells gained in the risk of developing an AIDS-defining event, such as an opportunistic infection or CD4s dropping below 200. This offers a hint that the additional CD4s gained by people on Selzentry might have made a difference in the risk of illness.

The authors caution that analyses conducted after a clinical trial has been completed can’t provide definitive answers to scientific questions. They can, however, uncover trends or hint at possible differences in efficacy or safety of a treatment.

The researchers conclude that people taking Selzentry had significantly higher CD4 increases than people on placebo, and that the CD4 increases appear to have influenced a person’s risk for developing an AIDS-defining event.