The Treatment Puzzle: By Vivienne Walz

In the case of HIV/AIDS, managing the disease is all about consistently inhibiting viral replication. This depends on many factors that all fit together in a unique way, including the potency of the regimen, drug resistance and exposure, dosing frequency, and some physiological factors such as the absorption of the drug by the body and how much of the drug is filtered out by the kidneys. But surprisingly, one of the most difficult factors to monitor and to control is not pharmacological, nor physiological. This factor is adherence.

Adherence is such a complex factor mainly because it depends on human behaviour. But contrary to focusing on raising average adherence, to prevent viral replication the crucial factor is actually to reduce the largest interdose interval. This means that the longer the treatment interruption, the greater the HIV-RNA replication. So, the time between missed doses is a crucial factor in preventing viral replication.

The reason for this relationship is that antiretroviral drugs have long half-lives, which means that they slowly deactivate once ingested. So, interspaced missed doses can occur without letting the drug’s concentration fall below therapeutic (effective) levels, since some of the drug is still left over in the bloodstream. However if too many doses are missed in a row, then the drug’s effects fall below the level at which they inhibit viral replication.

This observation puts into question the importance given to a 95% adherence goal, and suggests that more importance should be put into making sure that less consecutive doses are missed instead of only increasing average adherence. This insight on adherence patterns will lead to better treatment counseling and therefore better treatment results for PHAs!

Source: Number of missed doses: why 1 x 7 does not make 7 x 1?. Parienti, Jean-Jacques; Paterson, David. AIDS. Volume 26(11).