Changing HIV treatment

If a current antiretroviral regimen is no longer suppressing HIV or is causing intolerable side-effects, it may be time to consider adding more drugs or switching one or more drugs in the combination.

Some newly developed drugs, new drug classes (entry inhibitors), and treatment strategies (protease inhibitor boosting) have made HIV therapy easier for many patients. It may be possible to switch to drugs that are taken less often or have a lower pill burden, including fixed-dose formulations that combine two or more drugs in a single pill. Treatment simplification usually works best when people are on one of their first regimens and have minimal drug resistance.

There is also reason to consider a change if a person is taking an older regimen that is no longer recommended, such as a combination containing only two drugs, a nucleoside/nucleotide (NRTI/NtRTI) backbone containing d4T (stavudine, Zerit), or an unboosted ‘first-generation’ protease inhibitor.

This is also true if a person has a change in health status, for example pregnancy or development of tuberculosis or hepatitis B or C, which may change which antiretroviral drugs are recommended.

Other patients switch because they are experiencing side-effects they find difficult to tolerate, including metabolic complications such as lipodystrophy (body fat changes) or elevated blood fat levels. Drug toxicity is the most common reason for changing a first antiretroviral regimen. With more than 20 antiretroviral drugs now available, it is often possible to switch to a new combination that causes fewer side-effects and enables better adherence.

Switching off d4T, for example, is likely to improve peripheral fat loss (although improvement is usually slow). Changing from a protease inhibitor to an NNRTI, or to atazanavir, can reduce elevated blood fat levels. But many side-effects can be managed effectively without changing antiretroviral therapy.

If viral load remains suppressed, HIV has probably not developed extensive drug resistance. Switching is generally safe under these circumstances and the focus can be on finding equally effective drugs with fewer toxicities. If a switch is done for simplification or to reduce side-effects, it may be possible to change just one problematic drug.

People who have successfully suppressed HIV may later experience viral rebound or breakthrough (rising viral load whilst still on therapy). Many patients experience transient viral load ‘blips’ that return to undetectable levels with no change in treatment. For this reason, experts recommend a repeat viral load test to determine a trend before changing drugs.

If viral load remains elevated, it is usually an indication that a new regimen is needed. An assessment of all possible causes for viral rebound should be considered. Causes might include adherence, drug resistance, drug exposure, regimen potency and toxicities, drug interactions with other medications or food, and clinician experience in constructing regimens and interpreting resistance data.

CD4 cell counts usually rise when treatment suppresses viral load, thereby allowing the immune system to recover. However, this does not always happen. If CD4 count is falling close to or below 200 cells/mm³, there is a strong argument for changing regimens.

Resistance testing can determine whether resistance has developed and if so, the mutations involved. Therapeutic drug monitoring (TDM) can also be used in some cases to see if adequate drugs levels are being achieved.