Changing HIV treatment

Derek Thaczuk

Antiretroviral regimens are usually changed for one or more of the following reasons:

  • An unacceptable level of drug toxicities and/or side-effects
  • Problems with adherence
  • Failure to control viral load
  • Being on a suboptimal regimen
  • Change in medical condition and/or acquisition of other illness.

Regimen change can include: 

  • Selecting all new drugs 
  • Adding an agent from a class not currently included in the regimen
  • Adding a boosting agent to increase trough drug levels 
  • Adding a drug to strengthen a suboptimal regimen
  • Switching out one drug for another from the same class to lessen pill burden, toxicity, or side-effects.

Newly developed drugs, new drug classes (entry and integrase 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 and/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.

Drug toxicity, whether related to a particular drug or to a whole drug class, is one of the most common reasons for changing a first antiretroviral regimen. Toxicity ranges in effect from manageable side-effects (headache) to adverse events that cause morbidity and mortality (hypersensitivity). Some side-effects lessen or resolve after continued exposure to a drug.  

Many patients change regimens if they are experiencing side-effects they find difficult to tolerate, including metabolic complications such as lipodystrophy (body fat changes) or elevated blood fat levels. Side-effects can be temporal (injection-site reactions), reversible (through changing the offending drug in the regimen), or long-term (atherosclerosis).

HIV has probably not developed extensive drug resistance if viral load remains suppressed. In this case, switching is generally safe and the focus can be on finding equally effective drugs with fewer toxicities. If the change is being made to simplify a regimen or to reduce side-effects with a particular drug, it may be possible to change just the one problematic drug. With over 20 antiretroviral drugs now available, it is often possible to change to a new regimen that causes fewer side-effects and enables better adherence. 

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.

Detectable viral load is an indicator to change the treatment regimen. Treatment failure usually results from drug resistance or inadequate adherence. An assessment of possible causes for viral rebound should be considered, including level of adherence, regimen potency, drug resistance, and amount of drug exposure.

Resistance testing can confirm the presence of resistance, identify the mutations involved, and guide selection of a subsequent regimen. Therapeutic drug monitoring (TDM) can also be used in some cases to see if adequate drugs levels are being achieved. Assessment of virological failure is best done by a clinician with experience in interpreting resistance data and constructing effective treatment regimens.

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

Suboptimal regimens are ones once recommended (such as monotherapy or dual nucleoside regimens), but whose continued use can no longer be supported. Even if a suboptimal regimen is controlling viral load, it leaves the door open for accumulating additional resistance mutations and the regimen should be changed if other treatment options are available. 

Regimens are also changed in response to alterations in health status (e.g. pregnancy) and to avoid adverse reactions with other underlying or acquired illness and/or treatment of such (e.g. tuberculosis, hepatitis).