Many people living with HIV, especially those who start treatment promptly using modern antiretrovirals, can stay on their first regimen for a long time. But others may have trouble taking their meds consistently, struggle with side effects, are unable to keep their viral load suppressed or may simply want a new regimen that is more convenient.

 

The good news is that treatment options have improved in recent years. Compared with older antiretrovirals, modern HIV meds are more potent, better tolerated, less prone to drug resistance and easier to take. Most people starting or switching treatment can use single-tablet regimens—single pills containing two or more drugs that are taken just once a day. Although heavily treatment-experienced people have fewer switch options, most can still find a regimen that maintains viral suppression.

 

There are several reasons for switching medications, including lack of viral suppression (virological failure), inadequate CD4 T-cell recovery (immunological failure), difficulty taking medications consistently, too many pills or too frequent dosing, side effects, drug interactions, pregnancy and medication cost or insurance issues.

 

Treatment failure means that some of the drugs in a regimen are not doing their job. The best way to tell whether your medications are working is to regularly measure viral load (the amount of HIV in the blood) and CD4 T-cell count.

 

Virus levels usually begin to decline soon after starting effective antiretrovirals. If your viral load does not fall to an undetectable level—or if it does not stay down—you are at risk for disease progression and could transmit the virus to others. However, it is important to look at trends over time. A single detectable viral load, or “blip,” is usually nothing to worry about, but if two consecutive tests show a rising virus level, it might be time to adjust your regimen.

 

One of the most common reasons for treatment failure is drug resistance, meaning the virus has developed mutations, or changes at the genetic level, that make it less susceptible to one or more antiretrovirals. This often happens due to poor adherence, or not taking medications as directed all the time, which allows HIV to resume replication. Factors that can interfere with good adherence include side effects, inconvenient dosing, forgetfulness, a hectic or unpredictable schedule, unstable housing and interrupted access to treatment due to cost. Poor absorption and drug interactions can also contribute to treatment failure.

 

Which new regimen to use depends on your treatment history and why you are switching. People who already have an undetectable viral load and wish to switch for other reasons will likely have more options. Some people still take older antiretrovirals and more complex regimens—figuring “if it’s not broke, don’t fix it”—but switching to newer combinations can make treatment easier.

 

Maintenance therapy—simplified regimens that aim to maintain viral suppression—is a switch option for many people who have already achieved an undetectable viral load. Traditionally, standard HIV regimens have included two nucleoside/nucleotide reverse transcriptase inhibitors plus a nonnucleoside reverse transcriptase inhibitor, protease inhibitor or integrase inhibitor. But people with viral suppression who have no history of treatment failure and no known resistance mutations may be able to switch to a two-drug regimen.

 

HIV treatment is moving in the direction of longer-acting regimens that are taken less often. Currently, the longest-acting complete regimen is Cabenuva (cabotegravir and rilpivirine), which is administered by injection once monthly or every other month. Once-weekly and once-monthly oral regimens and injectables that can be taken just twice a year are now in the pipeline.

 

When switching due to virological failure, it’s important to have a discussion with your doctor about adherence, side effects and other factors that could prevent your meds from working as they should. Resistance tests can show which drugs in your regimen are not active due to viral mutations and which alternative antiretrovirals are likely to work best.

 

Switching treatment is more challenging for people who have already used many drugs and have developed resistance to multiple medications, known as multidrug-resistant HIV. But with a better understanding of resistance and the development of new antiretrovirals that work in different ways, even people who have been living with HIV for years and have taken many prior regimens can usually find a treatment approach that keeps the virus in check.