Antiretroviral Alternatives: What Works When First-Line Drugs Fail

When someone with HIV needs to switch meds, it’s not just about finding another pill—it’s about finding the right antiretroviral alternatives, medications used to suppress HIV when first-line treatments stop working or cause intolerable side effects. Also known as HIV salvage therapy, these options are chosen based on resistance patterns, side effect profiles, and how well they fit into a person’s daily life. The goal isn’t just to lower viral load—it’s to keep it low for decades without new problems.

Many people start with combinations like tenofovir plus emtricitabine plus efavirenz, but over time, side effects like weight gain, nerve pain, or sleep issues can make those drugs hard to stick with. That’s where dolutegravir, a modern integrase inhibitor known for high effectiveness and fewer side effects comes in. Or maybe rilpivirine, a once-daily pill with less impact on cholesterol and mood. For those with drug resistance, ibalizumab, a monoclonal antibody given by infusion offers a completely different mechanism, bypassing common resistance pathways. These aren’t just backups—they’re smarter tools built on years of clinical data.

What most people don’t realize is that switching isn’t just about the drug—it’s about the whole package. Some antiretroviral alternatives come in single-pill forms, reducing pill burden. Others have fewer interactions with common meds like statins or antidepressants. And for those worried about bone or kidney health, newer options like tenofovir alafenamide (TAF) are gentler than older versions. The key is matching the drug to the person—not just the virus.

Below, you’ll find real comparisons of HIV meds people actually use, from generic versions that cut costs without cutting efficacy to newer drugs that help with long-term side effects. These aren’t theoretical guides—they’re based on what’s working for people right now, with honest takes on what to expect, what to watch for, and when to ask for a change.