Question

Do side effects from using early HIV drugs still affect long-term health now?

25 September 2026. Related: All topics, Living with HIV long-term, Side effects.

Answer

Answer: Simon Collins

Hi there

Thanks, this is a great question.

The answer is very relevant for those of us that have been on ART for many years and are now getting older.

The answer will also depend on someone’s individual HIV and treatment history.

Some early side effects were not reversible, so people still have these, even after switching to better HIV drugs years ago.

Although there might be a small residual risk from using those early drugs, switching to better drugs will have limited any other long-term problems. These early drugs were mainly used when there were few other options. This means that it is difficult to know whether any small residual risk is related to untreated HIV itself rather than the treatment.

For many people these were also life-saving drugs and we needed to use them until better drugs came along later. Some early drugs, including lamivudine (3TC), emtricitabine (FTC), tenofovir DF are still very widely used and didn’t cause such difficult problems.

Luckily, recent HIV drugs have a very low risk of complications. There are also more alternative meds to chose from if one drug is causing problems.

A more detailed response is below.

Which drugs and which side effects

Some early nukes (NRTIs) were difficult, especially the d-drugs (ie ddC, ddI and d4T).  Also, AZT and abacavir, to a lesser extent. Anyone who developed peripheral neuropathy then probably still suffers from this today as the nerve damage was rarely reversible. Similarly, the fat loss they caused is unlikely to have been reversed.

The mitochondrial damage from these drugs might also increase the long-term risk of some age-related complications. However, these might also be higher because of the time many of us spent with detectable HIV viral load before treatment became available. Untreated, HIV itself can cause similar long-term complications.

Early protease inhibitors like indinavir, saquinavir, nelfinavir and full-dose ritonavir also increased the risk of metabolic complications, including diabetes and body shape changes (lipodystrophy).

All these drugs were commonly used during the first 10 years of ART, roughly from 1995-2005.

You also mentioned efavirenz, which quickly became first-line therapy from 1998, especially after it was coformulated with AZT and lamivudine (3TC) in 2006. Efavirenz continued to be recommended globally in a generic combination (with tenofovir DF and lamivudine) called TLE. WHO guidelines recommend using dolutegravir now (in a combination called TLD) instead of efavirenz.

Luckily, most HIV drugs developed since 2000, including tenofovir, darunavir and newer NNRTIs (etravirine, rilpivirine and doravirine) had much fewer serious side effects and have been much easier to take. From 2012, this also covers combinations based on integrase inhibitors, especially dolutegravir, bictegravir which are now recommended as first-line ART, and the injectable cabotegravir-LA.

Will side effects from older HIV meds like indinavir, efivirenz and from early nukes and protease inhibitors, still impact people years later? Do they affect my long-term health now?