Question

Which HIV drugs cause lipodystrophy?

4 January 2016. Related: All topics, Side effects, Starting treatment.

I’m not on treatment yet but I am trying to learn about it before I start.

I am very worried about lipoatrophy and lipodistrophy. Can you tell me which is the best treatment combination for not producing these side effects?

From my reading the integrase inhibitor raltegravir (Isentress) and entry inhibitor maraviroc sound like the best option. What do you think?

Answer

Answer: Simon Collins

Hi

It is good that you are looking at treatment options before starting treatment. Although lipoatrophy was a worry oin the past, none of the drugs used in 2016 for starting treatment  have this side effect.

Lipoatrophy is the term for fat loss and lipohypertrophy is the term for fat gain.

Lipodystrophy is a term for general changes in body fat, which includes fat loss and fat accumulation. Although everyone is likely to worry about this side effect, luckily the chance that it will occur is very low.

Body changes are reported less often with all the first line combinations in UK or US treatment guidelines. So these are side affects that related to when treatment was first developed 20 years ago.

Fat loss was almost entirely related to use of d4T (stavudine) or AZT (zidovudine) – neither of which are recommended in Western countries anymore.

Fat accumulation is more complex because it has been reported with all types of combinations. Although this was first linked with early protease inhibitors, it was also reported with NNRTIs like nevirapine and efavirenz.

It seemed plausible that drugs that increased blood lipids like cholesterol and triglcerides  might also be causing fat accumulation. So when newer lipid neutral drugs like atazanavir and raltegravir were developed it was hoped they would also not cause lipodystrophy.

However, this wasn’t seen in studies. Atazanavir, even unboosted by ritonavir, didn’t show less fat distribution compared to lopinavir/ritonavir (Kaletra), for example. Similarly, the hope that integrase inhibitors might have a clean lipodystrophy profile was not seen in studies, where raltegravir was similar to efavirenz.

The mechanism behind fat accumulation has still not been explained. Luckily fat accumulation seems much less common with little difference between efavirenz, atazanavir/ritonavir, darunavir/ritonavir or raltegravir, when any of these four first-line options are used with either tenofovir/FTC or abacavir/3TC.

Although maraviroc had less of an impact on cholesterol and triglycerides compared to efavirenz, I haven’t seen any reports of the impact on lipodystrophy. Also, maraviroc is not currently licensed for first-line therapy.

This means it is probably best to pick your choice based on other properties of these drugs, in discussion with your doctor, knowing that if you get side effects you could at lest switch to alternatives.

Frist line options are listed in the i-Base introduction to combination therapy, especially in the ‘which drug, which combination‘ section.

The i-Base guide to side effects includes about 14 pages on lipodystrophy and metabolic changes.

This answer was updated in January 2016 from a question first posted on 4 September 2012.