Efavirenz dreaming
*Alan, from Suffolk Park NSW, writes*: I’ve been on 3TC, ritonavir, indinavir, abacavir and efavirenz since the beginning of 2000 and have tolerated the regimen except for two occasions two years apart. Because the incidents started during sleep I presumed they were a reaction between what I had consumed and efavirenz (usually taken before going to bed). The first was after drinking the liqueur “Jagermeister” and the second was after having poached pears in a liquid containing (as best as I can ascertain) galangal root and five spices. I continued taking efavirenz and had no further problems. At the time of the incidents I felt I was losing my mind for a few hours. Have any other readers had similar experiences that could be related to mysterious concoctions?
Dr Nick replies: Pharmacokinetic interactions — when one drug (or herb) affects the blood level of another drug — are important, particularly with a complicated regimen like yours. Ritonavir, for example, increases the level of indinavir in the bloodstream by increasing the absorption of indinavir from the intestine and decreasing the rate at which it is broken down by the liver. With more coming in and less going out the blood level will be higher. In the case of indinavir this approach allows more convenient twice-daily dosing without strict dietary requirements.
The herb St John’s wort can increase the breakdown of many drugs in the liver, leading to lower drug levels and potentially leading to the development of antiviral drug resistance.
Diet also has an effect. When taken with a fatty meal the absorption of efavirenz is increased: blood levels increase and the possibility of side effects is also increased.
Another, less often-discussed, sort of interaction is the interaction of the different drugs on different parts of the body. For example, if efavirenz has an effect on your brain and so do the herbs that you are taking, there might be an additive effect in the CNS toxicity that is experienced.
Efavirenz’s side effects are still being debated. One recent study was unable to find any differences between placebo and efavirenz on sleep patterns after the first four weeks of treatment. This doesn’t mean that no one experiences sleep disturbances, but that the proportion experiencing them or the severity of the symptoms was too small to appear in this study.
In your situation, the interactions are complex. The presence of ritonavir may dramatically increase the blood levels of the active substances present in the herbs you are taking, in the same way that it increases the blood levels of indinavir. These might interact to increase the brain effects or toxicities present.
In short, people taking ritonavir need to be very careful about what other substances they ingest.
Shagged out
*Ben, from Marrickville NSW, writes*: I’ve been positive for more than 15 years and I’ve been doing well on the same combination (efavirenz, 3TC and abacavir) for the last four years. My T-cells are about 400 and my viral load is undetectable. My problem is that a lot of the time I’m really tired. I sleep 11 or 12 hours a night but even when I feel like I’ve slept soundly, my body aches and just getting out of bed can be a struggle. I’m not anaemic and there doesn’t seem any other direct cause. Could my medications be doing this to me?
Dr Nick replies: Tiredness, fatigue and exhaustion are extremely common physical symptoms in positive people. They can also be the most difficult to get to the bottom of. The main reason for this is that they are what are called “non-specific” symptoms — they can be the result of a myriad of causes or, probably most commonly, they are caused by a combination of different factors.
So the short answer to your question is that the medications could be causing your symptoms but it is not really possible to know if they are causing your symptoms in your particular case.
The first thing to do is exclude a specific medical cause for your tiredness. It sounds from your letter like you might have already done this. A full blood count to exclude anaemia, but also thyroid function tests (some people develop an underactive thyroid gland unrelated to HIV), a morning testosterone level (many people have declining levels over time), iron, B12 and folic acid levels (to exclude deficiencies) and a resting lactic acid level to exclude a serious metabolic side effect of your treatment. I would also want to exclude depression as a cause.
If nothing shows up, then lifestyle factors including drugs, alcohol, diet, exercise, stress levels and sleeping patterns will all need to be examined. Your dietician may be able to assist you in increasing energy levels. Complimentary therapies (including naturopathy and herbal medicine) can have a positive effect in this situation.
Ultimately if you and your doctor think that this medication might be causing the problem you might even consider changing or stopping temporarily as an experiment. This is not something you should do without in-depth discussion with your doctor. The risks and benefits need to be weighted up. Stopping treatment can promote the development of resistance, so you might need to change to a different combination for a few days to prevent this happening.
Percentage puzzle
*John, from Bendigo Vic, writes*: This is only a small question but as I live in the country I don’t get to see my doctor much to ask questions like this. I have gone through periods in the past ten years when I’ve had very low T-cell counts (below 50) and now I’m doing really well on a regimen of d4T, 3TC, amprenavir, ritonavir and tenofovir. For the first time in ten years I now have 500 T-cells and a viral load of 2000. (I’m happy with the viral load because it is much better than the six-figure counts I’ve had in the past.) But my T-cell percentage is still only 14 percent. It has been as low as 11 percent and I’m glad it’s got to 14, but I’m told though that a reading of over 20 percent is necessary before you are really out of the woods clinically. What do you think? How important is the percentage count and what exactly does it show?
Dr Nick replies: Most of the research in the risk of AIDS-related illnesses has been done on the absolute CD4 count rather than the percentage, which is a bit of a shame as the total count seems to vary a lot more than the percentage which seems to stay stable.
When thinking about CD4 cells (the more precise term for the T-cells we are interested in) it is important to remember that these cells mostly live in the lymph nodes and spleen and use the bloodstream to move around the body. Because the bloodstream is easier to sample than lymph nodes, we rely on blood levels of CD4 cells. The CD4 count is the estimated total number of cells in every millionth of a litre of blood.
The percentage is a different way of looking at it: out of all the lymphocytes in the blood stream at any particular time, what percentage of them are CD4 cells? The total number can vary from hour to hour, but the percentage stays a little more stable.
Having said that, for most people most of the time there is a rough correlation between CD4 count and percentage. A CD4 count of 200 or greater, or a CD4 percentage of 14 percent or greater is associated with much reduced risk of AIDS-related illnesses (not 20 percent as you mention). Being on treatment and having a low viral load are also independent factors for a reduced risk.
Some people have a high count and a surprisingly low percentage and others have the reverse — a low count despite a high or rising percentage. The exact risks in these individuals have not been well quantified.
I think that in your case, your counts really are reassuring.
