Isentress and Modafinil (PROVIGIL)


Hi, I have been Hiv positive for 18 years. I am 34 and my viral load is 759 and cd-4 is 387. I have had my cd-4 count down to single digits in the past. I am currently taking Isentress/Epzicom/viread. I am also on Valtrax for Herpes. Now My question is this. I sleep around 13-17 hours a day and have absolutely no energy. I fell no better now (energy wise) than I did with a cd-4 count of 6 and a viral load of 750,000. I have read some blogs on the use of Modafinil to give energy and improve me always sleeping. I was wondering your imput on this. I know there is a study underway in New York on this matter. It will not be over till the end of 2009. I just can not wait this long. If you think its a good idea, is there any where I can find information supporting this combo of drugs . I go to a Infections Disease for my Hiv but he will only perscribe me Hiv meds only. So I am going to my Primary Care Doctor for the Modafinil. But he needs something to support this because he is not familiar with using Modafinil to traet fatigue and Hiv.

Thanks , Michael in Georgia


Hi Michael in Georgia,

Your first stop should be your HIV specialist for a comprehensive evaluation of your fatigue. The best approach to HIV-associated fatigue is to determine the underlying cause or causes of the fatigue. Fatigue is not a disease, but rather a symptom of an underlying condition. HIV-associated fatigue is extremely common and often multifactorial in nature. Your HIV specialist should be able to help you identify the exact cause or causes of your fatigue. Begin by reading the chapter in the archives of this forum pertaining to causes of HIV-associated fatigue. Make a list of the common causes (anemia, occult infection, drug side effects, psychological causes, hormonal imbalances, etc.) as well as the not-so-common causes (sleep apnea, etc.) and discuss each of these with your doctor. He will order the appropriate laboratory tests (thyroid studies, testosterone level, hemoglobin level, etc.). With a bit of cooperative detective work the two of you should be able to identify underlying causes. Specific treatment can then be started to combat each of these problems. (You can read about these specific treatments in the chapter in the archives devoted to treatment of HIV-associated fatigue.) Certainly HIV itself, like many acute and chronic viral illnesses, can cause fatigue. Once all underlying causes have been identified and treated, if your fatigue persists, a trial of modafinil may be warranted. There are no significant drug interactions among Provigil, Isentress, Epzicom, and Viread.

I'll post below some information from the archives pertaining to modafinil (Provigil). It is indeed being used for HIV-associated intractable fatigue. As you mentioned, there is also a clinical trial in progress.

Good luck Michael.

Dr. Bob

Fatigue - Provigil effectiveness seems to be waning? Dec 28, 2008

I've been trying to deal with my HIV / AIDS related fatigue for over eight years now. Recently I thought I'd finally found some relief with Provigil but I'm afraid it's effectiveness seems to be waning. Can that happen? I'm already taking 200mg a day and on occassion 300mg a day just to survive but my fatigue is coming back with a vengance and I'm worried I'm throwing good money away on a drug thats losing it's effectiveness. Have you heard of other HIV / AIDS patients who's Provigil isn't working for them?

Here's my history.

over eight years ago I walked into my doctors office and said, "Dr. I'm sick and tired of being sick and tired. HELP! I can sleep fifteen hours a day and it's still not enough. I cannot get rid of this fatigue"

Initially my well respected DC specialist assumed it was depression and prescribed Prozac. That did NOT work. Later that year I moved to Los Angeles with my partner and my new Doctor prescribed Paxil. That didn't help at ALL. Assuming it was all in my head I gave up on fighting fatigue and lived with it. For many years I had little to no sex drive, little enthusiasm for anything and sustained no longterm friendships outside my relationship with my partner. It was all I could do to run my own home much less interact with others.

In 2003 we moved back to DC and found a new HIV / AIDS specialist. He prescribed Welbutrin XL and found I had low testosterone. He prescribed a gel but due to a skin condition we switched to 1 ML injections of Testoserone Cypionate every three weeks.

While the combination of the two helped a little it was NOT without it's side effectcs. I eventually gained 30 lbs and developed hyperhydrosis.

Only this year did my doctor finally suggest a sleep clinic. I came back with a diagnosis of only "Borderline" sleep apnea. Thankfully that was good enough for my Docotor and he finally prescribed 200mg of Provigil taken dailey.

As soon as I started the Provigil I was a completely new person. An actual contributing member of the household. I actually started enjoying life again and started seeking out new friends. I quit taking th Welbutrin XL and within four months had gone from 226lbs to 196 lbs. My partner called it the "Great Awakening".

My problem is that the fatigue is creeping back into my life. I've charted my daily sleep and fatigue cycles so I KNOW it's not just a feeling. It's real. Where can I go from here? I can't go back to being a zombie again.

Any suggestions would be greatly appreciated.

Response from Dr. Frascino


Fatigue in the setting of HIV disease is common. The cause is often multifactorial, which means there are multiple underlying conditions working in tandem to drain your energy batteries. This certainly seems to be the case with you. Not only are you HIV positive, but you also have hypogonadism (low serum testosterone), depression and borderline sleep apnea. The best way to combat HIV-associated fatigue is to identify all the underlying conditions contributing to the fatigue and treat each one individually.

Your HIV specialist should perform a thorough evaluation of your HIV-associated fatigue and rule out the common and not-so-common causes. (You can learn about these by reviewing the chapter on causes of HIV-associated fatigue in the archives.) Hopefully your HIV infection is under good control. If not, that should be a top priority. Next, have you checked to see if your testosterone supplementation is adequate? You should get an AM "free testosterone" level drawn prior to your next injection. Third, what about your depression? You didn't do well on Prozac, Paxil or Wellbutrin XL. However, perhaps counseling or one of the newer antidepressant drugs could be tried.

Provigil may still be helping in its own way. But it will not help low serum testosterone or depression or many other conditions possibly contributing to fatigue.

I would suggest you and your HIV specialist undertake some cooperative detective work to further investigate exactly what is underlying your fatigue and then aggressively treat each contributing factor.

Good luck.

Dr. Bob

Provigil Jul 9, 2007

What are your thoughts about using Provigil to improve fatigue?

Advertisement Response from Dr. Frascino


My thoughts haven't changed since the last time I addressed this question. (See below.)

Dr. Bob

Provigil Oct 20, 2006

Simple.Whatttay think about the use of the drug Provigil for the fatigue/sleepiness/brain-fog etc,syndromes that we talk about here...It sounds very interesting.Would love to hear your feedback on this. Thanks for all you do. Best Regards Dr.Bob, S.

Response from Dr. Frascino

Hi S,

This topic comes up frequently, as we are all looking for a quick fix for our energy drain. I'll post a few questions from the archives that address Provigil and HIV-related fatigue.

Be well.

Dr. Bob

Tired of HIV, but also just tired Jul 18, 2006

I have looked at a few of your earlier responses to the question of whether or not Provigil is a good drug for HIV fatigue, and you seemed at the time to really not be a fan. Time has passed and it looks like a few studies have shown its effectiveness. What are your thoughts now? I am a 31 year old woman with HIV/AIDS for 14 years. I work full time, take my meds (Truvada and Lexiva), and have done pretty well considering everything. I currently have low level virus and a Tcell count in the 400 range, but I am tired. Not just a little bit, but falling asleep at my desk tired. The fatigue didn't come on suddenly, but has progressed over the last few years. It isn't constant, but is really starting to affect my life. My doctor has ruled out other causes such as hypothyroid, anemia, etc. He suggested medication for 'HIV related fatigue" and offered ritalin type drugs or Provigil. It seems to me like Provigil has fewer side effects and is generally a better tolerated medication than true stimulants. What are your thoughts? Do you still have reservations about the drug? Should I explore other options besides drugs? Thanks for your time.

Response from Dr. Frascino

Hello Tired,

Fatigue in the setting of HIV disease is common and the underlying cause or causes can be difficult to diagnose. I would certainly continue to work closely with your HIV specialist to try to identify any underlying problems that might be contributing to feelings of fatigue, including psychological causes, such as depression; occult unrecognized infections; hormonal imbalances; inadequate sleep, rest, diet or exercise; drug side effects, toxicities or interactions; etc. Review the archives of this forum for additional details about the common, as well as host of not-so-common, causes of HIV related fatigue and discuss these with your HIV specialist.

Regarding Provigil, yes, we do have more experience with this agent and yes, some folks have found it helpful. My biggest concern remains its metabolic pathway (the cytochrome P-450 enzyme system), because many HIV drugs also use these same enzymes. A competent and experienced HIV specialist should be able to make any necessary dose adjustments, if Provigil is tried. In general I, too, would prefer the non-amphetamine drugs, like Provigil, over the amphetamine-type agents, such as Ritalin. I'll post a few questions form the archives that address the use of Provigil for HIV-associated fatigue.

Good luck! If you do try it, let us know if it works for you!

Dr. Bob

What about Provigil (energy booster)-is it addictive? Jul 5, 2004

two different specialists recommended Provigil to me because i get extremely tired very early. The FDA approves of it for narcolepsy, which i don't think i have. Any how, a month after starting it, I found a flyer at GMHC i think about being a part of a study using Provigil for HIV people. The drug works so well for me and so consistently well, meaning I don't get used to it and so i don't have to increase3 the dosage of 200 mg. (Sometimes, rarely) i take 300 mg. I was worried because i'm in 12-Step programs and thought it was an addictive substance since i felt good and energetic with it (i have insomnia as well). But i researched the heck online about it and could not find anything saying it was addictive. In fact, it is not a triplet prescription (very controlled substance), though it is slightly controlled (but so is everything you need a prescription for). It does not work the same for everyone and most likely you'll need prior approval -- it's $193.00 a month without approval with my HMO and not covered by adap. But $5 after it's approved. It is an amazing drug and was recommended as i said above by both my specialist pain doctor and my psychiatrist. My question is, since it is a relatively new drug, is it addictive. I know that if I stop abruptly, i will be very tired for a few days but that seems to be the only withdrawal effect it has. But i am concerned. Thanks.

Response from Dr. Frascino


You mention two different specialists a pain specialist and a psychiatrist recommended Provigil. Have you discussed this with your HIV specialist as well? Since this is an HIV information website and you found the flyer at GMHC, I'm assuming you are HIV positive, correct?

Is Provigil addictive? I have seen some clinical studies that indicate it could be. We know it is "reinforcing," as evidenced by its self-administration in monkeys previously trained to self-administer cocaine. Consequently, misuse and/or abuse of Provigil can potentially occur. However, if you are being monitored closely by your specialists, hopefully that won't be a problem for you. I'll post two questions from the archives that discuss Provigil and again remind everyone that Provigil can interact with some HIV meds.

Dr. Bob

Provigil: Posted: Jun 24, 2002

Hi Dr. Frascino,

Thanks for all of the information you provide. Quick question. What are you thoughts about using Provigil to treat fatigue??


Hi, Provigil? To tell you the truth, I have never used this medication to treat fatigue in HIV-positive folks. And to the best of my knowledge, its effects in people with the virus or on anti-HIV meds have not been studied. Provigil is approved for use in narcolepsy to improve wakefulness and excessive daytime sleepiness. My biggest concern with this medication is that it is metabolized in the liver by an enzyme system (cytochrome P-450) which many HIV drugs also use. This means that if Provigil is added to someone's regimen, the dose of certain HIV drugs may well need to be modified. Provigil also produces psychoactive and euphoric effects as well as alterations in mood, perception, thinking, and feelings. In other words, it can be a bit like reliving the 60's, which may not be entirely a bad thing, mind you. Personally, I would be quite cautious with this agent, especially if you're on antivirals. Of course, if you're into Austin Powers movies, it could be rather "shag-a-delic." Hope that helps.

Dr. Bob

Provigil and fatigue: Posted: Jun 16, 2003

Dar Dr. Bob,

I am an addiction psychiatrist in New York City, and I work with many patients with HIV. I read your comment about the use of Provigil with great interest. Generally, Provigil is a great advancement in "stimulant" medications because it doesn't directly work on dopamine, the neurotransmitter that is responsible for the euphoria or the "hard-wired" repetitive behavior that we see in addiction. For that reason, it's been extremely helpful for many of my addiction patients who suffer from fatigue. However, I do share your concern about using it with patients with HIV. In particular, it is an INDUCER of P450 3A4, which a major pathway of metabolism for medications such as Kaletra. Theoretically, this could lower Kaletra levels and cause sub therapeutic levels of antiretrovirals. These patients may improve fatigue, but they also may worsen their HIV. Unfortunately, there's no published data to support this yet. As far as "psychodelic effects," none of my patients yet have reported this, though some have reported some anxiety, notably much less than with dopaminergic stimulants, such as Ritalin or Dexedrine. But my HIV patients generally require much smaller doses. As with all psychotropics, because HIV affects the CNS in profound and unpredictable ways, we should always use them with some caution. I appreciate your column and look forward to reading more!



Hello Steve,

Thanks for writing! I totally agree! The P450 3AY enzyme pathway can be a problem. Improving fatigue at the cost of worsening HIV is generally not a good option. Subtherapeutic drug levels can lead to drug resistance, which then allows HIV to flare while concurrently decreasing potential options for effective future therapies. Fatigue in the setting of HIV is often multifactorial. Certainly psychological causes rank high in the differential diagnosis. I've found that the best approach is to evaluate all potential causes and treat aggressively those most amenable to therapy (anemia, hypothyroidism, depression, infections, etc.). With this approach plus the occasional Starbucks, I haven't needed to use stimulants. Thanks for your insight!

Dr. Bob

Extreme fatique - HIV or depression? Jun 20, 2006

I'm currently taking Reyataz, Zerit, andViread for HIV, and Lexapro and Trazadone for depression. I have been infected for about 20 years. When I was first diagnosed, by CD4 was 8 (eight.) My vral load is currently undetectable, and my CD4 is around 60. I have been fortunate enough to have avoided many of the symptoms, but I have constant fatigue. I constantly feel like I'm walking in molasses. It's very frustrating because I don't know if the fatique is caused by the depression, the HIV, or the meds, but I suspect it to be a combination of the three which are all related. My questions are: How common is this fatigue, and what can be done about it?

Response from Dr. Frascino


Fatigue is one of the most common and annoying symptoms associated with HIV disease. Its cause often turns out to be multifactorial, i.e. multiple underlying causes all working in tandem, just as you surmised. So could your fatigue be related to your depression, medications and HIV itself? Yes. Not only that, but there are many other potential contributing factors as well, including anemia; inadequate sleep, rest, exercise or diet; occult infections; hormonal imbalances; etc.; etc.; etc.

What can be done about it? The first thing is to identify as many of the underlying problems as possible and then to treat each of these conditions aggressively. To do that, I would suggest you begin by reading the archives of this forum and familiarize yourself with the common and not-so-common causes of HIV-associated fatigue. Make a list of these and then bring it to your HIV specialist and develop a plan to evaluate and treat your specific underlying problems. This process may well take some collaborative detective work to isolate the problems. But it's worth the effort, because HIV-associated fatigue can often be significantly improved if appropriate attention is given to this very important quality-of-life problem! Once all the underlying causes have been attended to, if you remain exhausted, you could try Provigil (modafinil). It's a non-amphetamine, pick-me-up-type pill that was initially approved to treat narcolepsy, but which is being increasingly used for fatigue. However, because Provigil is processed in your liver by an enzyme system also used by many HIV medications, there is some risk of drug interactions, especially with Norvir and Fortovase, so discuss this with your HIV specialist as well.

Good luck!

Dr. Bob