I wrote this for Test Positive Aware Network’s Positive Aware magazine, one of the best free HIV magazines in the country. Their link is https://www.tpan.com/
Sustiva
One of the “preferred drugs” in the DHHS guidelines due to its very good efficacy. It was the first drug to be approved for once-a-day dosing, so everyone jumped on it. Some people seem to get over the nightmares and fatigue in the first 2-3 weeks, but others seem not so lucky. Sustiva put a stop to my life for four months due to depression and fatigue, so I have my biases. But I have met many people who love it and are doing great on it. Also, unlike Viramune, Sustiva can increase lipids just like most protease inhibitors. I am waiting to see when BMS and Gilead will successfully co-formulate Truvada with Sustiva, since I think that will revolutionize the market with a convenient once-a-day pill to treat HIV with three meds. This will probably shift the paradigm in the industry to collaborate to improve patient adherence and pill burden. I just hope these two companies do the right thing and make that combo available to developing countries at low cost.—
KALETRA
Still the PI with the most robust long-term data and a “preferred” drug for treatment naïve patients. A tablet formulation of Kaletra was approved in the United States in October 2005. Abbott hopes to replace the original capsule formulation with the new tablets soon. The new formulation requires two fewer tablets a day and no refrigeration. The most common side effects of Kaletra in the past have been diarrhea and increases in cholesterol and triglycerides. Abbott claims that the new formulation may have fewer GI side effects but no improvements in triglycerides. The Kaletra market share is being eroded by Reyataz and may be further decreased with the introduction of TMC-114
FUZEON
This injectable product has had a difficult uptake in the community due to fear of needles, injection site reactions, and the fear that it is a “last resort drug before you die.” Studies have shown the obvious: starting Fuzeon with at least one more active agent may improve the duration of response. Unfortunately, most people who started it after approval did not have any other active agent left in their genotype, so they had to start it on top of a failing regimen, which only provided viral control for a few weeks. We have now seen the Aptivus RESIST and the TMC-114 POWER studies say the same thing: those who used these products with Fuzeon did better. I am happy to see that those who are running out of options can start Fuzeon with Aptivus or TMC-114, and possibly entry inhibitors soon. To minimize ISRs, people stopped using the needles provided in the kit and went for smaller insulin syringes. Also, a bioinjector needle-free device which is expected to be launched soon may help some people. Fuzeon is the most expensive single drug in the market at $26,000 a year (Aptivus plus Norvir is the highest boosted PI at $28,000). A very huge problem has been access for patients who do not have insurance in states with ADAP systems that have a cap on the number of people who can get Fuzeon. Roche would not give free drugs to those who apply after the cap has been met in those states.
Fuzeon is here to stay as a backbone to new drugs in the pipeline. But its price, administration and difficult access need to improve for it to be accepted as part of standard of care in the U.S.
REYATAZ
The new darling in the PI class. It is taken once a day, does not have food restrictions and has little effect on lipids. If you are taking antacids or PPIs, you need to talk to your doctor, since many of them are contraindicated with Reyataz. Also, many people have increases in bilirubin that may make them jaundiced. As an activist, I have been concerned about how BMS priced this expensive PI and how they have marketed this drug by implying it does not cause lipodystrophy. The price is the highest for a protease inhibitor and set the tone for all drugs approved later, so it was a terrible hit to publicly funded programs. Also, there is not a single study that proves that Reyataz does not cause lipodystrophy. Actually, Reyataz showed the same high incidence of lipodystrophy as Viracept (a well-known PI that can cause lipo). Just because this drug may not have the negative lipid effects caused by most PIs, it does not mean that it may not cause fat accumulation. If it was that easy, lipid lowering drugs could prevent or reverse lipo, and they have not shown to do that! I would love to see lipo data on Reyataz/Norvir + Truvada, a popular once a day combo that doctors prescribe hoping that it does not cause body changes. Reyataz is here to stay and growing stronger as more comparison data against Kaletra are generated
INVIRASE
Invirase is a protease that has been reformulated three times. I remember being in the first study in 1995 with high hopes. Unfortunately we found out later that very little of the drug got absorbed, so I developed PI resistance early. Roche reformulated it in capsules later for better absorption, but with greater pill burden and GI side effects. The latest formulation seems to be the friendliest of all, taken with Norvir boosting, with lower GI side effects and pill burden. Too bad Roche launched this last formulation with little exciting data for doctors to prescribe it, since the drug has been around for so long. I would love to see comparison data with Kaletra and Reyataz for efficacy and lipids. The new Invirase formulation could find its niche for those who have to stop Kaletra for GI and lipid side effects, or Reyataz for bilirubin. It is also important to see more solid data on double PI boosted combos for salvage patients
APTIVUS
The first protease inhibitor exclusively approved for patients who have developed PI resistance. Two 250 mg capsules of Aptivus plus two 100 mg capsules of Norvir should be taken with food twice a day. Like Norvir, it requires refrigeration. It can cause diarrhea, increased cholesterol and triglycerides, and liver problems. Close monitoring of liver enzymes is imperative with this drug. It works a lot better if started with another drug that shows up as active in your genotype test. Those taking Fuzeon with it had a better response than those who started Aptivus with drugs that they had resistance to. One big problem with Aptivus is that it does not play well with others, so the list of contraindicated drugs is long. Aptivus should never be taken with another protease inhibitor, since it decreases PI blood levels. Aptivus is a complicated drug, but I welcome its introduction in the market for a population that has few to no options left. Too bad it is the most expensive protease inhibitor, with an annual wholesale cost (with Norvir) of $28,840 as of October 2005. If you use it with Truvada and Fuzeon, the total annual wholesale cost jumps up to $66,000, an exorbitant amount for salvage therapy
LEXIVA
It was hard to say anything about Lexiva. It is a second generation Agenerase with fewer side effects and lower pill count. It has not gained the acceptance that Reyataz and Kaletra have gained in the market. It has interactions with Kaletra and Sustiva. I took it with Norvir for a few months, but had to stop it due to severe fatigue, a side effect not usually reported with this PI (we are all very different in how we respond to meds). But many people are taking it successfully and like its lower incidence of GI side effects and lipids. It can be used with or without Norvir. It can cause rash in some patients, especially if you are allergic to sulfa drugs, such as Bactrim
TMC 114 (NOT YET APPROVED AS OF APRIL 2006)
This new promising PI has not been approved yet but is available through expanded access for those with CD4 cells of 200 or under, and who have failed most drugs available in the market. So far, Phase II data look very good in those patients with multi-drug resistance. It seems to have most of the common PI-related side effects. The most commonly used dose will be 600 mg along with 100 mg of Norvir as a booster, both twice a day. I am looking forward to seeing more data of TMC-114 plus entry inhibitor combinations in salvage patients soon. Tibotec is also starting a combination study of its non-nuke TMC-125 plus TMC-114, a first in the HIV drug development world where two investigational agents are combined prior to approval. I applaud Tibotec for this courageous step, which will set the tone for future research studies encouraging Multi-Experimental Agent Trials (MEAT)
TRUVADA
This is one of the bestselling HIV drugs nowadays, and for many reasons. It is taken once a day, is durable, can treat hepatitis B, and does not cause lipoatrophy, neuropathy, and lipid problems. Many doctors are switching their patients from drugs that may cause lipoatrophy (d4T and AZT) to this drug since some studies show that lipoatrophy may improve slowly after that switch. But Viread is starting to worry some people when it comes to kidney dysfunction, especially in the older and more advanced patient population. Be very careful if you are still taking it with ddI, even at 250 mg of ddI (see ddI). Also, have your doctor calculate your creatinine clearance every three months just to make sure you are not developing early kidney disease. You can visit this web site for an easy calculation of your creatinine clearance: https://www.intmed.mcw.edu/clincalc/creatinine.html
VIRAMUNE
Viramune was the first non-nuke to be approved, and has proven to work as well as Sustiva, although some docs may not think it has the same “punch” as its competitor. It can cause a rash that can be treated without discontinuation. Viramune may have a higher incidence of symptomatic liver toxicity which consists of elevated liver enzymes plus at least one symptom, typically rash, but may include flu-like symptoms or fever. The severity of symptomatic liver toxicity ranges from mild symptoms with liver enzyme abnormalities to rapidly occurring liver failure and death. Studies have found that females have a three-fold higher risk of symptomatic Viramune liver toxicity than males, and females with CD4+ counts above 250 T-cells have a 12-fold higher risk of symptomatic liver toxicity than those with less. Males with CD4+ counts above 400 T-cells have a five-fold higher risk of symptomatic liver toxicity than those with less. Viramune has been found to prevent mother-to-child transmission in a single dose, although it needs to be used with nukes to prevent the easy emergence of HIV resistance. Because of its seeming lack of negative effects on the central nervous system, cholesterol, triglycerides, glucose, and possible lipodystrophy, Viramune is still a popular drug 10 years after approval. I would love to see studies looking at Viramune+Truvada and its effect on lipodystrophy and long term viral suppression. Many doctors are prescribing this combo without any research data backing it up
ZERIT
Zerit (d4T) has fallen out of grace after years of reports of lipoatrophy, neuropathy and higher lipids due to toxic effects on the cells’ mitochondria (energy factories of our cells). It was dropped from a “preferred drug” to an “alternate” one by the DHHS guidelines committee for the treatment of naïve patients. I just wish that they had done it sooner, since this fact has been known well since 2001. Unfortunately, Zerit is becoming one of the most commonly used drugs in the developing world. I feel horrible for people in countries like mine (Venezuela) who will endure these side effects even after we have learned so much in the developed world. Zerit is still a valuable drug in salvage therapy, when the benefits outweigh the risks. Some studies seem to indicate that lower-dose Zerit may work as well without as many side effects, but I do not think doctors are totally buying that concept
VIDEX- DDI
I have a lot of biases against this drug and get criticized for it sometimes. It is known to increase the chances of pancreatitis and neuropathy, and its role on lipoatrophy is not well known yet. The good thing is that it is a great nucleoside that can control HIV in a once-a-day dose. After years of being exposed to the ddI+d4T combo, many people developed facial wasting and general lipoatrophy, and irreversible neuropathy, so the DHHS guidelines panel prohibited its use in that combo. Too bad for those thousands of patients who were exposed to it. I have the strong feeling that we will soon see a ban on the ddI+Viread combo, even at lower ddI doses. This combo can increase the ddI blood levels too high in some, which can increase risk of pancreatitis. Kidney dysfunction due to potential intracellular interaction with Viread is also being observed. For some strange reason that no one can answer for me yet, many people I have met in the past year on that combo are also experiencing involuntary weight loss on ddI+Viread. Just make sure that you are taking a lower dose of 250 mg or below (depends on body weight) if you are taking ddI with Viread and that your T-cells and weight are not decreasing. We have a lot better nucleosides in the developed world now to not have to endure all the risks I have mentioned
AZT
I am one of the people who are still alive from the original high dose placebo-controlled AZT study in the late ‘80s and early ‘90s. In 1993 we were shocked and depressed after finding out that high dose AZT was killing us faster. Fortunately, we later found out that a lower dose would work well in combination with other meds. AZT is now available alone or in a combo of AZT + Epivir called Combivir. There is also a new generic version available that may be lower in price (we are waiting to see). It is one of the few drugs shown to penetrate the blood-brain barrier, so it may have some protective effects on neurological complications like dementia. Too bad it can cause anemia, muscle weakness, and fatigue in some, and now we are also learning that it may cause lipoatrophy. There are also some studies suggesting that AZT may have a “protective role” in preventing a key mutation, K65R, in all nuke regimens. This mutation may render most HIV resistant to several nucleosides
ZIAGEN
Another very effective nucleoside analog that has shown to be key to many backbones for NNRTIs and PIs. But it can cause a hypersensitivity reaction that can be lethal if not dealt with quickly. If you feel like you are coming down with the flu a few days after starting the drug, call your doctor immediately. This problem occurs in less than 10% of people. Ziagen is now gaining a lot more momentum after several studies showed that it may not cause lipoatrophy. I have my own biases about this drug, however. I experienced increased anxiety while on it. I am glad that a few reports came up in the literature about this problem after that, but it is something that has not been studied at all and that is ignored by doctors due to lack of information. Ziagen is available alone or in a combo with Epivir (Epzicom) or in a 3-drug combo with AZT and Epivir (Trizivir). Warning: Trizivir alone may not be effective to treat HIV in most patients. Also, do not take Epzicom plus Viread, since you may fail this regimen too quickly and develop resistance to most nucleosides
EPIVIR
We used to think this was a wimpy drug back a few years ago, since resistance to it is developed quite easily. But we have learned that virus resistant to 3TC seems to be weaker than ones that are not, so doctors still prescribe it even if you have resistance to it (the mutation is 184V). It does not seem to cause severe side effects, although some people have reported fatigue and changes in pigmentation in the palms of their hands. It can treat hepatitis B also. It is available alone or in combination with Ziagen (Epzicom) or AZT (Combivir) or in a three-drug combo with Ziagen + AZT (Trizivir). An interesting study showed that people who have to stop their meds due to toxicity but kept taking Epivir had a lower CD4 cell drop than those who stopped all drugs