An Incomplete Guide to the Anti-HIV Drugs Winter 1999
13, 14, 15 and Counting… |
It has become almost impossible, and certainly not particularly useful, to discuss the anti-HIV drugs (anti-virals) one at a time. With fifteen of them currently available, including two through expanded access programs, the possible combinations number in the hundreds. In practice, people who are on combination therapy are using at least three drugs (hopefully!). Many PWAs are using combinations that have never been studied in clinical trials—and probably never will be. So although there's something to learn by looking at each drug individually, each one has to be considered primarily in the context of its interactions with the other anti-virals, other medications and street drugs, side effect possibilities (short and long-term), dosing schedules, resistance/cross-resistance profiles, availability for pediatric use, etc.
The discussion that follows is an attempt to look at each anti-viral with this context in mind. We refer to most of the drugs by their brand names, since that's the way most of us know them best. The one exception is AZT which for most people will always and forever be known as AZT rather than by its brand name, Retrovir. The drugs are listed by class and in order of approval (1987 through 1998). For further specific information about dosing, food restrictions, availability, drug interactions and more, speak to your doctor or pharmacist. Or call us at the PWA Health Group: (212) 255-0520.
| NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS or NUCLEOSIDE ANALOGUES (NUKES) |
This class of anti-virals works by getting in the way of the HIV virus' ability to infect cells in the body. HIV uses an enzyme called reverse transcriptase to change its genetic material (RNA) into a form that can get inserted into the DNA in the "brain" of human cells (often T-cells). Once this happens, the human cell starts producing new HIVs. With the nukes, HIV gets fooled, and inserts the drug in the place of one of the building blocks of reverse transcriptase. Once this happens, the virus can't change its genetic material into DNA and can't be inserted into human cells. If HIV can't get into the genetic material of the human cell, then it can't reproduce. If HIV can't reproduce, it can't spread to other cells. Nucleoside analogues do not help cells that have already been infected with HIV. But they slow down the spread of HIV from cell to cell. They don't kill HIV. AZT, a nucleo-side analogue, was approved in 1987 as the first anti-HIV drug. The newest nucleoside analogue, Ziagen, was approved in December 1998.
AZT [Retrovir] | Zerit [d4T] | Videx [ddI] | Epivir [3TC] | Hivid [ddC] | Combivir (combination of AZT & 3TC) | Ziagen [abacavir]
AZT (Retrovir). The rollercoaster history of AZT in many ways mirrors that of the epidemic—the price gouging, the battles, the hopes raised, dashed, then raised again.
Yet, despite its reputation, it remains an incredibly useful treatment option. It may not be the best bet to include in first-line treat-ment because it slows down white blood cell production and can gunk up your cells so that other drugs may not work as well in the future. But it remains a solid anti-viral with plenty of data to support its use in a wide variety of combinations.
The first thing many of us think of when we hear AZT mentioned is the enormous hope followed by crushing disappointment that we experienced when it was introduced as "close to a cure" in 1986. Of course, at that time PWAs were taking two or three times the cur-rent recommended dose. And after six months of AZT monotherapy, most people had developed resistance and were essentially taking a toxic placebo. The side effects weren't minimal—feeling (and looking) sick, fatigue, headache, muscle weakness, and sometimes life-threatening anemia and sup-pressed white blood cell counts. These side effects still occur, of course, even at lower doses, including darkened nails in people of color.
But lots of folks who would never go near AZT, fearing that it will kill them, have no negative physical reaction to "Retrovir"—even though it's the same thing. And the drug's ability to cross the blood-brain barrier has been shown to be useful in preventing neu-rological disease like dementia.
Two important interactions to be aware of—don't use it with Zerit, and methadone raises AZT levels so much that most people need to cut their AZT dose in half.
Videx (ddI). When Videx was approved in 1991, lots of people used it instead of AZT monotherapy, switched back and forth between the two, or began combination ther-apy with both. In fact, Videx taken alone was shown to be generally superior to AZT taken alone. Because Videx resistance takes a long time to develop, the drug is useful in a wide variety of triple combinations. Combining it with Zerit can be especially useful because the two drugs seem to work well together (the total is more than the sum of its parts). Both drugs can cause peripheral neuropathy, nerve damage that can be permanent if you don't stop the drugs, but combining the two doesn't increase the risk.
Avoid a combination using Videx with Hivid. Hivid can also cause neuropathy, Hivid and Videx are cross-resistant, and the two drugs don't work well together anyway. The other serious side effect of Videx is the risk of pan-creatitis, which is increased with alcohol use. The buffer that's mixed with Videx can cause diarrhea, so combinations that include other diarrhea-causing anti-virals like Norvir or Viracept may make it worse. Videx's once a day dosing is appealing, but, because it has to be taken on an empty stomach, using it in combination with Crixivan is almost impossible. You'd never get to eat! Don't waste your options with a Videx/Rescriptor-containing regimen, either. A large trial (1,200 people) was stopped when the combination of the two didn't show any benefit over Videx alone. Using Videx with hydroxyurea, an old cancer drug, is becoming increasingly popular as part of a first-line regimen or for folks with Videx-resistant virus because of the intriguing way hydroxyurea works.
The interaction to be most aware of is Videx and dapsone; Videx's buffer reduces stomach acidity and dapsone needs an acidic environment in order to be absorbed properly. Figuring out the best Videx dose in kids can be tricky because of absorption problems, but it's a popular and useful pediatric anti-viral, available in a powder that's mixed with flavored antacid.
Hivid (ddC) has never lived up to its initial promise. Early studies in 1991 and '92 showed its inferiority to AZT as first line monotherapy. People whose virus had become resistant to AZT weren't resistant to Hivid, so for a while it was widely used. Nowadays, its use is limited—mostly by people who have few options available after they've gone through just about everything else. Even the federal treatment guidelines suggest that it only be used in combination with AZT and a protease or non-nuke. It doesn't work well in combination with Videx, Zerit, or Epivir. The side effects aren't pretty: liver and kidney problems, possible pancreatitis, worse neuropathy than either Zerit or Videx, and sores in the mouth and throat that are like herpes eruptions or canker sores. Overall, not a very useful drug. Between Hivid and Invirase, Hoffmann-LaRoche hasn't exactly been a leader in developing the most exciting HIV therapies.
Zerit (d4T). Like Epivir, Zerit has few side effects and an easy dosing schedule. Combinations including Zerit and Epivir seem to be at least as effective as those including AZT and Epivir. Zerit/Videx combinations are popular, too. Two small but important studies showed no significant difference in the short-term between AZT/Epivir/Crixivan and Zerit/Epivir/ Crixivan in one case and AZT/Epivir/Crixivan and Zerit/Videx/Crixivan in the other. Zerit may not work as well for people switching immediately from an AZT-containing regimen. If you've been using AZT, you may want to wait a bit before going to a combination that includes Zerit. And, because Zerit and AZT compete chemically in the body, don't combine the two. Two
pre-protease trials show that Zerit with AZT doesn't work any better than Zerit alone.
Like the other "d" drugs, Zerit's most serious side effect is peripheral neuropathy (15-20%), so be aware. Monitor liver enzymes carefully, too. The drug seems to be pretty good at getting into the brain and central nervous system, adding to its popularity as a substitute for AZT. The version for kids is a fruit-flavored powder that you mix with water.
Epivir (3TC). With its minimal side effects, easy dosing schedule and high potency, Epivir may be the most useful of the nucleosides—if it's used strategically. It also has the potential to make HIV that's AZT-resistant sensitive to AZT again. Figuring out when and how to use it is important when you're developing a treatment plan. Epivir resistance usually happens within a few weeks when it's taken alone. This may lead to some cross-resistance with Videx, Hivid and, to a lesser degree, Ziagen. In combination with other anti-virals, though, Epivir resistance can be put off indefinitely. There's plenty of data showing that Epivir slows disease progression and increases survival when used in combina-tion. Epivir combinations with AZT or Zerit and a protease or non-nucleoside (Viramune or Sustiva) are common.
An added attraction is Epivir's ability to reduce hepatitis B. The hepatitis B action can be tricky—if you have active Hep B and start Epivir, you're going to be really sick for a month or two while the infected liver cells die off. Be prepared. Check for Hep B before-hand. An Epivir quality of life side effect that doesn't show up in Glaxo's ads is hair loss. The drug's most serious possible side effects are peripheral neuropathy (relatively uncom-mon) and, in kids, dangerous swelling of the pancreas. The strawberry-banana flavored liquid for kids is reportedly quite tasty.
Ziagen (abacavir), the newest nucleoside, is made by Glaxo Wellcome, which also manufactures AZT and Epivir. So most of the little information we have compares AZT/Epivir to AZT/Epivir/Ziagen. What a surprise! The three-drug regimen shows better results than the two-drug regimen, decreasing viral load and raising T-cells. Like every company, Glaxo wants its data to look as good as possible, so most early studies have been in people with little or no previous anti-viral experience. Whatever your first combi-nation, you're likely to see dramatic results. Early, short-term studies of Ziagen suggest that it may be a strong contender as part of a first line regimen. It may even be the most potent nucleoside yet. The data in people with previous anti-viral experience doesn't look as good. It seems that the more nucleo-sides you're resistant to, the less likely you are to benefit from Ziagen. The drug's potential to cross the blood-brain barrier may be useful in preventing neurological disease.
The allergic reaction that some people have to Ziagen can be very serious—especially if you go back on the drug after stopping it. The company was less-than-forthcoming about the danger of the allergic reaction when it first appeared over a year ago. Be aware and take it very seriously. Another warning: alcohol increases Ziagen levels. So lay off the sauce. It's too soon to tell the extent and range of other potential side effects, since so few people have used the drug and only for short periods of time. The liquid version for kids is strawberry-banana flavored, and the pediatric data is similar to that in adults.
Combivir. What an unusual occurrence! A pharmaceutical marketing idea that actually makes life a little easier for PWAs (some, at least). What next? Glaxo Wellcome also makes Ziagen, the new nucleoside, which is dosed twice daily. Glaxo is reportedly working on a one-pill product containing AZT/Epivir/Ziagen to be called (what else?) Trivir. Since this three-nucleoside pill will be relatively easy to take, it will probably be widely prescribed, whatever the data. Combinations that include Epivir and Bristol Myers-Squibb's Zerit are increasingly popular. Lots of folks find Zerit more tolerable and want to save AZT for possible use later on. A one-pill combination of Epivir with Zerit would be even more useful than Combivir's Epivir and AZT. But imagine these two companies working together to make such a product available. Maybe in the next world.
| NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NON-NUKES) |
The non-nucleosides are a relatively new class of anti-virals. They work in a slightly different way than the nucleosides, but at the same place in the life cycle of HIV. They directly interfere with reverse transcriptase, sort of like gum getting stuck in a zipper. If HIV can't use reverse transcriptase to work itself into the DNA of the human cell, it can't reproduce and spread to other cells. Non-nucleosides don't help cells that have already been infected with HIV. But they slow down the spread of HIV from cell to cell. They don't kill HIV. The newest non-nuke, Sustiva, was approved in September 1998.
Rescriptor [delavirdine] | Viramune [nevirapine] | Sustiva [efavirenz]
Rescriptor (delavirdine) was the first approved non-nucleoside. Because of cross-resistance throughout the class and its three times a day dosing, it's not very popular. And the data fall somewhere between weak and contradictory. Most of it comes from trials comparing three drug regimens to two drug regimens. As you'd expect, the three-drug arms show better results in terms of reduced viral load. So far, there's no data comparing Rescriptor and two nucleosides with a protease and two nucleosides. Next to Norvir, Rescriptor has the most drug interactions of them all. The way that it interacts with protease inhibitors is complicated—saquinavir levels triple, Crixivan and Norvir levels increase enough to warrant reducing your protease dose, and Viracept decreases Rescriptor levels by half! Confused? Who isn't? Rescriptor may be most useful to boost your protease levels—if you're not worried about developing resistance to all the non-nucleosides. We need head-to-head trials that compare the three non-nukes. Until then, deciding which one to use, if that's the way you're leaning, is like comparing bananas and canta-loupes. To add to Rescriptor's lack of substantial data, there's none on its use in kids.
Viramune (nevirapine) may be the most underused antiviral. Like the other non-nukes, Viramune shows potential as a useful option whether you're just beginning antiviral treatment or you've already gone through a lot of combinations and can use it with a couple of other new drugs. Unfortu-nately, most of the data come from poorly designed trials that compare three drug regi-mens to two drug regimens. This offers very little useful information since using three drugs almost always compares favorably to using only two. Roxanne hasn't conducted as aggressive a marketing campaign as its competitors, either, which tells us more than we might want to know about the effect of direct-to-consumer pharmaceutical advertising on sales.
Starting with the lower dose and building up over the first two weeks is important because of the possibility of rash (20% of people experience rash, and up to 7% get one serious enough to require hospitalization). The twice-a-day dosing schedule is great, especially if you're able to create a complete twice-a-day combination using Videx, Zerit and/or Epivir. Once-a-day dosing is being studied and looks promising. Viramune decreases saquinavir levels substantially enough to recommend avoiding the combination. Crixivan and Viracept levels don't seem to decrease enough to cause concern, but some people increase their protease doses (1,000mg Crixivan or 1,000mg Viracept). Viramune also seems to decrease methadone levels. You may need an increase in your meth dose.
Sustiva (efavirenz), the newest and sexiest of the antivirals, is very popular with lots of doctors—partly because it's new, partly because there's good data to back it up. Comparing AZT/Epivir/Crixivan to AZT/Epivir/Sustiva in people who had never used a protease, non-nuke or Epivir, showed similarly significant viral load drops at the end of six months. This accounts for the heavily marketed phrase, "protease-sparing regimen."
Dupont visited AIDS service and treatment organizations all around the country early on—they were our partner and friend. Company representatives talked about the possibility that Sustiva resistance wouldn't cause cross-resistance with the other non-nukes. That hope bit the dust. And once FDA approval time came around in September of '98, Dupont gave the shaft to everyone living with HIV by setting an obscenely high price. Is the price worth it? It's too soon to tell.
The once-a-day dosing is attractive, of course. But the side effects! Those that affect the nervous system (muddled-thinking, dizziness, disorientation, flashbacks and nightmares) usually go away within the first couple of months. But some people literally feel like they're going crazy. And if you're in recovery, Sustiva may not be a viable option. If it's used in combination with Crixivan, your Crixivan dose has to be upped to 1,000mg every 8 hours. Sustiva lowers Fortovase levels by 60%, so don't combine the two. Combining it with Viracept may create the same problem. One last thing: useful as Sustiva may be, it has caused serious birth defects in animals. Humans, beware!
Protease inhibitors created a big sensation when the first ones were approved in late 1995 and early 1996. They work at a later stage of the HIV life cycle than the nukes and non-nukes¾once the HIV has already made its way inside the T-cell. They block (inhibit) a protein called protease. When HIV inserts into the DNA of a human cell (a T-cell, for example), the T-cell starts making new HIVs. The cell produces lots of chemicals in a big lump that need to be put together into the shape and structure of HIV. HIV uses protease to assemble full HIVs from this lump of raw materials. Protease inhibitors block protease, so new full HIVs can't be made and released from the infected cell.
In addition to some of the immediate and short-term side-effects talked about below, long-term side-effects have surfaced in people who have used protease regimens. These include: fat redistribution from the face, arms and legs to the abdomen, breasts and/or upper back (sometimes called lipodystrophy); increased blood sugar levels which can lead to diabetes; and abnormally high cholesterol and triglycerides, which are associated with an increased risk of heart disease. Others are likely to surface as people are on strong three or four-drug combination therapy for longer periods of time. The newest protease inhibitor, Agenerase, is available only through an expanded access program.
Invirase [hard-gel saquinavir] | Fortovase [soft-gel saquinavir] | Crixivan [indinavir] | Norvir [ritonavir] | Viracept [nelfinavir] | Agenerase [amprenavir]
Invirase (hard-gel saquinavir). When Invirase was approved at the end of 1995, lots of people began using it in triple combinations, only to discover that its low absorption led to rapid resistance. What's more, Invirase resistance usually means resistance to all the protease inhibitors, drastically limiting future treatment options. Thank you, Hoffmann-LaRoche! It was the beginning of a tough lesson—the promise of protease isn't everything it's cracked up to be.
Invirase is used now mostly in combination with Norvir or Viracept to increase Invirase absorption levels. Don't combine it with Crixivan, Viramune or Sustiva. And avoid it as the only protease in a combination. The long-term side effects of protease are becoming clearer as people have been on them for longer periods of time. So if you're considering a protease, choose one that will give you the biggest bang for your buck. Invirase won't be in the running.
Fortovase (soft-gel saquinavir). Considering the absorption problems that Hoffmann-LaRoche had with its original formulation of saquinavir, Invirase, it's no wonder that the soft gel formulation requires 18 horse pills a day in order to keep enough drug in your system to do anything. A lot of people have trouble just getting the pills down. Alternatives include combining smaller doses of Fortovase with Norvir or Viracept, both of which significantly increase Fortovase drug levels. These double-protease regimens are pretty common, both in studies and in real life. Fortovase should not be combined with Crixivan though. And beware of anyone prescribing a combo that includes Fortovase and one of the non-nukes—Rescriptor greatly increases Fortovase levels, but Viramune and Sustiva decrease Fortovase levels so much (27% and 60% respectively) that combining either of them with Fortovase is definitely a no-no!
Fortovase's gastro-intestinal side effects can be pretty bad (diarrhea, nausea, gas and stomach pain), but the ones to monitor carefully through your bloodwork are high liver enzymes and cholesterol. As with the other protease inhibitors, if you develop Fortovase resistance it usually means that your virus will be resistant to the others.
Crixivan (indinavir). Merck stopped its twice-daily dosing study last fall when results at six months showed that the twice-daily dose didn't suppress HIV as well as the standard dose of three times a day. Of 87 people, 91% of those on Crixivan three times daily had undetectable viral loads (<400) at the end of the six months compared to 64% of those on the twice-daily dose. It's a big disappointment. Crixivan's dosing schedule (two 400mg capsules every eight hours), combined with its severe food restrictions (on an empty stomach or with a light, no-fat snack), makes it arguably the most difficult antiviral to take properly. How many of us know people who assume that three times a day means breakfast, lunch and dinner? Not so!
The data for Crixivan is strong. In the longest and largest study so far (1,156 people), the combination of Crixivan/Epivir/AZT (or Zerit) greatly reduced the incidence of serious opportunistic infections and increased survival for people with 50 or fewer T-cells compared to Epivir/AZT. These people had been on AZT for at least three months previously, although not Epivir or any protease. The same trend was seen in people with T-cell counts between 51 and 200.
Remember: drink lots of water to avoid kidney stones (which are even more likely in kids), skip the grapefruit juice (it reduces Crixivan blood levels), and don't combine Crixivan with saquinavir (Invirase or Fortovase). Crixivan dose adjustments are necessary if it's combined with any of the non-nukes: Rescriptor (not a great idea), Viramune or Sustiva. If you're using Crixivan with Videx, take them an hour or two apart on an empty stomach. A combination that includes Crixivan and Videx will practically starve you, so you may want to look at other possibilities. The notorious "Crix belly" isn't limited to Crixivan use. Severe metabolism changes are being seen in people who have used the other protease inhibitors as well. Even in folks who've been on anti-virals but never used a protease. Go figure!
Norvir (ritonavir) can cause more negative side effects than any other anti-viral: nausea, farting, gas, diarrhea, vomiting, gagging, numb mouth, liver damage and more. It has the most serious drug interaction profile of them all. You have to be careful when combining anything with it – painkillers, sedatives, methadone, street drugs – the list is endless. Norvir is now only available in a liquid form that is so revolting that figuring out how to get it down has become a cottage industry. And it's the highest priced antiviral of them all. Sound attractive? Well, there's a flip side.
Norvir's twice a day dosing, taken with or without food, is relatively convenient. In studies and real life, the drug is useful in double-protease combinations, substantially raising blood levels of saquinavir and Viracept when you take a lower Norvir dose (400mg twice a day) with lower doses of either. The jury's still out on Norvir/Crixivan combinations. Solid data shows that Norvir used in combination can slow disease progression and increase survival in people with less than 50 T-cells. So Norvir remains a useful tool in the woodshed, but, like the others, it needs to be considered strategically.
Some folks who begin treatment with a Norvir combination swear off combo therapy completely because of the initial side effects. Two-week dose escalation can alleviate them for some people. If you're using Norvir in a combination that includes Videx, be careful to take them an hour or two apart; Videx affects absorption of Norvir. Norvir for kids has the longest (48 weeks) and best data of any of the protease inhibitors.
Viracept (nelfinavir), the newest and least studied of the approved protease inhibitors, is also the most widely prescribed. It doesn't have Crixivan's food restrictions (you take it with a meal or snack), the side effects pale compared to those caused by Norvir, and it's much stronger than Invirase. But the nausea and, especially, the diarrhea can be debilitating. The diarrhea often gets better over time, particularly if you use Lomotil—but not always. Although the approved dose is 750mg three times a day, some people take 1,250mg twice a day. The twice-daily dosing looks promising, but there isn't enough sub-stantial data to support it yet—be careful. The data on Viracept is based on decreased viral loads and higher T-cells. We don't know the effect on disease progression and survival yet.
Double-protease regimens combining Viracept with Norvir, saquinavir or Crixivan are certainly being used. Although combining Viracept with any one of these proteases raises Viracept levels, ongoing studies have a ways to go to figure out the best dosing. Combining Viracept with Rescriptor lowers Rescriptor levels by 50%, so take that into account. Viracept shows similar results in children ages 2-13 as it does for adults, although that's only short-term data.
Agouron originally centered its marketing campaign on claims that Viracept resistance wouldn't cause cross-resistance with the other protease inhibitors. Now that that claim is questionable (to say the least), their campaign is completely different. Viracept resistance isn't as likely to cause cross-resistance across the protease class as Crixivan resistance is, but it's by no means a safe bet to assume that you can use Viracept first and still have the option to go to any of the other protease.
Agenerase (amprenavir). People have been following the development of this protease for a long time—since it was known simply as Vertex. Over a year ago, prelimi-nary, short-term data of double-protease combinations with Agenerase showed dra-matic drops in viral load. But it's way too early to tell whether this drug will be more useful than any of the approved protease inhibitors. The dosing requires eight capsules, twice a day, the side effects are similar to those of Viracept (including rash in 20% of study participants), and a small study of peo-ple with protease-resistant virus showed only a small anti-viral effect. Cross-resistance with the approved protease is likely.
We only have data up to four months in peo-ple with little or no previous anti-viral experi-ence. For these folks, the results of triple combinations with Agenerase are similar to those of other protease-containing triple combinations. Glaxo proudly proclaims that Agenerase doesn't lead to the high triglyceride and cholesterol levels seen with other protease inhibitors, but studies haven't gone on long enough for these effects to show up. There's no data on Norvir/Agenerase combinations, and there's reason to believe that this combi-nation isn't a good idea. Don't combine it with Sustiva, either; Sustiva decreases Agenerase levels considerably, and the right dosage adjustment hasn't been figured out yet. It's available in both liquid and capsule formula-tions for kids.
So far, there's only one nucleotide available for HIV (and only through expanded access). Nucleotides work at the same place in HIV's life cycle as the nucleosides and non-nukes, by getting in the way of the reverse transcriptase enzyme. The chemical process required for a nucleotide like Preveon to do the job is quite a bit simpler than that for the other drugs.
Preveon (adefovir). PWAs who are running out of options face a tough call about whether or not to add Preveon to a regimen. Early, short-term studies show only minimal anti-HIV effects. The side effects, on the other hand, can be very serious. But Gilead isn't giving up yet. The promise of this drug, the first in a new class of antiviral, crashed and burned dramatically last spring when it was reported that 40% of the people who had taken it for six months or more developed signs of serious kidney damage. It's usually reversible if you stop taking the drug and if you catch it in time by carefully monitoring kidney function. Watch your liver enzymes, too.
Proper dosing is unclear. 120mg a day seems best for drug delivery but can lead to side effects. 60mg and 30mg doses are being looked at, but neither has enough data yet. Preveon may be most useful to people who have developed resistance to a lot of the nucleosides, with the exception of people who have high levels of resistance to AZT. Interestingly, people who are resistant to Epivir seem to have a better response to Preveon than people who aren't. Preveon has shown activity against hepatitis B, reducing viral levels up to 99%. Bottom line: we have very little information about Preveon, and the little we do have is not encouraging.
| AND ONE OTHER ANTI-HIV DRUG |
Hydroxyurea. This 30-year old cancer drug is exciting for many reasons. Most intriguing is the widely reported case of two newly infected people who took hydroxyurea with Videx for a year, stopped treatment, and still have sustained undetectable viral loads two years later. Unlike the other drugs available for HIV, hydroxyurea is not an antiviral. It has no contact with the virus. Instead, it interferes with the cells that HIV targets, so the chance of developing resistance is very small. Impressive viral load decreases have been seen in many small studies combining hydroxyurea with Videx or Videx/Zerit.
T-cell increases aren't as impressive, especially for people with low T-cell counts to start with. Hydroxyurea works particularly well with Videx, even for people with Videx-resistant virus. Preveon demonstrates a similarly powerful interaction with hydroxyurea, which may lead to finding a lower, safer dose of Preveon that's also useful.
The lack of significant T-cell increases is troublesome. Hydroxyurea's primary side effect is bone marrow suppression, which can mean low red blood cells, low white blood cells, and/or low platelets. If you have low T-cells, you may want to approach hydroxyurea with caution. On the other hand, the drug's ability to penetrate the brain and lymph tissue is appealing. Hydroxyurea is being used in first-line as well as salvage therapies, but until we have long-term data from large studies, it's a crapshoot.
Some of this material was originally written for and published by Positively Aware, the wonderful treatment magazine from our friends at Test Positive Aware Network in Chicago.
See also: How do I choose what drugs to take? | Protease at-a-Glance - 1999 | antivirals list 1999
Home