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New Antiretroviral Agents

Fall 1998

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Despite the progress that has been made over the last several years, many HIV infected individuals have experienced intolerance to the medications currently available. Current therapies are accompanied by inconvenient dosing schedules, a high pill burden, major side effects and multiple drug interactions. These circumstances leave a growing number of people with HIV and AIDS without very many choices.

Recently, five drugs have become the center of attention, efavirenz (Sustiva, DMP 266), adefovir-dipivoxil (Preveon, bisPOM), abacavir (1592), amprenavir (141W94) and hydroxyurea (Hydrea).

Sustiva just received approval by the FDA. Preveon and abacavir are currently available through an expanded access track and should receive FDA approval by the end of 1998. Amprenavir is expected to become available through expanded access sometime before the end of 1998 or early 1999. Hydroxyurea has been available since 1963 but is just recently the topic of new clinical research to fight HIV.


Sustiva is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Due to its long half-life (how long it remains in the body) it can be taken once a day, preferably at bedtime. It comes in 200mg capsules and the dosing requires three pills once a day (600mg). Also available in pediatric liquid form.

The major side effects can include dizziness, light-headedness, a feeling of "disengagement," nightmares and rash. If you had a rash from taking nevirapine or delavirdine, it does not necessarily mean that a rash will occur with sustiva. The drug should be started with caution. Most of the side effects that may occur with sustiva seem to be related to the nervous system and tend to happen within the first several weeks of taking it. However, side effects can be minimized by taking the drug at bedtime.

Recently, a safety alert was issued regarding findings from an ongoing study in animals which indicated sustiva may cause birth defects, if the drug is taken during pregnancy. This information came from studies done in monkeys. It is still unknown what would happen in humans. Yet, until further information is available, the use of this drug during pregnancy or in women attempting to become pregnant, is not recommended.

Information from the 12th World AIDS Conference held in Geneva, indicated that AZT+3TC+Sustiva may be as effective as AZT+3TC+Indinavir as an initial combination therapy. It may work even better in antiretroviral naive (never taken antivirals before) patients with relatively high T-cells and low viral load. This is very encouraging news. The long-term durability of this combination is not yet known.


Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) similar to AZT, d4T or ddI. Abacavir is dosed at 300mg twice daily with or without food. Early studies show that abacavir appears to cross the blood-brain barrier and hamper HIV replication in the CSF (spinal fluid). Abacavir does not appear to have any drug interactions with other antiretroviral agents. However, drinking alcoholic beverages increases abacavir levels which could increase its side effects.

Abacavir seems to be well tolerated. The major sides effects can be nausea, headache, malaise (fatigue), abdominal pain, diarrhea, and rash. In 2-5% of patients receiving abacavir, a potentially serious allergic reaction has been reported which includes nonspecific flu-like symptoms (low-grade fever, nausea and that run-down feeling) occurring in the first few days to six weeks of taking medication. A red rash may be present within a day or two of the start of symptoms. If this happens, call your doctor immediately! Do not take another dose of abacavir until you see your doctor. If you stop the drug and the reaction goes away, do not restart the drug. A very serious reaction which could require hospitalization and could be life-threatening happens if you start the drug again.

Slight elevations in liver and kidney tests have also been reported. These symptoms may continue until the drug is stopped and then resolve after the drug is discontinued.


Adefovir is the first nucleotide analogue to be developed for use in HIV infection. Unlike other nucleosides, adefovir is a monophosphate and therefore may prove to be more active in a broader range of cells. Adefovir has a long half life and can be taken once a day. The recommended dose is between 60-120mg once a day. Kidney problems and protein in the urine, may occur with prolonged usage of adefovir. It is not yet known if lower doses of the drug will prevent these problems from developing.

Adefovir appears to be well tolerated. Major side effects that have been reported include, nausea, vomiting, malaise, and diarrhea. Laboratory abnormalities were mild with increases in liver enzyme levels and reductions in serum carnitine (an essential amino acid). This drug is also very hard on the kidneys. Close to 40% of people taking Preveon for six months or longer have reduced kidney function. If kidney problems occur, they seem to get better once the drug is stopped. Adefovir appears to have a limited cross resistance to other nucleosides and seems to have an increased activity in vitro (test tube) against a particular mutation (commonly associated with 3TC therapy). Adefovir may prove to be useful as part of "salvage" therapy (for people who have tried everything else). The drug has modest anti-HIV activity in treatment experienced patients, including those infected with strains of HIV resistant to most currently approved therapies. But the long term safety of this agent remains an important issue to resolve.


Amprenavir is a protease inhibitor. It is in a phase III clinical trial and the hopes are that amprenavir will become available through expanded access sometime in late 1998 or early 1999. This drug also has a long half-life, allowing for twice daily drug dosing. It may be taken with or without food. Each capsule is 150mg with dosing of 1200mg (8 pills) twice daily. This means an increase in pill burden along with other medications.

Similar to other protease inhibitors, amprenavir should not be administered with Hismanal, or Cisapride and caution should be used with anti-convulsants and other medications that may require P450 CYP 3A metabolism. Other data is limited regarding its long-term safety and tolerability. In a small study, nausea, diarrhea and headache were all reported but were typically mild. Rash can also occur and should be monitored. Amprenavir appears to be effective in combination with AZT+3TC. Studies combining amprenavir with abacavir and other protease inhibitors are in progress. It is not yet known whether amprenavir will offer any benefit to people who have developed a rise in viral load on other protease inhibitors.


Hydroxyurea is an inhibitor of DNA synthesis that has been used for years (since 1963) to treat myeloproliferative disorders (high White Blood Cell counts) and to reduce the painful crisis in sickle cell anemia. This drug appears to be well tolerated with a dosing of 500mg twice daily. Hydroxyurea has no clinical benefit when used as monotherapy. In a recent small clinical trial, hydroxyurea was combined with ddI in patients whose T-cell count was between 100 and 350. There was a reduction in viral load, without a significant change in CD4 counts. Another small study showed at a one year follow-up that 20 patients who received hydroxyurea and ddI experienced a drop in viral load of 2.0 logs2.

Hydroxyurea has shown some promise when used with a protease inhibitor plus ddI. It's shown to possibly reduce the CD8-mediated killing of CD4 cells. This is very preliminary data and further studies need to be conducted. Hydroxyurea is not an anti-HIV drug but, it may enhance the antiretroviral potency of nucleoside analogs, in particular ddI. The combination of hydroxyurea plus ddI plus d4T may offer a drug combination for those individuals who are not ready to begin a regimen containing protease.

The major side effect of Hydrea is neutropenia (decrease in White Blood Cells). This requires close monitoring of laboratory values.


The benefits of antiretrovirals are reduced when patients don't take their medications, take them in unprescribed amounts or off the prescribed schedule, or don't match the dose with food as directed.

There is no clear data to indicate the number of times a drug combination may be missed before resistance begins. The goal is to take all of the scheduled doses on time. There is no clear answer for each person. It's important to establish an open dialogue with your health care provider. With an open line of communication, concerns can be discussed and answers can be sought as a partnership. Many times the side effects or confusion of how to take the prescribed medications can be alleviated or directions may be made more clear.

New insights about resistance to antiretrovirals suggest that HIV replications in the presence of low levels of drug causes selection of resistant mutants. Both less active regimens and inadequate adherence to highly active regimens allow HIV to continue to replicate. Both create selective pressure that increase the likelihood of resistance to current and perhaps future drug regimens. Once resistance develops the response to future drug combinations may be limited.


In conclusion, patients and clinicians must work together to reach a common goal of achieving durable suppression of viral replication with medications. Patients must make a commitment to take their medications as directed and report all side effects early in their therapeutic regimen instead of waiting. Clinicians must assess their patient's life-style to determine the best combination of medications with a dosing that will assist patients to remain compliant.

Patients starting on a new antiviral regimen may need to be seen on a weekly basis until the patient has made it through any potential side effects and appears to be tolerating their new drugs.

In general a successful drug regimen is a simple drug regimen. Try to reduce the number of pills and doses as much as possible. The key to success is a strong clinician-patient relationship based on mutual respect, trust and a willingness to share. Providers and patients must work together to establish a drug combination that improves both the quality as well as the quantity of life.

[Pregnant HIV-positive women and their neonates may be adversely affected by the combination antiretroviral therapy that is administered to prevent vertical HIV transmission. As reported at the 12th World AIDS Conference in Geneva, 21 of 37 women and 17 of 30 babies studied developed one or more adverse events when treated with tow reverse transcriptase inhibitors and a protease inhibitor. Complications among the women studied included grade 1 and 2 anemia, leukopenia, hypertension, and insulin-dependent diabetes. Prematurity was cited as the most common adverse effect in neonates as well as anemia, transient hepatitis, and cryptorchidia. (Find out more about anemia and how it relates to health and survival in the next issue of Women Alive)]

Back to the Women Alive Fall 1998 Contents Page.

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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This article was provided by Women Alive. It is a part of the publication Women Alive Newsletter.
See Also
More on HIV Medications
More on HIV Drugs in Development