Chemical structure of zalcitabine.
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Zalcitabine (2'-3'-dideoxycytidine, ddC), also called dideoxycytidine, is a nucleoside analog reverse transcriptase inhibitor (NARTI) sold under the trade name HividĀ®. more...

Heparin sodium
Hexal Diclac
Hexal Ranitic

Zalcitabine is the least potent of all antiretroviral drugs, is inconvenient to take, and has serious side effects. For these reasons it is now rarely used to treat human immunodeficiency virus (HIV).


Zalcitabine was developed in the National Cancer Institute (NCI) by Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan at the National Cancer Institute (NCI). Like didanosine, it was then licensed because the NCI may not market drugs. The National Institutes of Health (HIH) thus licensed it to Hoffman LaRoche Co.

Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV infection and AIDS. It was approved on Jun 19, 1992 as a monotherapy and again in 1996 for use in combination with Zidovudine (AZT). Using combinations of NRTIs was in practice prior to the second FDA approval and the triple drug combinations with dual NRTIs and a protease inhibitor (PI) were not far off by this time.

Mechanism of action

Zalcitabine is an analog of pyrimidine. It is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl group in position 3' with a hydrogen.

It is phosphorylated in the T cell and other HIV target cells into its active triphosphate form, ddCTP. This active metabolite works as a substrate for HIV reverse transcriptase, and also by incorporation into the viral DNA, hence terminating the chain elongation due to the missing hydroxyl group. Since zalcitabine is a reverse transcriptase inhibitor it possess activity only against retroviruses. It is used for the treatment of HIV infection only in combination with zidovudine.

Zalcitabine has a very high oral absorption rate, of over 80%. The most common side effect in the beginning of the treatment is nausea and headache. The more serious side effects are peripheral neuropathy, oesophagitis and pancreatitis.


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Treatment news from recent conferences: Finding web reports
From AIDS Treatment News, 10/26/01 by John S. James

Much treatment information came out at several conferences in October and early November. It did not get major press attention because there was no big headline story or single coherent message. Unless you know someone who was there, the best way to learn about these conferences shortly after they happen is through Web reports by researchers, physicians, or other experts. While few will read all this material, patients and medical professionals can scan to find information about problems they are having, treatments they are using, or relevant leads.

You can scan the lists of major topics, below, to decide what you want to see, then go to the Web sites to read the selected summaries. Note that these reports are written mainly for medical professionals, and some are more difficult than others.

These conference Web reports provide quick, accessible treatment education updates in areas you choose. This article lists major topics reported (as of mid November 2001, when we went to press).

Recent Conferences

* IDSA 2001 (annual conference of the Infectious Diseases Society of America), October 25-28 in San Francisco;

* The 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, October 23-26 in Athens, Greece;

* The 8th European Conference on Clinical Aspects and Treatment of HIV Infection (EC-CATH), October 28-31 in Athens, Greece (by the European AIDS Clinical Society);

And for reports on liver diseases,

* 66th Annual Scientific Meeting of the American College of Gastroenterology, October 19-24, Las Vegas;

* AASLD (American Association for the Study of Liver Diseases), will be held November 9-13, Dallas.

Web Sites with Conference Coverage

The following four sites have extensive reporting on these conferences (though only The Body covered all five of them).

Note the more specific Web addresses for some of the conference coverage, further below. But if one of these addresses does not work (perhaps because the site has been reorganized), use the address here to get to the home page, and then look for the conference coverage on the site. Some sites take down their conference reports after one year.

* The Body,, has the most extensive conference coverage.

* HIV and, has perhaps the most extensive coverage of AIDS and hepatitis treatment news on the Web.

* Medscape, has many excellent medical resources. (You need to register and choose a password to use this site, but the registration is free.)

* NATAP (National AIDS Treatment Advocacy Project), has valuable information, though some of it has been technical and hard to read.

While these Web sites are credible, nothing is perfect. These rapid Web reports, often online within days of a meeting, sometimes within a day, do not always leave time for thorough fact checking. And the pervasive "spin" throughout the entire U.S. medical field, especially pharmaceuticals, makes all treatment reporting difficult. The trials conducted and results published reflect complex, often secret negotiations between corporate, professional, regulatory, organizational, personal and other interests. There is no way to cover a field as complex as AIDS and even be aware of all of the important spin.

Approved HIV Drug Names

We use generic drug names in this article -- or the more familiar abbreviations AZT (generic name zidovudine), ddI (didanosine), d4T (stavudine), and 3TC (lamivudine). Generic names are usually but not always used on the sites. For those more familiar with the brand name, here is a table of the brand names and generic names of the anti-HIV drugs currently approved in the U.S. Since all antiretrovirals are patented in this country, there is only one brand name here for each generic (except for saquinavir, which has an earlier, weaker formulation named Invirase).

Major Topics Covered

Here are some of the most important topics on each site, as of November 14. New reports may still be added. If we have missed other sites that should be included, please let us know.

Also note that the same research is often presented at more than one conference. So the same Web site can have different writeups on the same research.

We wrote the title lines below to give a less technical view of the contents of each summary. You can usually spot the corresponding writeup by following the link provided to reach a table of contents for that conference Web report. Many of the summaries are short, a page or less; a few are considerably longer.

IDSA (39th Annual Meeting of the Infectious Diseases Society of America), October 25-28, San Francisco

The Body (click "Conference Summaries")

* Can short-term changes in viral load predict long-term response?

* Transmission of drug-resistant HIV;

* Lopinavir/ritonavir in heavily pretreated patients;

* Starting therapy at a T-cell count of 350;

* Simplifying protease-inhibitor treatment by switching to abacavir;

* Nevirapine and liver toxicity in HIV patients with hepatitis C;

* Nevirapine vs. protease inhibitors -- long-term cohort study;

* Using amprenavir after nelfinavir use;

* Amprenavir+abacavir+3TC, 48-week data;

* Abacavir+efavirenz+AZT+3TC, preliminary 48-week results;

* Four-drug study, efavirenz+abacavir+AZT+3TC;

* Hepatitis G co-infection and HIV treatment;

* EPO (erythropoietin, Epoetin Alfa) in anemic HIV patients;

* Prior antiretroviral therapy and genotype testing;

* How well can patients predict their T-cell and viral load test results?

* Cutting-Edge Issues in HIV Medicine (symposium)

- Challenges of Antiretroviral Therapy in the Developing World;

- Future Horizons in Antiretroviral Drugs;

- Structured Treatment Interruption: Panacea or Pandora?

- HIV and HCV Co-Infection -- Current Status and Future Directions.


"Report on Salvage Therapy from the 39th Annual Meeting of the IDSA," by Daniel R. Kuritzkes, M.D. This essay looks at real-world experience in very heavily pretreated patients with: lopinavir/ritonavir (Kaletra); indinavir+ritonavir; delavirdine strategy to boost protease inhibitor levels; and amprenavir use after nelfinavir.

Medscape mmaries.html (then select 39th Annual Meeting of the Infectious Diseases Society of America)

These are the HIV-related titles now on the site:

* Antiretroviral Agents and Response to Therapy

* Optimizing Long-term HIV Treatment Strategies Through a Greater Understanding of Disease Pathogenesis

* Metabolic Complications and Adverse Drug Reactions in HIV

* Update: Incidence, Diagnosis, and Clinical Manifestations of HIV-Related Opportunistic Infections

* PI vs. Boosted PI vs. Efavirenz: And the Winner (Again) Is?

* Switching from a Protease Inhibitor: The Answers Are Known, It's Time to Move On

* Four-Drug HAART Regimen in Patients with Advanced HIV Disease

* HIV Evolution Limited by Successful HAART

* A New and Simple Way to Diagnose Pneumocystis carinli Pneumonia

* Evidence for Increased Risk of Heart Disease in Treated HIV Infection

* Myocardial Infarction: A Consequence of HIV Disease, Treatment, or Both?

* Has HAART Really Improved Mortality in Patients with Advanced HIV Disease?

* Rates of Most HIV-Related Diseases No Longer Falling

Note: Bioterrorism, and other infectious diseases, have separate sections in this Web report from the IDSA conference.

8th European Conference on Clinical Aspects and Treatment of HIV-lnfection

The Body (click "Conference Summaries")

* TMC-125, experimental NNRTI, produced 2-log HIV reduction in volunteers; [Note: "NNRTI" is an abbreviation for "non-nucleoside reverse transcriptase inhibitor," a class of anti-HIV drug. Two drugs in this class are currently approved, nevirapine and efavirenz.]

* Indinavir/ritonavir vs. saquinavir/ritonavir;

* NNRTI use and lipodystrophy study;

* Nevirapine and HDL cholesterol ("good cholesterol");

* Tipranavir, a new kind of protease inhibitor;

* Tenofovir intensification study;

* Cardiovascular risk factors, association with antiretroviral therapy;

* First-line treatment choice and lipid metabolism;

* Switching from protease inhibitors to NNRTIs;

* Tenofovir, antiretroviral activity regardless of baseline demographics, CD4, viral load;

* Long-term followup of switching from protease inhibitors to NNRTIs with undetectable viral load;

* Lack of drug interaction between tenofovir and several other anti-HIV drugs;

* Once-daily treatment with experimental drug emtricitabine (FTC, brand name Coviracil), ddI, and efavirenz, 2-year followup;

* Atazanavir (experimental protease inhibitor) 48week data on lack of lipid elevation;

* Nevirapine, ddl, and d4T long-term followup;

* Minor interaction between efavirenz and saquinavir/ritonavir.

HIV and

* Atazanavir at 48 weeks;

* Saquinavir/ritonavir new dosage regimen;

* Lopinavir (Kaletra) 3-year data in treatment naive patients;

* Switching from protease inhibitor(s) to NNRTI;

* Once daily d4t;

* T-20 (experimental fusion inhibitor, a new class of antiretroviral);

* Saquinavir and efavirenz interaction corrected with ritonavir;

* Efavirenz, ddI, and FTC (Coviracil) combination, 96-week study;

* Nevirapine and lipid profile improvement;

* Once daily vs. twice daily nevirapine;

* No important drug interaction between tenofovir and indinavir, lopinavir, 3TC, or efavirenz;

* TMC 125, experimental NNRTI;

* Efavirenz vs. nevirapine in treatment-naive patients;

* Switching from a protease inhibitor to efavirenz.

NATAP -- select 'Conference Reports' (on left), then '2001' (if necessary), then select the conference by name

* Atazanavir vs. nelfinavir;

* T-20 late phase II results;

* Extended-release d4T;

* Tibotec/Virco presentations, including TMC 125 (an NNRTI), and a method for predicting response to protease inhibitors;

* T-20 data in adults and children, and T- 1249 data in adults. (T-1249 is a "second generation" T-20.)

* Indinavir/ritonavir vs. saquinavir/ritonavir, both twice daily;

* Hepatitic C and B.

3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV

The Body

http:f/www.thebody.comfconfs/adrl200l/adrl200l.html (click "Conference Summaries")

* Mitochondrial function may not be causing lactate elevation;

* Increased lipolysis (fat destruction) in HIV, with or without fat redistribution;

* Inhibiting lipolysis improves insulin sensitivity;

* Lactate risk factors in antiretroviral therapy;

* More tumor necrosis factor released from skin fat in HIV patients with lipodystrophy;

* Lab studies comparing indinavir, nelfinavir, and amprenavir effects on fat cells -- and protection by rosiglitazone;

* Lipodystrophy and metabolic disorders 48 weeks after switching from protease inhibitors to Trizivir, vs. not switching;

* Prospective study of lipid elevation with two antiretroviral regimens.

HIV and

In an excellent summary of the lipodystrophy workshop, ten well-written papers by leading experts describe what happened in various areas:

By Andrew Carr, M.D.: Mitochondrial Toxicity and Lactic Acidemia; Liver Disease; Hypersensitivity; and Thyroid Disease.

By Graeme Moyle M.D., M.B.B.S.: Insulin Resistance; Adipocytes (fat cells); Clinical Data; Switch Studies; Cardiovascular Disease; and Clinical Risk.

NATAP, select 'Conference Reports' (on left), then '2001'

* Overview;

* Lipodystrophy;

* Amprenavir;

* List of conference highlights;

* Abacavir;

* Mitochondrial toxicity and lipodystrophy;

* Nevirapine;

* Thyroid abnormalities;

* Lactic acidosis and mitochondrial toxicity;

* Potential therapy for lipodystrophy;

* Heart disease risk;

* Abnormalities of glucose metabolism.

Liver Disease Conferences Coverage

The following conferences are most relevant for coverage of hepatitis or other liver-related illness.

66th Annual Scientific Meeting of the American College of Gastroenterology, October 19-24, Las Vegas

The Body (click "Conference Summaries")

* Hepatitis C;

* Liver disease in AIDS;

* New treatments for hepatitis C;

* PEG-interferons: When to use them;

* PEG-interferons: How to use them;

* Lamivudine (3TC) for hepatitis C: When to start, when to stop.

AASLD (American Association for the Study of Liver Diseases), November 9-13, Dallas

The Body

Check the site; coverage incomplete as we went to press.

HIV and

Check the site; coverage incomplete as we went to press.

NATAP,, select 'Conference Reports' (on left), then '2001'

Check the site; coverage incomplete as we went to press.

COPYRIGHT 2001 John S. James
COPYRIGHT 2001 Gale Group

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