Bye to Zido

IUPAC name 1-4-azido-5-hydroxymethyl tetrahydrofuran-2-yl-5-methylpyrimidine-2,4-dione. Formula C10H13N5O4. Zidovudine or azidothymidine (AZT), also called ZDV is a nucleoside analog reverse transcriptase inhibitor (NRTI), a type of antiretroviral drug. It was the first approved for treatment of HIV. It is also sold under the names Retrovir and Retrovis, and as an ingredient in Combivir, Epzicom and Trizivir.

Zidovudine was the first drug approved for the treatment of AIDS and HIV infection. Jerome Horwitz of Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine first synthesized AZT in 1964, under a US National Institutes of Health (NIH) grant. AZT was originally intended to treat cancer, but was shelved after it proved ineffective in treating cancer in mice.

In February 1985, Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan, three scientists in the National Cancer Institute (NCI), collaborating with Janet Rideout and several other scientists at Burroughs Wellcome (now GlaxoSmithKline), started working on it as an AIDS drug. After showing that this drug was an effective agent against HIV in vitro, the NCI team conducted the initial phase 1 clinical trial that provided evidence that it could increase CD4 counts in AIDS patients.

Modern treatment regimens typically use lower dosages (e.g. 300 mg) two times a day. As of 1996, AZT, like other antiretroviral drugs, is almost always used as part of highly active antiretroviral therapy (HAART). That is, it is combined with other drugs in order to prevent mutation of HIV into an AZT-resistant form.

Common side effects of AZT include nausea, headache, changes in body fat, and discoloration of fingernails and toenails. More severe side effects include anemia and bone marrow suppression, which can be overcome using erythropoietin or darbepoetin treatments. These unwanted side effects might be caused by the sensitivity of the alpha-DNA polymerase in the cell mitochondria. AZT has been shown to work additively or synergistically with many anti-HIV agents; however, acyclovir and ribavirin decrease the antiviral effect of AZT. Drugs that inhibit hepatic glucuronidation, such as indomethacin, acetylsalicylic acid (Aspirin) and trimethoprim, decrease the elimination rate and increase the toxicity.

AZT does not destroy the HIV infection, but only delays the progression of the disease and the replication of virus, even at very high doses. During prolonged AZT treatment HIV has the ability to gain an increased resistance to AZT by mutation of the reverse transcriptase. A study showed that AZT could not impede the resumption of virus production, and eventually cells treated with AZT produced viruses as much as the untreated cells. So as to slow the development of resistance, it is generally recommended that AZT be given in combination with another reverse transcriptase inhibitor and an antiretroviral from another group, such as a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.

I had been on my first month on the Lamivudine+Zidovudine combination, so I had been scheduled by the doctor yesterday for a complete blood count. I took the afternoon off from work, and trekked to the RITM, getting there at exactly 2:00 pm. I was sent straight to the lab to have my blood extracted, so the results would be available the same time the doctor was ready to meet me. I never realized it took as little as less than 30 minutes to complete a CBC lab test. Technology rocks.

After hanging out a couple of hours with the other clients there, even having an afternoon snack with the regular counselor, the results were finally realeased and the doctor had finished all the other clients before me. I was a bit surprised by the verdict, another change in medication. The doctor and Ate discussed a bit and agreed they were to make the change. Apparently, my Hemoglobin count had dropped from 140+ units to 100+ units, a side effect of Zidovudine. Ate even pointed out that my lips were a bit pale, something I never noticed myself. The doctor looked under my lower eyelid, and said it still wasn't too noticeable. But yes, they'd shift me over to another medication.

I hadn't brought what was left of my Lamu+Zido meds, so I promised I'd bring it on my next visit. I was given in place of it, solo Lamivudine tablets, plus the new one, Tenofovir, under the brand name Viread. It all seemed like a great move, as the doctor pointed out I'd just have to drink all three of my medications once a day in the evening. One tablet of Efavirenz, two tiny tablets of Lamivudine, and one teardrop-shaped tablet of Tenofovir. Not too bad. When I asked if I'd need to watch out for any side effects, the doctor said there are none. Even better.

So last night, I started my new nightly habit. The doctor advised me to comeback after about three months for another CBC, just to make sure my Hemoglobin has bounced back, but no other problems should be encountered. Hopefully, things will be all good.

Goodbye, Zidovudine.