Product Information

By John G. Bartlett, M.D. and
Joel E. Gallant, M.D., M.P.H.
The Hopkins HIV Report:
A bimonthly newsletter for healthcare providers
Volume 9, Number 1, January 1997


Hydroxyurea:

Studies presented in Vancouver comparing ddI with ddI/hydroxyurea (500 mg bid) showed a decrease in viral burden of approximately one log that was sustained at 24 weeks only in the group receiving combination treatment. There was no increase in CD4 cell count, presumably due to the "cytostatic" nature of hydroxyurea. The presumed benefit is that hydroxyurea preserves the sensitivity of HIV to ddI and possibly to other nucleoside analogues, thus sustaining the antiviral effect, which has been noted to persist for up to one year. Potential advantages of this drug are that it is non-toxic, inexpensive, and has a simple dosing regimen (two pills twice daily). The effect is independent of prior treatment and resistance has not been noted. [JGB]


Confide Home Kit for HIV Testing:

The initial experience with "Confide," the home kit for HIV testing, has been reported for the first 15,000 samples. Results showed 98.9% were negative, 1% were positive and 0.1% were indeterminate. About 96% of consumers called for results. Those with negative results hear a recorded counseling message that lasts about five minutes and they have the option of talking with a counselor; about 2% elect this option. Persons with positive results speak with a counselor for an average interview time of 20 minutes. The impression of the counselors is that 13% have "an intense emotional response," and one person was considered suicidal. [JGB]


The Blood Supply and HIV:

All blood donations in the U.S. are screened for HIV1, HIV-2, HTLV-1, hepatitis B, hepatitis C and syphilis. HIV screening has reduced the risk of transmitting this virus from 12,500 units in 1985 to 1/420,000 in 1996. The current estimate is that 18-27 units/year will be falsely negative by routine HIV serology. The number of documented HIV transmissions despite negative serologic screening through mid-1995 was 35. [JGB]


Zidovudine (AZT, Retrovir) Now Available in 300 mg Tablet:

This formulation should improve patient acceptability. It also represents "official sanction" by the FDA of twice daily dosing with the standard dose of 300 mg bid. [JGB]


Recommendations for Rifampin and Protease Inhibitors:

The U.S. Public Health Service has made recommendations for the concurrent use of rifampin for treatment of active tuberculosis and protease inhibitors for HIV [MMWR 45: 922, 1996]. All three manufacturers of protease inhibitors advise against concurrent use with rifampin due to drug interactions. The options outlined below are suggested:

  • Protease inhibitor not yet started: Give the standard short-course four-drug treatment for TB before initiating a protease inhibitor.

  • Protease inhibitor already initiated: Option one is to discontinue the protease inhibitor for the duration of the standard four drug treatment of tuberculosis. Option two is to discontinue the protease inhibitor and give the four drug TB treatment regimen with rifampin for >2 months (until sputum conversion and sensitivity test results are returned), then switch to a 12 month regimen of INH (15 mg/kg) plus etham-butol (50 mg/kg) twice weekly and restart the protease inhibitor. Option three is to continue indinavir and give a four drug tuberculosis regimen with a substitution of rifabutin (150 mg/day) for rifampin. [JGB]

Nevirapine Combined with Indinavir:

Nevirapine induces hepatic cytochrome P450 enzymes, lowering plasma levels of concurrently administered drugs that use this metabolic pathway. These drugs include protease inhibitors, and substandard levels are potentially problematic due to resistance. Pharmacologic studies of nevirapine plus indinavir showed that concurrent administration reduces indinavir plasma concentration by 28%. The conclusion is that the proper dose is indinavir, 1000 mg q8h (instead of 800 mg q8h) plus nevirapine, 200 mg bid. It is emphasized that there is no clinical experience to document efficacy or side effects of this combination. [JGB]


Ritonavir: Update on Toxicity, Drug Interactions and the Name:

Side effects added to the package insert include:

  1. hypersensitivity reactions including urticaria, rash, bronchospasm, angio-edema, anaphylaxis and Stevens-Johnson syndrome;

  2. clinical hepatitis with trans-aminase levels >5x upper limits of normal;

  3. as with other protease in-hibitors, possible increased bleeding in hemophiliacs. Drug interactions have resulted in the addition of pimozide (Orap) and ergot alkaloids as drugs forbidden for concurrent use. Other drugs that show im-portant interactions are disopyramide, mexiletine, nefazodone (Serzone) and fluoxetine (Prozac). Finally, there has been confusion by pharmacists in distinguishing "Ritonavir" and "Retrovir." The suggested solution is to prescribe by the trademark name "Norvir." [JGB]

Albendazole Approved:

The anti-helmintic agent, albendazole (Albenza, SmithKline Beecham Pharmaceuticals), has been approved by the FDA and is now commercially available. The drug is licensed for the treatment of neuro-cysticercosis (Tinea solium) and hydatid disease (Echinococcus granulosus), but it can be useful for microsporidiosis. Microsporidiosis due to Septata intestinalis and Encephalitozoon species generally responds better than disease due to Enterocytozoon bieneusi. Albendazole was available for microsporidiosis through a com-passionate use program. The typical dose is at least 400 mg twice daily. Albendazole is available in 200 mg tablets. [JEG]


Ritonavir plus Saquinavir Hepatotoxicity with HBV or HCV:

Results of the clinical trial of these two protease inhibitors have shown high rates of hepatotoxicity in patients with chronic hepatitis due to HBV or HCV. Among 150 participants in the clinical trial, 11 had hepatotoxicity with ALT levels 5x the upper limit of normal; 7 of the 11 had HCV Ab or HBVs Ag. Consequently, caution is advised in patients with these markers of hepatitis viral infection who are to receive ritonavir plus saquinavir.


This article is from The Johns Hopkins University AIDS Service,
The Hopkins HIV Report: A bimonthly newsletter for healthcare providers.