Research Initiative Treatment Action (RITA!); Vol 5, No. 4 October 1999
After an extended absence the capsule formulation of ritonavir (Norvir) is finally back on drug store shelves. At the end of June, the US Food and Drug Administration approved the reformulation of the protease inhibitor. Abbott officials report the new soft-gel formulation has undergone a number of tests to ensure its stability. The new formulation does not require refrigeration if taken within thirty days as long as the temperature does not exceed 76 degrees Fahrenheit.
A report in the July issue of Clinical Infectious Diseases (1999 Jul;29(1):223-4) describes two cases of what appear to be hydroxyurea-induced hepatitis. In one case a forty-five year old woman without history of alcohol or illicit drug use who had been treated with zidovudine (Retrovir), lamivudine (Epivir) and saquinavir (Fortovase) was switched to a regimen of nelfinavir (Viracept), stavudine (Zerit), didanosine (Videx) and hydroxyurea (Hydrea). The dose of hydroxyurea was 500 mg twice a day. After three months the woman developed fulminant hepatitis and died. The second case was a 42-year-old man with HIV and hepatitis C. When hydroxyurea was added to his regimen he developed abdominal pain and nausea and his liver function declined. When the antiretrovirals and hydroxyurea were withheld his liver function gradually improved. Finally, the patient was placed back on his antiretroviral therapy without the hydroxyurea and no further liver toxicity was reported. The authors speculate that hydroxyurea may potentiate the mitochondrial toxicity of nucleoside analogs.
The Society of General Internal Medicine AIDS Task Force reported on the most recent data on HIV disease management in the July 20 issue of the Annals of Internal Medicine (1999 Jul 20;131(2):136-43). In that report the task force states that doctors who are experienced in caring for persons with HIV provide better overall care and that actual patient care experience contributes to better patient management than subspecialty training. They point out that primary care physicians should not be expected to have sufficient expertise to care for HIV-infected patients without expert consultation. However, primary care physicians should be able to screen patients for HIV risk, identify symptoms of HIV infection or development of opportunistic infections and have basic knowledge of HIV treatment options and prophylactic drugs.
In a report appearing in the journal AIDS (1999 Jul 9;13(10):1207-12), researchers from Johns Hopkins University School of Medicine detail a retrospective study in which patients who experienced virologic breakthroughs with indinavir (Crixivan) or nelfinavir had effective responses to subsequent therapy with a combination of ritonavir and saquinavir. Twenty-three patients failing indinavir-containing regimens and 6 patients failing nelfinavir-containing regimens were switched to a ritonavir and saquinavir regimen. Most of the patients also were able to change reverse transcriptase inhibitors and nine of the patients were able to add a nonnucleoside reverse transcriptase inhibitor. Thirteen of the 23 patients failing indinavir had a durable response (below 400 copies) for a median of 37 weeks and 4 of 6 patients failing nelfinavir therapy experienced similar responses. This study is in contrast to previous studies reporting less success using the ritonavir/saquinavir combination in indinavir failing patients. The responders in this study tended to be those who switched to the new therapies when their viral loads were much lower and the researchers speculate that this early switch may be a factor in the successful response to subsequent therapies.
French researchers report in the journal AIDS (1999 Jul 30;13(11):F71-7) a durable 24-week response to a combination of ritonavir, saquinavir, efavirenz (Sustiva) and two recycled nucleosides in patients who had previously failed triple therapy with either indinavir or ritonavir. Patients were naïve to both efavirenz and saquinavir. Ritonavir was given at 100 mg twice daily and saquinavir was given at 1000 mg twice daily. Thirty-nine percent of the patients had genotypic mutations at positions 48 and 90—mutations that are generally associated with resistance to saquinavir. At the 24 week follow-up 45% of the patients had viral loads below 50 copies and 71% had viral loads below 500 copies. According to the investigators "phenotypic resistance to saquinavir, but not genotypic mutation resistance patterns, was predictive of failure to salvage therapy."
The increased incidence of nephropathy (kidney disease) in HIV-infected African-Americans may be explained by an inherited susceptibility to renal failure. Investigators identified two hundred and one black patients with HIV-associated nephropathy and compared their family histories to a control group of 50 HIV-infected black patients without renal disease. Black patients with nephropathy were 5.4 times more likely to have close relatives with end-stage renal diseases than patients in the control group.
Two studies published in the New England Journal of Medicine (1999 Aug 5;341(6):385-93 & 1999 Aug 5;341(6):441-3) report that a mother's viral load at the time of delivery may be the most critical factor in determining the HIV status of the infant. Data from Pediatric AIDS Clinical Trials Group Study 185 on 480 HIV-infected women and their infants who participated on in a trial of zidovudine used prophylactically were analyzed. All the women in the trial were receiving zidovudine and 14% were receiving dual or triple nucleoside analog therapy. The analysis showed viral load levels to be the only independent predictor of transmission. In the second study, members of the Women and Infants Transmission Study Group measured viral load levels in 552 pregnant women. The rate of transmission increased in proportion to the increase in viral load. Women with viral loads of less than 1,000 copies had a zero transmission rate and the rate increased up to 40.6% among women with more than 100,000 copies.
Breastfeeding an infant almost doubles the risk of vertical transmission. As such, is it not recommended that HIV-infected mothers breastfeed their children. In certain areas of the world, however, alternative forms of feeding are not safe, affordable or acceptable. In the August 7 issue of The Lancet, researchers from the South African Vitamin A Study Group found that infants who were exclusively breastfed for the first three months of their lives had a lower risk of HIV infection than those who received mixed feedings during those first three months. The rate of HIV transmission among children who were exclusively breastfed was 14.6%; for children who were never breastfed the rate was 18.8% and for those who received mixed feedings the rate was 24.1%. Researchers caution that it is still too early to make broad recommendations based on this single study observation. In a related study appearing in the Journal of the American Medical Association (1999 Aug 25;282(8):744-9), researchers found that the risk of becoming infected with HIV through breastfeeding is highest during the first few months of life.
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Copyright © 1999 - Research Initiative Treatment Action (RITA!). Reproduced with permission. RITA! is published by The Center for AIDS. Contact Thomas Gegeny, MS, ELS, Editor, RITA! for permission to reproduce RITA!. tom@centerforaids.org. http://www.centerforaids.org
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