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Being Alive
Medical Update-March 18, 1996
Mark Katz MD and reported by Jim Stoecker
April 5, 1996
Being Alive 1996 Apr 5: 3

Physician Experience and PWA Survival A few years back we talked about a study that showed survival for hospitalized people with AIDS increased with the experience that the hospital had with treating PWAs. Now a report in the New England Journal of Medicine (March 14, 1996) looks at the impact that a primary care physician's experience with treating AIDS has on the survival of his/her patients with AIDS.

Group Health in Seattle, a large managed care organization, conducted a retrospective study of the patients of some 125 primary care physicians. Patients were grouped according to whether they were their doctor's first patient with AIDS, their doctor's second to fifth such patient, or greater than their physician's fifth patient with AIDS. Survival from time of initial consultation after diagnosis was then calculated for the three groups of patients. The researchers found that the median survival for patients who were their doctor's first experience with AIDS was only 14 months. For the second to fifth patient with AIDS, median survival time increased to 21 months. And if the patient was over the fifth PWA that the doctor had treated, median survival was calculated to be 26 months.

Researchers suggested that the more experienced physicians were more likely to call in specialists for consultations and were also more likely to advocate prophylaxis for PCP and other opportunistic infections. Whatever the explanation, the data do show that there is a learning curve for primary care physicians in treating people with AIDS. HIV+ people need to be aware of this and choose their physicians accordingly.

Low CD4 Count and Survival Researchers will soon publish a study of survival time for people with HIV after their CD4 count falls below 50. Several hundred PWAs were included in the data, and this study calculated a median survival time of 19.7 months after CD4 count has dropped to less than 50. This median survival time is in contrast to previous studies that showed around 12 or 16 months. The new data reinforces what we have known for some time: people with HIV infection are living longer than in the earlier years of the epidemic. It is important to keep in mind that a low CD4 count does not necessarily mean that the end is at hand.

Low CD4 Count and Protease Inhibitor Therapy As you probably know, Abbott Laboratories' protease inhibitor, ritonavir, was recently approved by the FDA. One of the studies used in seeking this approval involved over one thousand PWAs with less than 100 T-cells. The study participants could be on any antiviral regimen and could continue that regimen during the course of the study. Participants were given either ritonavir or a placebo. Median baseline CD4 counts were calculated to be 18 in the ritonavir arm and 22 in the placebo group. Median follow-up was 6.1 months. Researchers found that in this time 26 or 4.8% of the participants on ritonavir had died, while 46 or 8.4% of those on placebo had died. What these data suggest is that even at a low CD4 count, antiviral therapy that combines the right drugs can make a difference in survival.

Another RT Inhibitor Glaxo-Wellcome, manufacturer of AZT and 3TC, is developing a new reverse transcriptase (RT) inhibitor that is currently only identified as 1592U89. This drug is reportedly synergistic with all the other RT inhibitors (AZT, 3TC, ddI, ddC and d4T) and protease inhibitors; this means that it enhances the antiviral effect of these other drugs. Researchers also report that 1592U89 has good central nervous system penetration and thus may prove useful in cases of dementia. In very early studies, viral load reduction was 2.1 logs after 12 weeks, with an average CD4 increase of 122. Stay tuned for further developments on this latest RT inhibitor.

Another Protease Inhibitor: Nelfinavir Nelfinavir (brand name Viracept) is the name of the protease inhibitor being developed by the drug company Agouron. Early data suggest that this is a potentially powerful antiviral. Thirty patients, with baseline viral loads ranging from 50,000-60,000 copies per ml., were involved in the dose-ranging studies. The higher doses proved to be the most efficacious. Ninety per cent of the participants receiving 2250 mg per day showed at least a 1.5 log drop in viral load; 60% of this dosage group showed no detectable viral load. Diarrhea was a common side effect of the drug; however, most cases were treatable with antidiarrheals.

Protocol 511 is part of the continuing studies of nelfinavir. Study participants need to have a baseline viral load of greater than 15,000 copies per milliliter of blood; there are no CD4 count restrictions. Participants also cannot have had any previous antiviral therapy, with the exception of less than one month on AZT. The study will last for 24 weeks, with subjects able to get the drug for six months more. All participants in protocol 511 will get AZT and 3TC. One-third of the participants will also get 1500 mg per day of nelfinavir and another third will add 2250 mg of nelfinavir daily.

Locally, there are two sites for this study: AIDS Research Alliance (310.358.2423) and Kraus Medical Partners (213.930.2324). You can also call Agouron directly for trial information at 800.501.2474.

Summary: Six Axioms of Antiviral Therapy Over the years, I have developed axioms for making decisions concerning antiviral therapy. With all we know today, here are my current axioms: * if the viral load is found to be greater than 100,000 copies per cubic milliliter, you should be on some form of antiviral therapy; * in most situations, the use of two drugs for antiviral therapy is preferable to the use of just one; * in combination therapy, you should use two reverse transcriptase inhibitors, one of which should be AZT for its superior ability to penetrate the central nervous system; * a protease inhibitor should never be used alone; * once you begin antiviral therapy with a protease inhibitor, you should stay on that particular drug and follow the dosing regimen faithfully; * you should start using a protease inhibitor in your antiviral regimen if you are already using two reverse transcriptase inhibitors and the viral load remains high.