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The Body Covers: The 38th Annual Meeting of the Infectious Diseases Society of America
Meet the Professor Session: Salvage Therapy and Resistance Testing: HIV Slide Session I
Symposium: Cutting Edge Issues in HIV Medicine

September 8, 2000

Meet the Professor Session: Salvage Therapy and Resistance Testing

At 7 AM and in a pouring rain, I questioned my sanity about trucking over for this session. Rich D'Aquila and Lisa Demeter, two experts in the topics under discussion, provided a tonic to my concern by chairing an excellent session. Although there were no bombshells of new data, they gave a spirited overview of the subject matter and then handled a steady stream of questions from the audience quickly using up the allotted time.

A few pearls from Lisa included:

  1. take a long-term view of the patient's situation
  2. the more into salvage one gets, the more the goal has to be a blend of an eye on future options as well as the clinical picture and CD4/RNA levels.

A few pearls from Rich included:

  1. resistance tests should be done within < 2 weeks of exposure to the drugs
  2. caution about the overall clinical usefulness of treatment interruptions in salvage

Based on the available data, both preferred genotypic tests versus phenotyping from the cost-effectiveness standpoint. They plugged a soon-to-be-open ACTG study comparing those two forms of testing in early salvage. It was clear from the discussion that more data is needed and that interest in clinical trials needs to remain high (and long-term) to help resolve the many issues where even the experts are confused.

HIV Slide Session I

I will focus on three presentations of clinical interest to me.

Abstract #12: Molecular epidemiology of recurrent invasive pneumococcal disease in HIV-infected patients in the Baltimore metropolitan area. M Catherine et al.

This study identified 2,722 cases of invasive pneumococcal disease, of which 413 (15%) were in HIV+ patients. The cases were recurrent in 30 cases (7%) and 23 of those isolates were available for testing. By a fancy lab test, it appeared that most of the recurrent infections were new infections (occurring an average of 64 weeks after first infection) while a minority were relapses (occurring an average of 16 weeks after first infection). Almost all the infections occurred with serotypes of pneumococcus that are included in either the 23- or 7-valent pneumococcal vaccines. More work will have to be done to determine whether vaccination can actually prevent serious infections.

Abstract # 13: Testing strategy for latent tuberculosis after initiation of HAART. T Fisk et al.

This group from Grady identified 110 patients who started HAART after having had a CD4 count < 100 cells/mm3 (average nadir CD4 = 12). At the time of the study the CD4 count = 185 cells/mm3 and the average RNA = 690 copies/ml. They found that after the CD4 count increased to over 100 cells/mm3, skin test reactivity was generally restored. A current CD4 > 100 correlated with skin test reactivity, but nadir CD4 count, duration of HAART, or viral load did not. Examples were given in which skin test reactivity to PPD (TB test) was identified after the CD4 increase above 100. That is a very practical point and they recommended that PPD tests be given to patients once their CD4 count reaches that level.

Abstract# 14: High prevalence of avascular necrosis (AVN) of the hip in HIV infection: magnetic resonance imaging of 339 asymptomatic patients. H Masur et al.

As a taxpayer, I get upset over reports of $600 toilet seats on nuclear submarines. Although I never could do an MRI study on 339 patients in my clinic, I am glad that there is someone who can (a good use for my tax dollar!). After Henry Masur and colleagues at the NIH observed several cases of AVN in one week, they undertook a study of 339 asymptomatic patients followed at the NIH clinical center, and 118 HIV- age/sex-matched controls. They found 15 cases of AVN of the hip in the HIV+ patients and none in the controls (p = 0.015 = significant). Factors that did not seem to be associated with AVN were CD4 level, RNA level, or use of a PI. Factors that did seem associated included corticosteroid use, lipid lowering drugs, use of testosterone, and body building/weight lifting. It is not clear what is going on but more study is needed. He did not recommend routine tests for AVN in the absence of symptoms. Of note is the fact that the AVN cases were mostly asymptomatic and did not seem to progress to symptoms at the rate one would usually expect.

Symposium: Cutting Edge Issues in HIV Medicine

Thom Quinn from Johns Hopkins gave an update on the global HIV/AIDS epidemic, again bringing the spirit of Durban to the audience in New Orleans. Although the statistics were numbing about the impact of HIV on Africa, some of the personal stories he recounted captured the disaster best. A farmer was quoted as saying, "we spend more time turning the bodies of the sick than turning the soil." A woman from Zimbabwe sadly said, "we no longer think that life will be better for our children." Those vignettes reflect the fatalism discussed at the opening session. One particular factoid caught my attention. In an economic analysis from the World Bank, the use of nevirapine for the prevention of maternal-child transmission was found to be the most cost effective treatment in all of medicine! With an estimated 620,000 new infections in children and 480,000 deaths this year, most being preventable, it is a cruel world indeed. All of us were implored to push for something to be done.

Bruce Walker from Harvard then provided an overview of immunopathogenesis of HIV infection and the potential role for immunotherapy. He painted a dim view of the value of drug interruptions in the setting of established HIV infection particularly when the virus was not under optimal control. Reasons for that included a wider range of viral diversity and impaired T-helper cell activity (as compared to the situation in primary infection). On the other hand, he was positive about the future of therapeutic vaccination in the setting of potent therapy as a means to assist the body in its effort to control the level of viral replication. He finished his session by stating that the immune system itself can control HIV -- but usually doesn't. How to change that balance is one of the major challenges of the next decade.

Finally, Bill Powderly from Washington University gave a talk on nucleoside toxicity and the mitochondrial toxicity hypothesis. He dissected the mitochondrial toxicity hypothesis and found proof lacking for some of the major nuke toxicities (i.e., neuropathy and pancreatitis). The data linking mitochondrial toxicity caused by the nukes for myopathy (AZT) and severe hepatic steatosis/lactic acidosis is fairly convincing but those are still relatively rare. More common are mild asymptomatic elevations in lactic acidosis which are not clearly linked to subsequent progression. He advised against routine use of venous lactic acid testing in asymptomatic patients. The linkage to stavudine is still difficult to separate from duration of nuke therapy but warrants further study. He nicely made the point again and again that more studies need to be done to understand the problem.

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Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.