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IV-Testing
A. Infections in American women
Doctors in New Jersey have been reviewing their records to determine which infections
were responsible for the deaths of their female patients in 1994. Of the 36 cases studied,
most died within 4 years of being diagnosed with HIV infection. "At the time of
death, 56% of the [patients] had less than 50 CD4+ cells." At the time of their
deaths, the following complications/diseases were present in these women in the
proportions indicated:
- 42% wasting
- 39% TB or MAC
- 31% bacterial pneumonia
- 28% PCP (in the past).
Other, less common complications were reported:
- 2 subjects had PML (progressive multifocal leucoencephalopathy -- a brain infection)
- one had severe brain damage due to HIV
- three had toxo.
During the years the patients visited the clinic, only 19% did not have cervical
cancer, while 78% had vaginal yeast infections.
Reference:
- Klose PC, Corell P, Eyassu R, et al. Rates of opportunistic infections and disease
conditons in clients of the Newark women's AIDS clinic (NWAC). We.C.3403.
B. Deciding if a drug works
Survival
According to one British researcher:
"There are many different anti-HIV drugs being developed and there is a great wish
to assess new treatments and complex drug combinations as quickly as possible. However,
the slow natural history of HIV-infection means that controlled trials using [death] as an
end-point inevitably take several years to complete. Even trials on [subjects with
symptoms who die] more rapidly, require many thousands of patient-years of observation. It
is therefore highly desirable that techniques should be developed which can assess more
quickly the effectiveness of drugs. In order to achieve this, [laboratory tests], have ben
adopted in the hope that they are reliable and effective."
CD4+
One lab test or marker that has been used is the CD4+ cell count. However, changes in CD4+
counts do not always result in decreased symptoms or decreased risk of death. Therefore,
pharmaceutical companies have now begun looking for other surrogate markers. Currently
their focus is on viral load, particularly the amount of viral RNA in the blood.
Why viral load?
One reason for choosing to measure viral load is that changes in this marker are supposed
to be linked to damage to the immune system. That is, as viral load increases, CD4+ cell
counts should fall and patients should normally be at increased risk of life-threatening
infections or death. "Repeated measurements can be easily performed on each patient
and changes in viral load accurately followed over weeks and months. Therefore only a
small number of patients needs to be studied to obtain a repeatable result." While
there are a number of problems with this rationale, and "there are no published data
from controlled clinical trials [of an anti-HIV agent] as yet," an American group of
researchers has recommended that regular monitoring of the amount of HIV RNA (viral load)
be used to help doctors manage their HIV-infected patients. Information from several
studies support that:
"There is a reasonable belief that the more viral load is suppressed and the
[longer it is kept suppressed], people with HIV/AIDS will get better." As more
doctors begin to monitor viral load, the benefits of this test will become clear.
References:
- Peto T. Surrogate markers in HIV disease. Journal of Antimicrobial Chemotherapy
1996;37(supplement B):161-170.
- Mellors JW, Rinaldo CR, Gupta P, et al. Prognosis in HIV-1 infection predicted by
the quantity of virus in the plasma. Science 1996;272:1167-1170.
- Saag MS, Holodniy, Kuritzkes DR, et al. HIV viral load markers in clinical
practise. Nature Medicine 1996; 2(6):625-629.
- Serum HIV-1 RNA levels and the time to development of AIDS in the multicentre
Hemophilia cohort story. Journal of the American Medical Association 1996;276(2):105-110.
- Phillips AN, Eron JJ, Bartlett JA, et al. HIV-1 RNA levels and the development of
clinical disease. AIDS 1996;10(8):859-865.
C. Practical uses for viral load
The American arm of the International AIDS Society recently convened a panel of
researchers to make recommendations about the use of viral load, that is the measurement
of HIV-1 RNA in the blood. Results of viral load measurements are reported as copies/ml,
for example, 5,000 copies/ml.
Regular use of viral load
- at the beginning of therapy: 2 viral load tests, 2 - 4 weeks apart
- every 3 to 4 months or when CD4+ cell counts are performed
- more frequently when considering a change in anti-HIV therapy
- 3 - 4 weeks after starting/changing therapy
When to start anti-HIV therapy?
"The goals of anti-[HIV therapy] are to limit or delay [worsening symptoms, falling
CD4+ cell counts] and, to increase survival." Doctors should begin treatment when: l
there are between 5,000 and 10,000 copies per ml and CD4+ cell counts are low or falling
and/or symptoms of HIV appear or become worse; l there are between 30,000 and 50,000
copies/ml regardless of [CD4+ cell counts], even if there are no or few symptoms of HIV
infection.
How low should viral load be suppressed?
The panel recommended that blood levels of HIV RNA be reduced as low as possible --
"undetectable". If this is not possible then a goal of less than 5,000 copies
per ml is "acceptable."
When is it time to change anti-HIV therapy?
When viral RNA levels in the blood rise "toward (or within 0.3 to 0.5 logs of)
pre-treatment values."
How can one tell that anti-HIV therapy is working?
For a treatment to be considered useful, levels of HIV RNA in the blood should decrease by
at least 0.5 log.
Which test should be used?
Currently there are three test kits in use:
- branched chain DNA
- NASBA
- RT-PCR
The panel recommends that the same test "should always [be used] in the same
individual patient."
References:
- Saag MS, Holodniy, Kuritzkes DR, et al. HIV viral load markers in clinical
practise. Nature Medicine 1996; 2(6):625-629.
- Kuritzkes DR. Plasma HIV RNA quantitation. Improving the Management of HIV
disease. 1996;4(2):11-15.
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