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CD4/CD8 ratio and CD4
Oct 13, 2002

Dear Judith, I have been recently diagnosed HIV+ (June 02) and have some questions regarding both the CD4/CD8 ratio and CD4 which do not seem to be spoken about as much as the CD4 absolute. My first question is what exactly are CD8 cells? What happens to them with HIV infection? My understanding is that they increase - is this correct and if so when in the course of infection (after how long)does this happen? Secondly what is the meaning/significance of the CD4/CD8 ratio? My doctor said that with HIV infection this declines/inverts - without meds what level does this ratio fall to and again when does this happen (immediately after infection or after a few months, a year??) Final question is re the CD4.How quickly does this fall on average per year without meds? What is the range? What weight do you place on the when someone has a >35 but a low CD4 because of a low WBC? Would you still start meds if the CD4 went below 350?

Thanks in advance for your response and for the great service you do - your work has certianly made the shock of HIV infection easier to deal with

Jim

Response from Dr. Little

This question has been forwarded to me since I specialize in primary HIV infection. CD8 cells are a type of white blood cell that is involved in fighting certain types of infection (such as HIV). The total CD8 cell count actually goes down immediately following infection (as does the CD4 cell count) for about 2-3 weeks - then over the course of the next month (i.e. roughly the second month of infection), the CD8 cell count increases (as does the CD4 count) to values higher than are typically seen in HIV negative individuals. During this period, the changes in the CD4/CD8 ratio are quite typical for HIV - though can be very difficult to distinguish from other viral infections such as EBV (i.e. mono). The CD4/CD8 ratio is an indicator of the overall level of immune suppression or damage done by HIV. The lower the CD4/CD8 ratio, the worse the damage. The CD4/CD8 ratio is rarely less than 1.0 in HIV negative individuals, but may drop as low as 0.1 in patients with recent HIV infection or very advanced disease. There is almost always substantial recovery of this ratio, even without antiretroviral therapy, during the 2-3rd month of HIV infection, which then persists for some time. The CD4/CD8 ratio will generally gradually decline over years of HIV infection in the absence of antiretroviral therapy. With therapy (administered fairly early after infection) this ratio may again rise to above 1.0 - a recovery rarely seen in patients with more advanced HIV infection who start on treatment.

The rate of CD4 cell count decline over time is difficult to predict without more information - but in general the rate of decline is proportional to the viral load (i.e. the higher the viral load, the more rapid the CD4 decline). For example, someone with a relatively stable viral load of 100,000 copies/ml might be expected to drop 50-100 CD4 cells per year. Much lower viral loads are associated with generally slower rates of CD4 decline. The decision of when to start treatment is very complex and in my opinion, should be very individualized. I follow the CD4 number, but if this is low because the total WBC count is low for some reason, then I follow the CD4 percentage and the viral load as the best indicators of the risk/rate of disease progression and then advise on the relative risks and benefits of treatment. In general, most physicians strongly advise treatment when the CD4 count is below 200. Between 500 and 200, there is much more room for weighing the pros and cons for each individual person before making this decision.

Finally, the CD4 and CD8 cell counts during the first 2 months of infection may reach very low levels (i.e. CD4 may fall below 200) - since there is nearly always some degree of recovery of these counts - without treatment - during the next couple of months, I would not be TOO concerned about how low the numbers go during this period - other than to say that the people who drop their CD4 cell counts the lowest, will probably have higher Viral loads after the seroconversion illness period resolves. Good luck.



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