|Pulse therapy as an option
Feb 4, 2004
I'm a 23 year old man in Australia who was infected in late April 2002, had a seroconversion illness in mid-May and in late May had two indeterminate tests before I got a positive result on June 3. On June 3, my vl was 10900 and my CD4 count was 742. On June 10, my vl was 2680. My doctor and I decided that I would start treatment for a period of 6 months, primarily to minimise damage to my immune system during the period of primary infection and to attempt to boost my immune response to HIV. I started Trizivir on 10 June. Two weeks later (June 24), my CD4 count was 1061 and my vl was at 152. I stopped meds on Dec 6 (I think) and in the six months I was on Trizivir, my vl was undetectable and my CD4 count was never below 998. My CD4 has been between 38 and 43 since I started meds and my CD4:CD8 ratio has been between 1.4 and 1.7.
Tomorrow, I'm going to get my first results since coming off meds in Dec and will be discussing future treatment strategies with my doctor. I've been trying to find as much information about different options but there doesn't seem to be a lot out there, particularly about pulse therapy, so I've got a few questions.
1/ Are these good results? I know there's no such thing as normal, but I'd really like to get an idea of how I'm doing. 2/ Do you think that pulse therapy would be appropriate as a future treatment strategy? My doctor and I have discussed monitoring my labs and putting me on meds for a month to boost my immune system and get my CD4s back up if they start to fall. 3/ If I were to try pulse therapy, what should I set as the lower limit for my CD4 count before starting meds again? I know the guidelines say 350 but is there any advantage to starting earlier, particularly in terms of response to antivirals or minimising damage to the immune system. 350 also seems like a long way to fall from my current levels before starting treatment. What sort of damage would be done to the immune system in the meantime and could use of pulse therapy be a way of occasionally boosting my immune response to HIV? 4/ Which meds would be best for use in pulse therapy? My doctor had mentioned using PIs, though I imagine he meant as a PI-based regimen, rather than as monotherapy. 5/ Where can I find more information (other than the body.com)? There doesn't seem to be a lot out there.
Sorry for the long question, am just feeling quite uncertain and would like some advice and info. Thanks
| Response from Dr. Pierone
Great questions, unfortunately not a lot of data upon which to base the answers. To begin, your response has been terrific with undetectable viral load and normal CD4 counts on therapy. You did not mention side effects, so I will assume you had none.
Everyone should understand that there is no proof that treatment of HIV infection within the first several months of infection is better than waiting off therapy until CD4 count drops below a threshold level some years into the future. The comparative studies simply have not been done yet. But there are intriguing data that early treatment with an STI (or pulse approach) might be an opportunity to alter the natural course of HIV infection by stimulating the intrinsic immune responses to HIV. Even with the lack of proof, if I were in your position, I would be doing the same type of thing that you are pursuing.
In one of the early STI studies in acute infection, the cut off for restarting therapy was a viral load of 5000 copies/ml rather than a CD4 count limit. If you used a CD4 count metric to restart treatment it would have to be very high or you would probably be off therapy for years.
It probably does not matter which class of antiretroviral medication is used, the primary determinant should be safety and tolerability of the regimen. Everyone on antiretroviral therapy should have high level adherence to prevent development of viral resistance.
Here are some references to some of the studies done on STI:
1. Oxenius A, et al. Stimulation of HIV-specific cellular immunity by structured treatment interruption fails to enhance viral control in chronic HIV infection. Proc Natl Acad Sci USA 2002; 99:13747-13752. (SSITT)
2. Kalams S, et al. Levels of human immunodeficiency virus type 1 specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia with highly active antiretroviral therapy. J Virol 1999, 73:6721-6728.
3. Oxenius A, et al. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ lymphocytes. Proc Natl Acad Sci USA 2000, 97:3382-3387.
4. Ruiz L, et al. HIV dynamics and T-cell immunity after three structured treatment interruptions in chronic HIV-1 infection. AIDS 2001; 15: F19-27. (+)
5. Ortiz G, et al. Structured antiretroviral treatment interruptions in chronically HIV-1 infected subjects. Proc Natl Acad Sci USA 2001; 98: 13288-13293.
6. Rosenberg ES, et al. Immune control of HIV after early treatment of acute infection. Narture 2000; 407:523-526.
7. Walker BD, et al. Immune control and immune failure in HIV infection. Program and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections. February 10th -14th 2003. Boston, MA. Abstract 164.
8. Miro JM, et al. Structured treatment interruptions (STI) in patients receiving HAART within 90 days after onset of primary HIV-1 infection (PHI) symptoms: spontaneous control of viremia in only one third of cases after four cycles off therapy. XIV International AIDS Conference. Barcelona, July 7-12, 2002. Abstract ThOrB1437.
9. Markowitz M, et al. Discontinuation of antiretroviral therapy commenced early during the course of human immunodeficiency virus type 1 infection, with or without adjunctive vaccination. J Infect Dis 2002; 186: 634-643.
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