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The Body Covers: The 6th Conference on Retroviruses and Opportunistic Infections
Abstract No. 325: Immune Reconstitution of Advanced HIV Patients (Following HAART)

February 2, 1999

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Another study, Abstract No. 325 from the University of California, also looked at immune reconstitution, although this time with advanced HIV patients following HAART therapy.

The authors looked at T cell proliferation assays to HIV antigens and opportunistic agents (CMV, MAC, toxoplasma, HSV and candida) in thirty HIV infected patients who had developed CMV retinitis prior to treatment with protease inhibitor containing regimens. HIV antigens included ten conserved peptides, HIV P24 protein and isolated virions.

At baseline, C responses (defined as a stimulation index of three or more) to any antigens were detected. The rate of CD4 rise and HIV RNA declined varied, but by 5-6 months, T cell responses developed in many of the patients, with each individual demonstrating a relatively consistent profile with repeated testing over time. 60-70% of the thirty patients responded to CMV and candida antigens, over 50% to MAC antigens, and 20-30% to toxoplasma and HSV antigens. Although individuals who developed responses to multiple antigens tended to have both lower ratio HIV RNA level and higher CD4 levels, correlation indicated a strong association between CD4 numbers and T cell response, than between HIV RNA levels and T cell proliferation. In about 40% of the advanced stage patients, T cells response was seen to at least one HIV antigen following treatment, compared to less than 10% before. Whole HIV virion preparations elicited responses in 30% of patients, and responses to peptides and P24 protein were also detected consistently in some patients. Thus, even in very advanced HIV disease, it appears possible to reconstitute some memory response to opportunistic antigens and HIV itself.

The authors also looked at induced cytokines, such as Interferon gamma. These Interferon levels correlated with T cell proliferation responses to HIV and other opportunistic antigens. In this particular study, 60% of patients were severely immunosuppressed and had restoration of T cell proliferation activity and cytokine production to both opportunistic agents, and HIV to some degree, with treatment. The authors commented that this observation was consistent with their clinical observation that treated patients are less susceptible to opportunistic infections. Secondly, the recovery of T cell proliferative activity is not directly related to reduction of viral load, but showed some correlation to CD4 levels. Some individuals maintained CD4/T cell responses to multiple antigens despite a sustained HIV RNA load that was quite high. Thirdly, the detection of response to HIV antigen in the advanced treated patients suggests that the CD4 response to HIV is not irreversibly lost. However, the frequency and magnitude of the response to HIV itself is lower than that to other frequently encountered antigens. With the exception of candida, the magnitude of the T cell response did not change markedly with treatment and was not different from HIV negative controls, but the frequency of response did increase, for both the opportunistic agents such as CMV, MAC, etc., and HIV. The time course recovery and the stability of T cell reactivity is variable from person-to-person and from antigen-to-antigen, but about 50% of patient who have fewer than 100 CD4 T cells before going on HAART did not show a sustained rise in CD4 T cells or increased T cell proliferation responses to a variety of antigens.

This data, along with the previous abstract, again supports the concept that the earlier patients are treated, the more likely there is to be effective immuno-reconstitution. Patients with CD4 counts below 100 were inferior in responses than those seen in patients who had relatively higher T cells. The data from other abstracts supports the fact that patients who have, for instance, CMV retinitis with below 50 CD4 T cells, have improved immunogenic response to CMV antigens and opportunistic infection as their T cells begin to rise above the 100 level. Indeed, there are other papers that support the concept of discontinuing maintenance therapy when CD4 counts rise above the 300-400 level and the viral load is completely suppressed. Again, another hopeful sign that the quest for effective therapy will continue to improve the quality of life in these patients.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Abstract: Immune Reconstitution of Advanced HIV Patients (Following HAART)
Authored by: R. Schrier, et al.

See Also
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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.

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