Abstract No. 323: Immunologic Reconstitution After 12 Months of Antiretroviral Therapy in Very Early Stages of Chronic HIV-1 Infection
In this first study from Barcelona, the authors looked at the effectiveness of four different antiretroviral combinations to reduce viral load, to correct T cell subset abnormalities and to restore immune function in asymptomatic HIV-1 infected patients with CD4 T cell counts greater than 500/mL and a baseline viral load of greater than 10,000 copies/mL.
150 asymptomatic HIV infected patients were randomized and received treatment with either AZT plus DDC, AZT plus DDI, d4T plus DDI, or d4T plus 3TC plus Ritonavir (HAART). Immunological studies were then performed on thirteen untreated patients, eighteen were treated with double combinations, eight with HAART, and an additional group of uninfected normal controls (eight). After 12-months of follow-up, as expected, the HAART group was the most effective in reducing plasma HIV RNA to undetectable levels, and returning the CD4:CDA ratio to near-normal levels, and increasing CD8 positive CD28 positive T cells, and reducing activated T cells. Proliferative responses to PHA and other mitogens were similar in both groups of untreated and treated HIV-1 patients, and were not significantly different from uninfected normal controls. Both groups of HIV negative subjects and untreated HIV-1 infected patients did not show T cell proliferative responses to HIV-1 recombinant proteins GP160, P24 and GP123. Treated patients, regardless of regimen, showed an increased responsiveness to CMV antigen but lacked significant T cell responsiveness to HIV-1 recombinant proteins.
The authors also looked at cytokine producing T cells: Among untreated HIV positive patients, a clear increase in IFN gamma producing CD3 positive T cells was seen, as was a decrease of IL2 producing CD3 positive T cells, and similar TNF and IL4 producing T cells, when compared with HIV negative controls.
Among treated patients, those on HAART had the most effective reducing in production of IFN gamma. Treated patients also showed a low decline in IL2 and TNFL producing T cells with respect to baseline levels.
One of the conclusions is that early initiation of effective antiretroviral therapy may prevent loss of some T cell responses; i.e., to CMV.
The authors note that unfortunately one year of HAART is not enough to restore HIV-1 specific T cell responses. It is their conclusion, and the data strongly supports, that the therapeutic imperative of starting aggressive antiretroviral therapy in the early stages of HIV infection can prevent the loss of memory responsiveness. However, in this subset of healthy patients, it becomes evident that HAART alone will not restore complete immunogenetic memory, and that immune based therapies will need to be used in combination in order to achieve complete restoration of immune function. There is not enough data at present to suggest which form of immunotherapy may be the most appropriate to use.