AEGiS-13IAC: Progressive recovery of T cell number and immune functions after 4 years of HAART in AIDS patients.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Progressive recovery of T cell number and immune functions after 4 years of HAART in AIDS patients.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB491)

Mezzaroma I, Pinter E, Carlesimo M, Bernardi ML, Alario C, Sacco G, Santini Muratori D, Fantini R, Aiuti F
I. Mezzaroma, University of Rome "La Sapienza", Division of Allergy and Clinical Immunology, Viale dell'Universite, 37, 00185 Rome, Italy, Tel.: +39 64 997 20 36, Fax: +39 64 46 62 09, E-mail: mezzaroma@uniroma1.it

BACKGROUND: To evaluate immunological reconstitution after 4 years of highly active antiretroviral therapy (HAART) in severely immunocompromised HIV-1 patients. Several studies have demonstrated the positive effects of HAART on clinical outcomes and reduction of HIV-1 replication, but conficting evidences on the levels and persistence of immune recovery. This is a crucial point for patients in advanced stage of disease.

METHODS: We analyzed T cell subsets and function during 42 months of HAART in 21 AIDS patients (mean baseline CD4+ 20/?L). Subjects were checked every 2 months for clinical signs and AIDS-related events, whereas laboratory parameters were assessed after 4, 12, 24, 36 and 42 months of HAART. Plasma HIV-1 RNA levels, T cell subsets (including memory and naive CD4+ cells), lymphoproliferative responses (LPR) to mitogens (phytohemoagglutinin, PHA, and anti-CD3 monoclonal antibody) and recall antigens (Candida mannoprotein, MP, tetanus toxoid, TT and rgp160), and in vivo response to ubiquitous antigens using skin test were assessed.

RESULTS: Increase in body weight, improvement of Karnofsky's score, and disappearance of opportunistic infections chacterized the clinical outcome. All patients showed an initial raise of CD4+ memory cells, whereas naive CD4+ cells began to increase only after the first year of HAART. Their increase reached the highest level during the last year of treatment. Patients recovered LPR to PHA and anti-CD3, whereas a functional response to MP was consistently observed after 36 months of HAART. No patients revealed a response to HIV-1 rgp160 or TT. Skin test reactivity, absent in all subjects before HAART, showed a slow but progressive increase starting in the second year of therapy and still continuing after 4 years. Immune recovery was stronger in subjects showing a reduction in viral load (VL) > 1 log₁₀. Patients who did not reach a sustained suppression of VL showed a similar, but lower, reconstitution.

CONCLUSIONS: The partial immune recovery observed may be sufficient to protect patients from opportunistic pathogens. These data suggest that HAART may be continued also in absence of a significant HIV-1 RNA decrease and that immune restoration can progress, slowly but consistently, up to 4 years of treatment.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, T-Lymphocytes, Acquired Immunodeficiency Syndrome, HIV-1, Viral Load, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, AIDS Vaccines, Antigens, CD4, VaxSyn HIV-1 (gp160) vaccine, Human, immunology
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WeOrB491