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Slower decline of plasma HIV-1 RNA following highly suppressive antiretroviral therapy in primary compared with chronic infection

Putter, Heina; Prins, Jan M.b; Jurriaans, Suzannea; Roos, Marijkec; Ferguson, Neil M.d; van Praag, Rienekeb; van der Hoek, Liaa; Schuitemaker, Hannekec; Anderson, Roy M.d; Goudsmit, Jaapa; Lange, Joep M. A.b; de Wolf, Franka

Basic Science

Objectives: To study the effect of highly suppressive antiretroviral therapy on the slopes of HIV-1 RNA decline in primary compared with chronic HIV-1 infection.

Methods: Slopes of HIV-1 RNA decline in plasma were compared before and after the start of highly suppressive antiretroviral therapy from five acutely infected patients who started treatment 2 to 5 weeks following the onset of clinical symptoms. Slopes of decline after the initiation of therapy were also compared with those found in 12 chronically infected individuals on the same therapy. Numbers and percentages of activated CD4 and CD8 T cells at baseline were compared as well.

Results: The pre-treatment slopes of HIV-1 RNA decline in the acutely infected individuals increased significantly (P = 0.0001) after the start of anti-retroviral therapy. However, these post-treatment slopes were lower than those found in the chronically infected individuals (P = 0.012). Slopes were inversely correlated (P = 0.012) with baseline HIV-1 RNA. Although the number of CD38+HLA-DR+ CD4 cells was higher in primary infection (P = 0.02), the percentage did not differ between primary and chronic infection.

Conclusions: These findings indicate that antiretroviral therapy contributes significantly to the clearance of HIV-1 during primary infection. Based on the mathematical model the less steep RNA slope following the start of treatment in primary infection can be predicted to be the result of lower clearance of productively infected cells and higher burst size per cell per unit time. This may indicate a growing immune response to HIV-1 in this very early stage of infection.

From the aDepartment of Human Retrovirology and bNational AIDS Therapy Evaluation Center (NATEC), Department of Internal Medicine, Division Infectious Diseases, Tropical Medicine and AIDS, University of Amsterdam, the cDepartment of Clinical Viro-Immunology and Laboratory for Experimental and Clinical Immunology of the University of Amsterdam at the CLB and the dWellcome Trust Centre for the Epidemiology of Infectious Diseases, University of Oxford, Oxford, UK.

Requests for reprints to Dr Frank de Wolf, Department of Human Retrovirology Academic Medical Centre, University of Amsterdam, Meibergdreef 15; 1105 AZ Amsterdam, The Netherlands.

Received: 1 February 2000;

revised: 5 June 2000; accepted: 5 July 2000.

Sponsorship: This study was supported by a private foundation that prefers not to be named.

© 2000 Lippincott Williams & Wilkins, Inc.