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Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection

Tilling, Richarda; Kinloch, Sabinea; Goh, Li-Eanb; Cooper, Davidc; Perrin, Lucd; Lampe, Fionae; Zaunders, Johnc; Hoen, Brunof; Tsoukas, Chrisg; Andersson, Janh; Janossy, Georgea; on behalf of the Quest Study Group

Clinical

Objectives: To monitor changes in the numbers of CD8 lymphocytes expressing the activated CD38++ phenotype in peripheral blood samples from patients with primary HIV infection (PHI) treated with highly active antiretroviral therapy (HAART).

Methods: Zidovudine, lamivudine, abacavir and amprenavir were initiated during PHI as part of the Quest study. Absolute numbers of CD8+/CD38++ T cells were determined using three-colour flow cytometry, and plasma viral load (VL) was measured using the Roche Amplicor method.

Results: The median, pre-therapy CD8+/CD38++ T cell count was 461/mm3 (interquartile range 216, 974) in 131 patients compared with normal control values of less than 20 cells/mm3. Levels fell markedly in parallel with VL within the first 2 weeks of HAART initiation, to a median of 47 cells/mm3at 28 weeks (median 436 cell decline;P < 0.001). At that time, 80% of patients had a VL less than 50 copies/ml, and 16.3% of all patients had less than 20 CD8+/CD38++ T cells/mm3. A continued decrease in CD8+/CD38++ T cell count occurred in 67.2% of patients whose VL was maintained below 50 copies/ml (median change from first to last value −18 cells/mm3;P < 0.001).

Conclusion: After the initiation of HAART in PHI, CD8+/CD38++ lymphocytes declined rapidly in parallel with VL, and allowed for a normalization of CD8+/CD38++ T cell numbers in a subset of patients at week 28. Cell numbers continued to decline in patients who maintained VL below 50 copies/ml, indicating that the CD8+/CD38++ T cell count may represent a marker of residual viral replication when VL falls below detectable levels after HAART intervention.

From the aDepartment of Immunology and Molecular Pathology, Royal Free and University College Medical School, Royal Free Campus, London NW3 2QG, UK; bDepartment of HIV and Opportunistic Infections, GlaxoSmithKline Research and Development, Greenford Road, Middx UB6 0HE, UK; cNational Centre in HIV Epidemiology and Clinical Research, University of New South Wales, 376 Victoria Street, Sydney, NSW 2010, Australia; dHôpital Cantonal, Département de Médecine interne, Division des Maladies Infectieuses, Laboratoire Central de Virologie, Rue Micheli-du-Crest 24, 1211 Genève 14, Switzerland; eRoyal Free Centre for HIV Medicine and Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK; fUniversite de Franche-Comte, Department of Infectious Diseases, University Medical Centre, 25030 Besancon, France; gMontreal General Hospital, Immune Deficiency Treatment Centre, Montreal, Quebec H3G 1A4, Canada; and hKarolinska Institutet, Division of Infectious Diseases, Huddinge University Hospital, Huddinge, Sweden.

Correspondence and requests for reprints to: Dr L. Goh, Department of HIV and Opportunistic Infections, GlaxoSmithKline Research and Development, Greenford Road, Middlesex UB6 0HE, UK. Tel: +44 020 8966 2980; fax: +44 020 8869 3310; e-mail: lg6017@glaxowellcome.co.uk

Received: 19 January 2001;

revised: 16 August 2001; accepted: 9 October 2001.

© 2002 Lippincott Williams & Wilkins, Inc.