Journal Article

Predictors of Virological Outcome and Safety in Primary HIV Type 1–Infected Patients Initiating Quadruple Antiretroviral Therapy: QUEST GW PROB3005

Bruno Hoen, David A. Cooper, Fiona C. Lampe, Luc Perrin, Nathan Clumeck, Andrew N. Phillips, Li-Ean Goh, Stefan Lindback, Daniel Sereni, Brian Gazzard, Julio Montaner, Hans-Jurgen Stellbrink, Adriano Lazzarin, Diane Ponscarme, Shlomo Staszewski, Lars Mathiesen, Don Smith, Robert Finlayson, Rainer Weber, Laurence Wegmann, George Janossy and Sabine Kinloch-de Loes

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 45, issue 3, pages 381-390
Published in print August 2007 | ISSN: 1058-4838
Published online August 2007 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/519428
Predictors of Virological Outcome and Safety in Primary HIV Type 1–Infected Patients Initiating Quadruple Antiretroviral Therapy: QUEST GW PROB3005

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Background. Initiation of antiretroviral therapy during primary human immunodeficiency virus (HIV)–1 infection may confer long-term benefit.

Methods. After initiation of zidovudine, lamivudine, abacavir, and amprenavir therapy in patients in the QUEST cohort, predictors of virological outcome, virological and immunological changes, and adverse events were evaluated over 48 weeks.

Results. One hundred forty-eight patients started antiretroviral therapy during primary HIV-1 infection with ⩽3 bands on Western Blot (median plasma HIV-1 RNA load, 5.4 log copies/mL; median CD4 cell count, 517 cells/mm3). By week 48, 36% of patients had stopped treatment or were lost to follow-up. Among the 115 patients receiving follow-up care at week 48 (102 of whom were receiving antiretroviral therapy), the median viral load decrease was -5.4 log copies/mL (interquartile range [IQR], -6.4 to -3.9 log copies/mL), and the median increase in CD4 cell count was 147 cells/mm3 (IQR, -1 to 283 cells/mm3); 84.2% of patients had a viral load ⩽50 copies/mL, and 44.7% of patients had a viral load ⩽3 copies/mL. The median cell-associated RNA level decreased from 3.4 log copies/million PBMCs (IQR, 2.9–4.1 log copies/million PBMCs) to 0.8 log copies/million PBMCs (IQR, 0.5–1.4 log copies/million PBMCs), and the median cell-associated DNA level decreased from 2.8 log copies/million PBMCs (IQR, 2.4–3.0 log copies/million PBMCs) to 1.6 log copies/million PBMCs (IQR, 1.2–1.9 log copies/million PBMCs); 33.3% of patients had an undetectable RNA level, and 9.5% of patients had an undetectable cell-associated DNA level. The median CD8+/CD38++ T cell count decreased from 459 cells/mm3 (IQR, 208–974 cells/mm3) to 33 cells/mm3 (IQR, 19–75 cells/mm3). Baseline CD8+/CD38++ T cell count and cell-associated DNA level were independent inverse predictors for reaching a viral load ⩽3 copies/mL. Eighty-three patients experienced a serious adverse event (median duration of an adverse event, 15 days).

Conclusions. Initiation of antiretroviral therapy during primary HIV-1 infection was associated with very significant antiretroviral activity and a decrease in immune activation. Lower baseline CD8+/CD38++ T cell count and cell-associated DNA level were predictive of achieving a viral load ⩽3 copies/mL.

Journal Article.  5877 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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