Journal Article

Viremia, Resuppression, and Time to Resistance in Human Immunodeficiency Virus (HIV) Subtype C during First-Line Antiretroviral Therapy

Christopher J. Hoffmann, Salome Charalambous, John Sim, Joanna Ledwaba, Graham Schwikkard, Richard E. Chaisson, Katherine L. Fielding, Gavin J. Churchyard, Lynn Morris and Alison D. Grant

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 49, issue 12, pages 1928-1935
Published in print December 2009 | ISSN: 1058-4838
Published online December 2009 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/648444
Viremia, Resuppression, and Time to Resistance in Human Immunodeficiency Virus (HIV) Subtype C during First-Line Antiretroviral Therapy

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Background.Episodes of viremia are common in African antiretroviral therapy (ART) programs. We sought to describe viremia, resuppression, and accumulation of resistance during first-line combination ART (cART) in South Africa.

Methods.Retrospective analysis of a cohort receiving zidovudine, lamivudine, and either efavirenz or nevirapine with human immunodeficiency virus (HIV) RNA monitoring every 6 months. We assessed viremia (HIV RNA >1000 copies/mL after initial HIV RNA response) and resuppression (HIV RNA <400 copies/mL after viremia). Genotypic resistance testing was performed using stored plasma on a subset of patients at first detection of viremia and subsequently among patients with persistent viremia.

Results.Between 2002 and 2006, 3727 patients initiated cART (median CD4, 147 cells/mm3). Of 1007 patients who developed viremia, 815 had subsequent HIV RNA assays, and 331 (41%) of these resuppressed without regimen switch. At identification of viremia, 45 (66%) of 68 patients had HIV-1 drug resistance, 42 (62%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 25 (37%) had M184V/I, and 4 (6%) had multi-nucleoside analogue drug mutations. By 12 months of persistent viremia among a subset of 14 patients with resistance testing to 12 months, 11 (78%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI)-resistance, 8 (57%) had M184V/I, and 2 (14%) had multi-nucleoside analogue drug mutations. Resistance was associated with a reduced probability of resuppression; however, 50% of patients with NNRTI resistance resuppressed while receiving an NNRTI.

Conclusions.The majority of patients had NNRTI resistance mutations at detection of viremia. However, 41% resuppressed without regimen switch. Our findings support maximizing first-line use while minimizing risk of significant cross-resistance by implementing intensive adherence support and repeat HIV RNA testing 3–6 months after detecting viremia, with regimen switch only if viremia persists.

Journal Article.  4226 words.  Illustrated.

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

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