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- Title
Viremia, Resuppression, and Time to Resistance in Human Immunodeficiency Virus (HIV) Subtype C during First-Line Antiretroviral Therapy in South Africa.
- Authors
Hoffmann, Christopher J.; Charalambous, Salome; Sim, John; Ledwaba, Joanna; Schwikkard, Graham; Chaisson, Richard E.; Fielding, Katherine L.; Churchyard, Gavin J.; Morris, Lynn; Grant, Alison D.
- Abstract
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 11000 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 multinucleoside 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.
- Subjects
SOUTH Africa; VIREMIA; HIV; ANTIRETROVIRAL agents; DRUG resistance; AZIDOTHYMIDINE; HIV-positive persons; MEDICAL care; MEDICAL research
- Publication
Clinical Infectious Diseases, 2009, Vol 49, Issue 12, p1928
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1086/648444