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

被引：91

作者：

Hoffmann, Christopher J. ^{[1
,2
]}

Charalambous, Salome ^{[2
]}

Sim, John ^{[3
]}

Ledwaba, Joanna ^{[4
]}

Schwikkard, Graham ^{[4
]}

Chaisson, Richard E. ^{[1
]}

Fielding, Katherine L. ^{[6
]}

Churchyard, Gavin J. ^{[1
,5
,6
]}

Morris, Lynn ^{[4
]}

Grant, Alison D. ^{[6
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA

[2] Aurum Inst Hlth Res, Johannesburg, South Africa

[3] Toga Labs, Johannesburg, South Africa

[4] Natl Inst Communicable Dis, AIDS Virus Res Unit, Johannesburg, South Africa

[5] Univ KwaZulu Natal, Ctr AIDS Res S Africa, Durban, South Africa

[6] London Sch Hyg & Trop Med, London WC1, England

来源：

CLINICAL INFECTIOUS DISEASES | 2009年 / 49卷 / 12期

基金：

美国国家卫生研究院;

关键词：

DRUG-RESISTANCE; IMMUNOLOGICAL RESPONSE; NAIVE PATIENTS; LOW-INCOME; PROGRAM; LAMIVUDINE; FAILURE; PREDICTORS; MORTALITY;

D O I：

10.1086/648444

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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/mm(3)). 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.

引用

页码：1928 / 1935

页数：8

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