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Open Access Research article

Virologic versus immunologic monitoring and the rate of accumulated genotypic resistance to first-line antiretroviral drugs in Uganda

Steven J Reynolds128*, Hakim Sendagire34, Kevin Newell5, Barbara Castelnuovo6, Immaculate Nankya7, Moses Kamya6, Thomas C Quinn12, Yukari C Manabe26 and Andrew Kambugu6

Author Affiliations

1 Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

2 Johns Hopkins University School of Medicine, Baltimore, MD, USA

3 Uganda Ministry of Health, Kampala, Uganda

4 Department of Microbiology, Makerere University College of Health Sciences, Kampala, Uganda

5 Clinical Research Directorate/Clinical Monitoring Research Program, SAIC-Frederick, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA

6 Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda

7 Joint Clinical Research Center, Kampala, Uganda

8 NIAID/NIH ICER Program, P.O. Box 7007, Kampala, Uganda

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BMC Infectious Diseases 2012, 12:381  doi:10.1186/1471-2334-12-381

Published: 27 December 2012

Abstract

Background

Viral load monitoring (VLM) to identify individuals failing antiretroviral therapy (ART) is not widely available in resource-limited settings. We compared the genotypic resistance patterns between clients with VLM versus immunological monitoring (IM).

Methods

Between 2004–2008, 559 ART naïve clients were enrolled in a prospective cohort, initiated on ART, and monitored with viral load (VL) and CD4+ cell counts every 6 months (VLM group). From February 2008 through June 2009, 998 clients on ART for 36–40 months (corresponding to the follow-up time of the VLM group) at the same clinic and monitored with CD4+ cell counts every 6 months were recruited into a cross sectional study (IM group). Samples from VLM clients at 12, 24 and 36 months and IM clients at 36–40 months with VL > 2000 copies/ml underwent genotypic drug resistance testing.

Results

Baseline characteristics were similar. Virologic failure (VL > 400 copies/ml) at 12, 24 and 36 months in the VLM group were 12%, 6% and 8% respectively, and in the IM group 10% at 36–40 months. Samples from 39 VLM and 70 IM clients were genotyped. 23/39 (59%) clients in the VLM group (at 12, 24 or 36 months) compared to 63/70 (90%) in the IM group, (P < 0.0001) had at least 1 non-nucleoside reverse transcriptase mutation. 19/39 (49%) of VLM clients had an M184V mutation compared to 61/70 (87%) in the IM group (P < 0.0001). Only 2/39 (5%) of VLM clients developed thymidine analogue mutations compared to 34/70 (49%) of IM clients (P < 0.0001).

Conclusions

Routine VL monitoring reduced the rate of accumulated genotypic resistance to commonly used ART in Uganda.

Keywords:
HIV-1; Antiretroviral therapy; Drug resistance