Residual Activity of Two HIV Antiretroviral Regimens Prescribed without Virological Monitoring

Dunn, D. T., Goodall, R. L., Munderi, P., Kityo, C., Ranopa, M., Bacheler, L., Van Houtte, M., Gilks, C., Kaleebu, P. and Pillay, D. (2011) Residual Activity of Two HIV Antiretroviral Regimens Prescribed without Virological Monitoring. Antimicrobial Agents and Chemotherapy, 55 10: 4575-4580. doi:10.1128/AAC.00580-11

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Author Dunn, D. T.
Goodall, R. L.
Munderi, P.
Kityo, C.
Ranopa, M.
Bacheler, L.
Van Houtte, M.
Gilks, C.
Kaleebu, P.
Pillay, D.
Title Residual Activity of Two HIV Antiretroviral Regimens Prescribed without Virological Monitoring
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
1098-6596
Publication date 2011-10
Year available 2011
Sub-type Article (original research)
DOI 10.1128/AAC.00580-11
Open Access Status File (Publisher version)
Volume 55
Issue 10
Start page 4575
End page 4580
Total pages 6
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Collection year 2011
Language eng
Formatted abstract
Virological residual activity (VRA) denotes the degree of HIV RNA suppression achieved by antiretroviral therapy in the presence of resistant virus. This concept is particularly important in resource-limited settings, where rapid switching after detection of virological failure may not be feasible. Using data from the NORA trial, we estimated VRA for two regimens—zidovudine-lamivudine-abacavir (ZDV-3TC-ABC) and zidovudine-lamivudine-nevirapine (ZDV-3TC-NVP)—and related this to the phenotypic drug sensitivity of the component drugs in the two regimens. Plasma samples at weeks 0, 48, and 96 were retrospectively assayed for HIV-1 RNA, and genotypic/phenotypic resistance testing was performed if HIV-1 RNA exceeded 1,000 copies/ml. Virological residual activity (VRA) was defined as the difference between log10(HIV RNA) at week 48 or 96 and week 0 and related to 50% inhibitory concentration (IC50) relative to wild-type virus for ZDV and ABC (fold change [FC]). Twenty-seven samples in the ZDV-3TC-NVP group and 56 in the ZDV-3TC-ABC group contributed to the analysis. Mean VRA was significantly higher in the ZDV-3TC-ABC group than in the ZDV-3TC-NVP at week 48 (1.62 versus 0.90) and week 96 (1.29 versus 0.78). There was a weak and nonsignificant relationship between VRA and ZDV FC, with VRA decreasing by 0.1 log10 copies/ml per 2-fold increase in ZDV. The association with ABC FC was much stronger, with a marked reduction in VRA occurring at ABC FC values greater than approximately 2. This information should be considered in future treatment guidelines relevant to resource-poor settings 
Keyword Reverse Transcriptase Inhibitors
Immunodeficiency-Virus Type 1
Drug Resistance
Phenotypic Resistance
Zidovudine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
 
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