Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/ tenofovir in the absence of real-time viral load monitoring

Lyagoba, Fred, Dunn, David T., Pillay, Deenan, Kityo, Cissy, Robertson, Val, Tugume, Stephano, Hakim, James, Munderi, Paula, Chirara, Mike, Ndembi, Nicaise, Goodall, Ruth L., Yirrell, David L., Burke, Andy, Gilks, Charles F., Kaleebu, Pontiano and DART Virology and Trial Team (2010) Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/ tenofovir in the absence of real-time viral load monitoring. JAIDS Journal of Acquired Immune Deficiency Syndromes, 55 2: 277-283. doi:10.1097/QAI.0b013e3181ea0df8


Author Lyagoba, Fred
Dunn, David T.
Pillay, Deenan
Kityo, Cissy
Robertson, Val
Tugume, Stephano
Hakim, James
Munderi, Paula
Chirara, Mike
Ndembi, Nicaise
Goodall, Ruth L.
Yirrell, David L.
Burke, Andy
Gilks, Charles F.
Kaleebu, Pontiano
DART Virology and Trial Team
Title Evolution of drug resistance during 48 weeks of zidovudine/lamivudine/ tenofovir in the absence of real-time viral load monitoring
Journal name JAIDS Journal of Acquired Immune Deficiency Syndromes   Check publisher's open access policy
ISSN 1525-4135
1944-7884
Publication date 2010-10-01
Sub-type Article (original research)
DOI 10.1097/QAI.0b013e3181ea0df8
Volume 55
Issue 2
Start page 277
End page 283
Total pages 7
Place of publication Philadelphia, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Objectives: To describe the resistance mutations selected by a first-line regimen of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring.

Design: A substudy of 300 participants from the Development of Antiretroviral Therapy in Africa trial in Uganda and Zimbabwe, which compared managing antiretroviral therapy with and without laboratory monitoring.

Methods: Stored plasma samples from selected time points were assayed retrospectively for HIV-1 RNA. The pol gene in all baseline samples and those with HIV RNA >1000 copies per milliliter at weeks 24 and 48 were sequenced.

Results: The proportion with HIV RNA >1000 copies per milliliter increased from 15% at 24 weeks to 24% at 48 weeks. Eighteen of 31 (58%) genotyped samples at 24 weeks had >=1 major nucleoside reverse transcriptase inhibitor-associated mutations compared with 41 of 47 (87%) at 48 weeks. Excluding 1 nonadherent patient, a mean of 2.0 (95% confidence interval: 1.3 to 2.8) thymidine analogue mutations (TAMs) developed between weeks 24 and 48 among 14 patients with HIV RNA >1000 copies per milliliter at both time points. K65R was detected in 8 of 63 (13%) patients and was negatively associated with number of TAMs (P = 0.01) but not viral subtype (P = 0.30).

Conclusions: A high rate of acquisition of TAMs, but not of K65R, among patients with prolonged viraemia was observed. However, most patients were virologically suppressed at 48 weeks, and long-term clinical and immunological outcomes in the Development of Antiretroviral Therapy in Africa trial were favorable.
Keyword No real-time viral load monitoring
Resistance
Thymidine analogue mutations
Triple NRTI
K65R
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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