Evolution of Drug Resistance During 48 Weeks of Zidovudine/Lamivudine/Tenofovir in the Absence of Real-Time Viral Load Monitoring
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 &gt1000 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.
Lyagoba, F.; Dunn, D.; Pillay, D.; Kityo, C.; Robertson, V.; Tugume, S.; Hakim, J.; Munderi, P.; Ndembi, N.; Gilks, C.; Yirrell, D.; Burke, A.; Kaleebu, P. Evolution of Drug Resistance During 48 Weeks of Zidovudine/Lamivudine/Tenofovir in the Absence of Real-Time Viral Load Monitoring. Journal of Acquired Immune Deficiency Syndromes (2010) 55 (2) 277-283. [DOI: 10.1097/QAI.0b013e3181ea0df8]