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Sensitive detection of HIV-1 resistance to Zidovudine and impact on treatment outcomes in low-to middle-income countries

引用

Infectious Diseases of Poverty 2017年第1期6卷 1449-1461页

作者： Richard M.Gibson gabrielle nickel Michael Crawford Fred Kyeyune Colin Venner Immaculate Nankya Eva Nabulime Emmanuel Ndashimye Art F.Y.Poon Robert A.Salata Cissy Kityo Peter Mugyenyi Miguel E.Quinones-Mateu Eric J.Arts Department of Microbiology and Immunology University of Western Ontario1151 Richmond St.Dental Sciences Bldg.Rm 3014LondonOntario N6A 5C1Canada Division of Infectious Diseases Department of MedicineCase Western Reserve UniversityClevelandOHUSA Department of Molecular Biology and Microbiology Case Western Reserve UniversityClevelandOHUSA Department of Pathology Case Western Reserve UniversityClevelandOHUSA Center for AIDS Research Uganda Laboratories Joint Clinical Research CentreKampalaUganda Department of Pathology and Laboratory Medicine University of Western OntarioKampalaUganda TREAT Joint Clinical Research CentreKampalaUganda

Background:Thymidine analogs,namely AZT(Zidovudine or Retrovir^(TM))and d4T(Stavudine or Zerit^(TM))are antiretroviral drugs still employed in over 75%of first line combination antiretroviral therapy(cART)in Kampala,Uganda despite aversion to prescribing these drugs for cART in high income countries due in part to adverse *** this study,we explored how the continued use of these thymidine analogs in cART could impact emergence of drug resistance and impact on future treatment success in Uganda,a low-income ***:We examined the drug resistance genotypes by Sanger sequencing of 262 HIV-infected patients failing a first line combined antiretroviral treatment containing either AZT or d4T,which represents approximately 5%of the patients at the Joint Clinical Research Center receiving a AZT or d4T containing *** generation sequencing(DEEPGEN^(TM)HIV)and multiplex oligonucleotide ligation assays(AfriPOLA)were then performed on a subset of patient samples to detect low frequency drug resistant ***4 cell counts,viral RNA loads,and treatment changes were analyzed in a cohort of treatment success and ***:Over 80%of patients failing first line AZT/d4T-containing cART had predicted drug resistance to 3TC(Lamivudine)and non-nucleoside RT inhibitors(NNRTIs)in the treatment regimen but only 45%had resistance AZT/d4T associated resistance mutations(TAMs).TAMs were however detected at low frequency within the patients HIV quasispecies(1-20%)in 21 of 34 individuals who were failing first-line AZT-containing cART and lacked TAMs by *** to lack of TAMs by Sanger,AZT was typically maintained in second-line therapies and these patients had a low frequency of subsequent virologic ***:Our findings suggest that continued use of AZT and d4T in first-line treatment in low-to-middle income countries may lead to misdiagnosis of HIV-1 drug resistance and possibly enhance a succession of second-and third-line treatment failu

关键词： Antiretroviral treatment Drug resistance Uganda

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