ArticleInfectious diseases of poverty2017
Sensitive detection of HIV-1 resistance to Zidovudine and impact on treatment outcomes in low- to middle-income countries.
Article in Infectious diseases of poverty, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Pooled it
- HIV-1 genetic diversity and reverse transcriptase resistance mutations in Benin before dolutegravir era, West Africa.PloS one · 2026Article
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- Determinants of virologic failure among adult HIV patients on first line antiretroviral treatment in Oromia, Central Ethiopia: 2022 a case-control study.AIDS research and therapy · 2024Article
- Nucleoside Analog 2',3'-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1.Pharmaceutics · 2023Article
- Article
- Subcutaneous Adipocyte Adenosine Triphosphate Levels in HIV Infected Patients.AIDS research and human retroviruses · 2020Article
- Risk factors for Blastocystis infection in HIV/AIDS patients with highly active antiretroviral therapy in Southwest China.Infectious diseases of poverty · 2019Article
- Synthesis of fluorescent drug molecules for competitive binding assay based on molecularly imprinted polymers.RSC advances · 2019Article
- Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay.AIDS research and therapy · 2018Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundThymidine analogs, namely AZT (Zidovudine or Retrovir™) and d4T (Stavudine or Zerit™) 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 events. For 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 country.
methodsWe 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 treatment. Next generation sequencing (DEEPGEN™HIV) and multiplex oligonucleotide ligation assays (AfriPOLA) were then performed on a subset of patient samples to detect low frequency drug resistant mutations. CD4 cell counts, viral RNA loads, and treatment changes were analyzed in a cohort of treatment success and failures.
resultsOver 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 Sanger. Due to lack of TAMs by Sanger, AZT was typically maintained in second-line therapies and these patients had a low frequency of subsequent virologic success.
conclusionsOur 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 failures.
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