Article Text

Download PDFPDF

  1. Cissy Kityo1,
  2. Tobias Rinke De Wit2,3,
  3. Immaculate Nankya1,
  4. Sheilla Balinda4,
  5. Kim Sigaloff2,5,
  6. Emmanuel Ndashimye1,
  7. Peter Mugyenyi1,
  8. Miguel Quinones-Mateu6,7
  1. 1Joint Clinical Research Centre, Kampala, Uganda
  2. 2Amsterdam Institute for Global Health and Development, The Netherlands
  3. 3Academic Medical Center, University of Amsterdam, The Netherlands
  4. 4MRC/UVRI and LSHTM Uganda Research Unit, Uganda
  5. 5Leiden University Medical Center, The Netherlands
  6. 6Case Western Reserve University, Cleveland, USA
  7. 7University Hospitals Cleveland Medical Center, USA


Background Although minority HIV-1 drug-resistant HIV-1 variants may be selected under antiretroviral pressure, leading to therapy failure, their clinical significance remains controversial. This is particularly relevant in the case of prevention of mother-to-child transmission (MTCT), where transmitted drug resistance can affect treatment outcomes.

Methods An ultrasensitive HIV-1 genotyping assay based on deep sequencing (DEEPGENHIV) with a 1% mutation frequency sensitivity, was used to quantify MTCT drug-resistant variants in 38 prenatally HIV-infected children experiencing (Group I, n=27) or not (Group II, n=11) virologic failure 12 months after initiating first-line antiretroviral therapy (ART) as part of a paediatric cohort in Uganda.

Results Infants were infected with subtype A(n=20), D(n=16) or C(n=2) HIV-1 strains, distributed equally between both patients’ groups. Similarly, no significant difference was observed in intra-patient HIV-1 diversity among viruses obtained from Group I or II individuals at baseline. DEEPGENHIV was able to detect all the mutations originally detected in samples obtained from four control patients in Group II, where drug resistance was identified at baseline using Sanger sequencing, e.g. K65R (78% mutation frequency), K103N (47%), or M184V (85%). More importantly, a series of low abundance (<20% detection limit of Sanger) primary and compensatory mutations associated with resistance to PIs (D30N, Q48V), NRTIs (D67N, K219Q), or NNRTIs (L100I, K103N) were identified in both groups of patients, although just a few seem to have been selected and became majority variants after 12 or 24 months of ART.

Conclusion DEEPGENHIV improves the detection of minority viral variants in infants following MTCT; however, most of the emergent HIV-1 drug resistance mutations were not present at low frequency at baseline in subjects failing ART, most likely being generated and selected following exposure to treatment. Further studies, using this or other ultrasensitive assays, are needed to better understand the transmission, dynamics and overall evolution of minority drug-resistant viruses in MTCT.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.