HIV Drug Resistance Mutations in Non-B Subtypes after Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa

Cissy Kityo, Jennifer Thompson, Immaculate Nankya, Anne Hoppe, Emmanuel Ndashimye, Colin Warambwa, Ivan Mambule, Joep J. Van Oosterhout, Kara Wools-Kaloustian, Silvia Bertagnolio, Philippa J. Easterbrook, Peter Mugyenyi, A. Sarah Walker, Nicholas I. Paton

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Objective: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs. Design: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, and Malawi were analyzed. Multivariable logistic regression was used to determine the association between specific DRMs and Stanford intermediate-/high-level resistance and factors including REGA subtype, first-line antiretroviral therapy drugs, CD4, and VL at failure. Results: The median first-line treatment duration was 4 years (interquartile range 30-43 months); 42% of participants had VL ≥100,000 copies/mL and 63% participants had CD4 <100 cells/mm 3. Viral subtype distribution was A1 (40%; Uganda and Kenya), C (31%; Zimbabwe and Malawi), and D (25%; Uganda and Kenya), and recombinant/unclassified (5%). In general, DRMs were more common in subtype-C than in subtype-A and/or subtype-D (nucleoside reverse transcriptase inhibitor mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, and H221Y). The presence of tenofovir resistance was similar between subtypes [P (adjusted) = 0.32], but resistance to zidovudine, abacavir, etravirine, or rilpivirine was more common in subtype-C than in subtype-D/subtype-A [P (adjusted) < 0.02]. Conclusions: Non-B subtypes differ in DRMs at first-line failure, which impacts on residual nucleoside reverse transcriptase inhibitor and NNRTI susceptibility. In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens.

Original languageEnglish (US)
Pages (from-to)e45-e54
JournalJournal of Acquired Immune Deficiency Syndromes
Volume75
Issue number2
DOIs
StatePublished - Jun 1 2017

Keywords

  • Africa
  • HIV
  • drug resistance
  • drug resistance mutations
  • first-line failure
  • non-B subtype

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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    Kityo, C., Thompson, J., Nankya, I., Hoppe, A., Ndashimye, E., Warambwa, C., Mambule, I., Van Oosterhout, J. J., Wools-Kaloustian, K., Bertagnolio, S., Easterbrook, P. J., Mugyenyi, P., Walker, A. S., & Paton, N. I. (2017). HIV Drug Resistance Mutations in Non-B Subtypes after Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. Journal of Acquired Immune Deficiency Syndromes, 75(2), e45-e54. https://doi.org/10.1097/QAI.0000000000001285