High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy

Shanmugam Saravanan, Selvamurthi Gomathi, Allison Delong, Bagavathi Kausalya, Sathasivam Sivamalar, Selvamuthu Poongulali, Katherine Brooks, Nagalingeswaran Kumarasamy, Pachamuthu Balakrishnan, Sunil Solomon, Susan Cu-Uvin, Rami Kantor

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Abstract

Objectives: Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. Methods: At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ≥6 months; GVL when PVL >2000 copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000 copies/mL. Wilcoxon rank-sumand Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Intercompartmental resistance discordance was evaluated using generalized estimating equations. Results: Of 200 women, 37% had detectable (>400 copies/mL) PVL and 31% had PVL >1000 copies/mL. Of women with detectable PVL, 74% had PVL >2000 copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34 years, median ART duration of 33months, median CD4 count of 217 cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10 copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. Conclusions: We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.

Original languageEnglish (US)
Pages (from-to)2152-2161
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number8
DOIs
StatePublished - Jan 1 2018

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ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Saravanan, S., Gomathi, S., Delong, A., Kausalya, B., Sivamalar, S., Poongulali, S., Brooks, K., Kumarasamy, N., Balakrishnan, P., Solomon, S., Cu-Uvin, S., & Kantor, R. (2018). High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy. Journal of Antimicrobial Chemotherapy, 73(8), 2152-2161. https://doi.org/10.1093/jac/dky154