HIV-1 Coreceptor Tropism in India: Increasing Proportion of X4-Tropism in Subtype C Strains Over Two Decades

Gupta, Soham MSc*,†; Neogi, Ujjwal MSc, PhD‡,§; Srinivasa, Hiresave MD; Banerjea, Akhil C. MSc, PhD; Shet, Anita MD*,¶,#

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000046
Basic and Translational Science
Abstract

Background: Recent studies show an increase in the frequency of X4-tropism in African HIV-1 subtype C (HIV-1C) strains and among Indian children with a longer duration of infection. There is limited availability of comprehensive data on HIV-1 tropism in Indian HIV-1C strains and impact on coreceptor antagonist drug susceptibility. We evaluated coreceptor tropism trends over 2 decades and maraviroc resistance-associated V3 loop substitutions among the Indian HIV-1C strains.

Methods: We performed genotypic tropism testing using Geno2Pheno10% on primary samples from patients (n = 224) and on Indian HIV-1C sequences downloaded from the Los Alamos database (n = 528, 1991–2010). We also studied maraviroc resistance–associated substitutions in R5-tropic HIV-1C (n = 992) and subtype B sequences (n = 576).

Results: Among primary samples, 88% belonged to HIV-1C and 11.2% was predicted as X4-tropic, with higher prevalence noted among patients from north-eastern India (19.1%) and significant association with intravenous drug users (P = 0.04). X4-tropism prevalence was higher among antiretroviral therapy–experienced (18.8%) compared with antiretroviral therapy–naive patients (9.1%). Indian database HIV-1C sequences showed X4-tropism at 4%. An increase in the X4 tropism frequency was seen over the years 1991 (1.6%) through 2012 (10%). We found a high frequency of 19T substitution (826/992; 83.3%) among HIV-1C V3 loop compared with subtype B.

Conclusions: The predominance of R5-tropism in Indian HIV-1C strains despite a marginal temporal increase in X4-tropism prevalence highlights the likely effectiveness of coreceptor antagonists in India. Our frequent observation of common maraviroc resistance–associated substitutions among Indian R5-tropic HIV-1C raises the possibility that they may be natural polymorphisms, indicating the need for further elucidation.

Author Information

*Division of Public Health and Infections, St. John's Research Institute, Bangalore, India;

Department of Microbiology, St. John's Medical College, Bangalore, India;

Hematology Research Unit, Division of Molecular Medicine, St. John's Research Institute, Bangalore, India;

§Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;

Virology-II, National Institute of Immunology, New Delhi, India;

Department of Pediatrics, St. John's Medical College Hospital, Bangalore, India; and

#Division of Global Health, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.

Correspondence to: Anita Shet, MD, Department of Pediatrics, St. John's Medical College Hospital, Bangalore 560034, India (e-mail: anitashet@gmail.com).

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Supported in part by the European Union Framework Program 7.

The authors have no conflicts of interest to disclose.

Received June 18, 2013

Accepted October 24, 2013

© 2014 by Lippincott Williams & Wilkins