HIV-1 coreceptor tropism in India: increasing proportion of X4-tropism in subtype C strains over two decades

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.