Background: Coreceptor switch from CCR5 to CXCR4 is considered to be less common in HIV-1 subtype C even in advanced stages of infection. In this study, we have examined viral genotypic coreceptor tropism and its clinical, virological, and host genetic determinants among perinatally infected children in India.
Methods: Genotypic coreceptor tropism analysis was conducted on env V3 sequences using Geno2pheno with a threshold of 10% false-positive rate. A total of 473 sequences were obtained from 72 isolates amplified from children aged 2-17 years. Factors associated with viral tropism in subtype C infections were studied using logistic regression.
Results: Among the samples, 98.6% (71 of 72) were HIV-1 subtype C. Coreceptor tropism analysis determined 81.7% (58 of 71) as R5 tropic, 9.9% (7 of 71) as X4 tropic, and 8.5% (6 of 71) as R5/X4 tropic or dual-tropic HIV-1 strains. Children with X4 or R5/X4 strains were more likely to be older than those with R5-tropic strains (P < 0.05), have lower CD4 counts (P < 0.05), and have viral populations with greater intrapopulation viral divergence (P < 0.01). Older age was a significant independent predictor for X4 or R5/X4 tropism in these children (P < 0.05). None were identified as being heterozygous or homozygous for the CCR5[INCREMENT]32 deletion.
Conclusions: The high prevalence of X4 and R5/X4 tropic strains among older perinatally infected children with HIV-1 subtype C in India indicate that this phenomenon is not uncommon as previously thought and suggest that coreceptor transition can occur with longer duration of infection and greater disease progression in this population of perinatally infected children living with HIV-1 subtype C.