High viremia and low level of transmitted drug resistance in anti-retroviral therapy-naïve perinatally-infected children and adolescents with HIV-1 subtype C infection

Abstract

Background: High plasma viremia in HIV-1 infection is associated with rapid CD4 cell decline and faster disease progression. Children with HIV infection have high viral loads, particularly in early childhood. In this study we sought to understand the relationship between duration of HIV-1 infection and viral dynamics among perinatally-infected children and adolescents in India along with transmitted drug resistance in this population.

Methods: During 2007-2011, cross-sectional samples were collected from ART-naïve children (n = 105) with perinatally-acquired HIV infection, aged 2-16 years from Bangalore, India. CD4 counts, viral load and in-house genotyping were performed and transmitted drug resistance mutations were identified using the World Health Organization recommendations for Surveillance of Drug Resistance Mutations (SDRM_2009) list.

Results: Among 105 children studied, 73.3% (77/105) were asymptomatic, but had a median viral load of 5.24 log copies/mL (IQR 4.62-5.66). In the adolescent age group, 54% (21/39) had high levels of viremia (median 5.14 log copies/mL) but were asymptomatic. HIV-1 subtyping identified 98% strains (103/105) as subtype C; one A1 and one unique recombinant form (URF). Transmitted NRTI resistance was 1.9% (2/105); NNRTI resistance was 4.8% (5/105) and overall prevalence of transmitted drug resistance was 5.7% (6/105).

Conclusions: The high burden of plasma viremia found among untreated asymptomatic adolescents needs to be addressed both from an individual angle to halt disease progression, and from a public health perspective to arrest horizontal transmission. The low level of transmitted drug resistance among perinatally-infected children is reassuring; however with improving ART access globally, regular genotyping surveillance is indicated.

Figure 1

Association between duration of infection and log transformed viral load. The graph represents association between log transformed viral load and length of the infection in perinatal transmission. No significant correlation between the parameters observed (Spearman rho = −0.189; p = 0.05).

Figure 2

Identification and characterisation of HIV-1 subtypes. The tree was constructed with cohort sequences and reference sequences downloaded from Los Alamos Database (http://www.hiv.lanl.gov) using general time reversible (GTR) model with gamma distribution and invariant sites (GTR + G + I) as observed best fitted model for the dataset. Cohort sequences are shown with filled circle.

Figure 3

Mosaic structure of identified unique recombinant forms (URF) strains. The strain, which was determined as URF_CH in RIP 3.0 program was further studied in details for its mosaic structure. The recombination patterns were determined by performing bootscan analysis with Simplot version 3.5.1 [21], using a window sliding of 100 nucleotide (nt) in 10nt steps, with 500 bootstrap replicates. The informative sites were presented inside the graph. The mosaic pattern of each segments were confirmed by phylogenetic analysis using reference subtype C and H strains downloaded from Los Alamos Database (http://www.hiv.lanl.gov). Two breakpoints were identified at 2816 and 2911 of HXB2 co-ordinates.