Origin and dynamics of HIV-1 subtype C infection in India

Abstract

Objective: To investigate the geographical origin and evolution dynamics of HIV-1 subtype C infection in India.

Design: Ninety HIV-1 subtype C env gp120 subtype C sequences from India were compared with 312 env gp120 reference subtype C sequences from 27 different countries obtained from Los Alamos HIV database. All the HIV-1 subtype C env gp120 sequences from India were used for the geographical origin analysis and 61 subtype C env gp120 sequences with known sampling year (from 1991 to 2008) were employed to determine the origin of HIV infection in India.

Methods: Phylogenetic analysis of HIV-1 env sequences was used to investigate the geographical origin and tMRCA of Indian HIV-1 subtype C. Evolutionary parameters including origin date and demographic growth patterns of Indian subtype C were estimated using a Bayesian coalescent-based approach under relaxed molecular clock models.

Findings: The majority of the analyzed Indian and South African HIV-1 subtype C sequences formed a single monophyletic cluster. The most recent common ancestor date was calculated to be 1975.56 (95% HPD, 1968.78-1981.52). Reconstruction of the effective population size revealed three phases of epidemic growth: an initial slow growth, followed by exponential growth, and then a plateau phase approaching present time. Stabilization of the epidemic growth phase correlated with the foundation of National AIDS Control Organization in India.

Interpretation: Indian subtype C originated from a single South African lineage in the middle of 1970s. The current study emphasizes not only the utility of HIV-1 sequence data for epidemiological studies but more notably highlights the effectiveness of community or government intervention strategies in controlling the trend of the epidemic.

Figure 1. Phylogenetic analysis of env (gp120) sequences from worldwide represent samples of HIV-1subtype C.

The ML tree of subtype C was inferred by using GTR+G+I model from an alignment of sequences from 28 different nations. The black triangles represent collapsed reference sequences unrelated to “South Africa-India-China” cluster. There were five Indian sequences dispersed in the collapsed cluster. SH-like support values are showed on the nodes. Brackets indicate geographic region of sampling. Line colors: Red, China; Blue, India; Green, South Africa. The names of the sequences are showed on the tips of the branches. The name of three sequences in India-China cluster are marked in black rectangles (C.MM1999mIDU101_3, 07_BC.TW2004.TW_D3 and C.CY2005.CY073), which are from Taiwan, Myanmar and Pakistan respectively.

Figure 2. Bayesian skyline plot (BSP) of Indian and China HIV-1 subtype C.

The plot begins at the median posterior Year 1975. The solid line is the traced median effective population size over a 30 year period with the 95% highest posterior density (HPD) interval. Bayesian skyline plot with relaxed molecular clock and non-parametric (BSP) estimates of demographic history were performed with BEAST version v1.7 by running two MCMC for 100,000,000 generations with sampling every 1,000th generation. The dotted vertical line is the lower 95% HPD on Indian C TMRCA.