Visualization and analytics tools for infectious disease epidemiology

Objectives:
We sought to comprehensively analyze the origin, transmission patterns and sub-epidemic clusters of the HIV-1 CRF01_AE strains in China.

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The rapidly expanding CRF01_AE epidemic in China is driven by multiple lineages of HIV-1 viruses introduced in the 1990s.

In 30 years, the HIV-1/AIDS pandemic has evolved into an increasingly complex disease composed of multiple epidemics, each influenced by a complex array of biological, behavioural and cultural factors [1–4]. The concentrated subtype B epidemics in Western world settings have been largely restricted to MSM and IDU populations [3]. The generalized heterosexual (HET) epidemics in Africa and Asia have expanded and diversified to include nine major HIV-1 subtypes (A–D, F–H, J and K) and mosaic circulating recombinant forms (e.g. CRF01_AE and CRF02_AG) [1,5,6]. Migration and globalization has contributed to the spread of non-B subtypes contributing to 20–60% of new infections in Europe, Asia and America [1,2,7].

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Phylogenetic inferences on HIV-1 transmission: implications for the design of prevention and treatment interventions.

The introduction of the National Free Antiretroviral Therapy Program (NFATP) in 2003 by the China National Center for AIDS/STD Control and Prevention has led to dramatic increases in antiretroviral therapy (ART) coverage among HIV-infected Chinese patients. Despite limitations in the number of available free antiretroviral drugs, the overall mortality associated with HIV/AIDS has dropped from 39.3 per 100 person-years in 2002 to 3.1 in 2014. In this review, we summarize the challenges, responses, and achievements of antiretroviral therapy (ART) in China over the past 20 years. Continuous optimization of the Chinese National Guidelines for HIV/AIDS Diagnosis and Treatment has been guided by data from serial domestic multi-center studies aimed at evaluating efficacy and toxicity of available ART regimens among Chinese patients with HIV, with the goal of maximizing adherence, access, and efficacy. In addition, increasing attention has been focused on the importance of continuity in the HIV care cascade to promote linkage to care, and address the multidisciplinary chronic care needs HIV/AIDS patients on lifelong ART. Great progress has been achieved in the past 20 years in terms of access to and optimization of antiretroviral treatment in China. As the number of patients receiving long-term ART continues to grow, the focus of HIV/AIDS treatment has gradually transitioned from urgent care to the management of non-AIDS-related chronic complications and control of chronic inflammation.

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Optimizing Treatment for Adults with HIV/AIDS in China: Successes over Two Decades and Remaining Challenges.

To determine the origin and evolutionary history of two predominant and closely-related circulating recombinant forms (CRF07_BC and CRF08_BC), recombinant structures and phylogenies of 7 unique recombinant forms comprised of subtypes of B' (Thai B linage) and C (designated URFs_BC) from archival specimens of injection drug users (IDUs) collected in 1996 to 1998 from western Yunnan and 4 circulating recombinant forms with B'/C recombinants recently identified (designated nCRFs_BC) in China were compared with those of CRF07_BC and CRF08_BC. The results showed that 5 of 7 URFs_BC and all the nCRFs_BC shared recombination breakpoints with CRF07_BC and/or CRF08_BC. Yunnan URFs_BC consistently occupied the basal branch positions compared with CRF07_BC, CRF08_BC, and nCRFs_BC in phylogenetic trees. The estimated most recent common ancestors (tMRCA) for Yunnan URFs_BC were from ~1987, approximately half a decade earlier than those for CRF07_BC (~1994) and CRF08_BC (~1992). Discrete phylogeographic and spatial diffusion analysis revealed that both CRF07_BC and CRF08 BC came from western Yunnan in the early 1990s. Our results provide compelling evidence for western Yunnan as the geographic origin of CRF07_BC and CRF08_BC, which emerged from a swarm of URFs_BC by a series of recombination events in western Yunnan in the early 1990s.

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Geographic origin and evolutionary history of China's two predominant HIV-1 circulating recombinant forms, CRF07_BC and CRF08_BC

Background 
China is experiencing a dynamic HIV/AIDS epidemic. While serology based surveillance systems have reported the spread of HIV/AIDS, detailed tracking of its transmission in populations and regions is not possible without mapping it at the molecular level. We therefore conducted a nationwide molecular epidemiology survey across the country.


Methods 
HIV-1 genotypes were determined from 1,408 HIV-positive persons newly diagnosed in 2006. The prevalence of each genotype was estimated by weighting the genotype’s prevalence from each province- and risk-specific subpopulation with the number of reported cases in the corresponding subgroups in that year.


Results 
CRF07_BC (35.5%), CRF01_AE (27.6%), CRF08_BC (20.1%), and subtype B' (9.6%) were the four main HIV-1 strains in China. CRF07_BC and CRF08_BC were the primary drivers of infection among injecting drug users in northeastern and southeastern China, respectively, and subtype B' remained dominant among former plasma donors in central China. In contrast, all four strains occurred in significant proportions among heterosexuals nationwide, pointing to an expansion of the HIV-1 epidemic from high-risk populations into the general population. CRF01_AE also replaced subtype B as the principal driver of infection among men-who-have-sex-with-men.


Conclusions 
Our study provides the first comprehensive baseline data on the diversity and characteristics of HIV/AIDS epidemic in China, reflecting unique region- and risk group-specific transmission dynamics. The results provide information critical for designing effective prevention measures against HIV transmission.

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Yutaka Takebe

Papers

A comprehensive mapping of HIV-1 genotypes in various risk groups and regions across China based on a nationwide molecular epidemiologic survey.