Introduction of Phylodynamics for Controlling the HIV/AIDS Epidemic in Korea.
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ABSTRACT:
SUBMITTER: Bae JM
PROVIDER: S-EPMC6283738 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Project description:This review provides an overview of the current status of the global HIV pandemic and strategies to bring it under control. It updates numerous preventive approaches including behavioral interventions, male circumcision (MC), pre- and post-exposure prophylaxis (PREP and PEP), vaccines, and microbicides. The manuscript summarizes current anti-retroviral treatment options, their impact in the western world, and difficulties faced by emerging and resource-limited nations in providing and maintaining appropriate treatment regimens. Current clinical and pre-clinical approaches toward a cure for HIV are described, including new drug compounds that target viral reservoirs and gene therapy approaches aimed at altering susceptibility to HIV infection. Recent progress in vaccine development is summarized, including novel approaches and new discoveries.
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Project description:Previous studies have shown that the HIV-1 epidemic in Cuba displayed a complex molecular epidemiologic profile with circulation of several subtypes and circulating recombinant forms (CRF); but the evolutionary and population history of those viral variants remains unknown. HIV-1 pol sequences of the most prevalent Cuban lineages (subtypes B, C and G, CRF18_cpx, CRF19_cpx, and CRFs20/23/24_BG) isolated between 1999 and 2011 were analyzed. Maximum-likelihood analyses revealed multiple introductions of subtype B (n≥66), subtype C (n≥10), subtype G (n≥8) and CRF18_cpx (n≥2) viruses in Cuba. The bulk of HIV-1 infections in this country, however, was caused by dissemination of a few founder strains probably introduced from North America/Europe (clades B(CU-I) and B(CU-II)), east Africa (clade C(CU-I)) and central Africa (clades G(CU), CRF18(CU) and CRF19(CU)), or locally generated (clades CRFs20/23/24_BG). Bayesian-coalescent analyses show that the major HIV-1 founder strains were introduced into Cuba during 1985-1995; whereas the CRFs_BG strains emerged in the second half of the 1990s. Most HIV-1 Cuban clades appear to have experienced an initial period of fast exponential spread during the 1990s and early 2000s, followed by a more recent decline in growth rate. The median initial growth rate of HIV-1 Cuban clades ranged from 0.4 year⁻¹ to 1.6 year⁻¹. Thus, the HIV-1 epidemic in Cuba has been a result of the successful introduction of a few viral strains that began to circulate at a rather late time of the AIDS pandemic, but then were rapidly disseminated through local transmission networks.
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Project description:DESIGN:We sought to investigate the evolutionary and historical reasons for the different epidemiological patterns of HIV-1 in the early epidemic. In order to characterize the demographic history of HIV-1 subtypes A and D in east Africa, we examined molecular epidemiology, geographical and historical data. METHODOLOGY:We employed high-resolution phylodynamics to investigate the introduction of HIV-1A and D into east Africa, the geographic trends of viral spread, and the demographic growth of each subtype. We also used geographic information system data to investigate human migration trends, population growth, and human mobility. RESULTS:HIV-1A and D were introduced into east Africa after 1950 and spread exponentially during the 1970s, concurrent with eastward expansion. Spatiotemporal data failed to explain the establishment and spread of HIV based on urban population growth and migration. The low prevalence of the virus in the Democratic Republic of Congo before and after the emergence of the pandemic was, however, consistent with regional accessibility data, highlighting the difficulty in travel between major population centers in central Africa. In contrast, the strong interconnectivity between population centers across the east African region since colonial times has likely fostered the rapid growth of the epidemic in this locale. CONCLUSION:This study illustrates how phylodynamic analysis of pathogens informed by geospatial data can provide a more holistic and evidence-based interpretation of past epidemics. We advocate that this 'landscape phylodynamics' approach has the potential to provide a framework both to understand epidemics' spread and to design optimal intervention strategies.
| S-EPMC2742553 | biostudies-literature
Project description:The HIV-1 subtype C accounts for an important fraction of HIV infections in east Africa, but little is known about the genetic characteristics and evolutionary history of this epidemic. Here we reconstruct the origin and spatiotemporal dynamics of the major HIV-1 subtype C clades circulating in east Africa. A large number (n = 1,981) of subtype C pol sequences were retrieved from public databases to explore relationships between strains from the east, southern and central African regions. Maximum-likelihood phylogenetic analysis of those sequences revealed that most (>70%) strains from east Africa segregated in a single regional-specific monophyletic group, here called C(EA). A second major Ethiopian subtype C lineage and a large collection of minor Kenyan and Tanzanian subtype C clades of southern African origin were also detected. A bayesian coalescent-based method was then used to reconstruct evolutionary parameters and migration pathways of the C(EA) African lineage. This analysis indicates that the C(EA) clade most probably originated in Burundi around the early 1960s, and later spread to Ethiopia, Kenya, Tanzania and Uganda, giving rise to major country-specific monophyletic sub-clusters between the early 1970s and early 1980s. The results presented here demonstrate that a substantial proportion of subtype C infections in east Africa resulted from dissemination of a single HIV local variant, probably originated in Burundi during the 1960s. Burundi was the most important hub of dissemination of that subtype C clade in east Africa, fueling the origin of new local epidemics in Ethiopia, Kenya, Tanzania and Uganda. Subtype C lineages of southern African origin have also been introduced in east Africa, but seem to have had a much more restricted spread.
| S-EPMC3407063 | biostudies-literature
Project description:The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses originating among immigrants from sub-Saharan Africa. The high rate of HIV evolution, combined with the availability of a very high density sample of viral sequences from routine clinical care has allowed the phylodynamics of the epidemic to be investigated for the first time. Sequences of the viral protease and partial reverse transcriptase coding regions from 11,071 patients infected with HIV of non-B subtypes were studied. Of these, 2774 were closely linked to at least one other sequence by nucleotide distance. Including the closest sequences from the global HIV database identified 296 individuals that were in UK-based groups of 3 or more individuals. There were a total of 8 UK-based clusters of 10 or more, comprising 143/2774 (5%) individuals, much lower than the figure of 25% obtained earlier for men who have sex with men (MSM). Sample dates were incorporated into relaxed clock phylogenetic analyses to estimate the dates of internal nodes. From the resulting time-resolved phylogenies, the internode lengths, used as estimates of maximum transmission intervals, had a median of 27 months overall, over twice as long as obtained for MSM (14 months), with only 2% of transmissions occurring in the first 6 months after infection. This phylodynamic analysis of non-B subtype HIV sequences representing over 40% of the estimated UK HIV-infected heterosexual population has revealed heterosexual HIV transmission in the UK is clustered, but on average in smaller groups and is transmitted with slower dynamics than among MSM. More effective intervention to restrict the epidemic may therefore be feasible, given effective diagnosis programmes.
| S-EPMC2742734 | biostudies-literature
Project description:BackgroundIn 2003, a phase III placebo-controlled trial (VAX003) was completed in Bangkok, Thailand. Of the 2,546 individuals enrolled in the trial based on high risk for infection through injection drug use (IDU), we obtained clinical samples and HIV-1 sequence data (envelope glycoprotein gene gp120) from 215 individuals who became infected during the trial. Here, we used these data in combination with other publicly available gp120 sequences to perform a molecular surveillance and phylodynamic analysis of HIV-1 in Thailand.Methodology and findingsPhylogenetic and population genetic estimators were used to assess HIV-1 gp120 diversity as a function of vaccination treatment, viral load (VL) and CD4(+) counts, to identify transmission clusters and to investigate the timescale and demographics of HIV-1 in Thailand. Three HIV-1 subtypes were identified: CRF01_AE (85% of the infections), subtype B (13%) and CRF15_AE (2%). The Bangkok IDU cohort showed more gp120 diversity than other Asian IDU cohorts and similar diversity to that observed in sexually infected individuals. Moreover, significant differences (P<0.02) in genetic diversity were observed in CRF01_AE IDU with different VL and CD4(+) counts. No phylogenetic structure was detected regarding any of the epidemiological and clinical factors tested, although high proportions (35% to 50%) of early infections fell into clusters, which suggests that transmission chains associated with acute infection play a key role on HIV-1 spread among IDU. CRF01_AE was estimated to have emerged in Thailand in 1984.5 (1983-1986), 3-6 years before the first recognition of symptomatic patients (1989). The relative genetic diversity of the HIV-1 population has remained high despite decreasing prevalence rates since the mid 1990s.ConclusionsOur study and recent epidemiological reports indicate that HIV-1 is still a major threat in Thailand and suggest that HIV awareness and prevention needs to be strengthened to avoid AIDS resurgence.
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Project description:OBJECTIVES:To manage evidence-based diseases, it is important to identify the characteristics of patients in each country. METHODS:The Korea HIV/AIDS Cohort Study seeks to identify the epidemiological characteristics of 1,442 Korean individuals with human immunodeficiency virus (HIV) infection (12% of Korean individuals with HIV infection in 2017) who visited 21 university hospitals nationwide. The descriptive statistics were presented using the Korea HIV/AIDS cohort data (2006-2016). RESULTS:Men accounted for 93.3% of the total number of respondents, and approximately 55.8% of respondents reported having an acute infection symptom. According to the transmission route, infection caused by sexual contact accounted for 94.4%, of which 60.4% were caused by sexual contact with the same sex or both males and females. Participants repeatedly answered the survey to decrease depression and anxiety scores. Of the total participants, 89.1% received antiretroviral therapy (ART). In the initial ART, 95.3% of patients were treated based on the recommendation. The median CD4 T-cell count at the time of diagnosis was 229.5 and improved to 331 after the initial ART. Of the patients, 16.6% and 9.4% had tuberculosis and syphilis, respectively, and 26.7% had pneumocystis pneumonia. In the medical history, sexually transmitted infectious diseases showed the highest prevalence, followed by endocrine diseases. The main reasons for termination were loss to follow-up (29.9%) and withdrawal of consent (18.7%). CONCLUSIONS:Early diagnosis and ART should be performed at an appropriate time to prevent the development of new infection.
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Project description:The number of persons infected by HIV/AIDS has consistently increased in Korea since the first case of HIV/AIDS infection in 1985 and reached 15,208 by 2016. About 1,100 new patients with HIV/ AIDS infections have emerged every year since 2013. In Korea, the Korea HIV/AIDS Cohort Study was established for the evidenced-based prevention, treatment, and effective management of patients infected with human immunodeficiency virus (HIV) in December 2006. This study monitored 1,438 patients, who accounted for about 10% of all patients with HIV/AIDS in Korea, for 10 years with the following aims: (1) to develop an administrative system for the establishment of a HIV/AIDS cohort-based study; (2) to standardize methodologies and the case report forms; and (3) to standardize multi-cohort data and develop a data cleaning method. This study aims to monitor at least 1,000 patients (excluding those for whom investigation had been completed) per year (estimated number of patients who can be monitored by January 2018: 939). By December 2016, the sex distribution was 93.3% for men, and 6.7% for women (gender ratio, 13.9:1.0), and 98.9% of all participants were Korean. More than 50.0% of the participants were confirmed as HIV positive after 2006. This study reports competitive, long-term research that aimed to develop policies for the prevention of chronic infectious diseases for patients with HIV. The data collected over the last decade will be used to develop indices for HIV treatment and health promotion.
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Project description:As proposed in the UNAIDSs 2014 report, to end global AIDS epidemic by 2030, 90% of people living with HIV need to be diagnosed, 90% of the diagnosed need to receive antiretroviral therapy (ART), and 90% of those on treatment need to achieve viral suppression (90-90-90 strategy). The strategies focus on the reservoir. It controls HIV spreading by reducing infectiousness of HIV infected individuals via diagnosis and treatment. In this manuscript, we compared the effects of HIV/AIDS interventions that focus on different individuals in MSM population through a dynamics model. Our results showed that, the success or not of the "90-90-90" strategies depends on a very important factor: the infectious strength among individuals taking ART. Without highly effective HIV treatment, the "90-90-90" strategies are likely to fail. Therefore, we call for the combination of both primary prevention among the susceptible with the 90-90-90 strategy among the infected to curb the HIV epidemic in Chinese MSM.
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Project description:To control the HIV/AIDS epidemics in Guangxi Zhuang Autonomous Region in China, Guangxi government launched the 5-year Guangxi AIDS Conquering Project (GACP, Phase I: 2010-2014, Phase II: 2015-2020). In the project, three measures are implemented, such as great improvements of the coverage of HIV/AIDS education, promotion of HIV voluntary counseling and testing, and enhancement of antiretroviral treatment. In this paper, we explore the effects of the three measures of GACP by construction of a Susceptible-Infected-Diagnosed-Treated population compartments model and via evaluation of the basic reproduction number derived from the model. A computational framework is developed for estimating the model parameters based on the HIV surveillance data, with application of the Markov-Chain Monte-Carlo method and Nonlinear Least Squares method. By estimating the new infections and evaluating the basic reproduction number, we find that the implementation of the three measures of GACP has a significant effect on controlling the rise of HIV/AIDS cases and the epidemic trend. Compared with HIV voluntary counseling and testing, strengthening HIV/AIDS education and expanding the coverage of antiretroviral treatment show a greater impact on HIV/AIDS epidemic control, which provides a reference project for other provinces with a similar epidemic situation in Guangxi Zhuang Autonomous Region. At the same time, our research fills the current research gap for the evaluation of large-scale AIDS prevention and control projects in developing areas.
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