English
Abstract
Human immunodeficiency virus (HIV), comprising two distinct types, HIV-1 and HIV-2, remains one of the most significant global health challenges, originating from multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) in the early 20th century. This review traces the evolutionary trajectory of HIV from zoonotic spillover to its establishment as a global pandemic. HIV-1, the principal strain responsible for AIDS, emerged from SIVcpz in Central African chimpanzees, with phylogenetic evidence indicating initial human transmission between the 1920s and 1940s in present day Democratic Republic of Congo. The virus disseminated through colonial trade networks, reaching the Caribbean by the 1960s before establishing endemic transmission in North America and Europe. HIV’s extraordinary genetic diversity—driven by high mutation rates (~10−5 mutations per base per replication cycle) and frequent recombination events—has generated multiple groups, subtypes, and circulating recombinant forms (CRFs) with distinct epidemiological patterns. HIV-1 Group M, comprising subtypes A through L, accounts for over 95% of global infections, with subtype C predominating in sub-Saharan Africa and Asia, while subtype B dominates in Western Europe and North America. The extensive genetic heterogeneity of HIV significantly impacts diagnostic accuracy, antiretroviral therapy efficacy, and vaccine development, as subtypes exhibit differential biological properties, transmission efficiencies, and drug resistance profiles. Contemporary advances, including next-generation sequencing (NGS) for surveillance, broadly neutralizing antibodies for cross-subtype prevention and therapy, and long-acting antiretroviral formulations to improve adherence, have transformed HIV management and prevention strategies. NGS enables near real-time surveillance of drug resistance mutations and inference of transmission networks where it is available, although access and routine application remain uneven across regions. Broadly neutralizing antibodies demonstrate cross-subtype efficacy, while long-acting formulations have the potential to improve treatment adherence. This review synthesizes recent evidence and offers actionable recommendations to optimize clinical and public health responses—including the routine use of genotypic resistance testing where feasible, targeted use of phylogenetic analysis for outbreak investigation, and the development of region-specific diagnostic and treatment algorithms informed by local subtype prevalence. While the understanding of HIV’s evolutionary dynamics has substantially improved and remains essential, translating this knowledge into universally implemented intervention strategies remains a key challenge for achieving the UNAIDS 95-95-95 targets and the goal of ending AIDS as a public health threat by 2030.
Keywords:
HIV; zoonotic transmission; viral evolution; genetic diversity; molecular epidemiology
1. Introduction
The discovery of human immunodeficiency virus (HIV) in the early 1980s marked a pivotal moment in modern medicine and public health. What began as isolated reports of unusual opportunistic infections among previously healthy individuals in the United States quickly evolved into recognition of a global pandemic that would fundamentally challenge our understanding of viral pathogenesis, immune function, and infectious disease control. The identification of HIV as the causative agent of acquired immunodeficiency syndrome (AIDS) represented both a remarkable scientific achievement and the beginning of an ongoing battle against one of the most genetically complex and evolutionarily adaptable pathogens known to science.
The ongoing evolution of HIV-1 continues to influence clinical management strategies in 2025. Given the 1.3 million new infections each year and 40.8 million people living with HIV globally [1], a comprehensive understanding of viral diversity is critical for effective and sustainable treatment approaches. Recent data demonstrate that 10–15% of new infections in sub-Saharan Africa involve drug-resistant strains [2], while non-B subtypes now account for >20% of new diagnoses in Western Europe and North America [3]—regions historically dominated by subtype B. These shifts directly impact diagnostic accuracy, with commercially available assays showing reduced sensitivity for divergent strains and treatment efficacy, as demonstrated by recent reports of virological failure in patients with subtype A6/A1 on long-acting injectable regimens [4].
The discovery of HIV was built upon earlier breakthroughs in retrovirology, particularly the identification of human T cell leukemia viruses (HTLV-1 and HTLV-2) in the late 1970s and early 1980s, which established that retroviruses could indeed cause human disease [5,6]. These foundational discoveries provided crucial technical and conceptual frameworks that enabled researchers to isolate and characterize HIV when the AIDS epidemic emerged rapidly. However, unlike HTLV, which is largely restricted to specific geographic regions and populations, HIV demonstrated an unprecedented scale of global dissemination and genetic diversification that would define the modern pandemic era.
The evolutionary story of HIV represents one of the most extensively documented examples of viral emergence, cross-species transmission, and pandemic spread in human history. Through sophisticated phylogenetic analyses, molecular clock studies, and recovery of viral sequences from historical samples, the evolutionary pathway of HIV has been reconstructed from its origins in Central African primates to its emergence as a global pandemic. This remarkable scientific detective work has revealed that HIV-1, the predominant pandemic strain, likely emerged in the early 20th century through cross-species transmission from chimpanzees, spreading through colonial trade networks and achieving global dissemination driven by patterns of human migration, urbanization, and social change characteristic of the latter half of the 20th century.
Understanding the origins of HIV, its evolution, and global spread is not merely of historical interest, but it also provides essential insights for contemporary public health challenges and future pandemic preparedness. The extraordinary genetic diversity of the virus, driven by high mutation rates and frequent recombination, continues to present significant challenges for diagnostics, treatment, and vaccine development. Different HIV subtypes and circulating recombinant forms exhibit distinct biological properties, geographic distributions, and clinical characteristics that directly impact disease management strategies. Moreover, the continued evolution of HIV under selective pressures from host immune responses and antiretroviral therapy necessitates ongoing molecular surveillance and adaptive public health approaches. This review synthesizes current knowledge of the zoonotic origins of HIV, evolutionary mechanisms, global dissemination patterns, and the continuing implications of viral genetic diversity for HIV prevention, treatment, and potential cure strategies.
2. Discovery of HIV and Its Link to AIDS
In the early 1980s, a novel syndrome marked by severe opportunistic infections, malignancies, and immune suppression emerged, rapidly spreading and raising global health concerns. The first U.S. cases, involving Pneumocystis jirovecii pneumonia and Kaposi sarcoma, were reported in 1981 [7]. Epidemiological patterns prompted urgent investigation. This culminated in 1983 with the isolation of a new virus, initially termed lymphadenopathy-associated virus (LAV) [8] by one group, and human T-lymphotropic virus type III (HTLV-III) [9] by others. In 1986, it was unified under the name human immunodeficiency virus (HIV).
HIV spreads primarily through sexual contact, blood exposure (including non-sterile medical equipment, transfusions, and shared needles) [10], and vertical transmission from mother to child during pregnancy, delivery, or breastfeeding. Without prophylaxis, vertical transmission rates may reach 45%, but with modern antiretroviral interventions, the risk drops below 2% [11]. The virus, a member of the Retroviridae family (genus Lentivirus), contains structural genes (gag, pol, env) encoding core proteins, enzymes, and envelope glycoproteins, as well as regulatory genes (tat, rev, nef, vif, vpr, vpu) that promote replication and immune evasion [12].
The HIV lifecycle begins with attachment to CD4+ T lymphocytes via gp120 and co-receptors (CCR5 or CXCR4), followed by fusion and entry. Reverse transcriptase converts RNA to DNA, which is inserted into the host genome by integrase. Host machinery then produces viral components that assemble and bud from the cell, leading to CD4+ depletion, immune dysfunction, and susceptibility to opportunistic infections and cancers. Infection progresses through acute HIV (2–4 weeks post-exposure, with fever, rash, and lymphadenopathy) [13], chronic latency (often asymptomatic) [14], and AIDS, which is defined by CD4+ < 200 cells/μL or AIDS-defining illnesses [15].
Insights into HIV’s molecular biology enabled antiretroviral therapy (ART), which has greatly improved prognosis and life expectancy. However, global control remains incomplete, demanding sustained prevention efforts and vaccine development.
Source: MDPI, original link: https://www.mdpi.com/1422-0067/26/22/10909
The FAI climbed 5.9 percent year-on-year in the first 11 months of 2018, quickening from the 5.7-percent growth in Jan-Oct, the National Bureau of Statistics (NBS) said Friday in an online statement.
The key indicator of investment, dubbed a major growth driver, hit the bottom in August and has since started to rebound steadily.
In the face of emerging economic challenges home and abroad, China has stepped up efforts to stabilize investment, in particular rolling out measures to motivate private investors and channel funds into infrastructure.
Friday's data showed private investment, accounting for more than 60 percent of the total FAI, expanded by a brisk 8.7 percent.
NBS spokesperson Mao Shengyong said funds into weak economic links registered rapid increases as investment in environmental protection and agriculture jumped 42 percent and 12.5 percent respectively, much faster than the average.
In breakdown, investment in high-tech and equipment manufacturing remained vigorous with 16.1-percent and 11.6-percent increases respectively in the first 11 months. Infrastructure investment gained 3.7 percent, staying flat. Investment in property development rose 9.7 percent, also unchanged.