The latest research tools are now being used to piece together how HIV has changed and spread in human populations over the past 100 years, according to a Review published Online First in The Lancet Infectious Diseases. This understanding has implications for control and prevention efforts, from predicting what might come next in the HIV pandemic to the development of vaccines.
"The evolution of HIV-1* has been rapid", write US researchers Denis M Tebit and Eric J Arts, from Case Western Reserve University, Cleveland, Ohio. This has resulted in worldwide spread and intermixing of strains: at least 48 circulating recombinant forms** are currently identified. "This extreme and divergent evolution has led to differences in virulence between HIV-1 groups, subtypes, or both", they write.
Since HIV was discovered in the 1980s, research tools to look at the genetic makeup of the numerous circulating forms have substantially advanced. Now, genomic sequencing can read a large proportion of the genetic makeup of the thousands to millions of viral variants found in individual patients. Testing individuals from different areas in the world and archival samples, collected for other reasons in the past, can be used to trace the origin of HIV and to piece together maps of how HIV has evolved and spread.
25 years of research have found that the viral ancestors of HIV – eg, simian immunodeficiency virus (SIV)- can jump between primate species. Then, Arts explains, the foreign virus needs to rapidly adapt to the new host, such as humans, to ensure survival, subsequent transmission, and possibly to seed a new pandemic.
HIV-1 is thought to have jumped species from chimpanzees to humans several times, the latest at the start of the 20th century. Tebit and Arts describe how HIV-1 spread to large urban centres during pre-independent and post-colonial times in Africa, when massive human emigration out of small villages in the dense tropical forests of Congo River Basin occurred, for example to Kinshasa in the Democratic Republic of Congo (DRC), which is near the origin of HIV.
Different HIV-1 strains have developed and spread differently around the globe, due to an element of chance and influenced by human behaviours, from migration to injecting drug use. This has led to huge heterogeneity in viral forms. In many instances, the pattern of virus diversity suggests introduction of an HIV-1 form by one individual and then rapid spread – the "founder theory". For example, the Caribbean HIV-1 epidemic could be the clearest reflection of such "founder events", given notable immigration, travel, and trade, especially between the DRC and Haiti, and between Angola and Cuba. "Constant and increasingly easy worldwide travel is a major contributor to HIV diversification", the authors note.
This global heterogeneity of HIV-1 has a significant effect on properties of the virus, which further impact the pattern of the pandemic. These properties include viral fitness***, transmissibility, ability to cause disease progression, and drug resistance. For example, research has shown that subtype C HIV-1 strains, which dominate the HIV-1 pandemic, are actually less fit than other subtypes in controlled experiments. This may be related to emerging studies suggesting that subtype C virus causes disease with a long symptom-free period, but which also increases the opportunity for transmission compared with other subtypes.
New forms "will continue to emerge and will definitely have major roles in the development of prevention and control strategies for HIV", predict Tebit and Arts. Given the history of HIV, a major recombination between types or groups, or even with its ancestor SIV, could result in a substantially different new virus.
Understanding the worldwide pattern of HIV and how it is evolving will greatly affect future methods and strategies for diagnosis, therapy, and prevention. For example, vaccines and vaginal virucidal gels will need to be able to prevent infections caused by many different viral forms, while viral mutations can cause antiretroviral resistance before patients have taken medication, which will impact on the effectiveness of treatment.
Dr. Denis Tebit, Division of Infectious Disease, Case Western Reserve University, Cleveland, OH, USA. T) +1-216-368-8902 E) denis.tebit@case.edu
For full Review, see: http://press.thelancet.com/tlidhivrev.pdf
Notes to Editors:
* Simian immunodeficiency virus has jumped species from chimpanzees and sooty mangabeys to humans and likely more than once, creating two main virus types – HIV-1 (the main pandemic virus) and HIV-2.
** HIV adapts by mutating within the body, leading to many viral variants in one individual. Also, different variants can mix their genes together – known as recombination – to create unique recombinant variants. When new variants are transmitted, new circulating HIV forms appear.
*** Viral fitness describes how effectively a viral variant can reproduce, which causes cell killing and leads to disease
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Journal
The Lancet Infectious Diseases