The Origins of The Origins of HIV/AIDS:HIV/AIDS:

Where Did it Come From?Where Did it Come From?

Early EvidenceEarly Evidence

First described in 1981First described in 1981 Thought to originate in HaitiThought to originate in Haiti This idea rapidly discreditedThis idea rapidly discredited

• Some recent evidence suggests that Some recent evidence suggests that first appearance in western hemisphere first appearance in western hemisphere was in Haitiwas in Haiti

Recent ThoughtRecent Thought

Origins in AfricaOrigins in Africa Means of transmission becoming Means of transmission becoming

clearerclearer HIV is an old infectionHIV is an old infection So, what is the evidence?So, what is the evidence?

Evidence Favoring West Evidence Favoring West African/Central African OriginAfrican/Central African Origin

Frequency of infectionFrequency of infection Genetic variation—greatGenetic variation—great Presence in non-human primatesPresence in non-human primates

Evidence of non-human primate Evidence of non-human primate origin origin See Hahn et al, Science 2000;287:607-614See Hahn et al, Science 2000;287:607-614

Geographic overlapGeographic overlap Prevalence in chimpsPrevalence in chimps

• SIV introduced into humans at least 7 times.SIV introduced into humans at least 7 times.• SIV—no morbidity or mortality in their hostsSIV—no morbidity or mortality in their hosts

Similarities or identical genome Similarities or identical genome structure in humans and chimpsstructure in humans and chimps

Phylogenetic relatednessPhylogenetic relatedness Transmission routesTransmission routes

Schematic, lineage, HIV-1 and HIV-2

Source: Hahn et al, Science, 2000

Human Exposure to Blood During BushmeatPreparation

SE Cameroon (red)Leopoldville (Kinshasa)-1896and 1955

Source: Sharp and Hahn, Nature, 2008

Based on liver , lymph node biopsies, and placental remains

Source: WorobeyEt al, Nature 2008

Evidence of Species JumpEvidence of Species Jump

SIV-HIV2 similaritiesSIV-HIV2 similarities HIV identified in chimpsHIV identified in chimps Intensity of infection in chimps—Intensity of infection in chimps—

parallels intensity in humans parallels intensity in humans geographapicallygeographapically

Pan troglodytes troglodytes (chimpanzee)

““Humans are not the natural hosts of Humans are not the natural hosts of either HIV-1 or HIV-2. Instead, these either HIV-1 or HIV-2. Instead, these viruses have entered the human viruses have entered the human population as a result of zoonotic, or population as a result of zoonotic, or cross-species, transmission. We now cross-species, transmission. We now know of at least 18 distinct primate know of at least 18 distinct primate lentiviruses that naturally infect African lentiviruses that naturally infect African primates.primates.””——Hahn et al, Hahn et al, ScienceScience 2000; 2000; 287:607287:607

Infection is OldInfection is Old

Serological (blood) studies Serological (blood) studies • Stored samples 1959-1981 (humans) Stored samples 1959-1981 (humans)

from Africafrom Africa• 21 samples HIV positive21 samples HIV positive• 1959—Bantu male, Leopoldville, Belgian 1959—Bantu male, Leopoldville, Belgian

Congo (Kinshasa, Democratic Republic Congo (Kinshasa, Democratic Republic of Congo)of Congo)

• Was HIV +Was HIV +• Pt.—Manchester UK, 1959Pt.—Manchester UK, 1959• Conclusion—present in humans 1959Conclusion—present in humans 1959

When Did HIV Originate?When Did HIV Originate?

Quite old in primates—subtle genetic Quite old in primates—subtle genetic variationsvariations

Humans—Humans—• Analysis of genetic variationsAnalysis of genetic variations• Rates of changeRates of change• Backwards simulation—as early as 1930Backwards simulation—as early as 1930• Very recent-maybe even 1900Very recent-maybe even 1900

Molecular Clock (relaxed)

Source: Gilbert et al, PNAS, 2007

CounterargumentsCounterarguments

CIA introduced HIV CIA introduced HIV (no (no evidence)evidence)

Introduced by oral polio vaccineIntroduced by oral polio vaccine• (Ed Hooper, (Ed Hooper, The RiverThe River• Now discreditedNow discredited

SIV predated oral polio vaccineSIV predated oral polio vaccine Vaccine specimens at Wistar Institute neg Vaccine specimens at Wistar Institute neg

for HIVfor HIV

Pres. Mbeke (South Africa)—Pres. Mbeke (South Africa)—• Denies relationship btw. HIV and AIDSDenies relationship btw. HIV and AIDS• Draws upon work by DuesbergDraws upon work by Duesberg