Adults and children estimated to be living Adults and children estimated to be living with HIV/AIDS as of end 2000with HIV/AIDS as of end 2000

Western Europe

540 000540 000North Africa & Middle East

400 000400 000Sub-Saharan

Africa

25.3 25.3 millionmillion

Eastern Europe & Central Asia

700 000700 000

South & South-East Asia

5.8 million5.8 million

Australia & New Zealand

15 00015 000

North America

920 000920 000Caribbean

390 000390 000

Latin America

1.4 1.4 millionmillion

Total: 36.1 Total: 36.1 millionmillion

East Asia & Pacific

640 000640 000

A global view of HIV infectionA global view of HIV infection 33 million adults living with HIV/AIDS as of end 199933 million adults living with HIV/AIDS as of end 1999

Spread of HIV over timeSpread of HIV over timein sub-Saharan Africa, 1984 to 1999in sub-Saharan Africa, 1984 to 1999

Estimated percentage of adults

(15–49) infected with HIV 20.0% – 36.0%10.0% – 20.0% 5.0% – 10.0% 1.0% – 5.0% 0.0% – 1.0%trend data unavailable

outside region

Spread of HIV over time in Asia, 1984 to 1999Spread of HIV over time in Asia, 1984 to 1999

2.0% – 5.0% 1.0% – 2.0% 0.5% – 1.0% 0.1% – 0.5% 0.0% – 0.1%trend data unavailable

outside region

About 15 000 new HIV infections a day About 15 000 new HIV infections a day in 1999in 1999

• More than 95% are in developing

countries

• 1 700 are in children under 15 years of age

• About 13 000 are in persons aged 15 to 49

years, of whom:— almost 50% are women

— about 50% are 15–24 year olds

• More than 95% are in developing

countries

• 1 700 are in children under 15 years of age

• About 13 000 are in persons aged 15 to 49

years, of whom:— almost 50% are women

— about 50% are 15–24 year olds

New

in

fect

ion

s

-

500,000

1,000,000

1,500,000

2,000,000

2,500,000

3,000,000

3,500,000

4,000,000

80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99

Highly industrialized countries

North Africa & Middle EastEastern Europe & Central asiaSub-Saharan AfricaLatin America & the Caribbean

Southern & Eastern Asia

Estimated annual number of new HIV Estimated annual number of new HIV infections by region, 1980 to 1999infections by region, 1980 to 1999

Where did HIV come from?

Why did it occur as an epidemic?

Why did it occur in the 1980’s?

Type B

Type E

All

A=60% B=2%C=4% D=4%E=8% F=6%G=7% H=1%J=1% O=5%

90% A,B,C,D,G

55%A,34%D

ABCD

94% C Homosexual85% B Heterosexual

Predominant Distribution of HIV1 by Subtype

96%C

Distribution of HIV-2

1985

1998

HIV-1 subgenomic regions utilized for epidemiological linkage analysis. A schematic representation of the HIV-1 genome is shown, with brackets denoting the subgenomic gag, gp120, gp41, and LTR fragments that were amplified for diagnostic PCR analysis. Overlapping gag and gp120 regions are denoted by capital letters (gagA to -H; gp120A to -C) and are referred to in Tables 2 to 4. Stanley A. Trask,1 Cynthia A. Derdeyn,2 Ulgen Fideli,3 Yalu Chen,1 Sreelatha Meleth,1 Francis Kasolo,4 Rosemary Musonda,5 Eric Hunter,2 Feng Gao,1 Susan Allen,3 and Beatrice H. Hahn1,2 Journal of Virology, January 2002, p. 397-405, Vol. 76, No. 1

TGATAA

ATAGCCT

GTTACCA

CGCTTA

Molecular linkage analysis for a subset of putative HIV-1 transmission pairs. A phylogenetic tree was constructed from partial gp41 sequences Horizontal branch lengths are drawn to scale (the scale bar represents 0.05 nucleotide substitutions per site); vertical separation is for clarity only. Asterisks indicate bootstrap values in which the cluster to the right is supported in >80% replicates (out of 1,000). Newly derived sequences from 42 transmission pairs (84 individuals) are shown, along with 26 reference sequences from the Los Alamos Sequence Database (http://hiv-web.lanl.gov/HTML/alignments.html). Viruses from 36 couples are closely related to one another and cluster together with significant bootstrap values, indicating that they are epidemiologically linked (highlighted in red and denoted by dots). Viruses from six couples do not cluster together and exhibit a range of within-couple diversity that is similar to that of the reference sequences (highlighted in blue and denoted by triangles), indicating that they are epidemiologically unlinked. Two small brackets denote viral subclusters, each involving viruses from two sets of couples (see text for details). Brackets on the far right indicate major group M sequence subtypes.

Journal of Virology, January 2002, p. 397-405, Vol. 76, No. 1

Within-group diversity among linked and unlinked Zambian transmission pairs and corresponding reference sequences. Subtype C reference sequences (n = 15) from the Los Alamos HIV/SIV Sequence Database (Table 1) were subjected to pairwise sequence comparisons in the region corresponding to the PCR-amplified gp41 fragment shown in Fig. 1. Pairwise sequence distances were also calculated for 66 subtype C transmission pairs classified as linked and 15 subtype C transmission pairs classified as unlinked in the same genomic region. The distribution of distance values for these three different groups is depicted as boxes, with the lower and upper limits of the box delineating the 25th and 75th percentiles and the bars indicating the 10th and 90th percentiles, respectively. The median distance of the linked viral group (median = 1.5) was significantly different from that of both the unlinked viral group (median distance = 8.8) and the reference sequence group (median distance = 8.2) (P < 0.0001, one-sided Mann-Whitney test [17]). In contrast, the median sequence distance of the unlinked viral group was not statistically different from that of the reference sequence group (P > 0.05, Mann-Whitney test).

Stanley A. Trask,1 Cynthia A. Derdeyn,2 Ulgen Fideli,3 Yalu Chen,1 Sreelatha Meleth,1 Francis Kasolo,4 Rosemary Musonda,5 Eric Hunter,2 Feng Gao,1 Susan Allen,3 and Beatrice H. Hahn1,2 Journal of Virology, January 2002, p. 397-405, Vol. 76, No. 1

Transmission networks within the ZUHRP cohort. Phylogenetic trees were constructed from gp41 sequences of viruses infecting four different transmission pairs putatively classified as linked by pairwise sequence analysis. Couple identifiers are indicated in red (F, female partner; M, male partner). Horizontal branch lengths are drawn to scale (the scale bar represents 0.05 nucleotide substitutions per site); vertical separation is for clarity only. Values at nodes indicate the percentage of bootstraps in which the cluster to the right was found; only values of 80% are shown. Representative subtype C (left) and subtype G (right) reference sequences are included in each tree. Donor partners are underlined. Journal of Virology, January 2002, p. 397-405, Vol. 76, No. 1

Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses.Chakrabarti L, Guyader M, Alizon M, Daniel MD, Desrosiers RC, Tiollais P, Sonigo P. Nature 1987 Aug 6-12;328(6130):543-7

Isolation and partial characterization of an HIV-related virus occurring naturally in chimpanzees in Gabon. Peeters M, Honore C, Huet T, Bedjabaga L, Ossari S, Bussi P, Cooper RW, Delaporte E. AIDS. 1989 Oct;3(10):625-30.

Genetic organization of a chimpanzee lentivirus related to HIV-1.Huet T, Cheynier R, Meyerhans A, Roelants G, Wain-Hobson S. Nature 1990 May 24;345(6273):

Origin of HIV-1 in Pan troglodytes troglodytes. a, Geographic ranges of the four subspecies of the common chimpanzee (Pan troglodytes) defined by mtDNA analysis (adapted from refs 19, 20 with permission).

Nature 397, 436 - 441 (1999)

Primate Lentivirus Evolution

SIVAGM

SIVSYK

HIV-1 type O

SIVSTM

SIVMAC

D

SIVSM

CA

BSIVSM

E

Source: McClure MA, Current Opinion in Genetics and Development, 1996, p 749Gao F, et al Nature 397 4:436, 1999

SIVCPZ ANT

A

BC

D

EF

G

Env and Pol Sequence Comparison

Gag Sequence ComparisonRT Sequence comparison

HIV-2, subtypes A-E

HIV-1, Type M

Documented Cross Species Transmissions

Subtypes A-GHIV-1/MVP6180

HIV-1/ANT70

SIVCPZUS

SIVCPZG

c, Unrooted neighbour-joining tree of partial Pol protein sequences (distances are drawn to scale).

Nature 397, 436 - 441 (1999)

b, Phylogenetic tree of mtDNA sequences. Positions of sequences from the SIVcpz-infected chimpanzees Marilyn (SIVcpzUS), GAB1 (SIVcpzGAB1), GAB2 (SIVcpzGAB2) and Noah (SIVcpzANT) are boxed. Horizontal branch lengths are drawn to scale with the bar indicating 0.1 nucleotide replacements per site. Numbers at each node indicate the percentage of bootstrap samples (out of 1,000) in which the cluster to the right is supported (only values >80% are shown). Brackets on the right indicate previously defined subspecies/species classifications19, 20 (P. t. troglodytes , P. t. schweinfurthii, P.t.verus, and P. t. vellerosus are colour coded as in a).

Nature 397, 436 - 441 (1999)

c, Schematic tree of Pol sequences, highlighting the position of HIV-1 group M, N and O viruses in relation to P. t. troglodytes (red) and P. t. schweinfurthii (blue) viruses. The position of SIVcpzGAB2 (indicated by broken line), for which only partial sequence is available10, is inferred from the phylogeny shown in Fig. 1c.

Nature 397, 436 - 441 (1999)

Distribution of HIV-1 env genetic subtypes in different geographic locales from the DRC.

JOURNAL OF VIROLOGY,Nov. 2000, p.10498–10507

Intra- and intersubtype genetic distances in the env V3-V5 region of HIV-1 isolates from the DRC. Range of lowest to highest distance within a subtype is in parentheses. A/E, CRF01-AE.

JOURNAL OF VIROLOGY,Nov. 2000, p.10498–10507

Figure 1. Phylogenetic analysis of HIV-1 group M and SIVcpz from Pan troglodytes troglodytes in different gene regions. Trees also include HIV-1 group O as the outgroup. Branch lengths were estimated by assuming unequal evolutionary rates along them. Horizontal branch lengths are drawn to scale with the bar indicating 0.1 nucleotide replacements per site. Nodes with asterisks were supported by greater than 95% bootstrap samples (out of 1,000). The branch length to the outgroup is mentioned on the branch. The strains are described in Materials and Methods. A) pol region, nt 2358-3809; B) full-length envelope.

Table 1. Divergence times of the major nodes of the HIV-1/SIVcpz phylogenetic tree

a The length of the branch was estimated using 1st + 3rd codon position clock-like evolving sites of pol. Standard errors are indicated. b The height of the branch was estimated using 656 out of 737 nucleotide clock-like evolving sites at 1st codon position of env. Standard errors are indicated. c 99% confidence intervals for the estimated year of origin are given in parenthesis.

Figure 1. Detection of HIV-1/HIV-2 cross-reactive antibodies in sera from 11 primate species by using a line immunoassay (INNO-LIA HIV Confirmation, Innogenetics, Ghent, Belgium). Varying patterns of reactivity to HIV peptides and proteins (HIV-1 gp120, gp41, p31, p24, and p17; HIV-2 gp130, and gp36) are shown. Samples from which Simian immunodeficiency virus (SIV) sequences were subsequently amplified by polymerase chain reaction are color-coded as in Figure 2. Plasma samples from HIV-1/HIV-2-negative and -positive persons are shown as controls on the left. The 3+, 1+ and +/- bands at the top of all test strips control for sample addition (presence of plasma immunoglobulin) and test performance (binding of secondary antibody).

EID Volume 8, Number 5, May 2002Risk to Human Health from a Plethora of Simian Immunodeficiency Viruses in Primate Bushmeat Martine Peeters,* Valerie Courgnaud,* Bernadette Abela,† Philippe Auzel,†‡ Xavier Pourrut,* Frederic Bibollet-Ruche,§ Severin Loul,† Florian Liegeois,* Cristelle Butel,* Denis Koulagna,¶ Eitel Mpoudi-Ngole,† George M. Shaw,§ Beatrice H. Hahn,§ and Eric Delaporte**

Figure 2. Identification of diverse Simian immunodeficiency virus (SIV) lineages in primate bushmeat. A 650-bp pol fragment was amplified from monkeys representing seven primate species, sequenced, and subjected to phylogenetic tree analysis. The positions of 21 SIV sequences from the present study (in color) are shown in relation to HIV/SIV reference sequences from the Los Alamos HIV/SIV Sequence Database (in black). The consensus length of the final alignment used for tree construction was 555 bp. The new species-specific SIV lineages are generally identified by a lower-case three-letter code corresponding to the initial letters of the common species name (e.g., SIVgsn for greater spot-nosed monkeys [Cercopithecus nictitans], SIVmus for mustached guenons [C. cephus] and SIVmon for mona monkeys [C. mona]). Lineages are defined as clusters of viral sequences from the same primate species that group together with significant (>80%) bootstrap values. We maintained the lineage designation of SIVtal previously assigned to a virus thought to be derived from a zoo animal of the species Miopithecus talapoin (28) since that sequence, and the two newly derived talapoin viruses from M. ogouensis, cluster together in a phylogenetic tree derived from additional pol nucleotide sequences (not shown). Branch lengths are drawn to scale (the bar indicates 10% divergence).

EID Volume 8, Number 5, May 2002Risk to Human Health from a Plethora of Simian Immunodeficiency Viruses in Primate Bushmeat Martine Peeters,* et al

Age Groups Subjects Tested 1976 Subjects Tested 1986

1976 & 1986

0-4 45 (6.8) 8 (8.9)5-9 78 (11.8) 3 (3.3)10-14 82 (12.4) 6 (6.7)15-19 29 (4.4) 22 (5.7) 3 (3.3)20-29 145 (22) 144 (37.1) 18 (20)30-39 105 (15.9) 119 (30.7) 20 (22.2)40-49 94 (14.3) 65 (16.8) 19 (21.1)50+ 74 (11.2) 38 (9.8) 13 (14.4)

Male 405 (61.5) 267 (68.8) 66 (73.3)Female 251 (38.1) 121 (31.2) 24 (26.7)Unknown 3 (0.5)Total 659 388 90

Age and Sex Distribution of Study Subjects Tested in 1976 and 1986 Yambuku, Zaire

Group Prevalence 95% CIHealthy Persons

1976 5/659 (0.8%) 0.1 - 1.41986 3/388 (0.8%) 0 - 1.6

Female Prostitutes (1986)

32/283 (11.3%) 7.6 - 15

Pregnant Women 3/136 (2.2%) 0- 4.7Hospitalized Patients (with 1 or more clinical criteria for AIDS)

6/31 (19.4%) 5.5- 33.3

Prevalence of HIV Antibody in Various Groups

Zaire 1976 and 1986

Subject # 1976 Age Sex 1976 Antibody

1985 Antibody

Clinical Outcome

T Cell Ratio

1 50 f + + Well 1.32 48 m + + Well 0.33* 36 f + ND Died, 1977 ND4 43 f + ND Died 1981 ND5 9 m + ND Died 1984 ND

*HIV was isolated from 1976 serum

1986 Follow-Up in Five Persons Who Were Seropositive to HIV in 1976

Related lentiviruses have been found infecting numerous species of primates in sub-Saharan Africa. The only species naturally infected with viruses closely related to HIV-2 is the sooty mangabey (Cercocebus atys) from western Africa,

Similarly, the only viruses very closely related to HIV-1 have been isolated from chimpanzees (Pan troglodytes), and in particular those from western equatorial Africa,

HIV-1 and HIV-2 have each arisen several times: in the case of HIV-1, the three groups (M, N and O) are the result of independent cross-species transmission events.

Consistent with the phylogenetic position of a 'fossil' virus from 1959, molecular clock analyses using realistic models of HIV-1 sequence evolution place the last common ancestor of the M group prior to 1940

Both the inferred geographical origin of HIV-1 and the timing of the cross-species transmission are inconsistent with the suggestion that oral polio vaccines could be responsible for the origin of acquired immune deficiency syndrome.

The origins of acquired immune deficiency syndrome viruses: where and when?Author(s): Paul M. Sharp ; Elizabeth Bailes ; Roy R. Chaudhuri ; Cynthia M. Rodenburg ; Mario O. Santiago ; Beatrice H. Hahn Source: Philosophical Transactions: Biological Sciences      Volume: 356 Number: 1410 Page: 867 -- 876

Lentiviruses, primates, HIV-1 and HIV-2 and Polio Vaccine

Population Growth outstripping available resources

195019601970198019902000201020202030

Years

0 1 2 3 4 5 6

Billions of People

More Developed RegionsLess Developed Regions

Urban Population (billions)1950-2030

1950 1960 1970 1980 1990 2000 2010

Years

0

100

200

300

400

500

600

Number of Urban agglomerations

Number of urban agglomerations with 1 million1 million or more inhabitants: 1950-2015

More Developed RegionLess Developed Region

Total

City 1920 1940 1950 1980 2000 Harare 7300 51800 72000 627000 2000000 % 0.75 3.61 2.64 8.80 17.63 Kinshasa 1600 35900 135000 2500000 6400000 % 0.03 0.35 1.21 9.26 12.32 Lubumbashi 17100 20,800 95000 506000 % 0.27 0.20 0.85 1.87 0.00 Lusaka 2400 30000 538000 1500000 % 0.26 1.23 9.50 15.65 Kampala 7400 40000 458000 900000 % 0.23 0.77 3.62 3.86 Kigali 7000 156700 % 0.34 3.04 Libreville 2000 8000 21600 340000 530000 % 0.51 2.04 4.69 42.18 43.87 Johannesburg 288000 550000 600000 3087000 6500000 % 3.97 5.32 4.51 10.45 14.97 Lagos 100000 137400 158500 1404000 8000000 % 1.03 0.63 0.47 1.79 6.49 Nairobi 24300 61300 119000 1340000 3020000 % 0.97 1.33 1.90 8.06 9.95

Average 1.39 1.59 1.57 5.79 9.80

Population Growth and % Total Population of Selected African Cities 1920 to 2000