“Dr. Livingstone, I Presume?” Origins of HIV-1 in humans

European Colonization of Africa in the early 20 th century

Rubber

Plunder of the Congo These famous authors saw a colonial regime that had abandoned its civilizing mission for plunder, slave labor, rape, and mutilation.

Dja river

The Congo Crisis (1960–1965)

Flight of the middle class, mainly to Hati

A person who has tested HIV positive is diagnosed with AIDS when: the person’s CD4 cell count falls below 200 cells/ml OR CD4 positive T-lymphocyte percentage of total lymphocytes of less than 14% OR the person is diagnosed with any of the following conditions or diseases: Candidiasis of bronchi, trachea, or lungs; Candidiasis, esophageal; Cervical cancer, invasive; Coccidioidomycosis, disseminated or extrapulmonary; Cryptococcosis, extrapulmonary; Cryptosporidiosis, chronic intestinal (>1 month duration); Cytomegalovirus disease (other than liver, spleen, or nodes); Cytomegalovirus retinitis (with loss of vision); Encephalopathy, HIV-related; Herpes simplex: chronic ulcer(s) (>1 month duration); Histoplasmosis, disseminated; Isosporiasis, chronic intestinal (> 1 month duration); Kaposi’s sarcoma; Lymphoid interstitial pneumonitis (in children); Lymphoma, Burkitt’s (or equivalent term); Lymphoma, immunoblastic (or equivalent term); Lymphoma, primary, of brain; Mycobacterium avium complex or M. Kansasii, disseminated or extrapulmonary; Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary); Mycobacterium, other species or unidentified species, disseminated or extrapulmonary; Pneumocystis carinii pneumonia; Pneumonia, recurrent; Progressive multifocal leukoencephalopathy; Salmonella septicemia, recurrent; Toxoplasmosis of brain; Wasting syndrome due to HIV; pulmonary tuberculosis; recurrent pneumonia. A person who is HIV negative or of undetermined serostatus may be diagnosed with AIDS when: other causes of immunodeficiency are ruled out and the person is definitively diagnosed with one of the AIDS indicator diseases listed above. MMRW, Vol. 41/No. RR-17

Patient Zero A study published in the American Journal of Medicine in 1984 traced many of New York City's early HIV infections to an unnamed infected homosexual male flight attendant. Gaëtan Dugas (April 20, 1953 – March 30, 1984) was a French Canadian who worked for Air Canada as a flight attendant. Dugas became notorious as the alleged patient zero for AIDS. Dugas is featured prominently in Randy Shilts's book And the Band Played On, which documents the outbreak of AIDS in the United States. Genetic analysis of HIV provides some support for the Patient Zero theory. Dugas is now believed to be part of a cluster of homosexual men who traveled frequently, were extremely sexually active, and died of AIDS at a very early stage in the epidemic.

-HIV is a relatively minor STD by sheer numbers. STI Rates in the U.S. (per year) - March

HIV is the only STD that causes substantial death totals worldwide. Deaths from HIV are increasing. Estimated annual mortality approximately doubled over the last 10 years. * 2012 stats from the CDC on disability life years (DALYs)

December 2009 Total: 33.4 million (31.1 – 35.8 million) Western & Central Europe [ – ] Middle East & North Africa [ – ] Sub-Saharan Africa 22.4 million [20.8 – 24.1 million] Eastern Europe & Central Asia 1.5 million [1.4 – 1.7 million] South & South-East Asia 3.8 million [3.4 – 4.3 million] Oceania [ – ] North America 1.4 million [1.2 – 1.6 million] Latin America 2.0 million [1.8 – 2.2 million] East Asia [ – 1.0 million] Caribbean [ – ] Adults and children estimated to be living with HIV, 2008

AIDS prevalence is distributed unequally across the world, with sub-Saharan Africa and Southeast Asia experiencing the worst of the pandemic.

Estimated number of people living with HIV globally, 1990–2007 UNAIDS 2008 Report of the global AIDS epidemic

December 2009 Estimated number of adults and children newly infected with HIV, 2008 Western & Central Europe [ – ] Middle East & North Africa [ – ] Sub-Saharan Africa 1.9 million [1.6 – 2.2 million] Eastern Europe & Central Asia [ – ] South & South-East Asia [ – ] Oceania3900 [2900 – 5100] North America [ – ] Latin America [ – ] East Asia [ – ] Caribbean [ – ] Total: 2.7 million (2.4 – 3.0 million)

December 2009 Over 7400 new HIV infections a day in 2008 More than 97% are in low- and middle-income countries About 1200 are in children under 15 years of age About 6200 are in adults aged 15 years and older, of whom: — almost 48% are among women — about 40% are among young people (15–24)

Estimated number of adult and child deaths due to AIDS globally, 1990–2007 Year Millions This bar indicates the range around the estimate UNAIDS 2008 Report of the global AIDS epidemic

December 2009 Estimated adult and child deaths due to AIDS, 2008 Western & Central Europe [ – ] Middle East & North Africa [ – ] Sub-Saharan Africa 1.4 million [1.1 – 1.7 million] Eastern Europe & Central Asia [ – ] South & South-East Asia [ – ] Oceania2000 [1100 – 3100] North America [ – ] Latin America [ – ] East Asia [ – ] Caribbean [9300 – ] Total: 2.0 million (1.7 – 2.4 million)

Life expectancy at birth, selected regions, 1950–1955 to 2005– Source: Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, World Population Prospects: The 2006 Revision, -HIV has had a huge impact of life expectancy in Southern Africa and has also affected other regions of Africa

-An array of different HIV subtypes infect various regions of the world. The subtypes can differ by 25-30% at the sequence level making it difficult to produce a single vaccine that can treat all HIV infections. AIDS AVERT

HIV-AIDS in the USA: Estimated deaths ( ) The sharp decrease in AIDS deaths from 1` coincides with the start of triple drug therapy (HAART) and was not from a decrease in HIV infections

Table 1 -HIV transfers poorly during sexual intercourse or even needle sharing but enough events will lead to transfer. A secondary STD will increase transfer about fold during sex.

Graph showing HIV copies and CD4 counts in a human over the course of a treatment-naive HIV infection Originally from English Wikipedia. -After a few months the level of HIV in blood has decreased over 100-fold from its peak and remains nearly steady for several years. Still ~10 billion new viruses are made each day during this clinical latent period and over 1 billion T4 helper cells are killed. The very slow decline in T cells over years results from replenishment of essentially all the killed cells each day. The reason for failure after several years remains unclear and highly controversial. One theory suggests that the body simply cannot sustain such a high rate of T-cell production and ultimately levels drop resulting in failure of the entire immune system which is highly dependent on T helper cells.

Intracellular infection Naïve B-Cell Naïve T8 cell Naïve T4 helper cell MHC I presentation of endogenous antigen MHC II presentation of exogenous antigen Cell-mediated (CTLs) Humoral (plasma cells / antibodies) Free antigen Th1Th2 Overview of Adaptive Immune Response Illustrating important role of T helper cells Extracellular infection APC Diagram courtesy of Dr. Samuel Anderson

-The body mounts a vigorous immune response to HIV infection but over the course of several years T4 cell levels drop and HIV leads to AIDS.

Dr. Richard Hunt

Modified from: (Baylor College of Medicine, Dept. of Molecular Virology and Microbiology) HIV inhibitors used in Highly Active Antiretroviral Therapy (HAART) by class Two classes: NNRT and NRT (Non-nucleoside and nucleoside reverse transcriptase inhibitors)

Good: -HAART has been very successful with about 80% of patients responding to treatment in controlled studies. -This therapy has been the primary reason for the decrease in AIDS deaths in the USA and other developed countries. -New single dose pills that contain combinations of different drugs are beginning to be marketed. Bad: -Most under-developed countries where most HIV infections occur do not have access to HAART. -Success rate estimates still leave about 20% of people who don’t respond. -Treatment with drugs ultimately leads to resistant forms and there have been several reports of new viruses resistant to some triple drug regiments. -Drug treatment is complex (10-12 pills a day) and expensive (about $10,000/yr per patient just for drugs). -Several of the drugs have potentially severe side-effects that cannot be tolerated by some patients. HAART, the good and bad

Comprehensive knowledge of HIV among young people, by type of question 4.4 MalesFemales (%) correct All 5 questions are correct Mosquitos do not transmit HIV A healthy looking person can have HIV Having only one faithful partner can protect against HIV Condoms can prevent HIV Sharing food does not transmit HIV Source: UNGASS Country Progress Reports QUESTION Ignorance among young people about HIV and AIDS is still widespread reflecting the limited success of education

Annual investment in preventive HIV vaccine research and development by source between 2000 and Year US$ Millions 2006 Multilaterals Other Public Sector Europe US Source: HIV Vaccines and Microbicides Resource Tracking Working Group, Vaccine efforts have been lead mostly by the US and worldwide input of funds has lagged.

Disbursements for HIV per US$ 1 Million GDP, 2006 H Sources: UNAIDS and Kaiser Family Foundation analysis, June 2007; Global Fund to Fight AIDS, Tuberculosis and Malaria online data query May 2007; International Monetary Fund, World Economic Outlook Database, April Italy 4 Japan 24 Canada 50 Germany 60 France 93 United States 120 United Kingdom 328 Ireland 408 Sweden 462 Netherlands US$ -US funding for HIV and AIDS is far greater than any other country in terms of total dollar while 4 countries spend higher proportions of GDP on HIV and AIDS

Total annual resources available for AIDS 1986– 2007 [i] data: Extracted from 2006 Report on the Global AIDS Epidemic (UNAIDS, 2006); [ii] data: Mann.&. Tarantola, 1996 Notes: [1] figures are for international funds only; [2] Domestic funds are included from 2001 onwards US$ million billion Signing of Declaration of Commitment on HIV/AIDS, UNGASS Less than US$ 1 million World Bank MAP launch Global Fund PEPFAR 257 UNAID S Gates Foundation billion 10 billion 7.1 Source: UNAIDS & WHO unpublished estimates, 2007 Global funds for AIDS initiatives (total from all sources) have risen sharply in the last 5 years to a total of ~10 billion worldwide -US total funds for HIV/AIDS in 2007 were ~21 billion with about 17% of that going toward global initiatives.

Selected events related to the treatment of AIDS Accelerating Access Initiative launched by UN/industry partnership 3 million people on treatment in developing countries UN General Assembly Political Declaration on Universal Access to Prevention, Treatment care and support 1996 Introduction of HAART World Bank MAP II includes ART in developing countries G8 Declaration for Universal Access to treatment First Global Fund Grants awarded for treatment WHO launches 3 x 5 initiative UniversalAccessTargets MillenniumDevelopmentGoals Midway to Millennium Development Goals Special Session on UN General Assembly HIV/AIDS June 2001/ 189 Member States signed the Declaration of Commitment Cooperation between several groups including the WHO, CDC, UN, and G8 has lead to a comprehensive plan for combating AIDS as part of the UNs Millennium Development Goals

Annual AIDS deaths comparing projected current rate of scale up and the phased scale-up strategy to reach universal access between 2010 and Source: UNAIDS, Number of AIDS deaths (Millions) Current Scale-Up Phased Scale-Up -Meeting the Millennium Development Goals could result in a 50% decrease in AIDS deaths by 2015