1 AIDS Acquired immune deficiency syndrome A group of illnesses resulting from immune system damage caused by infection with HIV.

2 Human Immunodeficiency Virus (HIV) structure. The outer shell of the virus is known as the viral envelope. Embedded in the viral envelope is a complex protein known as env, which consists of an outer protruding cap glycoprotein (gp) 120, and a stem gp41. Within the viral envelope is an HIV protein called p17 (matrix), and within this is the viral core or capsid, which is made of another viral protein p24 (core antigen).

3 The major elements contained within the viral core are: - two single strands of HIV RNA - a protein p7 (nucleocapsid) - three enzyme proteins p51 (reverse transcriptase) p11 (protease) p32 (integrase)

4 HIV Replication HIV has a diameter of 1/10,000 of a millimetre. HIV belongs to class of viruses called retroviruses These have genes composed of ribonucleic acid (RNA) molecules. Retroviruses, like all viruses, can only replicate within a living host cell because they contain only RNA and they do not contain DNA. Retroviruses use RNA as a template to make DNA.

5 Infection begins when HIV particle encounters a T-Helper cell with a surface molecule called CD4. Virus particle uses gp120 to attach itself to the cell membrane Then enters the cell. Within cell, virus particle releases its RNA The enzyme reverse transcriptase then converts the viral RNA into DNA.

6 New HIV DNA moves into the cell's nucleus With the help of the enzyme integrase its then inserted into the host cells DNA. Once in the cell's genes HIV DNA is called a provirus. The HIV provirus is then replicated by the host cell, which can then release new infectious virus particles.

7 Origins of HIV 1). Simian Virus HIV part of family of viruses – Lentivirusus Lentiviruses found mainly in non human primates Primate Lentiviruses collectively known as Simian (monkey) viruses (SIV) Simian immunodeficiency virus (SIV) HIV accepted as a descendant of SIV HIV – 1 corresponds to SIV in green monkey HIV – 2 corresponds to SIV in chimpanzee

8 2). Crossed species? Virus crossed from chimps to humans Zoonosis – transfer of virus from animals to humans e.g. Eating chimp for food Iatrogenic transfer (via medical experiments) - Oral polio vaccine Chat. Grown in chimp kidney cells in Congo. Contamination of vaccine with chimp SIV - Vaccine given to 1x10 6 people in Belgium Congo, Ruanda and Urundi

9 Transmission of HIV Cannot survive dry conditions. No air transmission, body fluids only Blood Products Drug Misuse Sexual Transmission Mother to child transmision- pregnancy - labour and delivery - breastfeeding

10 HIV Subtypes 2 types of HIV: - HIV-I, predominant type - HIV-2, less easily transmitted Both HIV-I and HIV-2 transmitted by: - sexual contact, through blood, and from mother to child They appear to cause clinically indistinguishable AIDS. However, HIV-2 is less easily transmitted Period between initial infection and illness is longer in the case of HIV-2.

11 HIV-I mutates readily HIV-I has many different strains Strains classified into 2 groups: - Group M - 10 distinct subtypes (A-J) - Group O - other subtypes Subtypes differ in: 1.Mode of transmission subtype B – homosexual contact / intravenous drug use subtype E / C – heterosexual transmission

12 2.Genetic composition 3.Subtype distribution B;Americas, Japan, Australia, Europe A,D;Africa C;South Africa, India E;Central Africa, Thailand, Asia F;Brazil, Romania G,H;Russia, Central Africa I;Cyprus O;Cameroon

13 The Groups of Antiretroviral Drugs There are three main groups of anti-HIV drugs. Each of these groups attacks HIV in a different way. - Reverse Transcriptase Inhibitors - Protease Inhibitors - Fusion or Entry Inhibitors

14 Reverse Transcriptase Inhibitors 2 Types: (a) Nucleoside Reverse Transcriptase Inhibitors (b) Non-Nucleoside Reverse Transcriptase Inhibitors

15 Nucleoside Reverse Transcriptase Inhibitors First type of drug available to treat HIV infection (1987) HIV needs enzyme reverse transcriptase to be able to infect healthy cells and reproduce itself in a person's body. NRTIs: - inhibit reverse transcriptase. - drugs slow down the production of the reverse transcriptase enzyme - make HIV unable to infect cells and duplicate itself.

16 Non Nucleoside Reverse Transcriptase Inhibitors Drugs started to be approved in 1997 These drugs also stops HIV from infecting cells by intervening with the trancriptase of the virus. The non-nucleoside drugs work slightly differently from the nucleoside analogues They bind in a different way to the cell's reverse transcriptase. The non-nucleoside drugs block the duplication and the spread of the HIV.

17 Protease Inhibitors The third type of antiretrovirals. Inhibit protease. Almost every living cell contains protease. Protease is a digestive enzyme that breaks down protein and is one of the many enzymes that HIV uses to reproduce itself. The protease in HIV attacks the long healthy chains of enzymes and proteins in the cells and cuts them into smaller pieces.

18 The infected smaller pieces of proteins and enzymes continue to infect new cells. Protease inhibitors (PI) take effect before the protease in HIV has the chance to break down the protein and enzymes. The PI slow down the duplication of the virus and so prevent infection of new cells. The NRTIs and NNRTIs only have an effect on newly infected cells. PI are able to slow the process of immature non- infectious virus becoming mature and infectious. PI also work in cells that have been infected for a long time, by slowing down the reproduction of the virus.

19 Fusion or Entry Inhibitors Fourth group of antiretrovirals called Fusion or Entry Inhibitors. These drugs have yet to be approved and are currently going through clinical trials in the UK and the USA. The surface of HIV carries proteins called gp41 and gp120. These are the proteins, which allow HIV to attach itself to, and enter into cells. By blocking one of these proteins, fusion inhibitors slow down the reproduction of the virus.

20 For example, T-20, the fusion inhibitor that is closest to approval, sticks to the protein gp41. The T-20 fusion inhibitor differs from the other antiretrovirals in that it needs to be injected. T-20 is a protein and cannot be taken orally, since it would be digested in the stomach. It is hoped that the results from the T-20 trials across the USA and Europe will completed and returned to the Federal Drug Agency (FDA) by autumn 2002.

21 Progression of HIV Acute retroviral syndrome – flu, cough, rash Asymptomatic phase – 5-6 years Symptomatic phase – AIDS Opportunistic infection – Pneumonia, cancers