Chair of Microbiology Virology and Immunology Human Immunodeficiency

Chair of Microbiology, Virology, and Immunology Human Immunodeficiency Virus

The first indication of new disease – Acquired Immunodificiency Syndrom (AIDS) began, when reports came from great cities of USA (New York, Los Angeles, San Francisco) of a sudden increase in the incidence of two very rare diseases: Ш 1981 - 5 cases of Pneumocystis carinii pneumonia in 8 months in young homosexuals ((before described as epidemics at the closed children’s establishments, 1967 to 1979 treatment was sought for 2 cases). Ш 1981 - In 30 months time 26 cases of Kaposi’s sarcoma in young They appeared to have lost their immnune competence, rendering them vulnerable to overwhelming and fatal infections with relatively avirulent microorganisms, as well as to lymphoid and other malignancies.

Kaposi’s Sarcoma Pneumocystis carinii

Ш New retrovirus from Lymphadenopathy in a homosexual in 1983 Prof. Luc Montagnier Pasteur institute, Paris named Lymphadenopathy Associated Virus (LAV) Ш Dr. Robert Gallo, National Cancer Institute confirmed that a retrovirus was the causative agent of AIDS in 1984, named HTLV-III (Human T-lymphotropic Virus). LAV = HTLV-III (Gallo et. al) Human Retroviurs subcommittee of the International committee on taxonomy of viruses (ICTV) recommended the name Human Immunodeficiency virus (HIV).

1986 - One HIV was isolated from a west African patient in Pasteur Institute. 1986 - Another HIV was isolated from a patient from Senegal in Harvard School of Public health. Difference antigenicity and clinical manifestations between Western HIV and African HIV. Human retrovirus sub committee on taxonomy of viruses (ICTV) subsequently recommended that HIV-isolated from western patient to be named-HIV-1. HIV isolated from African patient was named HIV-2 (1986).

A. I. D. S. stands for Acquired Immunodeficiency Syndrome. Ш Acquired – means that the disease is not hereditary but develops after birth from contact with a disease causing agent (in this case, HIV). Ш Immunodeficiency – means that the disease is characterized by a weakening of the immune system. Ш Syndrome – refers to a group of symptoms that collectively indicate or characterize a disease.

A global view of HIV infection 33 million people [30– 36 million] living with HIV, 2007 Children (<15 years) estimated to be living with HIV, 2007 2. 0 million (1. 9 – 2. 3 million) More than 25 million people died of AIDS since 1981 and AFRICA has more than 12 million orphans

Over 7400 new HIV infections a day in 2007 ØMore than 96% are in low and middle income countries ØAbout 1000 are in children under 15 years of age ØAbout 6300 are in adults aged 15 years and older of whom: — almost 50% are among women — about 45% are among young people (15 -24)

Regional HIV and AIDS statistics and features, 2007 Adults & children living with HIV Sub-Saharan Africa Middle East & North Africa South and South-East Asia 380 000 40 000 [280 000 – 510 000] [20 000 – 66 000] 4. 2 million [3. 5 – 5. 3 million] 330 000 [150 000 – 590 000] 740 000 Latin America 52 000 [29 000 – 84 000] 1. 7 million 140 000 [1. 5 – 2. 1 million] [88 000 – 190 000] 230 000 Eastern Europe & Central Asia Western & Central Europe North America 20 000 [210 000 – 270 000] Caribbean TOTAL 1. 9 million [1. 6 – 2. 1 million] [480 000 – 1. 1 million] East Asia Oceania 22. 0 million [20. 5 – 23. 6 million] Adults & children newly Adult prevalence (15‒ 49) [%] infected with HIV [16 000 – 25 000] 1. 5 million 110 000 [1. 1 – 1. 9 million] [67 000 – 180 000] 730 000 27 000 [580 000 – 1. 0 million] [14000 – 49 000] 1. 2 million [760 000 – 2. 0 million] 54 000 [9600 – 130 000] 74 000 13 000 [66 000 – 93 000] [ 12 000 – 15 000] 33 million 2. 7 million [30 – 36 million] [2. 2 – 3. 2 million] 5. 0% [4. 6% – 5. 4%] 0. 3% [0. 2% – 0. 4%] 0. 1% [<0. 1% – 0. 2%] 0. 5% [0. 4% – 0. 6%] 1. 1% [1. 0% – 1. 2%] 0. 8% [0. 6% – 1. 1%] 0. 3% [0. 2% – 0. 4%] 0. 6% Adult & child deaths due to AIDS 1. 5 million [1. 3 – 1. 7 million] 27 000 [20 000 – 35 000] 340 000 [230 000 – 450 000] 40 000 [24 000 – 63 000] 63 000 [49 000 – 98 000] 14 000 [11 000 – 16 000] 58 000 [41 000 – 88 000] 8000 [4800 – 17 000] 23 000 [0. 4% – 1. 0%] [9100 – 55 000] 0. 4% [0. 3% – 0. 5%] [<1000 – 1400] 0. 8% [0. 7% - 0. 9%] The ranges around the estimates in this table define the boundaries within which the actual numbers lie, based on the best available information. 1000 2. 0 million [1. 8 – 2. 3 million]

HIV, the etiologjcal agent of AIDS, belongs to the lentivirus subgroup of the family Retroviridae. The Lentivirus subgroup (L. lentus = slow) includes the causative agents of the slow virus diseases visna/maedi in sheep and others. Besides HIV, the related animal immunodeficiency viruses also are assigned to this group. HIV-1 isolated in 1984, and HIV-2 in 1986

Human Immunodeficiency Virus Knob engages CD 4 receptor on lymphocyte; virus carries preformed RT and integrase enzymes; 107 particles/m. L; 0 billion made per day as opposed to 2 billion CD 4 cells/day 12

HIV-1 Virion

HIV can be inactivated by - Boiling-water in seconds (<Minute) - 70% Ethanol - 2% Glutaraldehyde - 1% House hold bleach (available in the market as 3. 5%) - Soap and Water - 5% Formaldehyde - 10% Sodium hypochlorite - 3% Hydrogen peroxide - 35% Isopropyl alcohol - 0. 5% Lysol - 2. 5% Tween-20 30 minutes

Viral genes and antigens. The genome of HIV contains the three structural genes (gag, pol and env) characteristic of all retroviruses, as well as other nonstructural and regulatory genes specific for the virus. The products of these genes, both structural and nonstructural, act as antigens. Sera of infected persons contain antibodies to them. Detection of these antigenes and antibodies is of great value in the diagnosis and prognosis of HIV infections. Ø Genome consists of 9200 nucleotides (HIV-1): Ø gag core proteins - p 15, p 17 and p 24 Ø pol - p 16 (protease), p 31 (integrase/endonuclease) env - gp 160 (gp 120: outer membrane part, gp 41: transmembrane part) Ø Ø Other regulatory genes ie. tat, rev, vif, nef, vpr and vpu

PATHOGENESIS

Types (Genotypes) of HIV Virus Types ( Ø HIV 1 Ø Ø Most common in sub-Saharan Africa and throughout the world Groups M (Main), N (New), and O (Outlayer) Ø Pandemic dominated by Group M Ø Group M comprised of subtypes A – K Ø Recombinant forms - AE, AG, AB, DF, BC, CD Ø As yet, different HIV-1 genotypes are not associated with different courses of disease nor response to antiviral therapy. Ø HIV 2 Most often found in West Central Africa, parts of Europe and India Ø

Virus travels through Bloodstream HIV attacks t-cells Killer T-cells destroy affected cells AIDS virus attaches to a CD 4 receptor Transcription Reverse Transcription Proteins cut and packaged with RNA Possible Infections Budding new viruses

HIV Life Cycle Reverse Transcriptase HIV RNA Protease RNA CD 4 RNA CCR 5 RNA DNA Nine (9) genes in the virus; uses nucleotides in cell to make DNA CD 4 T -Lymphocyte RNA RNA Proviral DNA Enveloped virus; Will not survive in the environment

Fig. 20. 24

PATHOGENESIS 1) PRIMARY INFECTION 2) LYMPHOID INFECTION 3) ACUTE SYNDROME 4) IMMUNE RESPONSE 5) LATENCY 6) AIDS

Pathogenesis of AIDS Ш A great number of different abnormalities of the immune system are seen in AIDS. Ш As a result of the biology of lentivirus infections, the pathogenesis of AIDS is highly complex. Ш These mechanisms are not mutually exclusive & it is probable that the underlying loss of CD 4+ cells in AIDS is multifactorial 'Trojan horse' mechanism - virus escapes recognition by replication inside monocytes, from where it can spread to other tissues and other hosts.

Direct Cell Killing: Ш Cell fusion resulting in syncytium formation is one of the major mechanisms of cell killing by HIV in vitro. Indirect Killing of HIV-Infected Cells: Ш Indirect effects of infection, e. g. disturbances in cell biochemistry and cytokine production, may also affect the regulation of the immune system. Ш However, the expression of virus antigens on the surface of infected cells leads to indirect killing by the immune system - effectively a type of autoimmunity. Ш The extent of this activity is dependent on the virus load and replication kinetics in infected individuals. Antigenic Diversity ШThis theory proposes that the continual generation of new antigenic variants eventually swamps and overcomes the immune system, leading to its collapse.

T-Cell Anergy: Ш Ш Ш Anergy is an immunologically unresponsive state in which lymphocytes are present but not functionally active. This is usually due to incomplete activation signals and may be an important regulatory mechanism in the immune system, e. g. tolerance of 'self' antigens. In AIDS, anergy could be induced due to HIV infection, e. g. interference with cytokine expression. There is experimental in vitro evidence that gp 120 -CD 4 interactions result in anergy due to interference with signal transduction. Many AIDS patients are anergic, i. e. fail to mount a delayedtype hypersensitivity (DTH) response to skin-test antigens. Impaired DTH responses are directly related to decreasing CD 4+ T-lymphocyte counts.

Apoptosis: Ш Ш Ш Like T-cell anergy, apoptosis could potentially be induced in large numbers of uninfected cells by factors released from a much smaller number of HIV-infected cells. In addition to clonal deletion as a normal part of the evolution of the T-cell repertoire, apoptosis may be induced following T-cell activation as a negative regulatory mechanism to control the strength and duration of the immune response. HIV infection of T-cells induces an activated phenotype, e. g. surface expression of CD 45 and HLA-DR markers, which suggests that these cells may be inevitably doomed due to activation of the apoptosis pathway. Because HIV establishes a persistent infection, it is by no means clear that apoptosis has an entirely negative effect - induction of cell death may well limit virus production and slow down the course of infection. Several HIV proteins have been identified as both inducers and repressors of apoptosis under various circumstances. However, the proportion of CD 4+ T cells in the later stages of apoptosis is about twofold higher in HIV-1 infected individuals than in uninfected people.

Superantigens: Ш Ш Ш Superantigens are molecules which short-circuit the immune system, resulting in massive activation of T-cells rather than the usual, carefully controlled response to foreign antigens. It is believed that they do this by binding to both the variable region of the b -chain of the T-cell receptor (Vb) and to MHC class II molecules, crosslinking them in a non-specific way. This results in polyclonal T-cell activation rather than the usual situation where only the few clones of T-cells responsive to a particular antigen presented by the MHC class II molecule are activated. The over-response of the immune system produced results in autoimmunity as whole families of T-cells which bind superantigens are activated, & immunosuppression as the activated cells are killed by other activated Tcells or undergo apoptosis. No superantigen has been conclusively identified in HIV, despite intensive investigation, thus the practical relevance of superantigens in AIDS is in doubt.

Superantigens:

TH 1/TH 2 Imbalance: u u u Immunological theory suggests that there are two types of CD 4+ T-helper (TH) cell: TH 1 cells which promote the cell mediated response and TH 2 cells which promote the humoral response. This theory suggests that early in HIV infection, TH 1 -responsive T-cells predominate and are effective in controlling (but not eliminating) the virus. At some point, a (relative) loss of the TH 1 response occurs and TH 2 HIVresponsive cells predominate. The hypothesis is therefore that the TH 2 -dominated humoral response is not effective at maintaining HIV replication at a low level and the virus load builds up, resulting in AIDS. Although this is largely a theoretical proposal which has not been proved, this thinking is shaping our understanding of the immune response to many different pathogens, not just HIV. However, no experimental study has demonstrated an actual switch from the TH 1 to TH 2 pattern of cytokine expression and secretion that is associated with disease progression, so there is no evidence for the involvement of these mechanisms in AIDS.

TH 1/TH 2 Imbalance

Virus Load & Replication Kinetics: Ø The average half-life of an HIV particle in vivo is 2. 1 days. Ø Up to 109 -1010 HIV particles are produced each day. Ø An average of 2 x 109 new CD 4+ cells are produced each day.

Some of the immune abnormalities in HIV infection include: Ø Altered cytokine expression Ø Decreased CTL and NK cell function Ø Decreased T-cell function Ø Decreased humoral and proliferative response to antigens and mitogens Ø Decreased MHC-II expression Ø Decreased monocyte chemotaxis Ø Depletion of CD 4+ cells Ø Altered monocyte/macrophage function Ø Impaired DTH reactions Ø Lymphopenia Ø Polyclonal B-cell activation It is not clear how much of the pathology of AIDS is directly due to the virus and how much is caused by the immune system itself. There are numerous models which have been suggested to explain how HIV causes immune deficiency:

Transmission Ш Sexual Ш Parenteral Ш Perinatal

Sexual Male Female · · · · Large surface area Higher concentration of HIV in semen Recipient of infectious material Menstruation Trauma is more frequent Dendritic cell Social cause

Route of Sexual Transmission

Factors increase the rate of HIV transmission in STD Ш Concentration of HIV is increased in sexual fluid. Ш Disruption of normal barrier of skin and mucus membrane.

Parenteral transmission ШBlood and blood product ШSyringe, needle, surgery, dentistry, tattooing ear-nose piercing, acupuncture, razor.

Perinatal ШIntrauterine Ш During delivery Ш Breast feeding

What body fluids transmit HIV Øblood Øsemen Øvaginal fluid Øbreast milk

You cannot become infected with HIV by: Ø Kissing, hugging or shaking hands Ø Sharing cups, glasses or knifes and forks Ø Using the same toilet

Clinical Chronology after exposure to HIV Ш Exposure Ш Incubation period Ш (Window period) Ш Acute infection Ш Carrier state Ш Constitutional symptoms Ш Opportunistic infections Ш Malignancy

Incubation period Ш 2 weeks to 12 weeks (Incubation period must not be confused with window period)

Window period Ш This period covers the terminal part of the incubation period. Longer incubation period shows longer window period. This period is associated with appearance of HIV but not anti-HIV in patient serum. So, the period of time from the date of infection until antibodies are produced. Time period ranges from 6 weeks to 6 months.

Evolution of Antibodies Window Period

Acute infection Following HIV transmission, approximately 50% of individuals will develop a febrile, flu-like illness with some or all of the following conditions: - Swollen glands - Rash - Oral ulcers - Muscle aches - Sore throat - Headache - Diarrhea - Nausea or vomiting

Asymptomatic infection All persons infected with HIV, whether they experience seroconversion illness or not, pass through a phase of symptom 1 ess infection; lasting for several months or years. They show positive HIV antibody tests during this phase and are infectious. In some, the infection may not progress any further, while in others it may lead to full brown AIDS, either directly or through cytopenias, minor opportunistic infection, persistent generalized lymphadenopathy or AIDS related complex (ARC) as described below.

Persistant Generalised Liphadenopathy (PGL) This has been defined as the presence of enlarged lymph nodes, at least 1, 0 cm, in diameter, in two or more noncontiguous extrainguinal sites, that persist for at least three months, in the absence of any current illness or medication that may cause lymphadenopathy. This by itself is benign but a proportion of the cases may progress to ARC or AIDS.

AIDS Related Complex (ARC) This group inc 1 udes patients with considerable immunodeficiency, suffering from various constitutional symptoms or having minor opportunistic infections. The typical constitutional symptoms are fatigue, unexplained fever, persistent diarrhea and parked weight loss of more than 10 per cent of body weight. The common opportunistic infections are oral candidiasis, herpes zoster, salmonellosis or tuberculosis. Generalized lyrnphadenopathy and splenomegaly are usually present. ARC patients are usually severely ill and many of them progress to AIDS in a few months.

AIDS This is the end stage disease representing the irreversible breakdown of immune defense mechanisms, leaving the patient a prey to progressive opportunistic infections and malignancies. The clinical severity of AIDS varies with the type of infection or malignancy present. In early AIDS, many patients are ill only during episodes of infection which may respond to treatment. Between episodes they may be relatively well and able to resume normal life.

Constitutional symptoms Ш Fever for >2 months Ш Diarrhoea for >2 months Ш Loss of weight > 10% of body wait within short period. Ш Night sweat Ш Loss of appetite Ш CD 4 cell count low Ш P 24 positive

Opportunistic infections of AIDS 1. Protozoal infections: a) Pneumocystis carinii b) Toxoplasma gondii c) Cryptosporidium d) Isospora belli e) Malaria

Opportunistic infections of AIDS 2. Fungal infections: a) Candida b) Cryptococcus c) Aspergillus

Opportunistic infections of AIDS 3. Bacterial infections: a) Mycobacterium b) Salmonella c) Pyogenic bacteria

Opportunistic infections of AIDS 4. Viral infections: a) Herpes simplex virus (HSV) b) Herpes zoster virus c) Cytomegalovirus (CMV)

Malignancy 1. Kaposi’s sarcoma 2. Non-hodgkin’s lymphoma

According to the system most affected patients present with various complaints, some of which are as follows: A. The commonest presentation is with increasing dry cough, dyspnea and fever. In the USA and other Western countries, the characteristic pathogen initially was P. carinii but now M. tuberculosis or an atypical mycobacterium such as M. avium-intracellulare is more often responsible. In the developing countries, the most important pathogen is M. tuberculosis, with many strains being multidrug resistant. In fact the poor nations are facing a double epidemic, jointly with HIV and tuberculosis. Pneumonia may be viral (CMV) or fungal (cryptococcus, histoplasma). Recurrent pneumonia is considered to be indicative of AIDS.

Pneumocystis carinii

Histoplasma capsulatum Cryptosporidium Cryptococcus neoformans (intestinal epithelium) (nervous system)

B. Gastrointestinal system. The mouth is often involved in AIDS, with thrush, herpetic stomatitis, gingivitis, Kaposi's sarcoma. Dysphagia may be due to esophageal candidiasis. A characteristic intestinal pathogen in AIDS is cryptosporidium. Salmonellae, mycobacteria, CMV or adenoviruses also frequently cause intestinal infections. Systemic strongyloidosis may occur. Chronic colitis is common in male homosexuals ( «gay bowel syndrome» ), from which ameba, lamblia and a host of diarrheagenic bacteria have been reported. Candidiasis

C. Central nervous system: The typical CNS opportunistic infections are toxoplasmosis and cryptococcosis. Infections are also seen with CMV, herpes simplex, papovaviruses, mycobacteria, aspergillus and Candida. Lymphomas of the central nervous system are common. D. Malignancies: Kaposi's sarcoma is the characteristic lesion seen in male homosexuals. It is an indolent multifocal nonmetastasising is mucosal or cutaneous tumor, probably of endothelial origin. The other tumors commonly seen are lymphomas, both the Hodgkin and non Hodgkin types. E. Cutaneous. Besides Kaposi's sarcoma, herpes lesions, candidiasis, xeroderma, seborrheic dermatitis, prurigo, folliculitis, impetigo and molluscum contagiosumn are common cutaneous lesions.

F. Dementia. HIV may cause direct cytopathogenic damage in tire central nervous system. It can cross the blood brain barrier and cause encepfialopathy leading to loss of higher functions, progressing to dementia. G. Pediatric AIDS. About one third to one half the number of babies born to infected mothers are infected with HIV. Many of them may not survive for a year. Children may also acquire the infection from b 1 ood transfusions or blood products. The definition of AIDS has since been broadened to include all seropositive persons (irrespective of clinical manifestations) with CD 4 T cell counts of less than 200 per mm 3.

Kaposi's sarcoma

Dermatomycosis Dermatitis Herpes zoster Herpes

Warts Sarcoma Еczema Herpetic infection

AIDS patients

Laboratory diagnosis Laboratory procedures for the diagnosis of HIV infection include tests for immunodificiency as well as specific tests for HIV. A. Immunological tests. The following parameters help to establish the immunodeficiency in HIV infection: l. Total leucocyte and lymphocyte count to demonstrate leucopenia and a lymphocyte count usually below 2, 000 /c. mm. 2. T cell subset assays. Absolute T 4 cell count will be usually less than 200/c. mm. T 4: T 8 cell ratio is reversed. 3. Platelet count will show thrombocytopenia. 4. Raised Ig. G and Ig. A levels. 5. Diminished CMI as indicated by skin tests. 6. Lymph node biopsy showing profound abnormalities.

B. Specific tests for HIV infection. These include demonstration of HIV antigens and antibodies and isolation of the virus. I. Antigen detection. The time course of appearance of detectable antigens and antibodies after НV infection is generally as follows: Following a single massive infection, as by blood transfusion, the virus antigens (p 24) may be detectable in blood after about two weeks. Ig. M antibodies appear in about 4 -6 weeks, to be followed by Ig. G antibodies. 2. Virus isolation. Once infected with HIV, a person remains infected for life. The virus is present in circulation and body fluids, mostly within the lymphocytes but some are also cell free. Virus titres are high early in infection, about a week before antibodies start appearing. Antibodies do not neutralize the virus and the two can coexist in the body.

Laboratory Diagnosis 3. Antibody detection. Demonstration of antibodies is the simplest and most widely employed technique for the diagnosis of HIV infection. Ø Ø Ø Serology is the usual method for diagnosing HIV infection. Serological tests can be divided into screening and confirmatory assays. Screening assays should be as sensitive whereas confirmatory assays should be as specific as possible. Screening assays - ELISAs are the most frequently used screening assays. The sensitivity and specificity of the presently available commercial systems now approaches 100% but false positive and negative reactions occur. Some assays have problems in detecting HIV 1 subtype O. Confirmatory assays - Western blot is regarded as the gold standard for serological diagnosis. However, its sensitivity is lower than screening ELISAs. Line immunoassays incorporate various HIV antigens on nitrocellulose strips. The interpretation of results is similar to Western blot it is more sensitive and specific.

ELISA for HIV antibody Microplate ELISA for HIV antibody: coloured wells indicate reactivity

Western blot for HIV antibody Ø There are different criteria for the interpretation of HIV Western blot results e. g. CDC, WHO, American Red Cross. Ø The most important antibodies are those against the envelope glycoproteins gp 120, gp 160, and gp 41 Ø p 24 antibody is usually present but may be absent in the later stages of HIV infection

Test-system for AIDS diagnosis

IMMUNOPROPHYLAXIS Types of HIV vaccines 1. Attenuated vaccines are made from genetically engineered strains lacking some crucial genes, so that the resulting virus causes a harmless infection. This approach has been tried successfully with simian immunodeficiency virus (SIV) 2. Killed virus vaccines. In humans, it has been proposed that vaccination with low doses of killed HIV enhances cellular immunity and favors (lie development of cell-mediated cytotoxicity. Evaluation is difficult because the end-point is a disease-free interval that is long and variable. 3. Recombinant viral particles made by inserting HIV glycoprotein genes in, for example, vaccinia-virus genomes induce neutralizing antibodies in animals. 4. Component vaccines have been prepared from isolated gpl 20, polymerized gpl 20, or gpl 20 peptides representing more conserved regions (such as the CD 4 -binding domain)

Therapy of HIV Infection: Ø Ø Ø Nucleoside-Analog Reverse Transcriptase Inhibitors (NRTI). These drugs inhibit viral RNA-dependent DNA polymerase (reverse transcriptase) and are incorporated into viral DNA (they are chain-terminating drugs). § Zidovudine (ZDV, Retrovir) first approved in 1987 § Didanosine (dd. I, Videx) § Zalcitabine (dd. C, Hivid) § Stavudine (d 4 T, Zerit) § Lamivudine (3 TC, Epivir) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). In contrast to NRTIs, NNRTIs are not incorporated into viral DNA; they inhibit HIV replication directly by binding non-competitively to reverse transcriptase. § Nevirapine (Viramune) § Delavirdine (Rescriptor) Protease Inhibitors. These drugs are specific for the HIV-1 protease and competitively inhibit the enzyme, preventing the maturation of virions capable of infecting other cells. § Saquinavir (Invirase) first approved in 1995 § Ritonavir (Norvir) § Indinavir (Crixivan) § Nelfinavir (Viracept) Ø Fusion inhibitors e. g. Fuzeon (IM only)

Prevention Ø Ø Ø The spread of HIV through blood transfusion and blood products had virtually been eliminated since the introduction of blood donor screening in many countries. AZT had been shown to be effective in preventing transmission of HIV from the mother to the fetus. The incidence of HIV infection in the baby was reduced by two-thirds. The management of health care workers exposed to HIV through inoculation accidents is controversial. Anti-viral prophylaxis had been shown to be of some benefit but it is uncertain what is the optimal regimen. ØThe risk of contracting HIV increases with the number of sexual partners. A change in the lifestyle would obviously reduce the risk. ØThe only methods which have strong evidence supporting their efficacy to protect against HIV infection are condoms and female condoms