While understanding the effect of HIV infection which causes immune deficiency or reduction of body's capability to fight various infections in human beings, a reminder of a system of body defence is a must. The most crucial and highly effective specific defence system is hosted in the blood where white blood cells are key cells in the fight against various diseases.

T Lymphocytes and B Lymphocytes together defend the body against all kinds of assaults the body is exposed to, at all times. Both T and B cells migrate from bone marrow, but T cells mature in thymus, where they develop special functions. Both kinds of lymphocytes when activated by antigen, multiply and change.

B cells develop into plasma cells, produce specific antibodies which trap and kill micro-organisms (bacteria mostly). This is called 'humoral immunity'. T lymphocytes are responsible for cell mediated immunity, very important defence against fungi, protozon, mycobacteria and virus.

T lymphocytes include helper T cells (CD4) and cytotoxic/ killer T cells (CD8). They release soluble factors lympho-kines (cytokines), can regulate humoral suppressor cells and can become memory cells. So, CD4 cell population is central in defending the body. It is the key cell and this is the cell HIV infects and destroys progressively.

Infection with HIV irrespective of type (HIV- 1 or HIV-2) sub-type and route of infection leads to protracted disease and depletion of CD4 cells in most cases resulting in AIDS. The rate of progression of disease depends upon viral characteristics on the one hand and host factors on the other hand and may take from 1 year to more than 15 years.

Cell free or cell associated HIV enters the body during high risk practices through any route via blood, semen and vaginal secretions where HIV is present in high concentration from an infected person. HIV infection is facilitated by presence of ulcerative and to a lesser extent non-ulcerative sexually transmitted infections.

HIV immediately targets on to cells displaying complementary receptors (CD4, CCR-5 and CXCR-4/fusin) which may be CD4 cells, resident macrophages or Langerhans cells depending upon the site of exposure. Virus gp 120 fits on the receptor like a lock and key system. Viral replication starts immediately after entry into the cell and dissemination occurs through circulatory and lymphoid systems.

During this stage HIV and HIV-infected cells reach the lymph nodes and other lymphoid tissues, where active immune response to viral antigens occurs and at the same time intense replication of virus occurs in activated T lymphocytes. This is a paradox because lympho-cytes are activated on account of infection and HIV replicates better in these activated cells.

The peak in number of virus expressing cells and spread of virus through out the lymphoid tissue precedes the increase in plasma viraemia i.e the virus in the blood. The virus spills over from lymph nodes. These phenomena occur during the first 2-3 week after infection and there is intense virus spreading during this period, so this period is called the stage of virus dissemination.

Clinically it coincides with flu-like illness and also known as acute HIV disease. There is significant fall in CD4 cells and viral levels may be as high as 106 to 107 viral copies/ml. The next stage is that of down regulation of viraemia.

This coincides with robust, intense immune response by the host. Both effective cell mediated immune response carried out by HIV specific cytotoxic T lymphocytes (CTL) and humoral response carried out by complement fixing and neutralizing HIV specific antibodies comes into play.

The period from the entry of HIV in the host and appearance of detectable levels of HIV specific antibodies is called 'Window period'. During this period an individual is infected and is infectious to others but is seronegative i.e HIV test for detecting antibodies are negative and as such they should avoid risk behaviour, avoid donating blood or organs/tissues etc during this period.

Windows period range from 3 weeks to 3 months on an average and can be longer sometimes. Upto 30% to 50% infected people have a recognizable acute illness at the time of infection characterised by fever, lymphadenopathy (enlargement of lymph nodes), night sweats, skin rash, headache and cough.

Both HIV specific antibodies and CTL kill the virus infected cells. As a result the viraemia drops and CD4 cells bounce back to levels slightly lower than the previous normal level. Most of the virus trapping and killing occurs in Follicular Dendritic Cells (FDC) of lymph nodes and lymphoid tissue. This may be one reason of generalised lymphadenopathy seen in HIV disease.

Appearance of neutralizing HIV specific antibodies heralds the transition from acute to chronic stage of HIV disease. Although the immune response succeeds in down regulating the viraemia, HIV is never completely eliminated and progression to chronic phase of HIV disease occurs in most cases. What determines the progression of HIV disease is the quality of T cell response which may be genetically determined.

The stage, clinically latent period/chronic illness is marked by disappearance of symptoms of acute viral disease, down regulation of viraemia, CD4 cell count becomes almost normal and the neutralizing and complement (C') fixing virus specific antibodies appear in the blood. All virological parameters in the peripheral blood (viral RNA copies/viral load, virus expressing mono nuclear cells etc) are very low.

However, active and continuous virus replication goes on in the lymph nodes and lymphoid organs which express virus 1-3 logs higher than the peripheral blood. As long as the CD4 counts are higher than 500 cells/ul, the immune response mounted by the lymphoid tissues is effective, there is follicular hyperplasia of germinal centres indicating immune activation of lymph nodes.

The important paradox to note is that cellular activation seen in lymph nodes is critical for viral replication i.e virus replication is better in activated CD4 cells. There is gradual reduction in number of CD4 cells and increase in virus load during the long asymptomatic stage.

Increase in virus load in peripheral blood indicates failure of an progressive deterioration of effective immune response. HIV-infected people may remain asymtomatic for a length of period as long as 10 or more years. People in these phase potentially play an important role in the transmission of HIV as they remain infectious and can be identified only by screening their serum for HIV antibodies.

However, humoral immunity is intact during the asymtomatic stage that is specific antibodies are produced against different viral proteins, but the antibodies are not protective, are not to able to interfere with cell to cell transmission and infectivity of virus on account of constant variation of virus. This period on an average lasts for 8-10 years.

Progressive impairment of HIV specific and non-specific cell mediated and humoral immune responses heralds the onset of AIDS. The CD4 cell counts range between greater than 200 to 500 cells/ul in peripheral blood.

Advanced stage of HIV infection so called AIDS (Acquired Immune Deficiency Syndrome) is characterised by increase in all virological parameters (virus load, p24 nitrogen etc) in both peripheral blood and lymph nodes. Lymphoid tissue is totally destroyed and replaced by fibrous tissue.

Virus trapping by whatever lymphoid tissue remains is minimal or nil. Rate of progression to AIDS are influenced by plasma viral load and CD4 T cell count. The higher the viral load (the amount of virus in the body) the lower the CD4 count and the higher the chances of progressing to AIDS and death.

There is profound immune suppression and opportunities infections may prove fatal at this stage. Consequent to sufficient immune damage, susceptibility to opportunistic infections and cancers increases. The CD4 count is usually less than 200 cells/ul and progressively falls.

CD4 cells are the main targets of HIV and progressive destruction of these cells is characteristic of all stages of HIV disease. CD4 cells serve as surrogate markers to monitor the progression of HIV infection. These cells can be destroyed by two mechanism.
i) Direct damage by the virus.
ii) And immune mechanisms triggered during the course of HIV infection.

HIV can kill cell singly or after giant cell and syncytia formation. Single cell killing occurs due to accumulation of unintegrated viral DNA and inhibition of cellular protein synthesis. Syncytium formation is induced by virulent strains of HIV in a multi-step mechanism.

CD4 cells expressing viral antigens on the surface attract CD4 uninfected cells and the membrances of these fuse producing giant cells and syncytia. One such HIV infected cell can eliminate hundreds of uninfected cells by syncytium formation. Glycoprotein 120 and other intracellular adhesion molecules bring about the cellular adhesion and subsequent damage.

The non-virolic mechanisms which can danger or destroy CD4 cells include auto-immune mechanisms, anergy, supe-rantigens, apoptosis (programmed cell death) and virus specific immune responses.

The course of progression of HIV infection are of three dominant patterns of HIV disease progression based upon the kinetics of immunologic and virologic events:
i) 80% to 90% of HIV infected are typical progres-sors with a median survival time of 10 years approximately.
ii) 5% to 10% of HIV infected individuals are rapid progressors with a median survival time of 3-4 years approximately and
iii) About 5% of HIV infected individuals do not experience disease progression for an extended period of time, may be 15 years or more without any therapy and are called long -term non progressors.

However, nowadays, there are ways in which people living with the virus can live relatively long, healthy and productive lives if they know their HIV status and take personal care. It is true that early detection and diagnosis of HIV followed by proper medical treatment, care and support increases the chance of living longer and better, healthy and productive lives for those who test HIV positive. The vision will significantly reduce the barriers of stigma associated with HIV and will make a significant impact on prevention of HIV/AIDS in our country.

Since AIDS was first recognised 20 years ago, a remarkable progress has been made in improving the quality and duration of life for HIV infected persons living in the world. During the first decade of the epidemic, this improvement occurred because of improved recognition of opportunistic disease process, improved therapy of acute and chronic complications, and introduction of chemoprophy laxis against key opportunities pathogens.

The second decade of the epidemic has witnessed extra-ordinary progress in developing combined anti-retroviral therapies (ART) as well as continuing progress in preventing and treating OIs (Opportunistic infections). ART has reduced the incidence of OIs and thus extended life substantially.

However, admittedly anti-retroviral regimens inhibit the efficient replication of the HIV virus, and reduces Viraemia to undetectable levels. Lower frequency of opportunistic infections significantly reduces the cost of management of HIV. This helps people lead more productive lives, with perceptibly reduced stigma and discrimination.

Successes achieved in terms of ART delaying the onset of AIDS, has now transformed the common perception about HIV from being an immediately fatal scourge to somewhat more manageable chronic illness, although devastating debilitating in the long run. Both HIV- I and HIV-2 are found in India, although the majority of infections (91%) are for HIV-I subtype C. HIV in India is overwhelmingly transmitted heterosexually.

Transmission for HIV due to right risk factors for HIV infection also include multiple homosexual partners. The other known routes of transmission are through contaminated blood and blood products, used of unsterilised syringes by injecting drug users (IDUs) and perinatal transmission.

NACO coordinates, each year a sentinel surveillance of HIV and the primary data obtained is used as much for discerning trends as for estimating numbers of people living with HIV.

According to the 2006 UNAIDS (United Nations Program on HIV/AIDS) report on the global AIDS epidemic, an estimated 65 million people have been infected with HIV, of whom some 25 million have died since the start of the epidemic 25 years ago.

The rate of new HIV infections continues to climb every year, with an estimated 4.1 million people having been infected in the twelve months ending December 2005. However, it is estimated that 5.026 million people are now living with HIV/AIDS in India. In India, women make up nearly 40% of the total number of people now living with the virus.

In Manipur, out of 1,65,747 blood samples screened upto September 2006, the total number of HIV positive is 24,198 out of this, 5491 are women.

In fact AIDS is increasingly affecting young people in the sexually active age group. The majority of the HIV infections (87.7%) are in the age group 15-44 years. The predominant mode of transmission of the HIV infection in NE states is through the use of unsterilised needles and syringes by Injecting Drug Users.

To conclude, at this stage of the global AIDS epidemic, there are more HIV infections every year than AIDS related deaths.

The National AIDS Control Programme Phase-III (NACP - III, 2007-2012) aims to support the Govt of India in achieving its goal of halting and reversing the HIV/AIDS epidemic by 2012 through integration of prevention and care, support and treatment programs.