1 Introduction
Human Immunodeficiency Virus (HIV), the causative agent in AIDS, has been a cause of serious concern to the medical personnel ever since it was first discovered (Barri–Sinnoussi et al., 1983; Gallo et al., 1983). There are two types of HIV, HIV 1 and HIV 2 which was discovered in 1986 (Clavel et al., 1986) and are differentiated based on the geographical origin and the pathogenicity where HIV 2 is considered as less pathogenic when compared to HIV 1. A series of case observations were made in the late 1970’s where young sexually active adults have been found to be suffering from skin lesions caused by Kaposi’s sarcoma (Centre for Disease Control, 1982b). The first description of the disease was done in 1981 even before its discovery when it was observed that a group of homosexual men who were previously healthy have been suffering from a combination of Pneumocystis carinii Pneumonia (now termed as Pneumocystis Jiroveci Pneumonia), oral thrush and chronic ulcerating peri-anal herpes viral infection (Siegal et al., 1981; Gottlieb et al., 1981b). These reports were followed later by cases of Pneumocystis Jiroveci Pneumonia and cryptosporidiosis in haemophiliacs in 1982 (Eyster  et al., 1982). Further reports of lymphadenopathy and severe dysfunction of cellular immunity have evolved in haemophiliacs in 1983 which have initiated a serious discussion on whether a virus that is responsible for such condition is transmitted through blood transfusions (Goldsmith  et al., 1983). It was hypothesized that a variant of Human T-Lymphocytotropic virus (HTLV-1) which also has the ability to infect CDT+ cells and shares similar transmission routes may be responsible for AIDS. Human Immunodeficiency Virus (HIV) is a retrovirus belonging to the Lentivirus group that also consists of Simian Immunodeficiency Virus (SIV) that causes AIDS in monkeys and have the ability to cause chronic infections (Zachary Ende et al., 2011). The origin of HIV is speculated by many researchers, some proposing it to have been evolved in 1950’s and 1960’s, others reporting on its evolution way back in 1880~1930 and was associated with urbanization of the African city Kinshasa of the democratic republic of Congo (Zhu et al., 2008; Worobey et al., 2008). Studies have also hypothesized that HIV might have originated from contaminated polio vaccine (Worobey et al., 2004). Evolutionary studies have demonstrated the presence of HIV type 1 (HIV-1) and HIV type 2 (HIV-2) that have separately evolved from viruses due to cross-species transmission that have been naturally infecting African non human primates (NHP), the SIV (monkeys) and SIV sm (sooty mangabeys) respecttively with different pathogenic consequences (Worobey  et al., 2010). Studies have confirmed that the natural infections of SIV in non human primate hosts (NHP) is relatively non pathogenic and the infected monkeys live their natural life span where as the reason for HIV that has evolved from various SIV’s is more pathogenic and result in AIDS in human remains a medical mystery (Sharp and Hahn, 2010). 

2 Complex Pathology of HIV disease
Experimental infections with HIV and SIV in human and non human primate hosts (NHP) revealed that at acute stages the plasma viral load remains almost the same in human as well as the NHP, where as in the later stages the plasma virus in human varied in different population where the plasma viral loads stabilizes at high set point, people progress faster towards AIDS and the population with low plasma viral load set point progress slowly (Picker et al., 2006). Other factors including the declining viral replication and the persistence of generalized immune activation may contribute to progressive immune dysfunction (Zachary Ende et al., 2011). Such trend was not observed in NHP and the exact mechanisms contributing to non progression is still not understood. Studying these mechanisms by which the NHP hosts are remaining non progressor’s will pave the way for better understanding of HIV pathogenesis and open the doors for better treatment and vaccine developments. Previous studies have confirmed the occurrence of opportunistic infections (OI’s) with bacteria, fungi, parasites and viruses in HIV infected individuals when CD4T+ cell counts fall below 200cells/mm³ (Ramana andMohanty, 2009). Studies have also highlighted the role of HIV infection in the development of carcinogenesis. Recently there have been many studies from around the globe establishing the role of HIV in the development of haematological, biochemical and metabolic disorders (Ramana et al., 2010; Ramana et al., 2012).

3 HIV disease diagnosis, treatment and management
It has been thirty years since the discovery of HIV and we still are plagued with many unsolved puzzles in the diagnosis, treatment and management of HIV infected individuals. Though a lot has improved in the laboratory diagnosis of HIV with the advent of newer generation detection methods, that considerably reduce window period, the cause of concern now is the effect of Highly Active Antiretroviral therapy (HAART), and the management of patients on HAART. A combination of three or more antiretroviral drugs belonging to different classes of chemotherapeutic agents used to treat HIV infected patients is termed as HAART. As more than 90% of the world’s population infected with HIV reside in poor, developing and financially constrained countries, HAART has been introduced late in 2003 as in India (Vajpayee and Mohan, 2011). It becomes really important to closely monitor patients on HAART as there might be possibility that the high turnover rate of HIV along with the error-prone reverse transcriptase leads to steady accumulation of resistance mutations if the viremic suppression is incomplete. Since the introduction of HAART, there has been a steady decrease in the mortality of HIV infected population. The cause of concern now is the association of HAART with conditions like Immune reconstitution inflammatory syndrome, cardiovascular complications and other metabolic disorders (Crum-Cianflone, 2006). Gastrointestinal and hepatic emergencies, pulmonary illness, psychiatric ailments, hematological, neurological, renal and oncological complications have been on the rise among HIV infected patients more so after initiation of HAART therapy (Friis-Moller, 2007).

Considering the fact that there is no available vaccine for HIV infection, and that HAART cannot clear the virus completely from the body, HIV remains a chronic infection where patients infected with HIV and those on HAART suffer from various virological, immunological and therapeutic complications. Right from the diagnosis, physicians involved in treatment of HIV infected individuals should closely monitor and regularly follow disease progression and treatment response. Monitoring the disease progression and the response to Highly Active Antiretroviral Therapy (HAART) is traditionally carried out using TCD4+ cell counts and HIV/RNA viral load. Many clinical and laboratory markers have been used to estimate disease progression in HIV1 infection. Markers of AIDS development include viral markers (plasma HIV RNA load, serum p24 Ag, serum anti p24 antibodies), Surrogate markers(antibodies against p17, gp 120, gp 41 and nef gene product) and nonspecific markers including CD4+T-cell counts, CD8+T-cell counts and Delayed Type Hypersensitivity test (DTH). Other Alternate markers include elevated serum β2microglobulin, neopterin (D-erythro-1’,2’,3’-trihydroprpylptrin), Dehydroepiandrosterone (DHEAS), serum cortisol and many others including CRP,ESR, serum albumin, Tumor Necrosis Factor (TNF), Interferon-γ, Interleukin-2 (IL-2), IL-4 . Biochemical parameters including Serum Albumin, Globulin, Serum Glutamate Oxaloacetae Transaminase (SGOT), Total protein, Total cholesterol, High density Lipoproteins (HDL), Low density Lipoprotein(LDL), Lactate Dehydrogenase (LDH), Creatine Kinase (CK/MB) and Gamma glutamyl transpeptidase (GGT) were also evaluated by some studies as useful markers to assess the disease progression and treatment response (Ramana , 2012;  Ramana et al., 2012a). Classically HIV disease progression is seen as a decline in CD4 cell counts and increase in the plasma HIV/RNA viral load. Many studies have evaluated certain alternate and cost effective biological markers that can be used to monitor HIV disease progression to AIDS and treatment response. Studies have also been carried out to predict death and time of progression to AIDS, in assessment of treatment adherence, reasons for therapeutic failure and development of drug resistance (Jerene et al., 2006).

4 Future of HIV diseases
HIV disease course is variable and is not the same in all infected population. HIV infected individuals may proceed slowly (10 years or more), intermediately (5~10 years) or rapidly (<5 years) towards AIDS and later to death. The pathophysiology of HIV is least understood but studies have confirmed the role of HIV in the development of many complication in various organs. It must be noted that as HIV disease pathogenesis is complex and has not been completely understood yet. HIV patient care should be multifaceted where the physicians treating such patients need to consider patient evaluation based on all such factors before and after initiation of HAART to effectively reduce morbidity and mortality. The government policies should concentrate on assessing the trends in HIV Seroprevalence in various demographic regions ensure easy and affordable access to HAART, improvement of information systems and access to low cost diagnostics, improving primary health care facilities and increasing the density of health care providers to improve patient outcome by establishing community based ART services.

5 Conclusion
Though there is a considerable decline in the mortality of HIV infected population after introduction of HAART, morbidity related to pharmacological toxicities remains as a big cause of concern. Studies now should concentrate on the effect of HAART in relation to the time of initiation, role of race, age, diet, presence of metabolic syndromes, co-infection with hepatotropic viruses, lifestyle, alcoholism, smoking and other demographic factors which may later prove to be potential risk factors for death in the management of HIV disease and treatment response. Physicians treating HIV infected patients should consider specific assessment for co morbidities and other related factors that could influence disease course before initiation of HAART and regularly monitor patients to initiate appropriate intervention strategies to achieve long term viral suppression and minimise consequences of drug toxicity. Expanded programmes for HIV screening, cost-effective strategies and analysis studies of antiretroviral therapy and treatment response, and genotypic resistance testing would be effective in future for making decisions on policies to be initiated for HIV disease management. HIV primary care should include wide range of prevention and treatment strategies including vaccination for Hepatitis A, B and others. The blue print for success in HIV treatment includes prompt diagnosis, initiation of therapy and retaining the patients under care.

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