PROVIDE INFORMATION OF THE IL-2 LEVELS IN VIROLOGICALLY SUPPRESSED HIV INFECTED INDIVIDUALS AND ITS POTENTIAL FOR TREATMENT OF HIV INFECTION

CHAPTER ONE

INTRODUCTION

The human immune deficiency viruses (HIV) are two species of lentivirus (a sub group of retrovirus) that causes HIV infection and over time acquired immune deficiency syndrome (AIDS). AIDS is a condition in humans in which progressive failure of the immune system allow life threatening opportunistic infection and cancers to thrive.(UNAIDS and WHO, 2007). Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both Lymphadenopathy associated virus (LAV) and human T- lymphotropic virus 3 (HTLV-III). HIV-1 is more virulent and more infective than HIV-2, (Glibert et al, 2003) and the cause of the majority of HIV infections globally. The lower infectivity of HIV-2, compared to HIV-1, implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission HIV-2 is largely confined to West African (Reeves and Doms, 2002).

       In must cases, HIV is a sexually transmitted infection and occurs by contacts with or transfer of blood, pre ejaculate Semen and vaginal fluid. Research has shown (for both same sex and opposite- sex couples) that HIV untransmissable through condomless sexual intercourse if the Hiv positive partner has a consistently undetectable viral load. (Rodger et al, 2009; Eisinger et al, 2019) contaminated blood transfusions, hypodermic needle and from mother to child during pregnancy, delivery or breastfeeding (Rom and Markowitz, 2007). Some body fluids, such as saliva and tears do not transmit HIV (CDC, 2006).

       The HIV attacks the body’s immune system specifically the CD₄ cells (T cell), which helps the immune system fight off infections. Untreated, HIV reduces the number of CD₄ cells (T cell) in the body, making the person more likely to get other infection, or infection related cancers. Over time, HIV can destroy so many of these cells that the body can’t fight off infections and disease. These opportunistic infections or cancer take advantage of  a very weak immune system and signal that the person has AIDs, the last stage of HIV infection (CDC, 2017).

       In topical and low income countries, HIV disease and AIDS is a major public health problem, socio-economic burden, and a serious treat to development. At the end of 2008, the joint United Nation program on HIV/AIDS (UNAIDS), estimated that globally there were 33.4 million of people living with HIV/AIDS. An estimated 2.7 million new infections, occurred, 2.3 million being adults and 430,000 been children under the age 15 years. About 67% of the total number of infected people live in sub-Saharan African an estimated 2.0 million deaths occurred during 2008.

       As of 2017, approximately 36.9 million people are infected with HIV globally, in 2018, approximately 43% are women. There were about 940,000 death from AIDs in 2017 (UNAIDS org, 2018).

       The management of HIV/AIDS normally include the use of multiple antiretroviral drugs in an attempt to control HIV infection. There use of multiple drugs that acts on different viral target is known as highly active antiretroviral therapy (HAART). HAART decreases the patient’s total burden of HIV maintains function of the immune system and prevent opportunistic infections that often leads to death (Moore and Chaisson, 1999). Highly active antiretroviral therapy (HAART) has resulted in more effective suppression of HIV replication and a slowing of slowing of immune deterioration. Evidence of immune restoration has been observed in patients who respond to HAART, even in those with advanced disease, (Mitsuyasu, 1999). However, complete restoration of immunity has not been observed. Consequently, as viral resistance to ARV therapy develops, further immune deterioration ensues.

A new paradigm for HIV therapy incorporates the use of immune stimulants that can help to expand the immune repertoire and enhance HIV-specific immunity. Such therapies are expected to delay HIV disease progression and decrease the occurrence of opportunistic infection/disease. Immune-based therapy was founded on the premise that stimulation of HIV- and pathogen-specific immunity will facilitate immune reconstitution and delay disease progression. Immune stimulation may also provide an opportunity for developing strategies to reduce or eliminate CD4+ memory cells with latent HIV infection. These cell may represent a major reservoir for HIV in HAART-treated individuals (Siliciano 1999; Chun et al, 1997 and Finzi et al, 1997). Several strategies for reducing the number of latently infected cells have been proposed including the use of DNA synthesis inhibitors (e.g., hydroxyurea), gene therapy, enhancement of HIV-specific immunity by massive immune activation with agents such as human ril-2, anti-CD3, multiple vaccination, and granulocyte-macrophage colony-stimulating factor, and other approaches, which may be implemented in the presence of cytotoxic therapies or suppressive ARV treatments (Saag and Kilby, 1999). Enhancement of immune restoration over and above that achievable with ART alone, using a number of strategies including cytokine therapy, has been of interest for many years. The most studied cytokine in this setting is recombinant interleukin (IL)-2 (rILn-2).