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).