Introduction:
HIV/AIDS is serious
health issue across the globe. HIV is exceptionally epidemic, target of HIV is
human line of defense i.e. our immune system. It has been seen that HIV/ AIDS
has high prevalence rate in developing states. Poverty, lack of community
education, hunger, lack of medical measurements, high illiteracy ratio are key
factors that triggered high incidence rates of HIV/ AIDS (Bhurgri, 2006).
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HIV
Structure:
HIV is a retrovirus,
categorized in separate genus lentiviruses and belongs to family Retroviridae. This
genus contains a large number of infectious agents particularly infecting
animals. Electron Microscopy reveals that HIV has core shaped, core is made up
of p25 (or p24) Gag protein (Leis et al., 1988). Nucleotide is in
form of 2 identical RNA strands within which reverse transcriptase is present (Gelderblom et al., 1987; Haase, 1986; Levy, 1986).
HIV
Genome information:
HIV is retrovirus, which
packs two copies of un-spliced RNA. Viral RNA as dimmer, both dimerization and
packing is mechanically coupled (Lu et al., 2011). It is believed
that due to cross specie events both HIV 1 and HIV 2 were evolved (Keele et al., 2006). Pandemic HIV is
classified into 9 subtypes. It has many recombinant forms, whereas 2 or more
than two subtypes encode their genetic makeup
(Thomson and Nájera, 2005). It’s a greatest
challenge for Therapeutic companies to design effective therapeutic drug against HIV 1 due to continuously changing
genetic makeup by HIV 1 (Korber et al., 2001).
Dominant subtype C makes
up 55 to 60% of worldwide HIV
infections (Thomson and Nájera, 2005). Whereas Non subtype B isolates differ from
subtype B isolates in terms of viral genetic makeup (Blackard et al., 2002; Centlivre et al.,
2006; Laeyendecker et al., 2006).
Estimated size of HIV genome is 9.8kb. Gag, Pol and Env are basic viral proteins
of HIV, translated by primary transcript of virus mRNA, which upon
proteolytic cleavage give rise to different sets of proteins needed by HIV.
Synthesis ratio of Gag, Gag-pol products is 20:1 (Luftig and Lupo, 1994). Regulatory
proteins Tat, Rev also known as RNA binding proteins control optimal activity
upon interacting with cellular factors. Negative factor Nef involved in down
regulation of viral expression. Vif, Vpr, Vpu/Vpx have important role in viral
assembly, packing, budding and synthesis of viral infectious agents (Levy, 1993).
HIV
Pathogenicity:
HIV is capable of down
regulating innate, adapted and intrinsic immunity (Bieniasz,
2004; Mahalingam et al., 2002). HIV life cycle
is too complicated. Its time duration, possible damaging effects to cell
depends upon type of cell and cell activation (Johnson and Coffin, 1999). Initially HIV
upon reaching to cellular components (gp 120 is 1st protein that
interacts with cell’s CD4+ receptor)
poses no lethal effects but entry of HIV triggers intracellular transduction
pathways which in turn might be beneficial in viral genome replication (Balabanian et al., 2004; Cicala et al., 2002). HIV is too clever to enter in human
cells by neutralizing and hiding from different types of immunological factors
and pathways, systems (Barré-Sinoussi,
1996; Emerman and Malim, 1998; Howley, 1996).
HIV
Prevalence globally:
38.6 million people are
estimated with HIV 1 globally. 25 million deaths have been reported up till
now. South Africa is still hot spot of HIV pandemic with significantly high
rate of HIV 1 infection (Simon et al., 2006).
Serial.NO
Year
New
HIV infection
HIV
related Deaths
People
living with HIV
1
2001
3.4
million
1.9
million
30.0
million
2
2002
3.3
million
2.1
million
31.0
million
3
2003
3.1
million
2.2
million
31.70
million
4
2004
3.0
million
2.3
million
32.2
million
5
2005
2.9
million
2.3
million
32.5
million
6
2006
2.8
million
2.3
million
32.8
million
7
2007
2.7
million
2.2
million
33.2
million
8
2008
2.6
million
2.1
million
33.5
million
9
2009
2.6
million
2.0
million
34.0
million
10
2010
2.5
million
1.9
million
34.4
million
11
2011
2.5
million
1.8
million
34.9
million
12
2012
2.3
million
1.6
million
35.3
million
Serial.NO
Region
New
HIV infection
HIV
Associate Deaths
People
living with HIV
1
Eastern and southern Africa
79000
million
420000million
19.4
million
2
Western and central Africa
370000million
310000million
6.1
million
3
Middle East and North Africa
18000
million
11000million
230000million
4
Asia and the Pacific
270000million
170000million
5.1
million
5
Latin America
97000
million
36000million
1.8
million
6
Caribbean
18000
million
9400
million
310000million
7
Eastern Europe and central Asia
190000million
40000million
1.6
million
This 1st table
data is according to (Organization,
2017) and 2nd
is according to ((Roser and Ortiz-Ospina, 2017).
HIV
prevalence in Pakistan:
Pakistan is largely
infected by HIV/AIDS due to unsafe blood transfusions, sharing of common
syringes and needles, unsafe sex, and with low level of condom usage, high
number of afghan refugees on border areas, truck drivers who move to remote
areas and do not acknowledge safe sex measures, local migrants presence, high
rate of sexually transmitted diseases and then there is no more proper sexually
transmitted care centers to deal these issues (Bhurgri).
Serial.NO
Year
New
HIV infection
HIV
related Deaths
People
living with HIV
1
2005
9400
<100 <100–<100 12000 2 2010 14000 1300 <1000–1800 66000 3 2015 19000 5500 4500–6600 13000 This data is according to (Johnston et al., 2015). Treatment by Drugs: ART (antiretroviral treatment) is best and most effective choice to control HIV/AIDS. It not only lessens death ratio but also significantly suppresses viral replication with long lasting impact. 20 antiretroviral drugs have been approved by FDA which specifically targets DNA dependent polymerase or proteases (Lalezari et al., 2003; Lazzarin et al., 2003). HIV 1 is prone to continuously changing its genome so only single drug is not effective against HIV. Highly active antiretroviral treatment is now being used because of high observed genetic mutation rate in HIV. A combination of multiple potent drugs is being used to at least delay resistance against HIV. HAART is being highly used by modern and developed countries which ultimately resulted in low death rates (Hogg et al., 1998; Mocroft et al., 1998; Palella Jr et al., 1998).
