Living Well With HIV

An estimated.two-thirds of the 36.7 million people infected with.the Human immunodeficiency.virus (HIV), reside on the African.continent 1. Once infection.has occurred, HIV destroys.the hosts CD4+ immune.cells, leading to acquired.immunodeficiency syndrome (AIDS) 2. .HIV/AIDS is wide.spread throughout.Sub-Saharan Africa and exacerbates various.socioeconomic issues 3. South Africa has.some of the highest prevalence.of HIV/AIDS.in the world, with an.estimated 7 million people.living with HIV 4. .An estimated 115 000.HIV-related deaths occurred in South Africa in 2018, .emphasizing the.need for HIV research.in Sub-Saharan.countries 4. The HIV-1 virus.consists of two copies.of non-covalently.linked, positive.sense, single-stranded.RNA molecules 5. This is enclosed.by a p24 viral.protein.conical capsid, situated.within a.viral envelope. .The viral envelope is derived from the.host cell membrane and.contains viral.glycoproteins; such.as gp120.and gp41, which.are imbedded.in the viral.envelope 2,6,7. .Once HIV-1 exposure.occurs, .the virus migrates.to CD4+ immune.cells. This occurs.due to the.affinity of the HIV-1 viral.envelope.gp120/gp41 complex.for CD4 antigen.receptors on the surface of host.CD4+ immune cells 2,6. Once.the gp120 subunit.of the viral envelope.interacts with a CD.antigen receptor, co-receptor binding.takes place 2,7. The co-receptor.binding results in conformation.changes in the HIV- 1 envelope, .leading to the exposure.of the gp41 hydrophobic.domain, allowing.fusion of the.envelope with.the cellular.membrane and the.subsequent delivery.of the viral core.into the cytoplasm 2. The.uncoating of the.viral core exposes.Reverse transcriptase, a HIV.enzyme, to deoxynucleotide.triphosphates (dNTP¿s), resulting in reverse transcription.and proviral DNA synthesis 2. After reverse.transcription is completed, .the formation.of a complex, consisting of.viral and cellular components is.formed, known as the viral pre-integration.complex. This is transported to the.cell¿s nucleus where the.HIV-1 enzyme, Integrase, catalyses.the integration of the viral.genome with the human.DNA 2,7. This maintains the.viral DNA.in the infected host cell and allows.transcription, thus the cell can express viral.mRNA and viral RNA. Once.transcription is initiated, the necessary viral.constituents move to the inside of the plasma.membrane and assemble to form an.immature HIV-1 virus 2. The newly.formed immature virus buds.off from the cell and releases.protease to break down large.HIV-1 protein chains. .These broken down HIV protein.chains, combine to form.a mature HIV-1 virus 2. The viral life.cycle, discussed above (shown in Figure 1.1), can be.subdivided into seven.distinct stages, namely binding; fusion; reverse.transcription; integration; replication; .virus assembly/production; and.budding. The HIV-1 lifecyclexpresents various.potential opportunities for.therapeutic intervention.and six distinctclasses of antiretrovirals (ARVs) havexbeen developed 2.