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AIDS is a chronic, potentially life-threatening condition caused by the human immunodeficiency virus (HIV). By damaging the immune system, HIV interferes with the body’s ability to fight the organisms that cause disease.

HIV is a sexually transmitted infection. It can also be spread by contact with infected blood, or from mother to child during pregnancy, childbirth or breast-feeding. It can take years before HIV weakens the immune system to the point that the patient has AIDS.

There’s no cure for HIV/AIDS, but there are medications that can dramatically slow the progression of the disease. These drugs have reduced AIDS deaths in many countries, but HIV continues to decimate populations in Africa, Haiti and parts of Asia.  (

Scientists believe a virus similar to HIV first occurred in some populations of chimps and monkeys in Africa, where they’re hunted for food. Contact with an infected monkey’s blood during butchering or cooking may have allowed the virus to cross into humans and become HIV.
How does HIV become AIDS?
HIV destroys CD4 cells — a specific type of white blood cell that plays a large role in helping the body fight disease. The immune system weakens as more CD4 cells are killed. It is possible to have an HIV infection for years before it progresses to AIDS.
People infected with HIV progress to AIDS when their CD4 count falls below 200 or they experience an AIDS-defining complication, such as:
• Pneumocystis pneumonia
• Cytomegalovirus
• Tuberculosis
• Toxoplasmosis
• Cryptosporidiosis

How HIV is transmitted?
To become infected with HIV, infected blood, semen or vaginal secretions must enter the body. One cannot become infected through ordinary contact — hugging, kissing, dancing or shaking hands — with someone who has HIV or AIDS. HIV can’t be transmitted through the air, water or via insect bites.
One can become infected with HIV in several ways, including:
• During sex. It is possible to become infected if one has vaginal, anal or oral sex with an infected partner whose blood, semen or vaginal secretions enters the body. The virus can enter the body through mouth sores or small tears that sometimes develop in the rectum or vagina during sexual activity.
• Blood transfusions. In some cases, the virus may be transmitted through blood transfusions. Hospitals and blood banks now screen the blood supply for HIV antibodies, so this risk is very small.
• Sharing needles. HIV can be transmitted through needles and syringes contaminated with infected blood. Sharing intravenous drug paraphernalia puts one at high risk of HIV and other infectious diseases such as hepatitis.
• From mother to child. Infected mothers can infect their babies during pregnancy or delivery, or through breast-feeding. But if women receive treatment for HIV infection during pregnancy, the risk to their babies is significantly reduced.
The symptoms of HIV and AIDS vary, depending on the phase of infection.

Primary infection
The majority of people infected by HIV develop a flu-like illness within a month or two after the virus enters the body. This illness, known as primary or acute HIV infection, may last for a few weeks. Possible symptoms include:
• Fever
• Muscle soreness
• Rash
• Headache
• Sore throat
• Mouth or genital ulcers
• Swollen lymph glands, mainly on the neck
• Joint pain
• Night sweats
• Diarrhea

Although the symptoms of primary HIV infection may be mild enough to go unnoticed, the amount of virus in the blood stream (viral load) is particularly high at this time. As a result, HIV infection spreads more efficiently during primary infection than during the next stage of infection.
Clinical latent infection
In some people, persistent swelling of lymph nodes occurs during clinical latent HIV. Otherwise, there are no specific signs and symptoms. HIV remains in the body, however, as free virus and in infected white blood cells.
Clinical latent infection typically lasts eight to 10 years. A few people stay in this stage even longer, but others progress to more-severe disease much sooner.
Early symptomatic HIV infection
As the virus continues to multiply and destroy immune cells, the patient may develop mild infections or chronic symptoms such as:
• Fever
• Fatigue
• Swollen lymph nodes — often one of the first signs of HIV infection
• Diarrhea
• Weight loss
• Cough and shortness of breath

If the patient receives no treatment for their HIV infection, the disease typically progresses to AIDS in about 10 years. By the time AIDS develops, the immune system has been severely damaged, making the patient susceptible to opportunistic infections — diseases that would not trouble a person with a healthy immune system. The signs and symptoms of some of these infections may include:
• Soaking night sweats
• Shaking chills or fever higher than 38˚ C for several weeks
• Cough and shortness of breath
• Chronic diarrhea
• Persistent white spots or unusual lesions on the tongue or in the mouth
• Headaches
• Persistent, unexplained fatigue
• Blurred and distorted vision
• Weight loss
• Skin rashes or bumps

If a person thinks they may have been infected with HIV or are at risk of contracting the virus, they should see a health care provider as soon as possible.

The worldwide spread of HIV-1 indicates that the virus effectively counteracts innate, adapted, and intrinsic immunity. Despite its modest genome size (less than 10 kb) and its few genes, HIV-1 excels in taking advantage of cellular pathways while neutralizing and hiding from the different components of the immune system. Markedly, our understanding of pathogenesis is often derived from studies of subtype B viruses and non-human primate studies.
The HIV-1 life cycle is complex and its duration and outcome is dependent on target cell type and cell activation. In the early steps, HIV-1 gains access to cells without causing immediate lethal damages but the entry process can stimulate intracellular signal cascades, which in turn might facilitate viral replication.
The two molecules on the HIV-1 envelope, the external glycoprotein (gp120) and the transmembrane protein (gp41), form the spikes on the virion’s surface. During the entry process, gp120 attaches to the cell membrane by first binding to the CD4+ receptor. Subsequent interactions between virus and chemokine co-receptors (e.g., CCR5, CXCR4) trigger irreversible conformational changes. The actual fusion event takes place within minutes by pore formation, and releases the viral core into the cell cytoplasm. After the core disassembles, the viral genome is reverse transcribed into DNA by the virus’ own reverse transcriptase enzyme.
Related yet distinct viral variants can be generated during this process since reverse transcriptase is error prone and has no proofreading activity. At the midpoint of infection, the viral protein integrase in conjunction with host DNA repair enzymes inserts the viral genome into gene-rich, transcriptionally active domains of the host’s chromosomal DNA. An integrase binding host factor, LEDGF/p75 (lens epithelium-derived growth factor), facilitates integration, which marks the turning point by irreversibly transforming the cell into a potential virus producer. In the late steps, production of viral particles needs host driven as well as virus driven transcription. Viral proteins are transported to and assemble in proximity to the cell membrane. Virus egress from the cell is not lytic and takes advantage of the vesicular sorting pathway (ESCRT-I, II, III), which normally mediates the budding of endosomes into multivesicular bodies.

HIV-1 accesses this protein-sorting pathway by binding TSG101 via its late domain, a short sequence motif. Cleavage of the Gag-Pol poly-protein by the viral protease produces mature infectious virions.
Since cytoplasmic molecules of the producer cell and components from its cell surface lipid bilayer are incorporated into the new viral particle, virions bear characteristics of the cells in which they were produced. Incorporated host molecules can determine the virus’ phenotype in diverse ways (e.g., shape the replicative features in the next cycle of infection or mediate immune activation of bystander cells.
Studies of the early events that happen after HIV-1 breaches the mucosal barrier suggest the existence of a window period in which viral propagation is not yet established and host defences could potentially control viral expansion. The important co-receptors for HIV-1 infection are two chemokine receptors—CCR5 and CXCR4. Independently of the transmission route, most new infections are established by viral variants that rely on CCR5 usage.64 CXCR4-tropic viruses generally appear in late stages of infection and have been associated with increased pathogenicity and disease progression.
Compelling evidence from non-human primate models (e.g., simian immunodeficiency virus [SIV] infection of rhesus macaques) suggest that vaginal transmission results in infection of a small number of CD4+ T lymphocytes, macrophages, and dendritic cells located in the lamina propria. Potential pathways for virus transmission involve endocytosis, transcytosis, and virus attachment to mannose C-type lectin receptors (e.g., DC-SIGN) located on dendritic cells and macrophages.66 The initial replication takes place in the regional lymph organs (e.g., draining lymph nodes) and is composed of few viral variants, and leads to modest primary amplification. With migration of infected T lymphocytes or virions into the bloodstream, secondary amplification in the gastrointestinal tract, spleen, and bone marrow results in massive infection of susceptible cells.
In close temporal relation with the resulting peak of viraemia (e.g., 106 to 107 copies per mL plasma), clinical symptoms can be manifest during primary HIV-1 infection. The level of viraemia characteristic for the chronic phase of infection in an individual (viral set point) differs from the peak viraemia by one or two orders of magnitude. This reduction is largely attributed to HIV-1 specific CD8+ responses but target cell limitation could also play a part.

The viral population is most homogeneous early after transmission, but as viral quasi-species diversify in distinct biological compartments, mutant viruses that are resistant to antibody neutralisation, cytotoxic T cells, or antiretroviral drugs are generated and archived in long-lived cells (i.e., viral reservoirs).
A pronounced depletion of activated as well as memory CD4+ T cells located in the gut-associated lymphoid tissues has been seen in individuals identified early after infection.67 The preferential depletion of the CD4+ cells in the mucosal lymphoid tissues remains despite years of antiretroviral treatment, a striking observation that contrasts with the fact that the number of CD4+ T lymphocytes in the peripheral blood can return to normal under antiretroviral treatment.
A gradual destruction of the naive and memory CD4+ T-lymphocyte populations is the hallmark of HIV-1 infection, with AIDS being the last disease stage. Despite the frequent absence of symptoms during early and chronic phase, HIV-1 replication is dynamic throughout the disease. The half-life of a single virion is so short that half the entire plasma virus population is replaced in less than 30 minutes, and the total number of virions produced in a chronically infected person can reach more than 10¹P particles per day. The turnover rates of lymphocyte populations are upregulated many fold during HIV-1 infection, whereas cell proliferation decreases once viral replication is reduced by antiretroviral treatment. Different depletion mechanisms have been proposed, with an emerging consensus favouring generalised immune activation as cause for constant depletion of the CD4+ cell reservoir.
Immune activation predicts disease progression and, thus, seems to be a central feature of pathogenic HIV-1 infections. Recently, Nef proteins from SIV lineages that are non-pathogenic in their natural hosts (e.g., African green monkeys) have proved to down-regulate CD3-T-cell receptors, resulting in reduced cell activation and apoptosis.75 HIV-1 Nef fails to quench T-cell activation, possibly leading to the high degree of immune activation seen in infected people.
Understanding the mechanisms that lead to protection or long-lasting control of infection will guide vaccine development by providing correlates of protection. Natural resistance to HIV-1 infection is rare and varies greatly between individuals. Two groups—long-term non-progressors and highly exposed persistently seronegative individuals—have been studied widely to identify innate and acquired protective determinants (table 1).

Host resistance factors consist of human leucocyte antigen (HLA) haplotypes, autoantibodies, mutations in the promoter regions, and coding regions of the co-receptors CCR5 and CCR2, as well as the up-regulation of chemokine production Indeed, individuals encoding a truncated CCR5 version (CCR5Δ32) have slower disease progression (heterozygote) or are resistant to CCR5-using viruses (homozygote). The CCL3L1 gene encodes MIP1α, a CCR5 co-receptor ligand and chemokine with antiviral activity. Recent findings show that CCL3L1 gene copies vary individually and higher numbers of gene duplications result in reduced susceptibility to infection, possibly by competitive saturation of CCR5 co-receptor. Cytotoxic T-lymphocyte responses, helper T-cell functions, and humoral responses are some of the acquired factors that modulate the risk of transmission in highly exposed persistently seronegative individuals, and could also contribute to spontaneous control of replication in long-term non-progressors. The putative protective role of cytotoxic T-lymphocyte activity has been suggested in seronegative sex workers and in some long-term non-progressors.
Mammalian cells are not welcoming micro-environments, but rather deploy a defensive web to curb endogenous and exogenous viruses. HIV-1’s ability to circumvent these defences is as impressive as its efficiency to exploit the cellular machinery. APOBEC3G/3F and TRIM5α are recently described intrinsic restriction factors that are constitutively expressed in many cells. Both gene loci have been under strong selective pressure throughout primate evolution, indicating an ancient need to neutralise foreign DNA and maintain genome stability that precedes the current HIV-1 pandemic.
APOBEC3 enzymes (A3) belong to the superfamily of cytidine deaminases, a group of intracellular proteins with DNA/RNA editing activity. Most representatives of the APOBEC3 group have some mutagenic potential and restrict endogenous retroviruses and mobile genetic elements. The deaminases A3G, A3F, and A3B have potent antiviral activity, with the first two being expressed in cells that are susceptible to HIV-1 infection (T-lymphocytes, macrophages). HIV-1 evades APOBEC3 mutagenesis by expressing Vif, which leads to APOBEC3G/3F but not A3B degradation.
We still need to establish how the mechanisms of DNA editing and antiviral activity are interwoven, since some antiviral activity can be maintained despite defective DNA editing. The early replication block in non-stimulated CD4+ T cells has been attributed to low molecular mass complexes of APOBEC3G.
Hypermutated genomes in HIV-1 infected patients and mutations in Vif resulting in abrogated or differential APOBEC3 neutralisation capacity have been described. The degree to which APOBEC3G/3F mRNA expression predicts clinical progression remains an area of intensive investigation.
Several representatives of the heterogeneous family of tripartite motif proteins (TRIM) inhibit retroviruses in a species-specific manner. TRIM5α from rhesus macaques and African green monkeys inhibit HIV-1 replication, whereas the human homologue is inactive against SIV and HIV-1, leading to the recorded susceptibility of human cells to both viruses.
Rhesus TRIM5α recognises the capsid domain of HIV-1 Gag and manipulates the kinetics of HIV-1 core disassembly within minutes after cell entry. Thus, experimental approaches to render HIV-1 resistant to rhesus TRIM5α could lead to immunodeficiency viruses capable of replicating in rhesus macaques. Such a non-primate model would allow testing of antiviral treatment and vaccine interventions with HIV-1 viruses instead of SIV or SIV/HIV chimeric viruses.
One is at greatest risk of HIV/AIDS if one:
• Has unprotected sex. Unprotected sex means having sex without using a new latex or polyurethane condom every time. Anal sex is more risky than is vaginal sex. The risk increases I people who have multiple sexual partners.
• Have another STI. Many sexually transmitted infections (STIs) produce open sores on the genitals. These sores act as doorways for HIV to enter the body.
• Use intravenous drugs. People who use intravenous drugs often share needles and syringes. This exposes them to droplets of other people’s blood.
• Are an uncircumcised man. Studies indicate that lack of circumcision increases the risk for heterosexual transmission of HIV.

There’s no vaccine to prevent HIV infection and no cure for AIDS. But it’s possible to protect one’s self and others from infection. That means being educated about HIV and avoiding any behaviour that allows HIV-infected fluids — blood, semen, vaginal secretions and breast milk — into the body.
To help prevent the spread of HIV:
Use a new condom every time during sex. If a person does not know the HIV status of their partner, they should use a new condom every time they have anal or vaginal sex. Women can use a female condom. Use only water-based lubricants. Oil-based lubricants can weaken condoms and cause them to break. During oral sex use a condom, dental dam — a piece of medical-grade latex — or plastic wrap.
Disclose HIV status. It’s important that people who test HIV-positive disclose their status to anyone with whom they have had sex. These partners need to be tested and to receive medical care if they have the virus. They also need to know their HIV status so that they do not infect others.
Use a clean needle. Injecting drug users should make sure that the needles they use are sterile and they should not share these needles.
Pregnant women should get medical care right away. Pregnant women who are HIV-positive may pass the infection to their baby. But if they receive treatment during pregnancy, they can reduce the baby’s risk by as much as two-thirds.
Consider male circumcision. There’s evidence that male circumcision can help reduce a man’s risk of acquiring HIV.

There’s no cure for HIV/AIDS, but a variety of drugs can be used in combination to control the virus. Each of the classes of anti-HIV drugs blocks the virus in different ways. It’s best to combine at least three drugs from two different classes to avoid creating strains of HIV that are immune to single drugs.
The classes of anti-HIV drugs include:
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs disable a protein needed by HIV to make copies of itself. Examples include efavirenz (Sustiva), etravirine (Intelence) and nevirapine (Viramune).
• Nucleoside reverse transcriptase inhibitors (NRTIs). NRTIs are faulty versions of building blocks that HIV needs to make copies of itself. Examples include Abacavir (Ziagen), and the combination drugs emtricitabine and tenofovir (Truvada), and lamivudine and zidovudine (Combivir).
• Protease inhibitors (PIs). PIs disable protease, another protein that HIV needs to make copies of itself. Examples include atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva) and ritonavir (Norvir).
• Entry or fusion inhibitors. These drugs block HIV’s entry into CD4 cells. Examples include enfuvirtide (Fuzeon) and maraviroc (Selzentry).
• Integrase inhibitors. Raltegravir (Isentress) works by disabling integrase, a protein that HIV uses to insert its genetic material into CD4 cells.
The South African National Department of Health has published guidelines which indicate when treatment should begin.
One such guideline is that all newly diagnosed patients irrespective of CD4 count must immediately start antiretroviral treatment. This is in an attempt to reduce the burden of disease. There has also now been a move from the single dose formulations to the Fixed Dose Combinations (FDC). FDC is when two or three different ARVs are combined into one single dose/pill. The announcement by Minister of Health, Aaron Motsoaledi, in 2012 that all newly diagnosed patients should receive the new FDC ARV as first line therapy is a significant step forward in the treatment of HIV. The most commonly prescribed FDC drug in the public sector in South Africa is Atripla which is a combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate. Atripla is also a one a day dosage making adherence so much better for patients along with a reduce risk of incorrect dosage seen with patients taking more than one tablet (Davies, 2013)
Treatment can be difficult. HIV treatment regimens may involve taking multiple pills at specific times every day for the rest of the patient’s life. Side effects can include:
• Nausea, vomiting or diarrhea
• Abnormal heartbeats
• Shortness of breath
• Skin rash
• Weakened bones
• Bone death, particularly in the hip joints.

Co-diseases and co-treatments
Some health issues that are a natural part of aging may be more difficult to manage I patients who are HIV-positive. Some medications that are common for age-related cardiovascular, metabolic and bone conditions, for example, may not interact well with anti-HIV medications. Patients should consult a doctor about other conditions they are receiving medication for. There are also known interactions between anti-HIV drugs and:
• Contraceptives and hormones for women
• Medications for the treatment of tuberculosis
• Drugs to treat hepatitis C

Treatment response
The response to any treatment is measured by the patient’s viral load and CD4 counts. Viral load should be tested at the start of treatment and then every three to four months during therapy. CD4 counts should be checked every three to six months.
HIV treatment should reduce the viral load to the point that it’s undetectable. That does not mean that the patient is cured. It just means that the test isn’t sensitive enough to detect it. Patients can still transmit HIV to others when their viral load is undetectable.

HIV is most commonly diagnosed by testing blood or saliva for the presence of antibodies to the virus. Unfortunately, these types of HIV tests aren’t accurate immediately after infection because it takes time for the body to develop these antibodies — usually up to 12 weeks. In rare cases, it can take up to six months for an HIV antibody test to become positive.
A newer type of test checks for HIV antigen, a protein produced by the virus immediately after infection. This test can confirm a diagnosis within days of infection. An earlier diagnosis may prompt people to take extra precautions to prevent transmission of the virus to others. There is also increasing evidence that early treatment may be of benefit.
Tests to tailor treatment
In patients who test HIV-positive, several types of tests can help the doctor determine what stage the disease is at. These tests include:
CD4 count. CD4 cells are a type of white blood cell that’s specifically targeted and destroyed by HIV. A healthy person’s CD4 count can vary from 500 to more than 1,000. Even if a person has no symptoms, HIV infection progresses to AIDS when his or her CD4 count becomes less than 200.
Viral load. This test measures the amount of virus in the blood. Studies have shown that people with higher viral loads generally fare more poorly than do those with a lower viral load.
Drug resistance. This blood test determines whether the strain of HIV will be resistant to certain anti-HIV medications and the ones that may work better.
Tests for complications
The doctor might also order lab tests to check for other infections or complications, including:
• Tuberculosis
• Hepatitis
• Toxoplasmosis
• Sexually transmitted infections
• Liver or kidney damage
• Urinary tract infection