OVERVIEW

HIV, an abbreviation for Human Immunodeficiency Virus, is a blood-borne virus that targets and destroys the immune system. The immune system is our body’s natural defense system against foreign bodies. The immune system is made up a network of proteins, cells, tissue, and organs that work together to protect the body against invaders such as microorganisms and toxins. The HIV attacks specifically the CD4 T cells, (a type of T cell known as the T helper cells} and also dendritic cells and macrophages of the immune system. CD4 T cell is known as T helper cells because its main function is to send signals to other immune cells such as T killer (CD8) cells to destroy infectious particles.

Destruction of CD4 T cells renders the immune system incapable of fighting off certain infections. This failure of the immune system is termed; immunodeficiency or the patient is said to be immunocompromised. This puts you at a higher risk for opportunistic infections and certain cancers. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of HIV infection which present a myriad of symptoms of certain illnesses. Not everyone with HIV develops AIDS. The human body can’t get rid of HIV completely, even with current treatments. So once you are infected with HIV, you have it for life. With that notwithstanding, with proper medical care, HIV can be controlled.

SUBTYPES OF HIV 

HIV can be divided into 2 major types known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2).

• HIV-1:

Which is more common in the US and worldwide, constitutes more than 75% of all HIV cases. HIV–1 causes the global HIV pandemic because of its virulence and very infective nature. HIV-1 is further classified into four groups: M (most common), N, O, and P. More than 90% of HIV-1 cases involve group M.

• HIV-2:

Known to be common in Western Africa and Southern Asia. Presents with similar illnesses as HIV-1 but it progresses more slowly. As of 2010, 8 known HIV-2 groups (A to H) were discovered. Among these groups, only groups A and B are pandemic. Group A is found mainly in West Africa, but has spread globally to other countries. Group B is mainly found in West Africa.
Note: Researches on vaccines and antiviral drugs on HIV is focused on HIV-1.

STAGES OF HIV INFECTION

The clinical presentation of HIV infection has been grouped into three main stages;

1) Acute HIV infection.
2) Clinical latency.
3) AIDS (acquired immunodeficiency syndrome).

Stage 1: Acute HIV infection.

This stage is usually within 2 to 4 weeks after infection with HIV. Infected people may experience flu-like symptoms which may last for a few weeks. Symptoms may include malaise, fever, swollen glands, sore throat, rash, muscle and joint aches and pains, and headache. This stage is also known as the primary HIV infection, where the body’s immune system tries to fight against the infection. This stage is very contagious because there is a large amount of virus in the blood. Also, people tend to spread the infection more at this stage because they are often unaware that they’re infected because they may not feel sick right away or at all. The virus at this stage uses CD4 T cells to replicate and destroys them in the process. As a result of this, your CD4 T cells can fall rapidly. It is advisable to start treatment immediately at this stage to prevent the infection from advancing to the next stage.

 

Stage 2: Clinical latency (Inactive Stage).

This stage is known as asymptomatic HIV infection or chronic HIV infection. During this stage, The virus is still present and active but reproduces at very low levels. Infected persons may not have any symptoms. This stage can last a decade or even longer, but some may progress to the next stage faster. People who are taking medicine to treat HIV may be in this stage for several decades without getting to the last stage. It’s important to know that people can still transmit HIV to others during this stage. A proportion of patients in this stage still maintain a relatively normal amount of CD4 T cells for more half a decade without any form of antiretroviral therapy. They are referred to as the “HIV Controllers”.

 

Stage 3: Acquired immunodeficiency syndrome (AIDS).

AIDS is the last stage and the most severe phase of HIV infection. People with AIDS have are severely immunocompromised such that they get an increasing number of severe disease, called opportunistic diseases. Symptoms of AIDS depends on the opportunistic disease, some of these common symptoms include malaise, chills, fever, sweats, swollen lymph glands, weakness, and weight loss. At this stage, diagnosis can be made when CD4 T cells count drops below 200 cells/mm or if there is a manifestation of opportunistic diseases. Without treatment, people who progress to AIDS usually survive for about 3 years. Once you have a dangerous opportunistic infection, life-expectancy falls to about 1 year without treatment. Treatment can be lifesaving for people who have AIDS when diagnosed.

PATHOGENESIS

HIV is a retrovirus belonging to the Retroviridae family, Lentivirus genus. After there’s a mucosal exposure, dendritic cells present at the site of infection transport them to the lymph nodes in an attempt to destroy it. HIV can only infect cells bearing the CD4+ molecule on their membrane surface.

One might be wondering the importance of the cells bearing the CD4+ molecule!…..CD4+ molecules aid cells communicate with other immune cells. Thus, very helpful when there’s an immune response to foreign pathogens. HIV targets this CD4+ molecule, and attaches to it via a protein called; gp120 found on its viral envelope. The virus uses a chemokine receptor 5(CCR5) as a co-receptor with CD4+ molecule found on the membrane of the host cells at the initial phase of the infection to get inside the cell. CD4+ molecules are found on T cells, macrophages, monocytes and dendritic cells. Thus, people with Homozygous mutation of the CCR5 have a natural immunity/resistance to HIV.

Even in cases of heterogeneous mutation, there is a slower disease progression(that is; the virus spreads slowly). There is a switch from the usage of chemokine receptor 5 to chemokine-related receptor 4(CXCR4) over time. This means that, without the CD4+ molecule and the Co-receptor, HIV cannot enter the cell.
When we say HIV is a retrovirus, it means, it uses a reverse transcriptase (an enzyme) to transcribe a complimenting piece of pro-viral DNA. A proviral DNA is one whose DNA can be integrated into its host’s DNA, leading to activation of the immune cells. Hence, transcription and translation of proteins needed for the immune response begin. As a result, when there’s an infection, the immune cells end up transcribing and translating new HIV viruses which in turn infect more cells. On maturation, these virions infect other CD4+ cells and the cycle is repeated.

Interestingly, this virus is known for making errors during replication, creating slightly different strands of the same virus. As a result, there are slight behavioral changes in them though they are still, ‘HIV’. The difference enables this virus to target different cells in the host. This act is called; Viral Tropism. There is a survival time of close to 1 day for CD4+ lymphocytes that are replicating the virus. As the virus increases, there is a decline in the amount of CD4+ cells. That is, a total of about 1.2 billion losses of T-cells per day. T-cells try to remain at about >500 cells/mm3, which are still able to fight other common infections. In asymptomatic patients, it is estimated that, more than 10^10 virions are produced and about 10^9 CD4 lymphocytes are destroyed daily.
A number of infected T-helper lymphocytes enter a post-integration latent phase. These latent cells are therefore unable to be destroyed by antiretroviral drugs since these drugs only target the replicating virus.

During the chronic phase, which is about 12weeks post-infection, there could be a mutation of the virus to develop an X4 strain, targeting the CXCR4 co-receptor, which is essentially only CD4 T cells. These remain dormant, steadily destroying CD4+ T cells within the lymphoid tissue. There is massive destruction of CD4 T cells as the lymphoid tissue contains about 90% of these cells. Yet, not all patients develop the X4 strain, as such, it is not completely clear as to what exactly the X4 strain of the virus tells us about the disease.

MODE OF TRANSMISSION

A lot of people have been stigmatized because of the myths about the transmission of HIV.HIV can only be spread through certain body fluids-blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, and breast milk. For transmission to occur, these fluids must come in contact with a mucous membrane or damaged tissue or be directly injected into the bloodstream.

Most commonly it’s spread through sexual activity: Anal sex, Oral sex, Vaginal Sex.

Other means of transmission include;
• Sharing needles or syringes with an infected person.
• Blood transfusion of infected blood.
• Deep kissing with both partners having sores in mouth or gum bleeding.
• From pregnant mother to baby through childbirth.
• Through breastfeeding.
• Accidental needle pricks(occupational hazard of health workers).
• Intravenous drug abusers sharing needles.
• The use of unsterilized equipment at saloons and barbering shops.
• Sharing of a razor blade or shaving sticks with an infected person.
• Being bitten by a person with HIV. No risk of transmission if there is no blood as a result of skin damage..

SIGNS AND SYMPTOMS

A patient becomes symptomatic when CD4 T cells level drops to about 200-500 cells/mm^3. They are as follows;

1. Flu-like symptoms:

(fever, headache, malaise, fatigue, body chills): This is mainly seen in the acute phase of the infection, the immune system waged a war against the virus in an attempt to control the amount of virus replicating, thus, keeping it low, yet at detectable levels by week 12 of infection. The patient then enters the chronic phase which can last about 2-10 years.

2. Generalized lymphadenopathy:

Also known as adenopathy, is a disease of the lymph nodes, in which they are abnormal in size, number, or consistency, and usually painless. This is common in the groin region and it can present for months. It is usually an idiopathic( has no known cause) or is due to an infection.

3. Weight loss:

This is a common finding in long term HIV patients. The HIV wasting syndrome, is said to be an AIDS-defining condition, is a explained as weight loss of more than 10% of normal body weight with or without unexplained chronic diarrhea, weakness and prolonged fever, all lasting over a month. This is a diagnosis of exclusion. In case the weight loss exceeds 1kg in a month, cancers or other opportunistic infections may be likely.

4. Generalized dermatitis:

The presence of skin lesions and scaly red patches on the skin, typically in the nasolabial folds and in hairy areas. This is very common in HIV-infected patients and is due to severity in a decrease of the CD4 T cells count. Mostly attributed to a fungal infection and can be treated well with a combination of topical anti-fungal and steroids.

5. Chronic diarrhea:

Usually unexplained diarrhea is present in advanced HIV patients, which can last over a month. This is a very important marker in the differential diagnosis as it helps to make a conclusive one.

6. Oropharyngeal candidiasis:

Also known as thrush, is present because the patient is immunocompromised. Patients present with white plaques or erythematous patches on the buccal mucosa, palate, tongue, or oropharynx.

DIAGNOSIS AND INVESTIGATIONS

1. Screening test assays:

ELISA which is a very simple method in screening for HIV, can detect HIV-1 type M, N, and O and HIV-2. A positive ELISA test is followed by a Western blot assay confirmatory test.

2. HIV Viral load:

It is a routine clinical test that measures the amount of HIV virus in a millimeter(mL) of blood. Obviously, the less the number of viruses in the blood, the better. Once the patient is on treatment, the virus might be reduced to an undetectable level.

3. CD4 Count:

Also a routine test in diagnosing and monitoring the progress of treatment, this measures the amount of CD4 cells, a type of white blood cells, also known as T- cells, which fights against bacteria and viruses that enter the body.

4. Confirmatory HIV test( HIV 1, HIV 2, HIV 1, and 2):

This test is aimed at determining which category of the disease the patient belongs to, to administer the right medication for treatment.

OTHER BASELINE TESTS

The following are other necessary laboratory tests performed to help make a conclusive diagnosis;
• Biochemical Tests: (BUE/Cr, LFT’s, FBS, cholesterol, and lipid profile).
• Routine Exam: Full Blood Count, Urinalysis, Stool examination.
• Respiratory Exam: Tuberculosis screening and Chest X-ray.
• Serological Exam: HBsAg.
• Supplementary tests: Pregnancy test and screening for other STI’s.
• Screening for other infections: Syphilis, Hepatitis (A, B, and C), TB, Cytomegalovirus, Anti-Toxoplasma antibodies, chlamydia and gonococcal infection.

PEP( Post-exposure prophylaxis)

This is a short term antiretroviral therapy, given to minimize the likelihood of infections after accidental exposure. This treatment is to either prevent the occurrence of infection or to prevent a new infection. It is recommended after a careful risk assessment in both occupational and non-occupational setups. Mostly health workers in case of an accidental needle prick(percutaneous injury). Also, rape victims. It is given as soon as possible within 6-8 hours of infection. It is particularly effective within the first 1-2 hours and not after 72hours.

Note that, PEP must not be given if the exposed person is already HIV infected. To rule out an infection, the exposed person should have an HIV antibody testing performed at 6, 12, and 24 weeks after exposure whiles on treatment.

 

RISK FACTORS

Usually, there’s a higher risk of becoming infected with HIV through sexual contact. Thus, the risk increases with people who;
• Have unprotected sex.
• Have multiple sex partners.
• Are homosexuals.
• Have recently had an STI such as syphilis or herpes.
• Is uncircumcised (i.e in males).
• Uses intravenous drugs.
• Uses unsterilized sharp objects.
• Is a baby born to an infected mother, through normal vaginal delivery.

COMPLICATIONS

Although antiretroviral therapy help to increased life expectancy for patients with AIDS, many patients still deteriorate and die eventually. Death may result from the following;

• Cancers.
• Liver failure due to hepatitis B and C.
• Tuberculosis (TB): TB is the most common opportunistic infection associated with HIV and the major cause of death among people with AIDS. Millions of people are currently infected with both HIV and tuberculosis and are considered to be twin epidemics.
• Salmonellosis: This is a bacterial infection contracted from contaminated food or water. Signs and symptoms include severe diarrhea, fever, chills, abdominal pain, and vomiting. Although anyone exposed to salmonella bacteria can become sick, salmonellosis is far more common in HIV-positive people.
• Cytomegalovirus: This is a common herpes virus, transmitted in body fluids such as saliva, blood, urine, semen, and breast milk. A healthy immune system inactivates the virus, and it remains dormant in your body. If your immune system is weak, the virus resurfaces causing damage to your eyes, digestive tract, lungs or other organs.
• Candidiasis: Candidiasis is a common HIV-related infection. It causes inflammation and a thick, white coating on the mucous membranes of your mouth, tongue, esophagus or vagina. Children may have severe symptoms in the mouth or esophagus, which can make eating painful.
• Cryptococcal meningitis: Meningitis is an inflammation of the membranes and fluid surrounding your brain and spinal cord (meninges). Cryptococcal meningitis is a common central nervous system infection associated with HIV, caused by a fungus found in soil. The disease may also be associated with bird or bat droppings.
• Toxoplasmosis: This extremely fatal infection is caused by Toxoplasma gondii, a parasite spread by cats. Infected cats pass the parasites in their stools, and the parasites may then spread to other animals and humans. It particularly affects pregnant women, thus causing severe symptoms to the fetus.
• Cryptosporidiosis: An infection caused by an intestinal parasite that is mostly found in animals. It is contracted when you ingest contaminated food or water. The parasite grows in your intestines and bile ducts, leading to severe, chronic diarrhea in people with AIDS.

TREATMENT

There is no effective cure currently for HIV. However, HIV can be controlled. Treatment for HIV is known as antiretroviral therapy or ART. If taken as prescribed, ART can prolong the lives of many people infected with HIV, and greatly lower their chance of infecting others.

Though HIV has no cure, this combination of drugs used in its management has really been effective over the years. It has further been able to transform HIV from a progressive disease with fatal end results in chronic manageable diseases.

It aims at;
• Reducing morbidity and mortality related to HIV.
• Promoting growth and neurological development in children.
• Reducing HIV transmission.
• Suppressing viral replication. Thus, reducing the viral load to an undetectable level, for as long as possible.
• Improving the quality of life without unacceptable drug toxicity.
• Improving CD4 T cells count to over 200 cells/ mm^3. This is aimed at helping the body fight against all opportunistic infections as well as HIV related diseases.

The ART’s are divided into first and second line drugs, patients are started on the first line drugs oftentimes, but in case of an adverse reaction to the drugs or due to ineffectiveness, the patient would be switched to the second line drugs.

Immune boosters, such as Septrin (which is contraindicated in G6PD patients) and pro-immune are given as supportive treatment to patients. Folic Acid may also be prescribed due to ART-induced anemia.

Certain medications such as food supplements and herbal medications can interact with the ART’s in the HIV treatment regimen, so patients are advised to stop other medications not prescribed by their physician.

EPIDEMIOLOGY

HIV-1 causes about 75% of HIV infection worldwide. HIV-2 causes a significant proportion of infections in West Africa. HIV-1 is more virulent than HIV-2, and in some areas of West Africa, both viruses are common and may co-infect patients.
In the first half of the 20th Century, Central Africa was the origin of HIV-1, when a chimpanzee virus first infected humans. The global spread began in the late 1970s, with the recognition of AIDS in 1981.
In 2016, close to 36.7 million people including 2.1 million children, less than 15 years of age were living with HIV worldwide, according to the World Health Organization ( WHO). About half of these infected people are not aware they were infected. About 1 million deaths were recorded in 2016 with 1.8 million newly infected cases. Less than half of these newly infected are women. There has been a rapid decline of new cases in children since 2010 by 47% from 300,000 to 160,000 ( in 2016). There has also been a marked decline in Sub-Saharan African countries over the years.
In 2015, the US estimated more than 1.1 million people between the ages of 13 years and above living with HIV, and about 15% undiagnosed persons amongst this number. Close to 50,000 new cases are estimated in the US annually. There has been a 19% decrease in new cases from 2005 to 2014. 38,782 cases were diagnosed in 2016. More than two-thirds of new cases were records amongst homosexual and bisexual men.

Factors that promote the spread include;
• Poverty.
• Poor education.
• The absence of good medical care, thus no access to HIV testing and antiretroviral drugs.
In 2016, 19.5 million people living with HIV were estimated to have access to antiretroviral therapy, decreasing deaths and transmission in many countries. Oftentimes, many of these opportunistic infections that worsen HIV are reactivations of latent infections. In many developing countries, the prevalence of TB and toxoplasmosis in the general population is higher than in developed countries, following HIV-induced immunosuppression in these countries. Similarly, the US records the incidence of coccidioidomycosis and histoplasmosis increasing due to HIV infection.
Human herpesvirus 8 infection, the causative agent of Kaposi sarcoma is common among homosexual and bisexual men, though uncommon in the US and Europe. Less than 90% of AIDS patients in the US who developed Kaposi sarcoma are either homosexual or bisexual men.