Human Immunodeficiency Virus (HIV), AIDS (Acquired immunodeficiency syndrome)
Human immunodeficiency virus (HIV)
- For serological tests, the serum is the best sample.
- These tests can be done on plasma as well.
- Oral fluids.
- Cerebrospinal fluids.
- Genital secretions.
- Breast milk.
Indications of Human immunodeficiency virus (HIV)
- These serological tests are done to diagnose HIV infection.
- For the diagnosis of Acquired Immune Deficiency Syndrome.
Definition of the human immunodeficiency virus (HIV)
- Human immunodeficiency viruses (HIV) are retroviruses, their genetic (genome) information is composed of RNA virus.
- It is a non-oncogenic retrovirus and is the causative agent of acquired immune deficiency syndrome (AIDS).
- It was first described in 1981 and the virus was isolated by the end of 1983.
Microbiology of Human immunodeficiency virus (HIV)
- HIV is also called a human T – cell lymphotropic virus.
- HIV is also known as the human T- lymphocyte virus (HTLV).
- This virus measures 80 to 130 nm in diameter.
- This is a single-stranded RNA virus, icosahedral, and enveloped.
- It contains a reverse transcriptase enzyme, which makes RNA to DNA.
- This is a member of the retrovirus family.
- Types of HIV:
- HTLV III or LAV (lymphadenopathy-associated virus).
- HIV type I. This is common in the USA and western Europe.
- HIV type II. This is more common in West African countries.
The difference between the two types is:
|Property||HIV I||HIV II|
|Envelope protein||GP 41 and GP 120||GP 36 and GP 105|
|Core protein||p 24 and p 18||p 34 and p 68|
|Spread||Parenteral and sexual||Sexual transmission|
|The course of the disease||Faster than HIV-1 to develop AIDS||Slow to develop AIDS|
|ELIZA test||Available||Not available (Western Blot can be used)|
|Prevalence||Worldwide pandemic||Endemic in West Africa and spread to India|
The viral genes are:
- Gag forms group-specific proteins, antigens, and these proteins are named p24 and p18.
- Env forms envelope proteins that are necessary for the interaction and presentation of target cells. These are gp120 and gp41.
- Pol forms polymerase, reverse transcriptase enzymes, and other enzymes like protease and integrase.
The mechanism of injury:
- HIV has a receptor present on the CD4+ cells, Helper cells, and macrophages.
- Virus gp 120 attaches to CD4+ molecules on cells that are present on the lymphocytes.
- It is then internalized in the cell with the help of the reverse transcriptase enzyme.
- It changes RNA to DNA and integrates with the target cell DNA with the help of viral integrase.
- These are known as provirus.
- This will enter into the DNA of the host.
- Now, this may become latent.
- When the virus is assembled and leaves the cells, it does so by budding out, incorporating the host cell membrane into its coat.
- HIV leads to the destruction of the host immune system, which can be summarized below:
- HIV destroys T lymphocytes, mainly T lymphocytes, which are CD4 positive cells (T-helper cells).
- HIV damages the immune system and leads to acquired immune deficiency syndrome (AIDS).
- HIV infection may be present for as long as 10 years before the patients develop signs and symptoms or become AIDs patients.
HIV infecting other cells on E/M:
Virus buds out of the cells and on electron microscopy show virus bud. This has a double layer envelops, a dense core, and a less dense intermediate layer.
HIV mode of transmission:
Body fluids with high concentrations of HIV:
- blood and contaminated blood products.
- vaginal fluid
- breast milk (contaminated).
- other body fluids containing blood
- There is a transplacental spread.
- Infants exposed to the virus during gestation or delivery.
- 2.8% mode of transmission is not known in the USA.
- 50% are homosexual.
- Between men is 60%.
- Between men and women, it is 12%.
- 20% is I/V drug users.
- 20% are blood transfusions before 1985.
- 10% are heterosexual.
- Roughly 40 million people are living with HIV/AIDS,
- 37.1 million adults.
- 18.5 million women.
Mode of HIV infection spread:
- The most common route is sexual:
- oral sex.
- Anal sex.
- Vaginal sex.
- Another mode of spread is:
- Blood products
- Perinatal exposure.
- In USA mode of transmission :
- Homosexual/Bisexual 50%.
- I/V drug user 20%.
- Blood transfusion before 1985 was 20%.
- Heterosexual 10%.
- The dose of HIV is exactly not known, but it is estimated that 10 to 100 viruses may cause infection.
High-risk patients are:
- Homosexuals in males.
- Bisexual men and women with multiple partners.
- Intravenous drug abusers.
- Contaminated blood transfusion.
- Infants exposed during delivery to positive mothers
The dose of HIV infection:
- Exactly not known but a rough estimate is 10 to 100 viruses that may lead to infection.
Stages of HIV infection:
HIV causes the disease in three stages:
Stage 1: Acute infection:
- After 2 to 4 weeks the infected patients will have early flu-like symptoms.
- These patients are very contagious. These patients may not come to know that they have an infection.
- To diagnose these patients you need to advise the fourth-generation antibody/antigen test or nucleic test.
Stage 2: HIV inactive or dormant or clinical latency :
- This is the stage called asymptomatic HIV infection or chronic infection.
- This stage may last for a longer period or for decades.
- These patients may still spread the disease to other people.
- Now CD4+ cell number starts decreasing and viral loads go up.
- Patients may start having symptoms, and the viral level is going up, and patients may go into stage III.
Stage 3: Acquired immune deficiency syndrome:
- This is the most severe phase of HIV infection.
- The immune system is severely damaged, and these patients are prone to get the opportunity for infection.
- Without treatment, these patients may live for about 3 years
- CDC revised the Classification based on the number of CD4+ lymphocytes. With the decrease in CD4+ cells, the patient will end up with AIDS.
|CD4+ cells||CD4+ cells %|| Clinical category A
Clinical category B
| Clinical category C
|≥ 500/ mL||> 29%||A1||B1||C1|
|200 to 400/ mL||14 to 28%||A2||B2||C2|
< 200/ mL
- A = ARC (Aids-related complex)
- B = Neurological disease.
- C 1 = opportunistic infection.
- C 2 = Secondary infection like candidiasis and H. Zoster.
- A 3, B 3, C 3 = Considered to have AIDS.
Common symptoms are:
- The incubation period is:
- 50% of the cases to develop AIDs syndrome takes roughly 10 years.
- 20% are symptoms free for more than 10 years.
- 20 to 30% show a sign of infection.
- Initial stage shows:
- Headaches, diarrhea, sore throat, myalgia, and arthralgia.
- The patients will have weakness and weight loss.
- Fever and chills.
- There is a macular rash.
- There are neurologic symptoms.
- Lymph nodes are swollen (lymphadenopathy).
- CD4+ cell number drops to <200 cells/cmm.
- These are highly infectious.
- Typical HIV positive patients (AIDS) show:
- Fatigue and night sweating.
- Persistent diarrhea.
- Weight loss.
- Frequent infections like Herpes, candidiasis.
- Candidiasis shows a thrush and vulvovaginal infection.
- HIV infection may lead to Kaposi’s sarcoma, B- cell lymphoma, and anal carcinoma.
- Two or more of the following signs and symptoms are needed to suspect HIV when these are persistent for more than 3 months:
- Pyrexia more than 38 °C.
- History of chronic diarrhea.
- Weight loss of more than 10%.
- Mailase and lethargy.
- Persistent generalized lymphadenopathy (PGL).
- Night sweating.
- Oral candidiasis.
- Hairy leukoplakia.
- Herpes Zoster infection.
|Bacterial infections||Mycobacterium tuberculosis|
|Atypical mycobacterial infection|
|Viral diseases||Herpes simplex|
|Parasitic diseases||Pneumocystis carinii|
HIV outside the body:
- HIV does not survive outside the body, making the possibility of environmental transmission remote.
- CDC studies have shown that drying even these high concentrations of HIV reduces the amount of infectious virus by 90 to 99% within several hours.
- HIV is unable to reproduce outside its living host, therefore it does not spread or maintain infectiousness outside its host.
Health care worker at risk:
- Although HIV transmission is possible in healthcare settings, it is extremely rare.
- Careful practice of infection control procedures is necessary.
- Protects patients as well as healthcare providers from possible HIV transmission in medical and dental offices and hospitals.
Diagnostic tests are:
- Screening test.
- This test detects antibodies. These are not confirmatory tests. These have to be confirmed by ELISA.
- These tests are done in blood banking for the screening of donors.
- This can also be done for the screening of blood products.
- This test is more specific than the screening antibody test.
- These tests detect viral antibodies and not the antigen.
- There is a window period in which the patient will be negative before seroconversion for the test to become positive.
- It is used for clinical diagnosis, screening of blood, and blood products.
- This cannot detect the HIV infection in the early phase, because there is an interval of 2 to 12 weeks, and this may be even 6 months.
- The person who is infected with HIV becomes a seropositive. This time period is called the window period.
- This is positive in 99% of the case in patients who have had an infection of HIV for the last 12 weeks or more.
- Oral fluid for the antibody to HIV is available instead of serum or plasma.
- This is a simple, non-invasive, and safe method.
- This is easier for the screening of the population and user-friendly.
- This portable method can identify a greater number of infected people with the goal of early detection, early treatment, and prevention.
- This method will decrease the transmission of the disease in the population.
- Western blot is a confirmatory test.
- This test is done to validate the reactive ELIZA.
- The p24 antigen capture assay may detect in the peripheral blood of the patient.
- This may be found as an antigen or antibody to p24.
- p24 antigen can be used to find the neonatal HIV infection, this detects before there is seroconversion and find the progress of AIDS.
- HIV in the urine.
- This test was approved in 1996 by the USA Food and Drug Administration.
- In 1998 license was given for the HIV 1- antibody.
- This is useful when there is a difficulty with venipuncture.
- This is easier, convenient, safer, and cheaper than the serum test.
- HIV viral load.
Interpretation of the serologic tests:
- Serologic antibody test when positive, should be repeated by the ELISA.
- When ELISA is positive then confirm by the western blot or by immunofluorescence assay (IFA).
- Viral RNA may do to confirm HIV.
- In positive ELISA and negative western blot or IFA, then repeat the test after 3 to 6 months.
- The patient with positive ELISA does not have AIDS until patients develop signs and symptoms of diminished immunity.
- Rarely false-positive results may occur.
- HIV RNA antigens may be detected to confirm the diagnosis.
- p24 antigen (protein p24) may be detectable as early as 2 to 4 weeks after infection.
- Recently oral fluids are taken to detect antibodies against HIV.
- Urine may be tested for the HIV antibody.
- These are seen in patients with autoimmune diseases.
- In patients with:
- Lymphoproliferative diseases.
- In patients with syphilis.
- These are seen in the early stage of infection.
- Or in the end stage of HIV infection.
Table showing various serological markers (Virus proteins)
|Test||Detection||Purpose of the test|
|ELISA||Ab to HIV||Screening test|
|Western blot||Ab to HIV||confirmatory test|
|P24 Ag||HIV-1 core protein||support western blot|
|Urine for HIV||Ab to HIV||screening test|
|HIV load||HIV- RNA||marker for diagnosis and AIDS|
|Home screening||Ab to HIV||Screening test|
|oral mucosa sample||Ab to HIV||Screening test|
Recommendation for antiviral treatments based on viral load and CD4+ positive cells:
|CD4+ count||HIV viral load (copies/mL)||Treatment|
|5000 to 30,000||Treatment recommended|
|350 to 500/cmm||<5000||Consider treatment|
|5000 to 30,000||Treatment recommended|
|5000 to 30,000||Consider treatment|
- Antiviral therapy like zidovudine (AZT), Zalcitabine (ddC), Lamivudine (3TC).
- Treatment for opportunistic infection is needed.
- Avoid contact with infected blood.
- Avoid contact with infected blood products and body secretion.
- Compulsory screening of the donor’s blood.
- Educate about safe sex.