AIDS Work

Providing help for people with HIV and AIDS

Laboratory Diagnosis of HIV

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Diagnosis is defined as the demonstration of HIV 1 and HIV 2 antibodies or antigens in blood or body fluids. Antibody detection tests are the most commonly used tests. Test to detect the virus are available but have largely remained research tools and confined to monitoring progress of infection of response to therapy rather than for diagnosis. However these test are ideal for the diagnosis of HIV in infants and during the window period.

For the diagnosis of HIV infection, at least two test systems of different antigen preparation or test principles must be used for each sample. Tests with a high specificity must be used to minimize the rate of false positive results. If the two tests are concordant, the result is reported, if discordant, the tests are repeated. If they continue to be discordant, a supplemental test or a tiebreaker is used to determine HIV infection status.

a) What is the Window period?
The window period represents the period of time between initial infection with HIV and when the body builds a measurable antibody response. During this period, HIV replicates in the blood and lymph nodes, but the infected person has no measurable antibody response. The virus can be detected during this phase by laboratory tests used to identify the virus itself. The window period can last from 2 to 12 weeks.

b) Types of HIV Tests: There are two main types of tests:

  1. The first is the antibody test, which is often just referred to as the HIV test. This shows whether a person is infected with HIV, the virus that causes AIDS.
  2. The second is the viral test. This test shows the level of virus in the blood. It is usually used to monitor the health of someone who already knows they are infected.

The sensitivity of test means the percent of those identified by the test as having the infection actually have it. The specificity of a test means the percent of those identified by the test as not having the infection that are actually infection free. With never methods of test and reagent development, the currently available assays have excellent sensitivity and specificity.

HIV tests are grouped into three categories:

  1. Screening tests
  2. Confirmatory or supplemental tests
  3. Antigen screening tests

Most commonly used screening tests are Enzyme linked immunoassays (ELISA) and simple/rapid tests.

ELISA is most appropriate for large laboratories where large numbers of samples are processed per day. ELISA’s however suffer from the disadvantage that they require skilled scientific/technical skills and specialized equipment, which can be expensive and usually are not readily available at smaller health institutions.

There are four types of rapid or simple tests:

  • Agglutination assays
  • Comb/dipstick assays
  • Lateral flow membrane assays
  • Flow through membrane assays

Rapid tests are most appropriate for the smaller health institutions where only a few samples are processed each day. Rapid tests are quicker and do not require specialized equipment. Rapid tests, by definition, take up to 10 minutes. Most are dot/blot immunoassays or agglutination assays requiring no instrumentation or specialized training and are fast to perform. Most rapid tests have to be given on the same day as testing thus reducing the number of visits made by the clients. There is also an increased likelihood of clients receiving test results as opposed to the numbers who may not return when same day testing regimes are not used.

Chronology of HIV/AIDS

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Here is a brief chronology of HIV/AIDS:

1930 – Some time between 1910 and 1950 with 1930 being the most likely date HIV-1 M appears as a unique new retrovirus. There is still much debate as to how HIV first appeared in human hosts.

1959 – The oldest confirmed case of HIV is discovered when a blood sample from a Bantu male who died in 1959 is found to be positive for HIV-1 through immunoassay, immunoflourescence, Western blotting, and radioimmunoprecipitation methods. In the 1985 retesting, Emory and Harvard University scientists used four different procedures on the samples and found one that was positive for HIV. The specimen, which came to be known as ZR59, had been taken from an unidentified African male from the area near Leopoldville (present-day Kinshasa) in 1959.

1978 – Gay men in the US and Sweden begin to show symptoms of what will latter be identified as HIV/AIDS. The first signs of heterosexual HIV/AIDS appear in Haiti and Tanzania.

1981 – Gay cancer (Kaposi’s Sarcoma) latter to be called GRID is noticed in New York and San Francisco. 181 die in the US from what is letter determined to be HIV/AIDS

1982 – The CDC’s Doctor Donald Francis and his team determine that GRID is a blood borne disease agent. 1,201 cases of AIDS and 463 death cases because of AIDS in the US.

1983 – The CDC warns blood banks of a potential problem with the nations blood supply. The Pasteur Institute in France isolates the HIV retrovirus. 3,145 cases of AIDS and 1,508 death cases due to AIDS in the US.

1984 – Dr. Robert Gallo claims that he found the virus that leads to AIDS; nevertheless, this is about a year after the French discovery. 9,035 cases of AIDS and 3,502 death cases because of AIDS in the US.

1985 – The US FDA sanctions an HIV antibody test. Blood products begin to be tested in the US and Japan. Atlanta hosts the first International Conference on AIDS. 11,990 cases of AIDS and 6,972 death cases because of AIDS in the US.

1986 – C. Everett Koop US Surgeon General issues a report calling for sex education to include information on HIV/AIDS. Europe begins to test blood supplies for HIV antibodies.  19,319 cases of AIDS and 12,110 death cases because of AIDS in the US.

1987 – Glaxo Wellcome’s drug Zidovudine (AZT) becomes first drug approved by the FDA for treatment of HIV/AIDS. Canada begins testing blood supply. FDA approved the first Western blot blood test kit – a more specific test. FDA Published regulations which require screening all blood and plasma collected in the U.S. for HIV antibodies. The US issues rules denying entrance visa’s to travelers and closes immigration for HIV infected people. After six years of deadly silence US President Ronald Reagan mentions the word AIDS in a public speech for the first time. Vice President George Bush calls for mandatory HIV testing. 28,999 cases of AIDS and 16,412 death cases due to AIDS in the US.

1988 – Surgeon General C. Everett Koop pushes forward the printing and distribution of 107 million copies of a booklet entitled “Understanding AIDS”. Trimetrexate was the first AIDS drug to be granted pre-approval distribution status under the FDA’s new Treatment IND regulations. 35,957 cases of AIDS and 21,119 death cases because of AIDS in the US.

1989 – First treatment for PCP (pentamidine mist) is approved for use by the FDA. FDA approved Cytovene (ganciclovir) infusion for use in the treatment of cytomegalovirus retinal infections in persons with AIDS. FDA Licensed the first diagnostic kit to detect the presence of HIV-1 by directly detecting the proteins, or antigens, of the virus. 43,168 cases of AIDS and 27,791 death cases due to AIDS in the US.

1990 – Ex-President Ronald Reagan apologizes for his neglect of the deadly HIV/AIDS epidemic during his presidency. FDA approved Diflucan (fluconazole) tablets to treat two serious AIDS-related fungal infections (Cryptococcal meningitis and candidiasis).  49,069 cases of AIDS and 31,538 death cases because of AIDS in the US.

1991 – Bristol Myers Squibb’s anti-retroviral medication Videx (ddI, didanosine) is approved for use in the US. The World Health Organization estimates that there may be as many as 10 million people infected with HIV world wide. A coalition of gay and HIV/AIDS activists campaign for accelerated approval of medications used in the treatment of AIDS and AIDS related illnesses in the US. The CDC estimates that there may be as many as 1 million HIV infected US citizens. 60,124 cases of AIDS and 36,616 death cases because of AIDS in the US.

1992 – Roche Labs gains FDA approval for Hivid (ddc, zalcitabine). Combo drug treatment regimens undergo first clinical trials in the US. The US government starts interim licensing (accelerated approval) for medications used to treat AIDS and AIDS related illnesses. 79,054 cases of AIDS and 41,270 death cases because of AIDS in the US.

1993 – The definition of AIDS used for reporting purposes by the CDC is modified to include new opportunistic infections. The controversial British-French Concorde study is released to the public, indicating that early use of AZT monotherapy does not delay the onset of AIDS. 79,034 cases of AIDS and 44,896 death cases because of AIDS in the US.

1994 – Bristol Myers Squibb’s Zerit (d4t) is approved for us in the US. FDA approved Bactrim and Septra (trimethoprim/sulfamethoxazole) for a new indication for prophylaxis against Pneumocystis carinii pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing Pneumocystis carinii pneumonia. 71,209 cases of AIDS and 49,311 death cases because of AIDS in the US.

1995 – For the first time there is a reduction in new AIDS cases compared to the previous year in the US. As a result of combo therapy the rate of growth in death cases due to AIDS also slows for the first time in 1995. In December the first Protease inhibitor class drug Roiche’s Saquinavir (invirase) is approved for use in the US. Glaxo Wellcome gains approval for Epivir (3TC, lamivudine). The US government admits that the discovery of HIV was first accomplished by the Pasteur Institute not Robert Gallo. 66,233 cases of AIDS and 49,897 death cases because of AIDS in the US.

1996 – With the first full year of widespread use of HAART death cases due to AIDS and new AIDS cases both are less then the previous year in the US. Crixivan, Norvir, and Viramune approved for use in the US. Researchers show that Kaposi’s sarcoma is most likely caused by the combination of diminished immune function and herpes virus. Dr. David Ho is the name in the news at the Vancouver BC International AIDS conference. 54,656 cases of AIDS and 37,359 death cases because of AIDS in the US.

1997 – FDA granted accelerated approval for Viracept (nelfinavir) the first protease inhibitor labeled for use in children, as well as adults. FDA approved Fortovase, a new formulation of Invirase (saquinavir) for the treatment of HIV-1.  New cases of AIDS and death cases due to AIDS continue to decline in the US. The WHO estimates that the total worldwide death count due to AIDS may be 6,400,000. The approximate number of HIV-positive people worldwide is said to be 22,000,000.  There are 31,153 new AIDS cases and 21,437 death cases because of AIDS in the US.

1998 – FDA approved Sustiva (efavirenz), DuPont Pharmaceuticals, to treat HIV and AIDS. Ziagen (abacavir) is approved for use in the US. New AIDS cases begin to rise in the US death cases because of AIDS continue to decline. There are 48,269 new AIDS cases and 17,171 death cases because of AIDS in the US.

1999 – Amprenavir is approved for use in the US. Genotype and Phenotype testing see increased use by US physicians in planning treatment for AIDS patients who have shown signs of failure on HAART. The CDC has not released the year end figures for 1999 as of this date.

HIV/AIDS Disease

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AIDS stands for Acquired Immune Deficiency Syndrome. “Acquired” means not innate nor inherited but transmitted from person to person; “Immune” is the body’s system of defense; “Deficiency” means not working to the appropriate degree; and “Syndrome” means a group of sings and symptoms. AIDS is the advanced stage of HIV infection. It is a disabling and deadly disease caused by HIV. Because HIV progressively destroys the immune system, without any treatment most people, particularly in resource-constrained settings, will die within a few years of the first signs of AIDS.

After the HIV virus enters a person’s body, it infects and starts to replicate in the person’s cells (essentially CD4 T cells and macrophages). It is believed that in a small number of people, HIV may enter a latent phase with limited replication. In the majority of people, the replication is significant and infection with HIV induces the body’s immune system to produce antibodies specific to HIV. The period between the acquisition of the infection and the production of HIV detectable antibodies is called the “window period”. The window period can last for 2-12 weeks. During this period the person is highly infectious but may not test positive on common HIV antibody tests. Up to 30-50% of people have a recognizable acute illness at the time to infection characterized by fever, lymphadenopathy) enlargement of lymph nodes), night sweats, skin rash, headache, and cough.

HIV-infected people may remain symptomatic for periods to as long as 10 or more years. People in this phase potentially play an important role in the transmission of HIV as they remain infectious and can be identified only by screening their scrum for HIV antibodies. After a variable period of time that varies from one individual to another, viral replication resumes and is accompanied by a destruction of CD4 lymphocytes and other immune cells resulting in a progressive immunodeficiency syndrome. The progression depends on the type and factors as that may cause faster progression including age less that 5 years, or over 40 years, other infections and possible genetic (hereditary) factors. As HIV infection progresses and immunity declines, people become more susceptible to opportunistic infections (Ols). The three most commonly reported Ols in South East Asia are tuberculosis (TB), Pneumocystis carinii pneumonia and extra pulmonary cryptococcosis (usually meningitis).

WHO has proposed a clinical staging system for HIV infection and disease in adults and adolescents in 1989 in four clinical stages. In addition to the signs, symptoms and diseases, physical activity was added to the framework using the performance scale, a modification of the Eastern Co-operative Oncology Group score. Patients are classified according to the presence of the clinical condition, or performance score, belonging to the highest stage. The staging system is hierarchic: once a stage is reached, the patient cannot revert to a lower stage, he/she can only progress to a higher once. A laboratory axis measuring CD4 count was introduced in 1990.

Rates of progression to AIDS are influenced by plasma viral load and CD4 T cell count. The higher the viral load (the amount of virus in the body) the lower the CD4 count and the higher the chances of progressing to AIDS and death. Death may be due to HIV, Ols, or malignant diseases. The prevention and better management of opportunistic infections can have a beneficial impact on the progression of HIV infection.

Brief History of AIDS

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AIDS describes itself – it is not a disease as such, rather a condition of various signs and symptoms (a syndrome) due to an immune deficiency that is not inherited, therefore it must be acquired from somewhere.

AIDS was first noticed in 1981 from reports of previously rare diseases appearing in unexpectedly high numbers of homosexual men.  Two years later a new, unique virus was isolated from a patient with persistent generalized Lymphadenopathy.  Subsequent characterization of the virus, and repeated isolations and antibody detection from at-risk populations as well as those with frank AIDS, further established this virus as the etiologic agent, eventually resulting in its naming as Human Immunodeficiency Virus.

Since that time HIV has been estimated to have infected over 33 million people worldwide, the vast majority in Africa.  Relatively few cases are seen in the developed nations, but they still number in the hundreds of thousands.  As of Dec 1999 North America was said to have 920,000 people currently living with HIV and AIDS and 16.3 million people are said to have died from AIDS worldwide.

What is HIV

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Human Immunodeficiency Virus (HIV) is the virus that causes AIDS. Two types of HIV are currently known: HIV-1 and HIV-2. World wide, the predominant virus is HIV-1. Although cases of HIV-2 have been reported in several parts of virus are transmitted by sexual contact, through blood, and from mother-to-child during pregnancy, delivery, or breast feeding. They both appear to cause clinically indistinguishable AIDS. However HIV-2 is less easily transmitted and the period between initial infection and illness is longer than in HIV-1 cases. Cases of concurrent infections with the two viruses have been described in West Africa.

HIV belongs to the family of retroviruses. Like all retroviruses HIV contains RNA in its core and to live and replicate it needs a host cell. HIV preferentially infects a specific subset of white blood cells (CD4) that are fundamental in the immune defense system of the human body. Once the contact is made between the virus and the human cell, the virus transfers its RNA into the human cell. The RNA is transformed with the help of a substance (enzyme) called reverse transcriptase into DNA that is inserted into the human cell’s DNA to become an integral part of the human cell’s genetic material and therefore making the infection permanent.

Outside of the human body, HIV is easily destroyed. Heat (temperature higher than 60o centigrade) and various disinfectants such as formaldehyde, bleach, alcohol, acetone, phenol, and others are effective ways to destroy HIV.