HIV and Related Infections

Part I Hassan Mohammad AlShehri

Intoduction
y

Acquired Immunodeficiency syndrome first described in 1981 HIV-1 isolated in 1983, and HIV-2 in 1986 AIDS first described at KSA in1985.

y

y

HIV ± The Virus

HIV - The Virus
y

Family of human retroviruses (Retroviridae)
Subfamily of lentiviridae

y

RNA viruses whose hallmark is the reverse transcription of its genomic RNA to DNA by the enzyme reverse transcriptase ‡ HIV-1 is the most common cause of AIDS worldwide. ‡ HIV-2 has been identified predominantly in western Africa. Small numbers of cases have also been reported in Europe, South America, Canada, and the U.S. Has ~40% sequence homology with HIV-1 More closely related to simian immunodeficiency viruses (monkeys)

y y

HIV - The Virus

HIV - The Virus

HIV - The Virus
y

Each viral particle contains 72 glycoprotein complexes, which are integrated into this lipid membrane, and are each composed of an external glycoprotein gp120 and a transmembrane spanning protein gp41. The bonding between gp120 and gp41 is only loose and therefore gp120 may be shed spontaneously within the local environment. The viral particle contains all the enzymatic equipment that is necessary for replication: a reverse transcriptase (RT), an integrase p32 and a protease p11

y

y

HIVHIV-1 Genotypes
y

There are 3 HIV-1 genotypes; M (Major), O (Outlayer), N ( non M non O), P (Pending the identification of further human cases) M group comprises of a large number subtypes and recombinant forms Subtypes - (A, A2, B, C, D, F1, F2, G, H, J and K) Recombinant forms - AE, AG, AB, DF, BC, CD O and N group subtypes not clearly defined, especially since there are so few N group isolates. Mainly seen in Africa like HIV-2 P a newly analyzed HIV sequence in 2009. Single case of Cameroonian woman residing in France. As yet, different HIV-1 genotypes are not associated with different courses of disease nor response to antiviral therapy.

y

y

y

y

How do you get HIV-AIDS? HIV-

Transmission Routes
y

HIV infection can be transmitted through:

‡ unprotected sexual intercourse with an infected partner. ‡ injection or transfusion of contaminated blood or blood products (infection through artificial insemination, skin grafts and organ transplants is also possible); ‡ sharing unsterilized injection equipment that has been previously used by someone who is infected; ‡ maternofetal transmission (during pregnancy, at birth, and through breastfeeding).

Transmission Routes

Sexual Intercourse
The higher the viral load, the more infectious the patient. y The lower the viral load, the less infectious the patient. y A prospective study of 415 HIV-discordant couples in Uganda showed that of 90 new infections occurring over a period of up to 30 months, none was from an infected partner with a viral load below 1,500 copies/ml.
y

Intravenous Drug Use
y y

IV drug abusers represent the second largest AIDS patient groups in the US and Europe. In contrast to the accidental needle stick injury, the risk of transmission through sharing injection equipment is far higher: the intravenous drug user ensures the proper positioning of the needle by aspiration of blood. Haemophiliacs were one of the first risk groups to be identified.

y

Mother-toMother-to-Child
y

In the absence of any intervention, an estimated 15-30 % of mothers with HIV infection will transmit the infection during pregnancy and delivery. In approximately 75 % of these cases, HIV is transmitted during late pregnancy or during delivery.10-15 % are caused by breastfeeding. In developed countries, vertical HIV infection has become rare since the introduction of antiretroviral transmission prophylaxis and elective cesarean section.

y

Occupational Transmission

Occupational Transmission
y

A 1995 study estimated that although 600,000 to 800,000 needlestick injuries occurred among healthcare workers every year in the USA, occupational infection was not frequent. The risk of occupational HIV transmission from contaminated needles to healthcare workers was found to be 0.3 % in case series performed prior to the availability of potent ART.

Occupational Transmission
y

Risk of transmission from an infected health care worker to patients is extremely low; in fact, too low to be measured accurately.

Transmission by other body fluids
y

Although the virus can be identified from virtually any body fluid, there is no evidence that HIV can be transmitted as a result of exposure to saliva, tears, sweat, or urine. Transmission of HIV by a human bite can occur but is rare.

y

You can't get HIV by:

Being in the same room with someone who has HIV. y Sharing a knife or fork, sheets, toilet seats, or phones with someone who has HIV y Kissing a person with HIV y Shaking hands with someone with HIV y Getting bitten by a mosquito or other bug
y

HIV Replication

HIV - The Virus

Replication
The first step of infection is the binding of gp120 to the CD4 receptor of the cell, which is followed by penetration and uncoating. y The RNA genome is then reverse transcribed into a DNA provirus which is integrated into the cell genome. y This is followed by the synthesis and maturation of virus progeny.
y

Natural history of the disease

HIV and AIDS
The cellular and immunological picture - The course of the disease

virus

CD4 cells

antibody

25

HIV and AIDS

HIV Pathogenesis
y

The profound immunosuppression seen in AIDS is due to the depletion of T4 helper lymphocytes. In the immediate period following exposure, HIV is present at a high level in the blood (as detected by HIV Antigen and HIV-RNA assays). It then settles down to a certain low level (set-point) during the incubation period. During the incubation period, there is a massive turnover of CD4 cells, whereby CD4 cells killed by HIV are replaced efficiently. Eventually, the immune system succumbs and AIDS develop when killed CD4 cells can no longer be replaced (witnessed by high HIVRNA, HIV-antigen, and low CD4 counts).

y

y

y

Acute Viral Syndrome
y

The natural history described in the following refers to HIV infection in the absence of HAART. Defined as the time period from initial infection with HIV to the development of an antibody response. Shows symptoms that often resemble those of mononucleosis. These appear within usually 2 - 12 weeks following exposure to HIV. However, clinical signs and symptoms may not occur in all patients. There is usually a high plasma viremia and frequently a marked decrease in CD4+ T-cells. The CD4+ T-cell count later increases again, normally to levels inferior to the pre-infection values

y y

y

Latency Period
y

y y

Term .latency period. may be misleading, given the incredibly high turnover of the virus and the relentless daily destruction of CD4+ T-cells. At the end of the latency period, a number of symptoms or illnesses may appear which do not fulfil the definition of AIDS Include slight immunological, dermatological, hematological and neurological signs. Many of them are listed in the Category B of the CDC classification system. Constitutional symptoms, such as fever, weight loss, night sweats, and diarrhea may also develop. In this situation, the level of 200 CD4+ T-cells/µl is an important cut-off, below which the risk of many AIDS-defining illnesses increases latency may last 8-10 years or more.

y

y

HIV and AIDS

Good correlation between number of HIV particles measured by PCR and progression to disease

33

HIV and AIDS

CD4 cell count is not a good predictor of progression to disease

34

Diagnosis

Laboratory Diagnosis
y

y

y

Serology is the usual method for diagnosing HIV infection. Serological tests can be divided into screening and confirmatory assays. Screening assays should be as sensitive whereas confirmatory assays should be as specific as possible. Screening assays - ELISA is the most frequently used screening assays. The sensitivity and specificity of the presently available commercial systems now approaches 100% but false positive and negative reactions occur. Some assays have problems in detecting HIV-1 subtype O. Confirmatory assays - Western blot is regarded as the gold standard for serological diagnosis. However, its sensitivity is lower than screening EIAs.

ELISA
y

False-positive results can occur with: x Antibodies to class II antigens x Autoantibodies x Hepatic disease x Recent influenza vaccination x Acute viral infections
ELISA

Western Blot
Most commonly used confirmatory test y Detects antibodies to HIV antigens of specific molecular weights y Antibodies to HIV begin to appear within 2 weeks of infection. y Period of time between initial infection and development of detectable antibodies is rarely >3 months.
y

Western blot for HIV antibody

The most important antibodies are those against the envelope glycoproteins gp120, gp160, and gp41

Western blot for HIV antibody

Algorithm of serologic testing

Direct Detection of HIV
y

These tests are useful in:
Patients with a positive or indeterminate EIA result and an indeterminate Western blot result or Patients in whom serologic testing may be unreliable (such as those with hypogammaglobulinemia)

Direct detection of HIV
y

Tests:
y

Immune complex dissociated p24 antigen capture assay
x Plasma p24 antigen levels increase during the first few weeks following infection, before the appearance of anti-HIV antibodies.

y y y

HIV RNA by polymerase chain reaction (PCR) HIV RNA by branched DNA HIV RNA by nucleic acid sequence-based assay
PCR

Rapid Tests
Rapid tests are similar to the standard ELISA test in that they look for antibodies to HIV in the patient¶s blood+/-saliva+/-serum. y They are called ³rapid´ because the results are available within an hour or less.
y

Reading Results: Genie II

Non-reactive

Reactive

Reading Results: Determine
Non- Reactive

Reactive

Reactive

Control line Sample Test line Pad
Lab workers Health workers Counselors

Reading Results: OraQuick

Reactive NonReactive

References
y y

http://www.cdc.gov/hiv/resources/reports/hiv_prev_us.htm http://www.cdc.gov/nchhstp/newsroom/docs/FastFacts-MSMFINAL508COMP.pdf http://www.co.sanmateo.ca.us/vgn/images/portal/cit_609/31/5/10214 25659factors_delayed_hiv_article.pdf Kumar and Clark Clinical Medicine Harrison principle of internal medicine Harrison's Principle of Internal Medicine plaza.ufl.edu/mounaht/Group%25209%2520Chapter%252030%252 0Lesson%25202%2520Powerpoint(new)%255B1%255D.ppt

y

y y y y

THANK

YOU!