Science and Society science basics of HIV/AIDS

Diagnosis of AIDS, Symptoms of AIDS-related disease(s), and Treatments

Steve Sipes and Michael Sugarman

Diagnosing AIDS

It is important to note that everyone who has AIDS is infected with HIV; however, not everyone with HIV has AIDS. AIDS is the secondary condition that occurs after the depletion of the immune system over a period of time. At different stages of depletion, the immune system becomes unable to fight infections and disease, the body begins to manifest different related illnesses accordingly.

Therefore, formal AIDS diagnosis in an HIV-positive individual is defined in two parts:

T-cell count.
History of an AIDS-defining disease

A T-cell count is a test to determine the actual level of specific T-lymphocyte cells, known as CD-4 cells, in the blood stream. These T-lymphocyte cells, or CD4 cells, help the immune system detect the presence of foreign matter within the body. They are responsible for “alerting” the immune system to these particles, which allow the immune system to create antibodies to fight the foreign matter. However, because these types of cells have receptor sites that allow HIV to attach and infect, they are the cells compromised by HIV infection which ultimately results in immune system failure. Once HIV infection and virus replication occurs, these cells die. This leads to the immune system being unable to combat other infections or diseases. The loss of these cells is directly related to the presentation of AIDS-defining diseases.

AIDS related Diseases

The Following list on Opportunistic Infections related to HIV has been copied from the AIDS Education Global Information System website (available at:htttp://www.aegis.com/topics/oi )

Bacterial and Mycobacterial

Mycobacterium Avium Complex (MAC, MAI)
Salmonellosis
Syphilis and Neuroshyphilis –
Turberculosis (TB)
Bacillary angiomatosis (cat scratch disease)

Fungal Infections

Aspergillosis
Candidiasis (thrush, yeast infection)
Coccidioidomycosis
Cryptococcal Meningitis
Histoplasmosis

Malignancies

Kaposi's Sarcoma
Lymphoma --

Systemic Non-Hodgkin's Lymphoma (NHL)
Primary CNS Lymphoma

Protozoal Infections

Cryptosporidiosis
Isosporiasis
Microsporidiosis
Pneumocystis Carinii Pneumonia (PCP)
Toxoplasmosis

Viral Infections

Cytomegalovirus (CMV)
Hepatitis
Herpes Simplex (HSV, genital herpes)
Herpes Zoster (HZV, shingles)
Human Papiloma Virus (HPV, genital warts, cervical cancer)
Molluscum Contagiosum
Oral Hairy Leukoplakia (OHL)
Progressive Multifocal Leukoencephalopathy (PML)

Neurological Conditions

AIDS Dementia Complex (ADC)
Peripheral Neuropathy

Other Conditions and Complications

Apthous Ulcers
Malabsorption

Depression
Diarrhea
Thrombocytopenia
Wasting Syndrome
Idiopathic thrombocytopenic purpura
Listeriosis
Pelvic inflammatory disease, particularly if complicated by tubo-ovarian abscess
Lymphoma, Burkitt's (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)

Treatments

While there is currently no cure once a patient is infected, there are drugs which are meant to inhibit HIV progression and thus reduce development of the related diseases that are secondary to infection. Anti-retroviral or anti-HIV medications approved by the Federal Drug Administration (FDA) are classified based upon how they interact with HIV, and can be divided into the following four categories:

I. Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

NNRTIs bind to reverse transcriptase, inhibiting its ability to bind to and transcribe the viral RNA into the DNA which would be incorporate into the host genome to form the Provirus.

II. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

NRTIs are modified nucleotides (building blocks of DNA or RNA) that compete with the normal nucleotides. When NRTIs are inserted by the reverse transcription process they block the insertion any more nucleotides causing early chain termination. Full length DNA cannot be made and the viral life cycle is interrupted..

III . Protease Inhibitors (PIs)

PIs target the HIV protease. These drugs inhibit the ability of this protease to cleave other viral proteins and thereby restrict the ability of HIV to infect new cells. This results in a reduced viral presence in the blood stream and an increased CD4 cell count.

IV. Fusion Inhibitors (FIs)

FIs bind to the glycoprotein spikes on the outer envelope of HIV. When bound to the glycoproteins, FIs prevent fusion of virus and host cells, thereby blocking entry of newly made virus into other CD4 cells.

Classes 1 to 3 target specific functions of the proteins of HIV once infection of a cell has occurred. However, Fusion Inhibitors (Class 4) interact with HIV before infection of a cell occurs by disallowing the virus to attach to other cell receptor sites.

Do some people possess a natural immunity to HIV?

At present, there is scientific debate concerning HIV immunity. Technically a person who is infected with HIV is HIV positive. Therefore, a person cannot stop the tran smission or being infected by HIV. However, AIDS-related symptoms may not be exhibited in some people and, in fact, might never manifest. Researchers have theorized that 10% of Northern Europeans exhibit this type of “immunity” to the virus.

Genome sequencing has shown that 10% of Northern Europeans and those of Northern European descent have a deletion of 32 base pairs in the gene for the CCR5 chemokine co-receptor that facilitates HIV attachment to a host cell. Researchers hypothesize that this genetic deletion in a CCR5 allele may have been selected for during either Black Plague or smallpox or other myxoma virus epidemics. This allele has also been found at 2-5% frequency throughout the rest of Europe, the Middle East , and the Indian subcontinent [ J. J. Martinson, et al., (1997) Nature Genetics 16 :100-3]. It is absent in African, Native American and East Asian populations. It is possible that pressure for mutation of this gene could have been caused by one of several disease causing agents that use this co-receptor to gain entry to host cells. Although Yersinia pestis (causative agent of Plague) does not use CCR5 to gain entry into host cells, it replicates with 30-fold lower efficiency in mice missing CCR5. Thus, the role of plague in the selection of the CCR5 deletion remains as a hypothesis, though less accepted.

This gene mutation which eliminates CCR5 function has been known to have a negative effect on some of the T-cell functions within the immune system. It actually appears to correlate with an increased risk of West Nile Virus illness—particularly the encephalitis (brain inflammation) of serious WNV infections. However it appears to protect against HIV by inhibiting viral attachment to the cell membranes and helping with immunity to small pox. The virus itself can be receptor-site specific, in that it needs the CCR5 protein in addition to CD4 for productive binding to a host cell, ie, without normal CCR5 the HIV particle cannot bind to a host cell. At least 50% of all HIV positive people have the CCR5-dependent type of virus.

This is important in that the CCR5-dependent viruses are the most predominant types during the transmission and the acute phase of the disease; this combined with the lack of functional CCR5 helps slow the progression of the virus in general. This means that it is still possible for people to contract HIV and become carriers of the virus rather than going to full-blown AIDS status.

Appendix

The Following list has been copied and partially modified from the U.S. Food and Drug Administration's Drugs Used in the Treatment of HIV Infection (available at: http://www.fda.gov/oashi/aids/virals.html )

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Brand Name	Generic Name	Manufacturer Name
Combivir	lamivudine and zidovudine	GlaxoSmithKline
Emtriva	FTC, emtricitabine	Gilead Sciences
Epivir	lamivudine, 3TC	GlaxoSmithKline
Epzicom	abacavir/ lamivudine	GlaxoSmithKline
Hivid	zalcitabine, ddC, dideoxycytidine	Hoffmann-La Roche
Retrovir	zidovudine, AZT, azidothymidine, ZDV	GlaxoSmithKline
Trizivir	abacavir, zidovudine, and lamivudine	GlaxoSmithKline
Truvada	tenofovir disoproxil/emtricitabine	Gilead Sciences, Inc.
Videx EC	enteric coated didanosine	Bristol Myers-Squibb
Videx	didanosine, ddI, dideoxyinosine	Bristol Myers-Squibb
Viread	tenofovir disoproxil fumarate	Gilead
Zerit	stavudine, d4T	Bristol Myers-Squibb
Ziagen	Abacavir	GlaxoSmithKline

Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Brand Name	Generic Name	Manufacturer Name
Rescriptor	delavirdine, DLV	Pfizer
Sustiva	Efavirenz	Bristol Myers-Squibb
Viramune	nevirapine, BI-RG-587	Boehringer Ingelheim

Protease Inhibitors (PIs)

Brand Name	Generic Name	Manufacturer Name
Agenerase	Amprenavir	GlaxoSmithKline
Aptivus	Tipranavir	Boehringer Ingelheim
Crixivan	indinavir, IDV, MK-639	Merck
Fortovase	Saquinavir	Hoffmann-La Roche
Invirase	saquinavir mesylate, SQV	Hoffmann-La Roche
Kaletra	lopinavir and ritonavir	Abbott Laboratories
Lexiva	Fosamprenavir Calcium	GlaxoSmithKline
Norvir	ritonavir, ABT-538	Abbott Laboratories
Reyataz	atazanavir sulfate	Bristol-Myers Squibb
Viracept	nelfinavir mesylate, NFV	Agouron Pharmaceuticals

Fusion Inhibitors

Brand Name	Generic Name	Manufacturer Name
Fuzeon	enfuvirtide, T-20	Hoffmann-La Roche & Trimeris

REFERENCES

http://www.aidsinfo.nih.gov/ContentFiles/ApprovedMedstoTreatHIV_FS_en.pdf

http://www.aidsinfo.nih.gov/Vaccines/Vaccines.aspx?MenuItem=Vaccines

http://www.fda.gov/oashi/aids/virals.html

http://www.cdc.gov/hiv/pubs/faq

http://www.aegis.com/topics/oi

J. J. Martinson, et al., (1997) Nature Genetics 16 :100-3.