Researchers have found human immunodeficiency virus (HIV) in virtually every body fluid, including: breast milk, tears, saliva, urine, blood, semen, mucus, vaginal and anal secretions. Despite that, HIV is not casually transmitted from one individual to another. The CDC estimates that in 2006, only 5 new HIV infections were generated by every 100 persons living with HIV.

3 conditions must be met for the transmission of HIV infection:

1. HIV must pass beyond the recipient host's barrier protection, either cutaneous or membraneous.
2. HIV must contact and gain access to a receptive host cell
3. HIV must replicate.

Efficient transmission of HIV is influenced by a number of factors:

• Concentration of HIV in the blood (plasma viral load), varies over the course of the disease. In the untreated patient, highest viral load occurs within a few weeks following initial infection then drops markedly during the intermediate phase and increase again during the AIDS phase. HIV is much more likely to be transmitted from one individual to another when there is a high concentration of HIV. Plasma viral load is reflected in other body fluids. The highest viral load is associated with fluids that contain large numbers of infected CD4⁺ cells.42
  
• Very low levels of HIV are found in saliva and tears.
• Moderate levels of HIV are found in anal and vaginal secretions.
• High levels of HIV are found in blood, semen, vaginal secretions during menses, and breast milk.
• Concurrent disease can increase the concentration of HIV in secretions of the infected host (hostⁱ⁾ and increase the susceptibility of the susceptible host (host^s)*:
  • Genital tract inflammation can increase the viral load of genital secretions in hostⁱ by increasing immune response and the number of infected CD4+ cells and viral shedding
  • Genital inflammation in host^s can increasing the number of CD4⁺ target cells in the mucosa.
  • Inflammatory sexually transmitted diseases (STDs) including gonorrhea, Chlamydia trachomatis, and trichomoniasis are associated with increased transmission and acquisition.
  • Ulcerative STDs including; syphilis, chancroid and genital herpes simplex are inflammatory and provide a breach in integumentary defenses.
  • Alterations in host^s genital microflora and pH, i.e. bacterial vaginosis, has been associated with increased HIV acquisition.
  • Douching, irritating contraceptive gels and traumatic sexual intercourse can produce inflammation.
• Gender differences:
  • Hormonal contraceptives can increase the HIV susceptibility of the endocervix which has a higher concentration of HIV receptive cells.
  • A window of enhanced HIV susceptibility exists between days 14-21 in the menstrual cycle as the female reproductive tract is preparing for implantation
  • Penile foreskin contains a high concentration of dendritic cells. It is generally accepted that circumcision significantly reduces risk of transmission.
• Treatment with highly active antiretroviral therapy (HAART) can supress the infected host HIV plasma load which can inturn reduce the risk of acquisition in a susceptible host.

Modes of transmission

• Mucocutaneous exposure to HIV is often the result of infected fluid contact during sexual intercourse, but HIV can be transmitted across other membranes as well. The immune defenses common to epithelial membranes make them capable of internalizing HIV. Dendritic processes of Langerhans cells, present within intact genitourinary, gastrointestinal, ocular and oral mucosa, sample the external environment for antigens. They are able to capture foreign antigen including HIV infected cells and cell free virions and present them to subepithelial T cells which activate the immune response.*, *,
  
  "Macrophages and Langerhans cells in epithelia such as in the genital tract are important both as reservoirs and vectors for the spread of HIV in the body. Langerhans cells (a subset of blood dendritic cells) act as antigen presenting cells for CD4 lymphocytes. Both macrophages and Langerhans cells can be HIV-infected but are not destroyed themselves. HIV can then be carried elsewhere in the body. Within lymph nodes, HIV virions are trapped in the processes of follicular dendritic cells (FDC's), where they may infect CD4 lymphocytes that are percolating through the node. The FDC's themselves become infected, but are not destroyed."*
  
  
• The incidence of seroconversion following topical contact of HIV⁺ body fluid with intact or non intact skin have been documented but very rarely. A study by Kawamura; Koyanagi; Nakamura; et al. indicates that Langerhans cells may play a critical role in virus dissemination from epithelium to cells located within subepithelial tissue. The study raises the the possibility that "initiation of antiretroviral drugs soon after percutaneous HIV exposure may not prevent infection of Langerhans cells, which is likely to occur rapidly, but may prevent or limit subsequent LC-mediated infection of T cells".*
  
  
• Parenteral exposure is defined as subcutaneous, intramuscular or intravenous contact with blood or other body fluid of an HIV-1 infected individual. Parenteral transmission of HIV increases when: a) the injury is deep; b) the injuring object is visibly contaminated with another person's blood; c) the injuring device was used to enter another person's blood stream; d) the source died of AIDS within two months following the percutaneous injury.*

  Each incident should be reported and treated as indicated. Rates of disease transmission are significantly reduced with timely and appropriate post-exposure antiviral prophylaxis.
  

• Transfusion with HIV infected blood products presents the highest risk of seroconversion among all modes of transmission.* In the U.S. HIV infection from transfusion is very rare. Voluntary deferral of donors at risk for HIV infection and routine HIV antibody testing of all blood donations has significantly reduced risk. The CDC estimates the risk for "acquiring HIV infection through blood transfusion today is estimated conservatively to be one in 1.5 million, based on 2007--2008 data".
  
  However, HIV antibody tests can fail to identify infected blood donated by a person who has not yet seroconverted. The time necessary for the infected person to produce enough HIV antibodies to be detectable is about 22 days. The HIV antigen p24 test can detect capsular protein at about 16 days. Nucleic acid amplification test (NAT) can detect HIV-1 RNA in as few as 11 day following infection. During these latent "window" periods occult viral replication continues and the donor is infectious. Every effort is being made to close these "window" periods.
  
  "In June 2008, a man in his forties donated whole blood at a blood center in Missouri. He was a repeat blood donor who reported no HIV risk factors on the routine eligibility screening questionnaire. He was not compensated for his blood donation. His whole blood donation was screened at a reference laboratory for HIV by enzyme immunoassay (EIA) (Genetic Systems HIV-1/HIV-2 Plus O EIA, Bio-Rad Laboratories, Redmond, Washington) and by nucleic acid amplification testing of minipools of plasma specimens (MP-NAT) from 16 donations (Procleix HIV-1 Nucleic Acid Test, Gen Probe, San Diego, California); both tests were negative. Components from this donation later were transfused into two recipients. No specimens from this donation were stored. In November 2008, the man donated blood again at the same blood center and again reported no risk factors on the routine eligibility screening questionnaire. At that time, his blood tested positive for HIV by EIA, MP-NAT, and indirect immunofluorescence assay (Fluorognost HIV-1 IFA, Sanochemia Corporation, Vienna, Austria). The man was placed on the list of donors who are indefinitely ineligible for future donation, all products from this donation were destroyed, and the man was notified by the blood center of his probable HIV infection. The Missouri Department of Health and Senior Services (MDHSS) was notified of this case on December 4, 2008. Because of the rare possibility that the donor might have been infected shortly before his June 2008 donation and donated blood that contained HIV at a concentration too low to be detected, an investigation was initiated to determine whether recipients of the June donation had been infected with HIV, consistent with regulatory requirements to investigate such events."
  
  The investigation initiated by the blood center identified two recipients of blood components (packed red blood cells and fresh frozen plasma) derived from the donor's June 2008 donation. In July 2008, one unit of packed red blood cells from the donor was transfused into a patient in Arkansas during cardiac surgery. This patient died 2 days later from cardiac disease; no premortem or postmortem material was available for testing, and it was unknown whether the patient had been infected with HIV.
  
  In August 2008, one unit of fresh frozen plasma from the donor was transfused into a patient receiving a kidney transplant in Colorado. The recipient's most recent negative serum test for HIV infection (using HIV EIA) was in July 2005. The patient had been receiving regular hemodialysis for management of kidney failure since July 2005. From that date to the date of kidney transplantation, the patient reported no behavioral or health-care--related risk factors for HIV infection and did not received blood components. The kidney donor tested negative for HIV infection by EIA and NAT at the time of organ donation.
  
  In December 2008, MDHSS notified the Colorado Department of Public Health and Environment (CDPHE) that the plasma was from a donor who subsequently tested positive for HIV, and CDPHE notified the recipient's transplant surgeon. When the recipient visited the transplant clinic in December 2008, serum was nonreactive by HIV EIA, but plasma HIV RNA viral load was 7,240 copies/mL, and CD4 cell count was very low (48 cells/µL). At this time, the recipient was placed on antiretroviral therapy. The patient also was receiving mycophenolic acid, a drug used to prevent rejection in organ transplantation that is also a potent inhibitor of both lymphocyte proliferation and HIV replication in CD4+ T cells and macrophages. Physical examination demonstrated no other signs or symptoms of HIV infection. After antiretroviral therapy was initiated, the patient's HIV RNA viral load became undetectable, and CD4 cell count increased to 88 cells/µL in June 2009. HIV EIA repeated in April 2009 was reactive, but the Western blot was indeterminate, with reactivity to the nonviral p38 and p42 bands and weak reactivity to gp120.
  
  HIV DNA from blood specimens collected from the donor and the recipient was amplified and sequenced at CDC. Comparison of these sequences demonstrated that the virus from the donor and recipient were greater than 99% identical, confirming that the donor's 2008 donation was the source of the recipient's HIV infection."*
  
• Transplantation associated unintentional HIV transmission is rare in America. 2013 Public Health Service Guideline for Reducing Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus Transmission Through Organ Transplantation. These new recommendations are intended, in part, to strengthen the procedures involved in donor risk assessment and donor screening for HIV, HBV and HCV. Some major changes from the previous guidelines include:
• Recommendation that donors be screened for both HBV and HCV, in addition to HIV. Although organ donors are routinely screened for HBV and HCV, there were no specific PHS recommendations for this screening included in the 1994 guideline.
• Recommendation for new, more sensitive laboratory testing. Since the 1994 PHS guidelinewas published, more sensitive tests for HIV, HBV and HCV have become available. The 2013 guideline recommends the use of more sensitive tests for living and deceased organ donors.
• Inclusion of a revised set of risk factors for HIV, HBV or HCV infection. Updated information about risk factors for these infections can give clinicians a clearer picture about possible risks associated with donated organs to improve recipient informed consent, and in certain circumstances, trigger more sensitive laboratory testing of the donor and recipients.
• Focus only on organs and vessel conduits recovered for transplantation, and not other tissues. The Food and Drug Administration (FDA) has implemented more comprehensive regulations for tissue and semen donors since the 1994 PHS guideline was published.•
  

Viral replication (click here for and interactive diagram of HIV replication)

Infection takes place only when the human immunodeficiency virus (HIV) enters the body and completes a specific set of processes:
1. Binding and fusion: The virus binds with receptors (CD4 and one additional) on the surface of a cell, then fuses with the host cell, inserting its RNA into the host cell.
2. Reverse transcription: An HIV enzyme (reverse transcriptase) uses the single-stranded HIV RNA to assemble a double-stranded HIV DNA molecule.
3. Integration: The HIV DNA enters the host cell's nucleus, where an HIV enzyme (integrase) integrates the HIV DNA into the host cell's own DNA. This now-integrated DNA is called a provirus and may remain inactive for several years, producing few or no new copies of HIV.
4. Transcription: When the host cells receives a signal to activate, the provirus uses a host enzyme called "RNA polymerase" to create copies of the HIV RNA. The RNA is used as a template by host ribosomes to create HIV protein strands.
5. Assembly: An HIV enzyme, called protease, cuts the long chains of HIV proteins at specific sites into smaller individual proteins. These small proteins come together with copies of HIV's RNA genetic material, to create a new viral particle.
6. Budding: The new virus pushes out, or buds, from the host cell. During budding, the new viruses take part of the cell's outer envelope, which acts as a covering, and is studded with protein/sugar combinations, called HIV glycoproteins. These HIV glycoproteins are necessary for the virus to bind CD4 and co-receptors on other host cells. The new copies of HIV can then move on and infect other cells

Symptoms of acute infection

A person who is HIV positive does not automatically have AIDS. AIDS, by definition, is a syndrome with multiple specific symptoms. At least 50% of patients will have symptoms of acute retroviral syndrome within 2-3 months of infection. However, some individuals remain asymptomatic during this period.

Criteria for AIDS

A diagnosis of AIDS means that a patient's HIV disease has progressed to include .

1. CD4 count below 200 cells/mm3 (cubic milliliter) and/or
2. Development of an "AIDS-defining" condition which includes any of the following:
   • Candidiasis - bronchi, trachea, lungs or esophagus
   • Cervical cancer (invasive)
   • Coccidioidomycosis, Cryptococcosis (extrapulmonary)
   • Cryptosporidiosis other than chronic intestinal
   • Cytomegalovirus (other than liver, spleen, or nodes)
   • Encephalopathy (HIV-related)
   • HIV-associated Dementia (HAD)
   • Herpes simplex (severe)
   • Histoplasmosis
   • Isosporiasis
   • Kaposi's sarcoma
   • Lymphoma
   • Mycobacterium avium complex
   • Pneumocystis carinii (now Pneumocystis jiroveci) pneumonia
   • Pneumonia (recurrent)
   • Progressive multifocal leukoencephalopathy
   • Salmonella septicemia (recurrent)
   • Toxoplasmosis (of the brain)
   • Tuberculosis
   • Wasting syndrome