Human Immunodeficiency Virus

Share


A micrograph of tiny green particles on the surface of a cell.
This micrograph shows HIV particles (green) budding from a lymphocyte (top right). (credit: modification of work by Centers for Disease Control and Prevention)

OpenStax Microbiology

Human T-lymphotropic viruses (HTLV), also called human immunodeficiency viruses (HIV) are retroviruses that are the causative agent of acquired immune deficiency syndrome (AIDS). There are two main variants of human immunodeficiency virus (HIV). HIV-1 occurs in human populations worldwide, whereas HIV-2 is concentrated in West Africa. Currently, the most affected region in the world is sub-Saharan Africa, with an estimated 25.6 million people living with HIV in 2015. Sub-Saharan Africa also accounts for two-thirds of the global total of new HIV infections.

Map of global prevalence of HIV in 2015. Global rate is 0.8%. Middle East and North Africa = 0.1%. Asia and the Pacific = 0.2%. Western and Central Europe and North America = 0.3%. Latin America and the Caribbean = 0.5%. Eastern Europe and Central Asia = 0.9%. West and Central Africa = 2.2%. East and Southern Africa = 7.1%
This map shows the prevalence of HIV worldwide in 2015 among adults ages 15–49 years.
Source: OpenStax Microbiology

HIV is spread through direct contact with body fluids. Casual contact and insect vectors are not sufficient for disease transmission; common modes of transmission include sexual contact and sharing of needles by intravenous (IV) drug users. It generally takes many years before the effects of an HIV infection are detected. HIV infections are not dormant during this period: virions are continually produced, and the immune system continually attempts to clear the viral infection, while the virus persistently infects additional CD4 T cells. Over time, the CD4 T-cell population is devastated, ultimately leading to AIDS.

When people are infected with HIV, their disease progresses through three stages based on CD4 T-cell counts and the presence of clinical symptoms.

  • Stage 1: Acute HIV infection. Two to 4 weeks after infection with HIV, patients may experience a flu-like illness, which can last for a few weeks. Patients with acute HIV infection have more than 500 cells/μL CD4 T cells and a large amount of virus in their blood. Patients are very contagious during this stage. To confirm acute infection, either a fourth-generation antibody-antigen test or a nucleic acid test (NAT) must be performed.
  • Stage 2: Clinical latency. During this period, HIV enters a period of dormancy. Patients have between 200 and 499 cells/μL CD4 T cells; HIV is still active but reproduces at low levels, and patients may not experience any symptoms of illness. For patients who are not taking medicine to treat HIV, this period can last a decade or longer. For patients receiving antiretroviral therapy, the stage may last for several decades, and those with low levels of the virus in their blood are much less likely to transmit HIV than those who are not virally suppressed. Near the end of the latent stage, the patient’s viral load starts to increase and the CD4 T-cell count begins to decrease, leading to the development of symptoms and increased susceptibility to opportunistic infections.
  • Stage 3: Acquired immunodeficiency syndrome (AIDS). Patients are diagnosed with AIDS when their CD4 T-cell count drops below 200 cells/μL or when they develop certain opportunistic illnesses. During this stage, the immune system becomes severely damaged by HIV. Common symptoms of AIDS include chills, fever, sweats, swollen lymph glands, weakness, and weight loss; in addition, patients often develop rare cancers such as Kaposi’s sarcoma and opportunistic infections such as Pneumocystis pneumonia,  tuberculosis, cryptosporidiosis, and toxoplasmosis. This is a fatal progression that, in the terminal stages, includes wasting syndrome and dementia complex. Patients with AIDS have a high viral load and are highly infectious; they typically survive about 3 years without treatment.
A graph with time on the X axis and two Y axes – CD4+ T  lymphocyte count (cells/mm cubed) and HIV RNA copies per ml plasma. The primary infection is set at time 0 when there is a high CD4 count (over 1000) and a low RNA count (near 0). During the first weeks -  macrophage infection, increase in virus production and HIV-1 reservoirs. At about 6 weeks – acute HIV syndrome, wide dissemination of virus, seeding of lymphoid organs. During this time the RNA count increases to about 10 to the 6 and the CD4 count decreases to about 500. From 9 weeks to about 12 weeks the CD4 count increases and the RNA count decreases. From 9 weeks to about 7 years is classic latency –  T-cell depletion/immune dysfunction and neurocognitive impairment.  During this time CD4 count steadily decreases to near 0 and RNA count steadily increases to over 10 to the 6.  Constitutional symptoms occur at about 8 years. After this, opportunistic diseases occur; HIV-D and HIVAN. Then death.
This graph shows the clinical progression of CD4 T cells (blue line), clinical symptoms, and viral RNA (red line) during an HIV infection. (credit: modification of work by Kogan M, and Rappaport J)

The initial diagnosis of HIV is performed using a serological test for antibody production against the pathogen. Positive test results are confirmed by Western blot or PCR tests. It can take weeks or months for the body to produce antibodies in response to an infection. There are fourth-generation tests that detect HIV antibodies and HIV antigens that are present even before the body begins producing antibodies. Nucleic acid tests (NATs) are a third type of test that is relatively expensive and uncommon; NAT can detect HIV in blood and determine the viral load.

As a consequence of provirus formation, it is currently not possible to eliminate HIV from an infected patient’s body. Elimination by specific antibodies is ineffective because the virus mutates rapidly—a result of the error-prone reverse transcriptase and the inability to correct errors. Antiviral treatments, however, can greatly extend life expectancy. To combat the problem of drug resistance, combinations of antiretroviral drugs called antiretroviral therapy (ART), sometimes called highly active ART or combined ART, are used. There are several different targets for antiviral drug action (and a growing list of drugs for each of these targets). One class of drugs inhibits HIV entry; other classes inhibit reverse transcriptase by blocking viral RNA-dependent and DNA-dependent DNA polymerase activity; and still others inhibit one of the three HIV enzymes needed to replicate inside human cells.

Source:

Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/microbiology


Advertisements
Advertisements

Leave a Reply