Articles on HIV-AIDS
Human immunodeficiency virus (HIV) facts
- The human immunodeficiency virus (HIV) is a type of virus called a retrovirus, which can infect humans when it comes in contact with tissues that line the vagina, anal area, mouth, or eyes, or through a break in the skin.
- HIV infection is generally a slowly progressive disease in which the virus is present throughout the body at all stages of the disease.
- Three stages of HIV infection have been described.
- The initial stage of infection (primary infection), which occurs within weeks of acquiring the virus, often is characterized by a flu-like or mono-like illness that generally resolves within weeks.
- The stage of chronic asymptomatic infection (meaning a long duration of infection without symptoms) lasts an average of eight to 10 years without treatment.
- The stage of symptomatic infection, in which the body's immune (or defense) system has been suppressed and complications have developed, is called the acquired immunodeficiency syndrome (AIDS). The symptoms are caused by the complications of AIDS, which include one or more unusual infections or cancers, severe loss of weight, and intellectual deterioration (called dementia).
- When HIV grows (that is, by reproducing itself), it acquires the ability to change (mutate) its own structure. These mutations enable the virus to become resistant to previously effective drug therapy.
- The goals of drug therapy are to prevent damage to the immune system by the HIV virus and to halt or delay the progress of the infection to symptomatic disease.
- Therapy for HIV includes combinations of drugs that decrease the growth of the virus to such an extent that the treatment prevents or markedly delays the development of viral resistance to the drugs.
- The best combination of drugs for HIV are those that effectively suppress viral replication in the blood and also are well tolerated and simple to take so that people can take the medications consistently without missing doses.
HIV vs. AIDS: Epidemic History and Drug Discovery
The history of the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) dates back to 1981, when gay men with symptoms and signs of a disease that now are considered typical of AIDS were first described in Los Angeles and New York. The men had an unusual type of lung infection (pneumonia) called Pneumocystis carinii (now known as Pneumocystis jiroveci) pneumonia (PCP) and rare skin tumors called Kaposi's sarcomas.
The patients were noted to have a severe reduction in a type of cell in the blood (CD4 cells) that is an important part of the immune system. These cells, often referred to as T cells, help the body fight infections. Shortly thereafter, this disease was recognized throughout the United States, Western Europe, and Africa. In 1983, researchers in the United States and France described the virus that causes AIDS, now known as HIV, belonging to the group of viruses called retroviruses.
While HIV infection is required to develop AIDS, the actual definition of AIDS is the development of a low CD4 cell count (<200 cells/mm3) or any one of a long list of complications of HIV infection ranging from a variety of so-called "opportunistic infections," cancers, neurologic symptoms, and wasting syndromes.
What tests are used in the diagnosis of HIV?
The test that for decades had been most commonly used for diagnosing infection with HIV was referred to as an ELISA. If the ELISA blood test found HIV antibodies, the results needed to be confirmed, typically by a test called a Western blot. Recently, tests have become available to look for these same antibodies in saliva, some providing results within one to 20 minutes of testing. As a result, the FDA has approved home HIV antibody testing that is self-administered using saliva. Antibodies to HIV typically develop within several weeks of infection. During this interval, patients have virus in their body but will test negative by the standard antibody test, the so-called "window period."
In order to decrease the number of people that are unaware of their HIV infection status, in 2006, the Centers for Disease Control and Prevention recommended that all people between 13 and 64 years of age be provided HIV testing whenever they encounter the health care system for any reason. In addition, resources are available to facilitate people finding local HIV testing centers (https://gettested.cdc.gov/).
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How is HIV spread (transmitted)?
In people infected with HIV, the virus appears in the blood and genital fluids. HIV spreads from person to person when genital fluids are exchanged during sex, through sharing needles for intravenous recreational drugs, or from mother to child in pregnancy, labor, or breastfeeding.
Sexual transmission is possible in vaginal, anal and oral sex between partners of any gender. Abstinence is the only sure way to prevent transmission, but safer sex practices like condoms and dental dams can help reduce the risk. Exposure to infected blood through transfusion or in the course of duty as a paramedic or other first responder is another transmission pathway. Transfusions in the U.S. are screened for HIV, so the risk of contracting it through donated blood is low in that country.
People who are infected with HIV can drastically reduce the risk of transmission to their sex partner by sticking to treatment and monitoring; if the viral levels are undetectable in the lab, the chances of transmission are low. This is also a strategy for long-term partners of people with HIV – Pre-exposure prophylaxis (or PrEP) refers to antiviral drugs administered to non-infected individuals at high risk of infection, such as the HIV-free partners of people with HIV.
What laboratory tests are used to monitor HIV-infected people?
Two blood tests are routinely used to monitor HIV-infected people. One of these tests, which counts the number of CD4 cells, assesses the status of the immune system. The other test, which determines the so-called viral load, directly measures the amount of virus in the blood (viral load).
Drug-resistance testing also has become a key tool in the management of HIV-infected individuals. Clearly, resistance testing is now routinely used in individuals experiencing poor responses to HIV therapy or treatment failure.
What is the initial therapy for HIV?
In the United States, guidelines for using antiviral therapy have been developed and are updated on a regular basis by an expert panel assembled by the Department of Health and Human Services (DHHS), the International Antiviral Society-USA (IAS-USA) panel, and others. The DHHS guidelines are available at https://aidsinfo.nih.gov/. The most recent IAS-USA guidelines were published in the Journal of the American Medical Association (JAMA) in the summer of 2018.
Antiviral treatment options have primarily included combinations of two nucleotide analogue reverse transcriptase inhibitors (NRTIs). NRTIs, often referred to as "nucs," and a third drug, typically being a boosted protease inhibitors (PI), a nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) often called "non-nucs," and integrase strand transfer inhibitors (InSTIs) such as RAL (raltegravir), EVG (elvitegravir), DTG (dolutegravir) or bictegravir (BIC). Many of these drugs are available in fixed-dose combinations[TA1] .
The following are the different drug types currently used in treatment regimens for HIV:
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Monitoring antiviral therapy
The goals of antiviral therapy are to enhance immunity and delay or prevent clinical advancement to symptomatic disease without inducing important side effects or selecting for drug-resistant virus. Currently, the best marker of a drug's activity is a decrease in the viral load.
What are the risks of missing doses or stopping antiviral therapy?
It is strongly advised that individuals on an antiviral regimen not miss any doses of their medications. Unfortunately, life is such that doses often are missed. Reasons for missing doses range from just forgetting to take the medication, leaving town without the medication, or because of a medical emergency, such as the need for urgent surgery. For example, after an appendectomy for acute appendicitis, a patient may not be able to take oral medication for up to several days. When a dose is missed, the patient should contact his or her physician without delay to discuss the course of action. The options in this situation are to take the missed doses immediately or simply resume the drugs with the next scheduled dose.
Although every missed dose increases the chance that the virus will develop resistance to the drugs, a single missed dose should not be cause for alarm. On the contrary, it is an opportunity to learn from the experience and determine why it happened, if it is likely to happen again, and what can be done to minimize missing future doses. Furthermore, if a patient cannot resume medication for a limited time, such as in a medical emergency, there still is no cause for alarm. In this circumstance, the patient should work with their HIV provider to restart therapy as soon as is feasible. Stopping antivirals is associated with some risks of developing drug resistance, and those who wish to stop therapy for any one of a number of reasons should discuss this with their health care professional in advance to establish the best strategy for safely accomplishing this.
What is the future for HIV-infected individuals with regards to treatment simplification and cure research?
Trends continue toward simplifying drug regimens to improve adherence and decrease side effects. In addition, the availability of multiple new drugs in new classes has made it possible to suppress viral load to undetectable levels even in many of the most treatment-experienced patients. Moreover, many are virologically suppressed taking a single well-tolerated pill per day. Another major advance could emerge with the availability of every one to two month injections of long-acting therapies.
With great success in treatment, the field has increasingly considered strategies that may someday allow patients to control viral replication without the use of antiretrovirals. This could be in the form of a true cure with complete eradication of HIV from the body or a functional cure where the virus persists but is unable to replicated, a situation analogous to what happens when patients are on effective antiretroviral therapy. Research is in the very earliest stages with regard to development of strategies for viral eradication. Studies to control viral replication in the absence of antiretroviral therapy are actively being pursued, although thus far with limited success. One strategy has been to use immune-based therapies to boost the natural immune response to HIV and allow for complete or partial control. Another area of research is to purge infected cells, so-called "latent reservoir," with various agents to facilitate eradication from the body. While research in these areas is under way, it has met with limited success.
The report of the so-called "Berlin patient" has stimulated a great deal of interest in cure research. This HIV-infected man had leukemia, which was treated with a bone marrow transplant. His health care providers were able to identify a tissue-matched donor who happened to be one of the rare individuals who carried a genetic defect resulting in the lack of CCR5 on the surface of their cells. CCR5 is required for certain types of HIV to enter the cells, and these unique individuals are relatively resistant to infection. After the bone marrow transplant, the patient was able to stop antiretroviral therapy and for years has not had detectable HIV in his body. It is worth noting that this individual experienced far more than the engraftment of unique bone marrow. He underwent intensive chemotherapy and radiation treatment to destroy most immune cells in the body, as well as graft-versus-host disease, which could have also further destroyed residual HIV-infected cells.
Together these events could have markedly reduced the reservoir of virus that persists in the body of all infected individuals, which could have facilitated the purported "cure" or set the stage for the ultimate success associated with the engraftment of the unique bone marrow. There was recently excitement about two individuals who underwent so-called "stem cell transplants" but without the unique donor that was used by the Berlin patient. While virus remained at very low levels in these individuals while on therapy, at three and eight months after treatment interruption, HIV came back.
Consequently, the experience with the Berlin patient has not yet been replicated and, even if it is, will not be an option for most people. First, bone marrow transplants are associated with very high risk of illness and death, and second, very few patients who need a bone marrow transplant for any reason are likely to find a tissue-matched donor who carries this rare genetic mutation. However, research is pursuing the potential role each part of this individual's treatment may have had on the successful control of HIV off therapy, as well as working on ways to genetically engineer an individual's own blood CD4 cells or stem cells to not have the CCR5 molecule. While this research is in the very early stages of development, it certainly provides hope for the future of research related to HIV eradication and/or cure.
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DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. "Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents." Washington D.C.: Department of Health and Human Services, 2018. <https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf>
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