AIDS research

HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

Transmission

A body of scientific evidence has shown that men who are circumcised are less likely to contract HIV than men who are uncircumcised. Research published in 2014 concludes that the sex hormones estrogen and progesterone selectively impact HIV transmission.

Pre- and post-exposure prophylaxis

"Pre-exposure prophylaxis" refers to the practice of taking some drugs before being exposed to HIV infection, and having a decreased chance of contracting HIV as a result of taking that drug. Post-exposure prophylaxis refers to taking some drugs quickly after being exposed to HIV, while the virus is in a person's body but before the virus has established itself. In both cases, the drugs would be the same as those used to treat persons with HIV, and the intent of taking the drugs would be to eradicate the virus before the person becomes irreversibly infected.

Post-exposure prophylaxis is recommended in anticipated cases of HIV exposure, such as if a nurse somehow has blood-to-blood contact with a patient in the course of work, or if someone without HIV requests the drugs immediately after having unprotected sex with a person who might have HIV. Pre-exposure prophylaxis is sometimes an option for HIV-negative persons who feel that they are at increased risk of HIV infection, such as an HIV-negative person in a serodiscordant relationship with an HIV-positive partner.

Current research in these agents include drug development, efficacy testing, and practice recommendations for using drugs for HIV prevention.

Progression of HIV

The progression of HIV infection is analyzed by measuring the concentration of  HIV virions (or viral load) and the concentration of CD4 T cells in the patient's bloodstream and lymphoid tissues. An untreated infection will progress in the following phases: Acute phase, chronic phase, and AIDs phase. In the Acute phase, the virions invade the host body and replicate expeditiously. The concentration of the virions increase vastly, while the concentration of CD4 T cells declines. After a spiked replication of HIV, the  viral load and CD4 T cell count drops back down. Symptoms of acute HIV infection include fever, chills, rash, night sweats, muscle aches, and swollen lymph nodes. Acute symptoms occur usually 2–4 weeks after initial HIV infection and can last between a few days and several weeks

During the chronic phase, HIV will continue to replicate, but the concentration of virions tend to stabilize for a period of time before rising again. The CD4 T cell count continues to fall. Indviduals int the chronic phase may not experience any symptoms. Left untreated, the chronic stage can last between 10–15 years. However, some individuals can move through this stage quickly to the AIDS phase.

An untreated HIV infection ultimately progresses to AIDS (acquired immunodeficiency syndrome). In the AIDS phase, the CD4 T-cell count significantly drops to below 200 cells per cubic millimeter. Individuals with aids become immunocompromised due to irreversible  damage to the immune system and lymph nodes. The immune system does not have the ability to generate new T cells. Opportunistic infections, that a robust immune system could fight off, now are capable of causing severe symptoms and illnesses. Without a comprehensive anti-HIV drug therapy, an individual diagnosed with aids is expected to have less than three years to live.

Immune System Response to HIV

Once the retrovirus invades the body, the immune system mobilizes to fight against HIV infection. The first line of defense for the immune system utilizes dendritic cells. These cells actively patrol vulnerable tissue (i.e. lining of the digestive and reproductive tracts). Once a dendritic cell apprehends the virion invader, it will transport the virus to lymphoid tissue and introduce parts of the virus's proteins to Naive helper T cells (which are specialized white blood cells). The transported viral protein binds to the naive helper T cell's receptor, and the T cell activates. As the helper T cells grow and divide, they produce effecter helper T cells (which help coordinate the immune system response to HIV). The effector T cells utilize cytokines to mobilize other immune cells to join the combat against HIV. The cytokines promote the maturation of B cells into plasma cells. Then the plasma cells secrete antibodies that will bind to the HIV virions and target them for destruction. Finally, activated killer T-cells come in to eradicate the infected host cells.

Within-host dynamics

The within-host dynamics of HIV infection include the spread of the virus in vivo, the establishment of latency, the effects of immune response on the virus, etc. Early studies used simple models and only considered the cell-free spreading of HIV, in which virus particles bud from an infected T cell, enter the blood/extracellular fluid, and then infect another T cell. A 2015 study proposes a more realistic model of HIV dynamics that also incorporates the viral cell-to-cell spreading mechanism, where the virus is directly transited from one cell to another, as well as the T cell activation, the cellular immune response, and the immune exhaustion as the infection progresses.

Virus characteristics

HIV binds to immune cell surface receptors, including CD 4 and CXCR4 or CD4 and CCR5. The binding causes conformation changes and results in the membrane fusion between HIV and cell membrane. Active infection occurs in most cells, while latent infection occurs in much fewer cells 1, 2 and at very early stages of HIV infection. 9, 35 In active infection, HIV pro virus is active and HIV virus particles are actively replicated; and the infected cells continuously release viral progeny; while in latent infection, HIV pro virus is transcriptionally silenced and no viral progeny is produced.

Management of HIV/AIDS

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining better sequences of regimens to manage drug resistance. There are variations in the health community in recommendations on what treatment doctors should recommend for people with HIV. One question, for example, is determining when a doctor should recommend that a patient take antiretroviral drugs and what drugs a doctor may recommend. This field also includes the development of antiretroviral drugs.

Age acceleration effects due to HIV-1 infection

Infection with the Human Immunodeficiency Virus-1 (HIV) is associated with clinical symptoms of accelerated aging, as evidenced by increased incidence and diversity of age-related illnesses at relatively young ages. A significant age acceleration effect could be detected in brain (7.4 years) and blood (5.2 years) tissue due to HIV-1 infection
with the help of a biomarker of aging, which is known as epigenetic clock.

Long-term nonprogressor

A long-term nonprogressor is a person who is infected with HIV, but whose body, for whatever reason, naturally controls the virus so that the infection does not progress to the AIDS stage. Such persons are of great interest to researchers, who feel that a study of their physiologies could provide a deeper understanding of the virus and disease. There are also two cases where HIV was apparently entirely cleared by a person's immune system without a therapy.

HIV vaccine

An HIV vaccine is a vaccine that would be given to a person who does not have HIV, in order to confer protection against subsequent exposures to HIV, thus reducing the likelihood that the person would become infected by HIV. Currently, no effective HIV vaccine exists. Various HIV vaccines have been tested in clinical trials almost since the discovery of HIV.

Only a vaccine is thought to be able to halt the pandemic. This is because a vaccine would cost less, thus being affordable for developing countries, and would not require daily treatment. However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.

In 2003 a clinical trial in Thailand tested an HIV vaccine called RV 144. In 2009, the researchers reported that this vaccine showed some efficacy in protecting recipients from HIV infection (31% efficiency). Results of this trial give the first supporting evidence of any vaccine being effective in lowering the risk of contracting HIV. Other vaccine trials continue worldwide including a mosaic vaccine using an adenovirus 26 vector as well as a newer formulation of RV144 called HVTN 702.

One recent trial was conducted by scientists at The Scripps Research Institute (TSRI) who found a way to attach HIV-fighting antibodies to immune cells, creating a HIV-resistant cell population.

HIV cure

Three people have been reported cured of AIDS. In 2019, the NIH and Bill & Melinda Gates Foundation announced making $200 million available for broad-based, multi-prong scientific efforts focused on developing a global cure for AIDS as well as for sickle cell disease, with NIH Director Francis S. Collins saying, "We aim to go big or we go home." In 2020, Dr. Tony Fauci’s division at NIH, NIAID, issued its first solicitation exclusively focused on methods to cure HIV infection. These announcements from NIH are not limited to stem cell therapies.

Excision is a biotechnology company with ''a first''-in-human CRISPR-based one-time gene therapy to be evaluated in individuals with HIV. Research Foundation to Cure AIDS is the first 501(c)(3) non-for-profit organization with a royalty-free license to research, develop and commercialize a cell engineering technology in the field of curing AIDS on a pro bono basis.

Microbicides for sexually transmitted diseases

A microbicide for sexually transmitted diseases is a gel which would be applied to the skin – perhaps a rectal microbicide for persons who engage in anal sex or a vaginal microbicide for persons who engage in vaginal sex – and if infected body fluid such as blood or semen were to touch the gel, then HIV in that fluid would be destroyed and the people having sex would be less likely to spread infection between themselves.

On March 7, 2013, the Washington University in St. Louis website published a report by Julia Evangelou Strait, in which it was reported that ongoing