Contributors:Ursula Florjanczyk, MScBMC, Tina Collins, Rachel Yancey, Anna Hernández, MD, Katrina Mikitik, RN
Human immunodeficiency virus, or HIV for short, is a retrovirus that targets the body’s immune system. Over time, HIV infection can lead to acquired immune deficiency syndrome or AIDS for short, making clients more vulnerable to other infections and certain tumors that a healthy immune system would usually be able to fend off.
All right, let’s quickly review some physiology. The immune system consists of white blood cells that protects us from pathogens, and destroys tumor cells. Now, the immune system has two main branches that work together, and include the innate and the adaptive immune responses.
So, the first is the innate immune response, which involves non-specific cells like neutrophils and macrophages that act as first-responders, as well as dendritic cells, which then activate the adaptive immune response. This response is highly specific, and is mediated by cells called lymphocytes, which include T and B cells. T cells can be further divided into CD4+ and CD8+ T cells. CD4+ T cells are also known as T helper cells, because they interact with dendritic cells, and in turn help activate the rest of the lymphocytes. On the other hand, CD8+ T cells, also known as cytotoxic T cells, are in charge of cell-mediated immunity, where they attack abnormal cells. Finally, B cells mediate a type of adaptive response, called humoral immunity, by secreting antibodies that bind to and destroy specific antigens.
Now, HIV infection is primarily caused by contact with certain bodily fluids from an infected person, such as blood, semen, vaginal and anal secretions, and breast milk. However, HIV is not present in saliva, sweat, urine, or feces.
The main risk factors for contracting HIV include having unprotected sex, especially anal sex, as well as having multiple or anonymous sexual partners. Other risk factors include using intravenous drugs, especially sharing needles, or unsterile cutting or piercing, as well as accidental needlesticks, and transfusing blood products from an infected donor. To prevent this, blood donations are always screened for infections like HIV, among others. Finally, pregnant clients are at risk of transmitting the infection to their fetus, either via the placenta or during childbirth, and afterwards via breastfeeding.
All right, so once HIV enters the body, it infects CD4+ T cells by binding to the CCR5 or CXCR4 receptors on the T cell’s membrane, and then inserting its viral RNA, as well as some viral enzymes. Within the cell, this viral RNA is transformed into DNA by a viral enzyme called reverse transcriptase. This viral DNA is then integrated into the host’s DNA by another viral enzyme called integrase. As a result, whenever the infected cell transcribes and translates its own DNA into RNA and proteins, it will end up inadvertently transcribing and translating HIV’s RNA and proteins too! Finally, a viral enzyme called protease cleaves the HIV proteins to assemble new HIV particles. Ultimately, these new HIV particles bud off from the cell membrane, destroying the infected cell, in order to infect more CD4+ T cells and keep replicating.
Okay, now HIV infection has four clinical stages. The first one is the acute stage, which is characterized by a big spike in HIV replication, while the T cell count declines dramatically. HIV replication continues to increase until it peaks at about week 6 from the primary infection. At this point, clients may begin to experience flu-like symptoms, such as fever, fatigue, lymphadenopathy, and joint or muscle aches. These symptoms typically last for about 2 weeks, during which the immune system mounts a counterattack. As a result, the viral count declines, while the T cell count rises again. This stage typically lasts for 2 months.
As the virus declines, the HIV infection enters its second stage, which is the chronic or clinically latent stage. Now, during this stage, the T cell count usually remains between 350 and 499 cells/mm3 HIV keeps slowly replicating in the lymph nodes, while the T cell count gradually decreases. As a consequence, the immune system progressively weakens; this can result in the reactivation of some latent or dormant infections, such as herpes simplex virus causing herpes, varicella-zoster virus causing shingles, as well as Mycobacterium spp. causing tuberculosis. This stage can last anywhere between 2 to 10 years.
Over time, the viral count keeps increasing as the T cell count progressively decreases, until it drops low enough, between about 200 to 349 cells/mm3 At this stage, clients become moderately immunocompromised, and may start developing relatively minor infections from opportunistic pathogens, such as Candida albicans causing oral thrush, or Epstein-Barr virus causing oral hairy leukoplakia. In addition, the client may develop unexplained symptoms, including persistent fever, severe weight loss, and diarrhea that lasts longer than 1 month, as well as ulcerative stomatitis or gingivitis.Finally, as the viral count continues to increase, the T cell count falls below 200 cells/mm3, leading to the fourth stage of HIV infection, called AIDS.
At this point, the client becomes severely immunocompromised and may present with some serious “AIDS-defining” conditions, caused by pathogens that a healthy immune system would typically be able to kill. These include bacteria like Streptococcus pneumoniae causing recurrent community-acquired pneumonia; as well as fungi like Pneumocystis jirovecii causing pneumocystis pneumonia, Histoplasma capsulatum causing histoplasmosis, Aspergillus fumigatus causing aspergillosis, and Cryptococcus neoformans causing pulmonary cryptococcosis or even cryptococcal meningitis; in addition to parasites like Toxoplasma gondii causing toxoplasmosis; and viruses like JC virus causing progressive multifocal leukoencephalopathy. Other conditions include tumors like Kaposi sarcoma and primary CNS lymphoma. Unfortunately, at this stage, many clients die from these “AIDS-defining” conditions.
Wow, that was a lot! To help you remember the four clinical stages of HIV infection, think of the Four Fs. The first F stands for the Flu-like symptoms characteristic of the acute stage. Then second F is when the client Feels Fine during the clinically latent stage. After that, there’s a Falling T cell count, which leads to the symptomatic stage. And lastly, there’s the Final crisis, where HIV infection progresses to AIDS.
Diagnosis of HIV starts with the client’s history and physical assessment; followed by laboratory tests. These include an antibody/antigen immunoassay to detect antibodies against the virus as well as the viral protein p24. A positive immunoassay result gives a presumptive diagnosis, which means that the infection is likely, but still needs to be confirmed with another test, such as an antibody test to look for antibodies against HIV; as well as nucleic acid tests, or NATs for short, to look for the viral RNA.
Once the diagnosis of HIV is confirmed, it is important to determine the disease stage; this involves T cell count, as well as an HIV viral load, such as PCR testing, which allows to determine the amount of viral RNA in the client’s blood.
Unfortunately, there’s no cure for HIV, but clients can be prescribed an HIV treatment regimen that can help them live longer and reduce the risk of transmission. The HIV treatment regimen involves antiretroviral therapy, or ART for short, which typically combines three antiretroviral medications.
There are seven main classes of antiretrovirals. The most widely used are nucleoside reverse transcriptase inhibitors, or NRTIs, which include zidovudine, stavudine, lamivudine, didanosine, abacavir, and tenofovir; as well as non-nucleoside reverse transcriptase inhibitors, or NNRTIs, such as efavirenz and nevirapine. The third antiretroviral class are integrase strand transfer inhibitors, or INSTIs for short, which include raltegravir, elvitegravir, and dolutegravir. The next class are protease inhibitors or PIs, which include atazanavir, darunavir, indinavir, lopinavir, saquinavir, and ritonavir! Then there’s fusion inhibitors, also known as entry inhibitors, which include enfuvirtide; as well as attachment inhibitors like fostemsavir. The last class are CCR5 antagonists, which only comprises maraviroc. If antiretroviral therapy fails to control the disease, HIV drug resistance testing is recommended.